Sample records for treatment delivery strategies

  1. Drug delivery strategies for Alzheimer's disease treatment.

    PubMed

    Di Stefano, Antonio; Iannitelli, Antonio; Laserra, Sara; Sozio, Piera

    2011-05-01

    Current Alzheimer's disease (AD) therapy is based on the administration of the drugs donepezil, galantamine, rivastigmine and memantine. Until disease-modifying therapies become available, further research is needed to develop new drug delivery strategies to ensure ease of administration and treatment persistence. In addition to the conventional oral formulations, a variety of drug delivery strategies applied to the treatment of AD are reviewed in this paper, with a focus on strategies leading to simplified dosage regimens and to providing new pharmacological tools. Alternatives include extended release, orally disintegrating or sublingual formulations, intranasal or short- and long-acting intramuscular or transdermal forms, and nanotechnology-based delivery systems. The advent of new research on molecular mechanisms of AD pathogenesis has outlined new strategies for therapeutic intervention; these include the stimulation of α-secretase cleavage, the inhibition of γ-secretase activity, the use of non-steroidal anti-inflammatory drugs, neuroprotection based on antioxidant therapy, the use of estrogens, NO synthetase inhibitors, and natural agents such as polyphenols. Unfortunately, these compounds might not help patients with end stage AD, but might hopefully slow or stop the disease process in its early stage. Nanotechnologies may prove to be a promising contribution in future AD drug delivery strategies, in particular drug carrier nano- or microsystems, which can limit the side effects of anti-Alzheimer drugs.

  2. Current challenges and emerging drug delivery strategies for the treatment of psoriasis.

    PubMed

    Hoffman, Melissa B; Hill, Dane; Feldman, Steven R

    2016-10-01

    Psoriasis is a common skin disorder associated with physical, social, psychological and financial burden. Over the past two decades, advances in our understanding of pathogenesis and increased appreciation for the multifaceted burden of psoriasis has led to new treatment development and better patient outcomes. Yet, surveys demonstrate that many psoriasis patients are either undertreated or are dissatisfied with treatment. There are many barriers that need be overcome to optimize patient outcomes and satisfaction. This review covers the current challenges associated with each major psoriasis treatment strategy (topical, phototherapy, oral medications and biologics). It also reviews the challenges associated with the psychosocial aspects of the disease and how they affect treatment outcomes. Patient adherence, inconvenience, high costs, and drug toxicities are all discussed. Then, we review the emerging drug delivery strategies in topical, oral, and biologic therapy. By outlining current treatment challenges and emerging drug delivery strategies, we hope to highlight the deficits in psoriasis treatment and strategies for how to overcome them. Regardless of disease severity, clinicians should use a patient-centered approach. In all cases, we need to balance patients' psychosocial needs, treatment costs, convenience, and effectiveness with patients' preferences in order to optimize treatment outcomes.

  3. [The development of novel tumor targeting delivery strategy].

    PubMed

    Gao, Hui-le; Jiang, Xin-guo

    2016-02-01

    Tumor is one of the most serious threats for human being. Although many anti-tumor drugs are approved for clinical use, the treatment outcome is still modest because of the poor tumor targeting efficiency and low accumulation in tumor. Therefore, it is important to deliver anti-tumor drug into tumor efficiently, elevate drug concentration in tumor tissues and reduce the drug distribution in normal tissues. And it has been one of the most attractive directions of pharmaceutical academy and industry. Many kinds of strategies, especially various nanoparticulated drug delivery systems, have been developed to address the critical points of complex tumor microenvironment, which are partially or mostly satisfied for tumor treatment. In this paper, we carefully reviewed the novel targeting delivery strategies developed in recent years. The most powerful method is passive targeting delivery based on the enhanced permeability and retention(EPR) effect, and most commercial nanomedicines are based on the EPR effect. However, the high permeability and retention require different particle sizes, thus several kinds of size-changeable nanoparticles are developed, such as size reducible particles and assemble particles, to satisfy the controversial requirement for particle size and enhance both tumor retention and penetration. Surface charge reversible nanoparticles also shows a high efficiency because the anionic charge in blood circulation and normal organs decrease the unintended internalization. The charge can change into positive in tumor microenvironment, facilitating drug uptake by tumor cells. Additionally, tumor microenvironment responsive drug release is important to decrease drug side effect, and many strategies are developed, such as p H sensitive release and enzyme sensitive release. Except the responsive nanoparticles, shaping tumor microenvironment could attenuate the barriers in drug delivery, for example, decreasing tumor collagen intensity and normalizing tumor

  4. Gene Delivery Strategies to Promote Spinal Cord Repair

    PubMed Central

    Walthers, Christopher M; Seidlits, Stephanie K

    2015-01-01

    Gene therapies hold great promise for the treatment of many neurodegenerative disorders and traumatic injuries in the central nervous system. However, development of effective methods to deliver such therapies in a controlled manner to the spinal cord is a necessity for their translation to the clinic. Although essential progress has been made to improve efficiency of transgene delivery and reduce the immunogenicity of genetic vectors, there is still much work to be done to achieve clinical strategies capable of reversing neurodegeneration and mediating tissue regeneration. In particular, strategies to achieve localized, robust expression of therapeutic transgenes by target cell types, at controlled levels over defined time periods, will be necessary to fully regenerate functional spinal cord tissues. This review summarizes the progress over the last decade toward the development of effective gene therapies in the spinal cord, including identification of appropriate target genes, improvements to design of genetic vectors, advances in delivery methods, and strategies for delivery of multiple transgenes with synergistic actions. The potential of biomaterials to mediate gene delivery while simultaneously providing inductive scaffolding to facilitate tissue regeneration is also discussed. PMID:25922572

  5. Delivery strategies for treatment of age-related ocular diseases: From a biological understanding to biomaterial solutions.

    PubMed

    Delplace, Vianney; Payne, Samantha; Shoichet, Molly

    2015-12-10

    Age-related ocular diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, result in life-long functional deficits and enormous global health care costs. As the worldwide population ages, vision loss has become a major concern for both economic and human health reasons. Due to recent research into biomaterials and nanotechnology major advances have been gained in the field of ocular delivery. This review provides a summary and discussion of the most recent strategies employed for the delivery of both drugs and cells to the eye to treat a variety of age-related diseases. It emphasizes the current challenges and limitations to ocular delivery and how the use of innovative materials can overcome these issues and ultimately provide treatment for age-related degeneration and regeneration of lost tissues. This review also provides critical considerations and an outlook for future studies in the field of ophthalmic delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Nanotechnological Strategies for Protein Delivery.

    PubMed

    Villegas, María Rocío; Baeza, Alejandro; Vallet-Regí, María

    2018-04-25

    The use of therapeutic proteins plays a fundamental role in the treatment of numerous diseases. The low physico-chemical stability of proteins in physiological conditions put their function at risk in the human body until they reach their target. Moreover, several proteins are unable to cross the cell membrane. All these facts strongly hinder their therapeutic effect. Nanomedicine has emerged as a powerful tool which can provide solutions to solve these limitations and improve the efficacy of treatments based on protein administration. This review discusses the advantages and limitations of different types of strategies employed for protein delivery, such as PEGylation, transport within liposomes or inorganic nanoparticles or their in situ encapsulation.

  7. Multidisciplinary perspectives for Alzheimer's and Parkinson's diseases: hydrogels for protein delivery and cell-based drug delivery as therapeutic strategies.

    PubMed

    Giordano, Carmen; Albani, Diego; Gloria, Antonio; Tunesi, Marta; Batelli, Sara; Russo, Teresa; Forloni, Gianluigi; Ambrosio, Luigi; Cigada, Alberto

    2009-12-01

    This review presents two intriguing multidisciplinary strategies that might make the difference in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The first proposed strategy is based on the controlled delivery of recombinant proteins known to play a key role in these neurodegenerative disorders that are released in situ by optimized polymer-based systems. The second strategy is the use of engineered cells, encapsulated and delivered in situ by suitable polymer-based systems, that act as drug reservoirs and allow the delivery of selected molecules to be used in the treatment of Alzheimer's and Parkinson's diseases. In both these scenarios, the design and development of optimized polymer-based drug delivery and cell housing systems for central nervous system applications represent a key requirement. Materials science provides suitable hydrogel-based tools to be optimized together with suitably designed recombinant proteins or drug delivering-cells that, once in situ, can provide an effective treatment for these neurodegenerative disorders. In this scenario, only interdisciplinary research that fully integrates biology, biochemistry, medicine and materials science can provide a springboard for the development of suitable therapeutic tools, not only for the treatment of Alzheimer's and Parkinson's diseases but also, prospectively, for a wide range of severe neurodegenerative disorders.

  8. Novel drug delivery strategies for porphyrins and porphyrin precursors

    NASA Astrophysics Data System (ADS)

    Morrow, D. I. J.; Donnelly, R. F.

    2009-06-01

    superficial lesions, such as actinic keratosis. In addition, photodynamic antimicrobial chemotherapy (PACT) is attracting increasing interest for the treatment of infection. However, delivery strategies for topical PDT and PACT are still based on application of rather simplistic cream and solution formulations, with little consideration given to thermodynamics, targeting or the physicochemical properties of the active agent. Purpose-designed dosage forms for topical delivery of aminolevulinic acid or its esters include creams containing penetration enhancers and/or iron chelators, pressure sensitive patches and bioadhesive patches. Such systems aim to enhance drug delivery across the stratum corneum and keratinised debris overlying neoplastic lesions and improve subsequent protoporphyrin IX (PpIX) production. The alternative to using porphyrin precursors is the use of pre-formed photosensitisers. However, owing to their relatively high molecular weights, conventional topical application is not appropriate. Innovative strategies, such as the use of needle-free injections and microneedle arrays, bypass the stratum corneum, enabling rapid and targeted delivery not only porphyrin precursors but also pre-formed photosensitisers. This presentation will review drug delivery work published to date in the fields of PDT and PACT. In addition, the benefits of employing the latest advances in pharmaceutical technology will be highlighted.

  9. Current and emerging formulation strategies for the effective transdermal delivery of HIV inhibitors.

    PubMed

    Ham, Anthony S; Buckheit, Robert W

    2015-02-01

    Current and emerging formulation strategies for skin permeation are poised to open the transdermal drug delivery to a broader range of small molecule compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Transdermal drug delivery offers several distinct advantages over traditional dosage forms. Current antiretroviral drugs used for the treatment of HIV infection include a variety of highly active small molecule compounds with significantly limited skin permeability, and thus new and novel means of enhancing transport through the skin are needed. Current and emerging formulation strategies are poised to open the transdermal drug delivery to a broader range of compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Thus, with continuing research into skin permeability and patch formulation strategies, there is a large potential for antiretroviral transdermal drug delivery.

  10. Current and emerging formulation strategies for the effective transdermal delivery of HIV inhibitors

    PubMed Central

    Ham, Anthony S; Buckheit, Robert W

    2015-01-01

    Current and emerging formulation strategies for skin permeation are poised to open the transdermal drug delivery to a broader range of small molecule compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Transdermal drug delivery offers several distinct advantages over traditional dosage forms. Current antiretroviral drugs used for the treatment of HIV infection include a variety of highly active small molecule compounds with significantly limited skin permeability, and thus new and novel means of enhancing transport through the skin are needed. Current and emerging formulation strategies are poised to open the transdermal drug delivery to a broader range of compounds that do not fit the traditional requirements for successful transdermal drug delivery, allowing the development of new patch technologies to deliver antiretroviral drugs that were previously incapable of being delivered through transdermal means. Thus, with continuing research into skin permeability and patch formulation strategies, there is a large potential for antiretroviral transdermal drug delivery. PMID:25690088

  11. Strategies for Controlled Delivery of Biologics for Cartilage Repair

    PubMed Central

    Lam, Johnny; Lu, Steven; Kasper, F. Kurtis; Mikos, Antonios G.

    2014-01-01

    The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications. PMID:24993610

  12. Non-Viral Nucleic Acid Delivery Strategies to the Central Nervous System

    PubMed Central

    Tan, James-Kevin Y.; Sellers, Drew L.; Pham, Binhan; Pun, Suzie H.; Horner, Philip J.

    2016-01-01

    With an increased prevalence and understanding of central nervous system (CNS) injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the CNS and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the CNS are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for CNS applications and will ultimately bring non-viral vectors closer to clinical application. PMID:27847462

  13. Schizophrenia treatment: content versus delivery.

    PubMed

    van Os, J

    2009-01-01

    To review the evidence supporting the importance of ensuring that patients with psychiatric disorders receive an optimal and appropriate level of non-pharmacological treatment, and how Assertive Community Treatment (ACT) may be able to contribute to this aim. Analysis of data from selected individual published studies on ACT, in addition to reviews from the Cochrane Library, and other study groups. Treatment management using ACT appears to offer benefits in terms of reduction in hospitalisation, although there is some debate as to whether this is the most representative outcome measure. Preliminary indications using remission as an outcome measure have also shown promising results in favour of ACT. While further investigation and validation are necessary, current data indicate that ACT may be an appropriate strategy to facilitate the delivery of treatment to patients with psychotic disorders.

  14. Update on Nanotechnology-based Drug Delivery Systems in Cancer Treatment.

    PubMed

    Ho, Benjamin N; Pfeffer, Claire M; Singh, Amareshwar T K

    2017-11-01

    The emerging field of nanotechnology meets the demands for innovative approaches in the diagnosis and treatment of cancer. The nanoparticles are biocompatible and biodegradable and are made of a core, a particle that acts as a carrier, and one or more functional groups on the core which target specific sites. Nanotech in drug delivery includes nanodisks, High Density Lipoprotein nanostructures, liposomes, and gold nanoparticles. The fundamental advantages of nanoparticles are: improved delivery of water-insoluble drugs, targeted delivery, co-delivery of two or more drugs for combination therapy, and visualization of the drug delivery site by combining imaging system and a therapeutic drug. One of the potential applications of nanotechnology is in the treatment of cancer. Conventional methods for cancer treatments have included chemotherapy, surgery, or radiation. Early recognition and treatment of cancer with these approaches is still challenging. Innovative technologies are needed to overcome multidrug resistance, and increase drug localization and efficacy. Application of nanotechnology to cancer biology has brought in a new hope for developing treatment strategies on cancer. In this study, we present a review on the recent advances in nanotechnology-based approaches in cancer treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

    PubMed

    Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

    2016-01-01

    The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

  16. Overcoming the Challenges of siRNA Delivery: Nanoparticle Strategies.

    PubMed

    Shajari, Neda; Mansoori, Behzad; Davudian, Sadaf; Mohammadi, Ali; Baradaran, Behzad

    2017-01-01

    Despite therapeutics based on siRNA have an immense potential for the treatment of incurable diseases such as cancers. However, the in vivo utilization of siRNA and also the delivery of this agent to the target site is one of the most controversial challenges. The helpful assistance by nanoparticles can improve stable delivery and also enhance efficacy. More nanoparticle-based siRNA therapeutics is expected to become available in the near future. The search strategy followed the guidelines of the Centre of Reviews and Dissemination. The studies were identified from seven databases (Scopus, Web of Science, Academic Search Premiere, CINAHL, Medline Ovid, Eric and Cochrane Library). Studies was selected based on titles, abstracts and full texts. One hundred twenty nine papers were included in the review. These papers defined hurdles in RNAi delivery and also strategies to overcome these hurdles. This review discussed the existing hurdles for systemic administration of siRNA as therapeutic agents and highlights the various strategies to overcome these hurdles, including lipid-based nanoparticles and polymeric nanoparticles, and we also briefly reviewed chemical modification. Delivery of siRNA to the target site is the biggest challenge for its application in the clinic. The findings of this review confirmed by encapsulation siRNA in the nanoparticles can overcome these challenges. The rapid progress in nanotechnology has enabled the development of effective nanoparticles as the carrier for siRNA delivery. However, our data about siRNA-based therapeutics and also nanomedicine are still limited. More clinical data needs to be completely understood in the benefits and drawbacks of siRNA-based therapeutics. Prospective studies must pay attention to the in vivo safety profiles of the different delivery systems, including uninvited immune system stimulation and cytotoxicity. In essence, the development of nontoxic, biocompatible, and biodegradable delivery systems for

  17. Clinical Considerations of Focal Drug Delivery in Cancer Treatment.

    PubMed

    Harris, Jamie; Klonoski, Samuel C; Chiu, Bill

    2017-01-01

    According to the US Center for Disease Control, cancer deaths are the second most common cause of mortality in both adults and children. Definitive treatment of solid tumors involves surgical resection with or without systemic chemotherapy and radiation. The advent of local drug delivery presents a unique treatment modality that can offer substantial benefits in cancer management. Three main phases in solid tumor management exist for the treating physician: initial diagnosis with tissue biopsy, surgical resection with or without chemotherapy, and management of metastatic disease. A literature review of both basic science as well as clinical trials using local drug delivery strategies in the management of solid tumors was done on PubMed. These were then further divided into the categories of initial tissue biopsy intervention, surgical resection, and management of metastatic disease. A total of 27 articles were review that included both pre-clinical as well as clinical investigation of local drug delivery therapies in the treatment of solid tumors. Treatments such as MRI guided therapies, FDA approved local therapies for intracranial gliomas as well as local therapy for single site metastatic disease were identified. This review focuses the current state of local drug delivery in the treatment of solid tumors in both the pre-clinical as well as clinical investigation settings. Local drug delivery therapy offers an exciting new treatment modality for solid malignancies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.

    PubMed

    Arshad, Azeem; Yang, Bin; Bienemann, Alison S; Barua, Neil U; Wyatt, Marcella J; Woolley, Max; Johnson, Dave E; Edler, Karen J; Gill, Steven S

    2015-01-01

    We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas.

  19. Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma

    PubMed Central

    Arshad, Azeem; Yang, Bin; Bienemann, Alison S.; Barua, Neil U.; Wyatt, Marcella J.; Woolley, Max; Johnson, Dave E.; Edler, Karen J.; Gill, Steven S.

    2015-01-01

    We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas. PMID:26186224

  20. Stepping through treatment: reflections on an adaptive treatment strategy among methamphetamine users with depression.

    PubMed

    Kay-Lambkin, Frances J; Baker, Amanda L; McKetin, Rebecca; Lee, Nicole

    2010-09-01

    Stepped-care has been recommended in the alcohol and other drug field and adopted in a number of service settings, but few research projects have examined this approach. This article aims to describe a pilot trial of stepped-care methods in the treatment of methamphetamine use and depression comorbidity. An adaptive treatment strategy was developed based on recommendations for stepped-care among methamphetamine users, and incorporating cognitive behaviour therapy/motivational intervention for methamphetamine use and depression. The adaptive treatment strategy was compared with a fixed treatment, comprising an extended integrated cognitive behaviour therapy/motivational intervention treatment. Eighteen participants across two study sites were involved in the trial, and were current users of methamphetamines (at least once weekly) exhibiting at least moderate symptoms of depression (score of 17 or greater on the Beck Depression Inventory II). Treatment delivered via the adaptive treatment (stepped-care) model was associated with improvement in depression and methamphetamine use, however, was not associated with more efficient delivery of psychological treatment to this population relative to the comparison treatment. This pilot trial attests to the potential for adaptive treatment strategies to increase the evidence base for stepped-care approaches within the alcohol and other drug field. However, in order for stepped-care treatment in this trial to be delivered efficiently, specific training in the delivery and philosophy of the model is required.

  1. Exploring Different Strategies for Efficient Delivery of Colorectal Cancer Therapy

    PubMed Central

    Lin, Congcong; Ng, Huei Leng Helena; Pan, Weisan; Chen, Hubiao; Zhang, Ge; Bian, Zhaoxiang; Lu, Aiping; Yang, Zhijun

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death in the world. Currently available chemotherapy of CRC usually delivers the drug to both normal as well as cancerous tissues, thus leading to numerous undesirable effects. Much emphasis is being laid on the development of effective drug delivery systems for achieving selective delivery of the active moiety at the anticipated site of action with minimized unwanted side effects. Researchers have employed various techniques (dependent on pH, time, pressure and/or bacteria) for targeting drugs directly to the colonic region. On the other hand, systemic drug delivery strategies to specific molecular targets (such as FGFR, EGFR, CD44, EpCAM, CA IX, PPARγ and COX-2) overexpressed by cancerous cells have also been shown to be effective. This review aims to put forth an overview of drug delivery technologies that have been, and may be developed, for the treatment of CRC. PMID:26569228

  2. Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

    PubMed

    Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

    2017-01-01

    Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Strategies to improve drug delivery across the blood-brain barrier.

    PubMed

    de Boer, Albertus G; Gaillard, Pieter J

    2007-01-01

    The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.

  4. Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

    PubMed Central

    Fonseca-Santos, Bruno; Gremião, Maria Palmira Daflon; Chorilli, Marlus

    2015-01-01

    Alzheimer’s disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood–brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease. PMID:26345528

  5. Novel Strategies for Anterior Segment Ocular Drug Delivery

    PubMed Central

    Cholkar, Kishore; Patel, Sulabh P.; Vadlapudi, Aswani Dutt

    2013-01-01

    Abstract Research advancements in pharmaceutical sciences have led to the development of new strategies in drug delivery to anterior segment. Designing a new delivery system that can efficiently target the diseased anterior ocular tissue, generate high drug levels, and maintain prolonged and effective concentrations with no or minimal side effects is the major focus of current research. Drug delivery by traditional method of administration via topical dosing is impeded by ocular static and dynamic barriers. Various products have been introduced into the market that prolong drug retention in the precorneal pocket and to improve bioavailability. However, there is a need of a delivery system that can provide controlled release to treat chronic ocular diseases with a reduced dosing frequency without causing any visual disturbances. This review provides an overview of anterior ocular barriers along with strategies to overcome these ocular barriers and deliver therapeutic agents to the affected anterior ocular tissue with a special emphasis on nanotechnology-based drug delivery approaches. PMID:23215539

  6. Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies.

    PubMed

    Mangraviti, Antonella; Gullotti, David; Tyler, Betty; Brem, Henry

    2016-10-28

    Despite recent technological advancements and promising preclinical experiments, brain tumor patients are still met with limited treatment options. Some of the barriers to clinical improvements include the systemic toxicity of cytotoxic compounds, the impedance of the blood brain barrier (BBB), and the lack of therapeutic agents that can selectively target the intracranial tumor environment. To overcome such barriers, a number of chemotherapeutic agents and nucleic acid-based therapies are rapidly being synthesized and tested as new brain tumor-targeted delivery strategies. Novel carriers include liposomal and polymeric nanoparticles, wafers, microchips, microparticle-based nanoplatforms and cells-based vectors. Strong preclinical results suggest that these nanotechnologies are set to transform the therapeutic paradigm for brain tumor treatment. In addition to new tumoricidal agents, parallel work is also being conducted on the BBB front. Preclinical testing of chemical and physical modulation strategies is yielding improved intracranial concentrations. New diagnostic and therapeutic imaging techniques, such as high-intensity focused ultrasound and MRI-guided focused ultrasound, are being used to modulate the BBB in a more precise and non-invasive manner. This review details some of the tremendous advances that are being explored in current brain tumor targeted therapies, including local implant development, nanobiotechnology-based delivery strategies, and techniques of BBB manipulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Current Strategies for Brain Drug Delivery

    PubMed Central

    Dong, Xiaowei

    2018-01-01

    The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature. PMID:29556336

  8. Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

    PubMed Central

    Vieira, Débora B; Gamarra, Lionel F

    2016-01-01

    This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood–brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer’s, Parkinson’s, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood–brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered. PMID:27799765

  9. Getting into the brain: liposome-based strategies for effective drug delivery across the blood-brain barrier.

    PubMed

    Vieira, Débora B; Gamarra, Lionel F

    This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood-brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer's, Parkinson's, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood-brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

  10. Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya

    PubMed Central

    Brooker, Simon J; Mwandawiro, Charles S; Halliday, Katherine E; Njenga, Sammy M; Mcharo, Carlos; Gichuki, Paul M; Wasunna, Beatrice; Kihara, Jimmy H; Njomo, Doris; Alusala, Dorcas; Chiguzo, Athuman; Turner, Hugo C; Teti, Caroline; Gwayi-Chore, Claire; Nikolay, Birgit; Truscott, James E; Hollingsworth, T Déirdre; Balabanova, Dina; Griffiths, Ulla K; Freeman, Matthew C; Allen, Elizabeth; Pullan, Rachel L; Anderson, Roy M

    2015-01-01

    Introduction In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal? Methods and analysis Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision—termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. Ethics and dissemination Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and

  11. Nanomedicines based drug delivery systems for anti-cancer targeting and treatment.

    PubMed

    Jain, Vikas; Jain, Shikha; Mahajan, S C

    2015-01-01

    Cancer is defined as an uncontrolled growth of abnormal cells. Current treatment strategies for cancer include combination of radiation, chemotherapy and surgery. The long-term use of conventional drug delivery systems for cancer chemotherapy leads to fatal damage of normal proliferate cells and this is particularly used for the management of solid tumors, where utmost tumor cells are not invaded quickly. A targeted drug delivery system (TDDS) is a system, which releases the drug at a preselected biosite in a controlled manner. Nanotechnology based delivery systems are making a significant impact on cancer treatment and the polymers play key role in the development of nanopraticlulate carriers for cancer therapy. Some important technological advantages of nanotherapeutic drug delivery systems (NDDS) include prolonged half-life, improved bio-distribution, increased circulation time of the drug, controlled and sustained release of the drug, versatility of route of administration, increased intercellular concentration of drug and many more. This review covers the current research on polymer based anticancer agents, the rationale for development of these polymer therapeutical systems and discusses the benefits and challenges of cancer nanomedicines including polymer-drug conjugates, micelles, dendrimers, immunoconjugates, liposomes, nanoparticles.

  12. Novel formulation and drug delivery strategies for the treatment of pediatric poverty-related diseases.

    PubMed

    Sosnik, Alejandro; Seremeta, Katia P; Imperiale, Julieta C; Chiappetta, Diego A

    2012-03-01

    Due to a lack of approved drugs and formulations, children represent the most vulnerable patients. Magistral, unlicensed formulations obtained by the manipulation of solid forms should undergo clinical evaluation to ensure bioequivalence. The development of new pediatric medicines is complex and faces technological, economic and ethical challenges. This phenomenon has contributed to the emergence of an adult-children gap. To improve the situation, the World Health Organization launched the global campaign 'Make medicines child size' and a number of international initiatives have been established. The situation is more critical in the case of poverty-related diseases (PRDs) that mainly affect poor countries. This review critically discusses different strategies to develop pediatric formulations and drug delivery systems (DDS) in PRDs and their potential implementation in the current market. Readers will gain an updated perspective on the development of pediatric medicines for the treatment of PRDs and the proximate challenges and opportunities faced to ensure an effective pharmacotherapy. There is an urgent need for the development of innovative, scalable and cost-viable formulations to ensure pediatric patients have access to appropriate medications for PRDs. The guidelines of the International Conference on Harmonisation constitute a very good orientation tool, as they emphasize physiological and developmental aspects that need to be considered in pediatric research. It is important to consider cultural, economic and ethical aspects that make developing nations facing PRDs different from the developed world. Thus, the best strategy would probably be to conceive and engage similar initiatives in the developing world, to address unattended therapeutic niches.

  13. PMO Delivery System Using Bubble Liposomes and Ultrasound Exposure for Duchenne Muscular Dystrophy Treatment.

    PubMed

    Negishi, Yoichi; Ishii, Yuko; Nirasawa, Kei; Sasaki, Eri; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo

    2018-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO) has been approved for clinical use in DMD. However, an efficient PMO delivery strategy is required to improve the therapeutic efficacy in DMD patients. We previously developed polyethylene glycol (PEG)-modified liposomes containing ultrasound contrast gas, "Bubble liposomes" (BLs), and found that the combination of BLs with ultrasound exposure is a useful gene delivery tool. Here, we describe an efficient PMO delivery strategy using the combination of BLs and ultrasound exposure to treat muscles in a DMD mouse model (mdx). This ultrasound-mediated BL technique can increase the PMO-mediated exon-skipping efficiency, leading to significantly increased dystrophin expression. Thus, the combination of BLs and ultrasound exposure may be a feasible PMO delivery method to improve therapeutic efficacy and reduce the PMO dosage for DMD treatment.

  14. Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

    NASA Astrophysics Data System (ADS)

    Roy Chaudhuri, Tista

    An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

  15. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

    PubMed

    Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

    2015-12-10

    The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel

  16. RNAi therapeutics for brain cancer: current advancements in RNAi delivery strategies.

    PubMed

    Malhotra, Meenakshi; Toulouse, André; Godinho, Bruno M D C; Mc Carthy, David John; Cryan, John F; O'Driscoll, Caitriona M

    2015-10-01

    Malignant primary brain tumors are aggressive cancerous cells that invade the surrounding tissues of the central nervous system. The current treatment options for malignant brain tumors are limited due to the inability to cross the blood-brain barrier. The advancements in current research has identified and characterized certain molecular markers that are essential for tumor survival, progression, metastasis and angiogenesis. These molecular markers have served as therapeutic targets for the RNAi based therapies, which enable site-specific silencing of the gene responsible for tumor proliferation. However, to bring about therapeutic success, an efficient delivery carrier that can cross the blood-brain barrier and reach the targeted site is essential. The current review focuses on the potential of targeted, non-viral and viral particles containing RNAi therapeutic molecules as delivery strategies specifically for brain tumors.

  17. Combinatorial drug delivery strategy employing nano-curcumin and nano-MiADMSA for the treatment of arsenic intoxication in mouse.

    PubMed

    Kushwaha, Pramod; Yadav, Abhishek; Samim, M; Flora, S J S

    2018-04-25

    Chelation therapy is the mainstream treatment for heavy metal poisoning. Apart from this, therapy using antioxidant/herbal extracts are the other strategies now commonly being tried for the treatment. We have previously reported individual beneficial efficacy of nanoparticle mediated administration of an antioxidant like 'curcumin' and an arsenic chelator 'monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)' for the treatment of arsenic toxicity compared to bulk drugs. The present paper investigates our hypothesis that a combination drug delivery therapy employing two nanosystems, a chelator and a strong antioxidant, may produce more pronounced therapeutic effects compared to individual effects in the treatment of arsenic toxicity. An in-vivo study was conducted wherein arsenic as sodium arsenite (100 ppm) was administered in drinking water for 5 months to Swiss albino mice. This was followed by a treatment protocol comprising of curcumin encapsulated chitosan nanoparticles (nano-curcumin, 15 mg/kg, orally for 1 month) either alone or in combination with MiADMSA encapsulated polymeric nanoparticles (nano-MiADMSA, 50 mg/kg for last 5 days) to evaluate the therapeutic potential of the combination treatment. Our results demonstrated that co-treatment with nano-curcumin and nano-MiADMSA provided beneficial effects in a synergistic way on the adverse changes in oxidative stress parameters and metal status induced by arsenic. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Iontophoresis-targeted, follicular delivery of minoxidil sulfate for the treatment of alopecia.

    PubMed

    Gelfuso, Guilherme Martins; Gratieri, Tais; Delgado-Charro, M Begoña; Guy, Richard H; Vianna Lopez, Renata Fonseca

    2013-05-01

    Although minoxidil (MX) is a drug known to stimulate hair growth, the treatment of androgenic alopecia could be improved by delivery strategies that would favor drug accumulation into the hair follicles. This work investigated in vitro the potential of iontophoresis to achieve this objective using MX sulfate (MXS), a more water-soluble derivative of MX. Passive delivery of MXS was first determined from an ethanol-water solution and from a thermosensitive gel. The latter formulation resulted in greater accumulation of MXS in the stratum corneum (skin's outermost layer) and hair follicles and an overall decrease in absorption through the skin. Anodal iontophoresis of MXS from the same gel formulation was then investigated at pH 3.5 and pH 5.5. Compared with passive delivery, iontophoresis increased the amount of drug reaching the follicular infundibula from 120 to 600 ng per follicle. In addition, drug recovery from follicular casts was threefold higher following iontophoresis at pH 5.5 compared with that at pH 3.5. Preliminary in vivo experiments in rats confirmed that iontophoretic delivery of MXS facilitated drug accumulation in hair follicles. Overall, therefore, iontophoresis successfully and significantly enhanced follicular delivery of MX suggesting a useful opportunity for the improved treatment of alopecia. Copyright © 2013 Wiley Periodicals, Inc.

  19. Erythrocytes-based synthetic delivery systems: transition from conventional to novel engineering strategies.

    PubMed

    Bhateria, Manisha; Rachumallu, Ramakrishna; Singh, Rajbir; Bhatta, Rabi Sankar

    2014-08-01

    Erythrocytes (red blood cells [RBCs]) and artificial or synthetic delivery systems such as liposomes, nanoparticles (NPs) are the most investigated carrier systems. Herein, progress made from conventional approach of using RBC as delivery systems to novel approach of using synthetic delivery systems based on RBC properties will be reviewed. We aim to highlight both conventional and novel approaches of using RBCs as potential carrier system. Conventional approaches which include two main strategies are: i) directly loading therapeutic moieties in RBCs; and ii) coupling them with RBCs whereas novel approaches exploit structural, mechanical and biological properties of RBCs to design synthetic delivery systems through various engineering strategies. Initial attempts included coupling of antibodies to liposomes to specifically target RBCs. Knowledge obtained from several studies led to the development of RBC membrane derived liposomes (nanoerythrosomes), inspiring future application of RBC or its structural features in other attractive delivery systems (hydrogels, filomicelles, microcapsules, micro- and NPs) for even greater potential. In conclusion, this review dwells upon comparative analysis of various conventional and novel engineering strategies in developing RBC based drug delivery systems, diversifying their applications in arena of drug delivery. Regardless of the challenges in front of us, RBC based delivery systems offer an exciting approach of exploiting biological entities in a multitude of medical applications.

  20. pH-sensitive liposomes for drug delivery in cancer treatment.

    PubMed

    Ferreira, Diego Dos Santos; Lopes, Sávia Caldeira de Araújo; Franco, Marina Santiago; Oliveira, Mônica Cristina

    2013-09-01

    In recent years, liposomes have been employed with growing success as pharmaceutical carriers for antineoplastic drugs. One specific strategy used to enhance in vivo liposome-mediated drug delivery is the improvement of intracytoplasmic delivery. In this context, pH-sensitive liposomes (pHSLip) have been designed to explore the endosomal acidification process, which may lead to a destabilization of the liposomes, followed by a release of their contents into the cell cytoplasm. This review considers the current status of pHSLip development and its applicability in cancer treatment, focusing on the mechanisms of pH sensitivity and liposomal composition of pHSLip. The final section will discuss the application of these formulations in both in vitro and in vivo studies of antitumor efficacy.

  1. Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya.

    PubMed

    Brooker, Simon J; Mwandawiro, Charles S; Halliday, Katherine E; Njenga, Sammy M; Mcharo, Carlos; Gichuki, Paul M; Wasunna, Beatrice; Kihara, Jimmy H; Njomo, Doris; Alusala, Dorcas; Chiguzo, Athuman; Turner, Hugo C; Teti, Caroline; Gwayi-Chore, Claire; Nikolay, Birgit; Truscott, James E; Hollingsworth, T Déirdre; Balabanova, Dina; Griffiths, Ulla K; Freeman, Matthew C; Allen, Elizabeth; Pullan, Rachel L; Anderson, Roy M

    2015-10-19

    In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal? Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision-termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a

  2. Intra-operatively customized implant coating strategies for local and controlled drug delivery to bone.

    PubMed

    Trajkovski, Branko; Petersen, Ansgar; Strube, Patrick; Mehta, Manav; Duda, Georg N

    2012-09-01

    Bone is one of the few tissues in the human body with high endogenous healing capacity. However, failure of the healing process presents a significant clinical challenge; it is a tremendous burden for the individual and has related health and economic consequences. To overcome such healing deficits, various concepts for a local drug delivery to bone have been developed during the last decades. However, in many cases these concepts do not meet the specific requirements of either surgeons who must use these strategies or individual patients who might benefit from them. We describe currently available methods for local drug delivery and their limitations in therapy. Various solutions for drug delivery to bone focusing on clinical applications and intra-operative constraints are discussed and drug delivery by implant coating is highlighted. Finally, a new set of design and performance requirements for intra-operatively customized implant coatings for controlled drug delivery is proposed. In the future, these requirements may improve approaches for local and intra-operative treatment of patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Lapatinib nano-delivery systems: a promising future for breast cancer treatment.

    PubMed

    Bonde, Gunjan Vasant; Yadav, Sarita Kumari; Chauhan, Sheetal; Mittal, Pooja; Ajmal, Gufran; Thokala, Sathish; Mishra, Brahmeshwar

    2018-05-01

    Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation. Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose. Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.

  4. A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles.

    PubMed

    Wang, Mingxin; You, Chaoqun; Gao, Zhiguo; Wu, Hongshuai; Sun, Baiwang; Zhu, Xiaoli; Chen, Renjie

    2018-08-01

    The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

  5. New avenues for improving pancreatic ductal adenocarcinoma (PDAC) treatment: Selective stroma depletion combined with nano drug delivery.

    PubMed

    Bhaw-Luximon, Archana; Jhurry, Dhanjay

    2015-12-28

    The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell. The two opposing schools of thought - non-depletion of the stroma vs its depletion - to better drug efficacy are here discussed. Disrupting stroma-cancer cell interaction to reduce tumor progression and promote apoptosis is identified as the new direction of treatment for PDAC. Clinical data have shown that elimination of fibrosis and blockade of the Hedgehog pathway in stroma effectively promote drug delivery to tumor site and apoptosis. Reduced stiffness of ECM, lower fibrosis, higher permeability and higher blood flow after stroma depletion increase drug delivery. Combination strategies involving selective stroma depletion coupled with chemotherapy is currently proving to be the most efficient at clinical level. Striking the right balance between fibrosis depletion and angiogenesis promotion resulting in enhanced drug delivery and apoptosis is a major challenge. The use of nano drug delivery devices coupled with stroma depletion is emerging as the next phase treatment for PDAC. The breakthrough to combat PDAC will likely be a combination of early diagnosis and the emerging chemotherapy strategies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Micelles As Delivery System for Cancer Treatment.

    PubMed

    Keskin, Dilek; Tezcaner, Aysen

    2017-01-01

    Micelles are nanoparticles formed by the self-assembly of amphiphilic block copolymers in certain solvents above concentrations called critical micelle concentration (CMC). Micelles are used in different fields like food, cosmetics, medicine, etc. These nanosized delivery systems are under spotlight in the recent years with new achievements in terms of their in vivo stability, ability to protect entrapped drug, release kinetics, ease of cellular penetration and thereby increased therapeutic efficacy. Drug loaded micelles can be prepared by dialysis, oil-in-water method, solid dispersion, freezing, spray drying, etc. The aim of this review is to give an overview of the research on micelles (in vitro, in vivo and clinical) as delivery system for cancer treatment. Passive targeting is one route for accumulation of nanosized micellar drug formulations. Many research groups from both academia and industry focus on developing new strategies for improving the therapeutic efficacy of micellar systems (active targeting to the tumor site, designing multidrug delivery systems for overcoming multidrug resistance or micelles formed by prodrug conjugates, etc). There is only one micellar drug formulation in South Korea that has reached clinical practice. However, there are many untargeted anticancer drug loaded micellar formulations in clinical trials, which have potential for use in clinics. Many more products are expected to be on the market in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Risk Factors for Uterine Atony/Postpartum Hemorrhage Requiring Treatment after Vaginal Delivery

    PubMed Central

    Wetta, Luisa A; Szychowski, Jeff M; Seals, Ms. Samantha; Mancuso, Melissa S; Biggio, Joseph R; Tita, Alan TN

    2013-01-01

    Objective To identify risk factors for uterine atony or hemorrhage. Study Design Secondary analysis of a 3-arm double-blind randomized trial of different dose-regimens of oxytocin to prevent uterine atony after vaginal delivery. The primary outcome was uterine atony or hemorrhage requiring treatment. Twenty-one potential risk factors were evaluated. Logistic regression was used to identify independent risk factors using 2 complementary pre-defined model selection strategies. Results Among 1798 women randomized to 10, 40 or 80U prophylactic oxytocin after vaginal delivery, treated uterine atony occurred in 7%. Hispanic (OR 2.1; 95% CI 1.3–3.4) and non-Hispanic whites (OR 1.6; 95% CI 1.0–2.5), preeclampsia (OR 3.2; 95% CI 2.0–4.9) and chorioamnionitis (OR 2.8; 95% CI 1.6–5.0) were consistent independent risk factors. Other risk factors based on the specified selection strategies were obesity, induction/augmentation of labor, twins, hydramnios, anemia, and arrest of descent. Amnioinfusion appeared to be protective against uterine atony (OR 0.53; 95% CI 0.29–0.98). Conclusion Independent risk factors for uterine atony requiring treatment include Hispanic and non-Hispanic white ethnicity, preeclampsia and chorioamnionitis. PMID:23507549

  8. New strategies for local treatment of vaginal infections.

    PubMed

    Palmeira-de-Oliveira, Rita; Palmeira-de-Oliveira, Ana; Martinez-de-Oliveira, José

    2015-09-15

    Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Effective teaching strategies and methods of delivery for patient education: a systematic review and practice guideline recommendations.

    PubMed

    Friedman, Audrey Jusko; Cosby, Roxanne; Boyko, Susan; Hatton-Bauer, Jane; Turnbull, Gale

    2011-03-01

    The objective of this study was to determine effective teaching strategies and methods of delivery for patient education (PE). A systematic review was conducted and reviews with or without meta-analyses, which examined teaching strategies and methods of delivery for PE, were included. Teaching strategies identified are traditional lectures, discussions, simulated games, computer technology, written material, audiovisual sources, verbal recall, demonstration, and role playing. Methods of delivery focused on how to deliver the teaching strategies. Teaching strategies that increased knowledge, decreased anxiety, and increased satisfaction included computer technology, audio and videotapes, written materials, and demonstrations. Various teaching strategies used in combination were similarly successful. Moreover, structured-, culturally appropriate- and patient-specific teachings were found to be better than ad hoc teaching or generalized teaching. Findings provide guidance for establishing provincial standards for the delivery of PE. Recommendations concerning the efficacy of the teaching strategies and delivery methods are provided.

  10. Novel delivery approaches for cancer therapeutics.

    PubMed

    Mitra, Ashim K; Agrahari, Vibhuti; Mandal, Abhirup; Cholkar, Kishore; Natarajan, Chandramouli; Shah, Sujay; Joseph, Mary; Trinh, Hoang M; Vaishya, Ravi; Yang, Xiaoyan; Hao, Yi; Khurana, Varun; Pal, Dhananjay

    2015-12-10

    Currently, a majority of cancer treatment strategies are based on the removal of tumor mass mainly by surgery. Chemical and physical treatments such as chemo- and radiotherapies have also made a major contribution in inhibiting rapid growth of malignant cells. Furthermore, these approaches are often combined to enhance therapeutic indices. It is widely known that surgery, chemo- and radiotherapy also inhibit normal cells growth. In addition, these treatment modalities are associated with severe side effects and high toxicity which in turn lead to low quality of life. This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis. Currently, cancer treatment is a highly dynamic field and significant advances are being made in the development of novel cancer treatment strategies. In contrast to conventional cancer therapeutics, novel approaches such as ligand or receptor based targeting, triggered release, intracellular drug targeting, gene delivery, cancer stem cell therapy, magnetic drug targeting and ultrasound-mediated drug delivery, have added new modalities for cancer treatment. These approaches have led to selective detection of malignant cells leading to their eradication with minimal side effects. Lowering multi-drug resistance and involving influx transportation in targeted drug delivery to cancer cells can also contribute significantly in the therapeutic interventions in cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Nanomedicine strategies for sustained, controlled and targeted treatment of cancer stem cells.

    PubMed

    Gao, Jie; Li, Wei; Guo, Yajun; Feng, Si-Shen

    2016-12-01

    Cancer stem cells (CSCs) are original cancer cells that are of characteristics associated with normal stem cells. CSCs are toughest against various treatments and thus responsible for cancer metastasis and recurrence. Therefore, development of specific and effective treatment of CSCs plays a key role in improving survival and life quality of cancer patients, especially those in the metastatic stage. Nanomedicine strategies, which include prodrugs, micelles, liposomes and nanoparticles of biodegradable polymers, could substantially improve the therapeutic index of conventional therapeutics due to its manner of sustained, controlled and targeted delivery of high transportation efficiency across the cell membrane and low elimination by intracellular autophagy, and thus provide a practical solution to solve the problem encountered in CSCs treatment. This review gives briefly the latest information to summarize the concept, strategies, mechanisms and current status as well as future promises of nanomedicine strategies for treatment of CSCs.

  12. Development In Drug Targeting And Delivery In Cervical Cancer.

    PubMed

    Aggarwal, Urvashi; Goyal, Amit Kumar; Rath, Goutam

    2017-10-09

    Cervical cancer is the second most common cancer in women. Standard treatment options available for cervical cancer including chemotherapy, surgery and radiation therapy associated with their own side effects and toxicities. Tumor-targeted delivery of anticancer drugs is perhaps one of the most appropriate strategies to achieve optimal outcomes from treatment and improve quality of life. Recently nanocarriers based drug delivery systems owing to their unique properties have been extensively investigated for anticancer drug delivery. In addition to that addressing the anatomical significance of cervical cancer, various local drug delivery strategies for the cancer treatment are introduced like: gels, nanoparticles, polymeric films, rods and wafers, lipid based nanocarrier. Localized drug delivery systems allows passive drug targeting results in high drug concentration at the target site. Further they can be tailor made to achieve both sustained and controlled release behavior, substantially improving therapeutic outcomes and minimizing side effects. This review summarizes the meaningful advances in drug delivery strategies to treat cervical cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, D; Li, X; Li, H

    2014-06-15

    Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beammore » segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly

  14. Evaluating Intra-Articular Drug Delivery for the Treatment of Osteoarthritis in a Rat Model

    PubMed Central

    Allen, Kyle D.; Adams, Samuel B.

    2010-01-01

    Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may provide for the development of more successful OA treatment outcomes that have potential to reduce local joint inflammation, reduce joint destruction, offer pain relief, and restore patient activity levels and joint function. As increasing interest turns toward intra-articular drug delivery routes, parallel interest has emerged in evaluating drug biodistribution, safety, and efficacy in preclinical models. Rodent models provide major advantages for the development of drug delivery strategies, chiefly because of lower cost, successful replication of human OA-like characteristics, rapid disease development, and small joint volumes that enable use of lower total drug amounts during protocol development. These models, however, also offer the potential to investigate the therapeutic effects of local drug therapy on animal behavior, including pain sensitivity thresholds and locomotion characteristics. Herein, we describe a translational paradigm for the evaluation of an intra-articular drug delivery strategy in a rat OA model. This model, a rat interleukin-1β overexpression model, offers the ability to evaluate anti-interleukin-1 therapeutics for drug biodistribution, activity, and safety as well as the therapeutic relief of disease symptoms. Once the action against interleukin-1 is confirmed in vivo, the newly developed anti-inflammatory drug can be evaluated for evidence of disease-modifying effects in more complex preclinical models. PMID:19943805

  15. Polymeric micelles for multi-drug delivery in cancer.

    PubMed

    Cho, Hyunah; Lai, Tsz Chung; Tomoda, Keishiro; Kwon, Glen S

    2015-02-01

    Drug combinations are common in cancer treatment and are rapidly evolving, moving beyond chemotherapy combinations to combinations of signal transduction inhibitors. For the delivery of drug combinations, i.e., multi-drug delivery, major considerations are synergy, dose regimen (concurrent versus sequential), pharmacokinetics, toxicity, and safety. In this contribution, we review recent research on polymeric micelles for multi-drug delivery in cancer. In concurrent drug delivery, polymeric micelles deliver multi-poorly water-soluble anticancer agents, satisfying strict requirements in solubility, stability, and safety. In sequential drug delivery, polymeric micelles participate in pretreatment strategies that "prime" solid tumors and enhance the penetration of secondarily administered anticancer agent or nanocarrier. The improved delivery of multiple poorly water-soluble anticancer agents by polymeric micelles via concurrent or sequential regimens offers novel and interesting strategies for drug combinations in cancer treatment.

  16. Strategies to improve treatment coverage in community-based public health programs: A systematic review of the literature.

    PubMed

    Deardorff, Katrina V; Rubin Means, Arianna; Ásbjörnsdóttir, Kristjana H; Walson, Judd

    2018-02-01

    Community-based public health campaigns, such as those used in mass deworming, vitamin A supplementation and child immunization programs, provide key healthcare interventions to targeted populations at scale. However, these programs often fall short of established coverage targets. The purpose of this systematic review was to evaluate the impact of strategies used to increase treatment coverage in community-based public health campaigns. We systematically searched CAB Direct, Embase, and PubMed archives for studies utilizing specific interventions to increase coverage of community-based distribution of drugs, vaccines, or other public health services. We identified 5,637 articles, from which 79 full texts were evaluated according to pre-defined inclusion and exclusion criteria. Twenty-eight articles met inclusion criteria and data were abstracted regarding strategy-specific changes in coverage from these sources. Strategies used to increase coverage included community-directed treatment (n = 6, pooled percent change in coverage: +26.2%), distributor incentives (n = 2, +25.3%), distribution along kinship networks (n = 1, +24.5%), intensified information, education, and communication activities (n = 8, +21.6%), fixed-point delivery (n = 1, +21.4%), door-to-door delivery (n = 1, +14.0%), integrated service distribution (n = 9, +12.7%), conversion from school- to community-based delivery (n = 3, +11.9%), and management by a non-governmental organization (n = 1, +5.8%). Strategies that target improving community member ownership of distribution appear to have a large impact on increasing treatment coverage. However, all strategies used to increase coverage successfully did so. These results may be useful to National Ministries, programs, and implementing partners in optimizing treatment coverage in community-based public health programs.

  17. Strategies to improve treatment coverage in community-based public health programs: A systematic review of the literature

    PubMed Central

    2018-01-01

    Background Community-based public health campaigns, such as those used in mass deworming, vitamin A supplementation and child immunization programs, provide key healthcare interventions to targeted populations at scale. However, these programs often fall short of established coverage targets. The purpose of this systematic review was to evaluate the impact of strategies used to increase treatment coverage in community-based public health campaigns. Methodology/ principal findings We systematically searched CAB Direct, Embase, and PubMed archives for studies utilizing specific interventions to increase coverage of community-based distribution of drugs, vaccines, or other public health services. We identified 5,637 articles, from which 79 full texts were evaluated according to pre-defined inclusion and exclusion criteria. Twenty-eight articles met inclusion criteria and data were abstracted regarding strategy-specific changes in coverage from these sources. Strategies used to increase coverage included community-directed treatment (n = 6, pooled percent change in coverage: +26.2%), distributor incentives (n = 2, +25.3%), distribution along kinship networks (n = 1, +24.5%), intensified information, education, and communication activities (n = 8, +21.6%), fixed-point delivery (n = 1, +21.4%), door-to-door delivery (n = 1, +14.0%), integrated service distribution (n = 9, +12.7%), conversion from school- to community-based delivery (n = 3, +11.9%), and management by a non-governmental organization (n = 1, +5.8%). Conclusions/significance Strategies that target improving community member ownership of distribution appear to have a large impact on increasing treatment coverage. However, all strategies used to increase coverage successfully did so. These results may be useful to National Ministries, programs, and implementing partners in optimizing treatment coverage in community-based public health programs. PMID:29420534

  18. Oral insulin delivery: existing barriers and current counter-strategies.

    PubMed

    Gedawy, Ahmed; Martinez, Jorge; Al-Salami, Hani; Dass, Crispin R

    2018-02-01

    The chronic and progressive nature of diabetes is usually associated with micro- and macrovascular complications where failure of pancreatic β-cell function and a general condition of hyperglycaemia is created. One possible factor is failure of the patient to comply with and adhere to the prescribed insulin due to the inconvenient administration route. This review summarizes the rationale for oral insulin administration, existing barriers and some counter-strategies trialled. Oral insulin mimics the physiology of endogenous insulin secreted by pancreas. Following the intestinal absorption of oral insulin, it reaches the liver at high concentration via the portal vein. Oral insulin on the other hand has the potential to protect pancreatic β-cells from autoimmune destruction. Structural modification, targeting a particular tissue/receptor, and the use of innovative pharmaceutical formulations such as nanoparticles represent strategies introduced to improve oral insulin bioavailability. They showed promising results in overcoming the hurdles facing oral insulin delivery, although delivery is far from ideal. The use of advanced pharmaceutical technologies and further research in particulate carrier system delivery predominantly nanoparticle utilization would offer useful tools in delivering insulin via the oral route which in turn would potentially improve diabetic patient compliance to insulin and the overall management of diabetes. © 2017 Royal Pharmaceutical Society.

  19. Systematic Assessment of Strategies for Lung-targeted Delivery of MicroRNA Mimics

    PubMed Central

    Schlosser, Kenny; Taha, Mohamad; Stewart, Duncan J.

    2018-01-01

    There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A). Intravenous (IV; via jugular vein), intraperitoneal (IP) and subcutaneous (SC) delivery served as controls. Relative levels of cel-miR-39 were quantified by RT-qPCR. Results: At 2 h post delivery, IT-L showed the highest lung mimic level, which was significantly higher than levels achieved by all other methods (from ~10- to 10,000-fold, p<0.05). Mimic levels remained detectable in the lung 24 h after delivery, but were 10- to 100-fold lower. The intrapulmonary distribution of cel-miR-39 was comparable when delivered as either a liquid or aerosol, with evidence of mimic distribution to both the left and right lung lobes and penetration to distal regions. All lung-targeted strategies showed lung-selective mimic uptake, with mimic levels 10- to 100-fold lower in heart and 100- to 10,000-fold lower in liver, kidney and spleen. In contrast, IV, SC and IP routes showed comparable or higher mimic levels in non-pulmonary tissues. Conclusions: miRNA uptake in the lungs differed markedly by up to 4 orders of magnitude, demonstrating that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of mi

  20. Green design "bioinspired disassembly-reassembly strategy" applied for improved tumor-targeted anticancer drug delivery.

    PubMed

    Wang, Ruoning; Gu, Xiaochen; Zhou, Jianping; Shen, Lingjia; Yin, Lifang; Hua, Peiying; Ding, Yang

    2016-08-10

    In this study, a simple and green approach 'bioinspired disassembly-reassembly strategy' was employed to reconstitute lipoprotein nanoparticles (RLNs) using whole-components of endogenous ones (contained dehydrated human lipids and native apolipoproteins). These RLNs were engineered to mimic the configuration and properties of natural lipoproteins for efficient drug delivery. In testing therapeutic targeting to microtubules, paclitaxel (PTX) was reassembled into RLNs to achieve improved targeted anti-carcinoma treatment and minimize adverse effects, demonstrating ultimately more applicable than HDL-like particles which are based on exogenous lipid sources. We have characterized that apolipoprotein-decoration of PTX-loaded RLNs (RLNs-PTX) led to favoring uniformly dispersed distribution, increasing PTX-encapsulation with a sustained-release pattern, while enhancing biostability during blood circulation. The innate biological RLNs induced efficient intracellular trafficking of cargos in situ via multi-targeting mechanisms, including scavenger receptor class B type I (SR-BI)-mediated direct transmembrane delivery, as well as other lipoprotein-receptors associated endocytic pathways. The resulting anticancer treatment from RLNs-PTX was demonstrated a half-maximal inhibitory concentration of 0.20μg/mL, cell apoptosis of 18.04% 24h post-incubation mainly arresting G2/M cell cycle in vitro, and tumor weight inhibition of 70.51% in vivo. Collectively, green-step assembly-based RLNs provided an efficient strategy for mediating tumor-targeted accumulation of PTX and enhanced anticancer efficacy. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Strategies for Enhanced Drug Delivery to the Central Nervous System

    PubMed Central

    Dwibhashyam, V. S. N. M.; Nagappa, A. N.

    2008-01-01

    Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system. PMID:20046703

  2. Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.

    PubMed

    Krishnaiah, Yellela S R; Khan, Mansoor A

    2012-01-01

    Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC.

  3. Application of Hydrogel Template Strategy in Ocular Drug Delivery.

    PubMed

    Shin, Crystal S; Marcano, Daniela C; Park, Kinam; Acharya, Ghanashyam

    2017-01-01

    The hydrogel template strategy was previously developed to fabricate homogeneous polymeric microparticles. Here, we demonstrate the versatility of the hydrogel template strategy for the development of nanowafer-based ocular drug delivery systems. We describe the fabrication of dexamethasone-loaded nanowafers using polyvinyl alcohol and the instillation of a nanowafer on a mouse eye. The nanowafer, a small circular disk, is placed on the ocular surface, and it releases a drug as it slowly dissolves over time, thus increasing ocular bioavailability and enhancing efficiency to treat eye injuries.

  4. Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning

    PubMed Central

    Liu, Shi; Wu, Yu; Wooten, H. Omar; Green, Olga; Archer, Brent; Li, Harold

    2016-01-01

    A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image‐guided radiation therapy (MR‐IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam‐on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam‐on time can be calculated using both the planned beam‐on time and the decay‐corrected dose rate. To predict the remain‐ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22 min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The

  5. Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning.

    PubMed

    Liu, Shi; Wu, Yu; Wooten, H Omar; Green, Olga; Archer, Brent; Li, Harold; Yang, Deshan

    2016-03-08

    A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image-guided radiation therapy (MR-IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam-on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam-on time can be calculated using both the planned beam-on time and the decay-corrected dose rate. To predict the remain-ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of

  6. Specializing in accountability: strategies to prepare a subspecialty workforce for care delivery redesign.

    PubMed

    Nambudiri, Vinod E; Sober, Arthur J; Kimball, Alexa B

    2013-12-01

    Accountable care organizations (ACOs) emphasize cost-effectiveness, rewarding health care systems that provide the highest-quality care delivered by the most cost-efficient providers. Transitioning to an ACO model introduces distinct challenges for specialist physicians within academic health centers. As skin diseases constitute a large number of visits to primary care providers and specialists and place a significant financial burden on the health care system, the authors sought to identify specialist-driven strategies for cost-effective, patient-centered care delivery in dermatology. As part of the Massachusetts General Hospital's transition to an ACO, the Department of Dermatology in 2012 employed a team-based strategy to identify measures aimed at curbing the rate of rise in per-patient medical expense. Their approach may represent a methodological framework that translates to other specialist workforces. The authors identified four action areas: (1) rational, cost-conscious prescribing within therapeutic classes; (2) enhanced management of urgent access and follow-up appointment scheduling; (3) procedure standardization; and (4) interpractitioner variability assessment. They describe the practices implemented in these action areas, which include a mix of changes in both clinical decision making and operational practice and are aimed at improving overall quality and value of care delivery. They also offer recommendations for other specialty departments Involving specialist physicians in care delivery redesign efforts provides unique insights to enhance quality, cost-effectiveness, and efficiency of care delivery. With increasing emphasis on ACO models, further specialist-driven strategies for ensuring patient-centered delivery warrant development alongside other delivery reform efforts.

  7. Strategies in Development and Delivery of Nanotechnology Based Cosmetic Products.

    PubMed

    Ahmad, Usama; Ahmad, Zeeshan; Khan, Ahmed Abdullah; Akhtar, Juber; Singh, Satya Prakash; Ahmad, Farhan Jalees

    2018-03-26

    The science of formulation involving cosmetic ingredients has always been a challenge since the release of active components greatly depends upon the carrier system involved and the selectivity of skin barrier. The principle obstacle of the skin resides in the epidermis and it's hard for many active components to cross it. The formulation related factors like size of particles, viscosity and lipophilicity of the components also play an important role in permeation of the dermal composition. Though widely used; conventional creams and gels still struggle in terms of success. This work focuses on nano based formulation strategies for successful delivery of cosmetic agents. Novel strategies like nanoemulsion, nanogels, liposomes, aquasomes, niosomes, dendrimers and fullerenes have paved way for successful delivery of dermal formulations to desire depths in the skin. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Formulation and delivery strategies of ibuprofen: challenges and opportunities.

    PubMed

    Irvine, Jake; Afrose, Afrina; Islam, Nazrul

    2018-02-01

    Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose.

  9. MO-D-BRB-02: SBRT Treatment Planning and Delivery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Y.

    2016-06-15

    Increased use of SBRT and hypofractionation in radiation oncology practice has posted a number of challenges to medical physicist, ranging from planning, image-guided patient setup and on-treatment monitoring, to quality assurance (QA) and dose delivery. This symposium is designed to provide current knowledge necessary for the safe and efficient implementation of SBRT in various linac platforms, including the emerging digital linacs equipped with high dose rate FFF beams. Issues related to 4D CT, PET and MRI simulations, 3D/4D CBCT guided patient setup, real-time image guidance during SBRT dose delivery using gated/un-gated VMAT/IMRT, and technical advancements in QA of SBRT (inmore » particular, strategies dealing with high dose rate FFF beams) will be addressed. The symposium will help the attendees to gain a comprehensive understanding of the SBRT workflow and facilitate their clinical implementation of the state-of-art imaging and planning techniques. Learning Objectives: Present background knowledge of SBRT, describe essential requirements for safe implementation of SBRT, and discuss issues specific to SBRT treatment planning and QA. Update on the use of multi-dimensional and multi-modality imaging for reliable guidance of SBRT. Discuss treatment planning and QA issues specific to SBRT. Provide a comprehensive overview of emerging digital linacs and summarize the key geometric and dosimetric features of the new generation of linacs for substantially improved SBRT. NIH/NCI; Varian Medical Systems; F. Yin, Duke University has a research agreement with Varian Medical Systems. In addition to research grant, I had a technology license agreement with Varian Medical Systems.« less

  10. Localized delivery of growth factors for periodontal tissue regeneration: role, strategies, and perspectives.

    PubMed

    Chen, Fa-Ming; Shelton, Richard M; Jin, Yan; Chapple, Iain L C

    2009-05-01

    Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. Localized delivery of growth factors to the periodontium is an emerging and versatile therapeutic approach, with the potential to become a powerful tool in future regenerative periodontal therapy. Optimized delivery regimes and well-defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of growth factors and to avoid unwanted side effects and toxicity. While adequate concentrations of growth factor(s) need to be appropriately localized, delivery vehicles are also expected to possess properties such as protein protection, precision in controlled release, biocompatibility and biodegradability, self-regulated therapeutic activity, potential for multiple delivery, and good cell/tissue penetration. Here, current knowledge, recent advances, and future possibilities of growth factor delivery strategies are outlined for periodontal regeneration. First, the role of those growth factors that have been implicated in the periodontal healing/regeneration process, general requirements for their delivery, and the different material types available are described. A detailed discussion follows of current strategies for the selection of devices for localized growth factor delivery, with particular emphasis placed upon their advantages and disadvantages and future prospects for ongoing studies in reconstructing the tooth supporting apparatus.

  11. Convection-Enhanced Delivery for the Treatment of Pediatric Neurologic Disorders

    PubMed Central

    Song, Debbie K.; Lonser, Russell R.

    2013-01-01

    Direct perfusion of specific regions of the central nervous system by convection-enhanced delivery is becoming more widely used for the delivery of compounds in the research and treatment of various neural disorders. In contrast to other currently available central nervous system delivery techniques, convection-enhanced delivery relies on bulk flow for distribution of solute. This allows for safe, targeted, reliable, and homogeneous delivery of small- and large-molecular-weight substances over clinically relevant volumes in a manner that bypasses the blood-central nervous system barrier. Recent studies have also shown that coinfused imaging surrogate tracers can be used to monitor and control the convective distribution of therapeutic agents in vivo. The unique features of convection-enhanced delivery, including the ability to monitor distribution in real-time, provide an opportunity to develop new research and treatment paradigms for pediatric patients with a variety of intrinsic central nervous system disorders. PMID:18952590

  12. Platelets as delivery systems for disease treatments

    PubMed Central

    Shi, Qizhen; Montgomery, Robert R.

    2010-01-01

    Platelets are small, anucleate, discoid shaped blood cells that play a fundamental role in hemostasis. Platelets contain a large number of biologically active molecules within cytoplasmic granules that are critical to normal platelet function. Because platelets circulate in blood through out the body, release biological molecules and mediators on demand, and participate in hemostasis as well as many other pathophysiologic processes, targeting expression of proteins of interest to platelets and utilizing platelets as delivery systems for disease treatment would be a logical approach. This paper reviews the genetic therapy for inherited bleeding disorders utilizing platelets as delivery system, with a particular focus on platelet-derived FVIII for hemophilia A treatment. PMID:20619307

  13. The treatment of mouse colorectal cancer by oral delivery tumor-targeting Salmonella

    PubMed Central

    Wang, Wei-Kuang; Lu, Meng-Fan; Kuan, Yu-Diao; Lee, Che-Hsin

    2015-01-01

    Systemic administration of Salmonella to tumor-bearing mice leads to its preferential accumulation in tumor sites, the enhancement of host immunity, and the inhibition of tumor growth. However, the underlying mechanism for Salmonella-induced antitumor immune response via oral delivery remained uncertain. Herein, we used mouse colorectal cancer (CT26) as tumor model to study the therapeutic effects after oral delivery of Salmonella. When orally administered into tumor-bearing mice, Salmonella significantly accumulated in the tumor sites, inhibited tumor growth and extended the survival of mice. No obvious toxicity was observed during orally administered Salmonella by examining body weight and inflammatory cytokines. As indoleamine 2, 3-dioxygenase 1 (IDO) is a crucial mediator for tumor-mediated immune tolerance, we examined the expression of IDO. We demonstrated that Salmonella inhibited IDO expression in mouse cancer cells. Furthermore, immunohistochemical studies of the tumors revealed the infiltration of neutrophils and T cells in mice treated with Salmonella. In conclusion, our results indicate that Salmonella exerts its tumoricidal effects and stimulates T cell activities by inhibiting IDO expression. Oral delivery of Salmonella may, represent a potential strategy for the treatment of tumor. PMID:26328252

  14. Literacy and Communication Technologies: Distance Education Strategies for Literacy Delivery

    ERIC Educational Resources Information Center

    Aderinoye, Rashid

    2008-01-01

    This article examines the promotion of literacy through information and communication technologies (ICTs) and through various modes of distance learning. After a general discussion of these approaches, the article focuses on efforts towards reducing illiteracy in Nigeria through integrated strategies for literacy delivery and especially through…

  15. Near-infrared remotely triggered drug-release strategies for cancer treatment

    NASA Astrophysics Data System (ADS)

    Goodman, Amanda M.; Neumann, Oara; Nørregaard, Kamilla; Henderson, Luke; Choi, Mi-Ran; Clare, Susan E.; Halas, Naomi J.

    2017-11-01

    Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.

  16. Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain.

    PubMed

    Upadhyay, Urvashi M; Tyler, Betty; Patta, Yoda; Wicks, Robert; Spencer, Kevin; Scott, Alexander; Masi, Byron; Hwang, Lee; Grossman, Rachel; Cima, Michael; Brem, Henry; Langer, Robert

    2014-11-11

    Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.

  17. Novel pharmacotherapeutic strategies for treatment of opioid-induced neonatal abstinence syndrome

    PubMed Central

    McLemore, Gabrielle L.; Lewis, Tamorah; Jones, Catherine H.; Gauda, Estelle B.

    2014-01-01

    Summary The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care in maternal and fetal/neonatal (M-F/N) medicine. The standard of care for illicit or prescription opioid dependence during pregnancy is opioid agonist (methadone or buprenorphine) substitution therapy, which are also frequently abused. The next generation of pharmacotherapies for the treatment of illicit or prescription opioid addiction in the M-F/N interactional dyad must take into consideration the interplay between genetic, epigenetic, and environmental factors. Addiction to illicit drugs during pregnancy presents unique challenges to effectively treat the mother, and the developing fetus and infant after delivery. New pharmacotherapies should be safe to the developing fetus, effective in treating the physical and psychological consequences of addiction in the mother, and reduce the incidence and severity of NAS in the infant after birth. More pharmacotherapeutic options should be available to the physician such that a more individualized rather than a one-drug/strategy-fits-all approach can be used. A myriad of new and exciting pharmacotherapeutic strategies for the treatment of opioid dependence and addiction are on the horizon. This review focuses on such three strategies: (i) pharmacotherapeutic targeting of the serotoninergic system; (ii) mixed opioid immunotherapeutics (vaccines); (iii) pharmacogenomics as a therapeutic strategy to insure personalized care. We review and discuss how these strategies may offer additional treatment modalities for the treatment

  18. [Strategy and collaboration between medicinal chemists and pharmaceutical scientists for drug delivery systems].

    PubMed

    Mano, Takashi

    2013-01-01

    In order to successfully apply drug delivery systems (DDS) to new chemical entities (NCEs), collaboration between medicinal chemists and formulation scientists is critical for efficient drug discovery. Formulation scientists have to use 'language' that medicinal chemists understand to help promote mutual understanding, and medicinal chemists and formulation scientists have to set up strategies to use suitable DDS technologies at the discovery phase of the programmes to ensure successful transfer into the development phase. In this review, strategies of solubilisation formulation for oral delivery, inhalation delivery, nasal delivery and bioconjugation are all discussed. For example, for oral drug delivery, multiple initiatives can be proposed to improve the process to select an optimal delivery option for an NCE. From a technical perspective, formulation scientists have to explain the scope and limitations of formulations as some DDS technologies might be applicable only to limited chemical spaces. Other limitations could be the administered dose and, cost, time and resources for formulation development and manufacturing. Since DDS selection is best placed as part of lead-optimisation, formulation scientists need to be involved in discovery projects at lead selection and optimisation stages. The key to success in their collaboration is to facilitate communication between these two areas of expertise at both a strategic and scientific level. Also, it would be beneficial for medicinal chemists and formulation scientists to set common goals to improve the process of collaboration and build long term partnerships to improve DDS.

  19. Carrier-Based Drug Delivery System for Treatment of Acne

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

    Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

  20. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

    PubMed Central

    Zhao, Shan; Lv, Yan; Zhang, Jian-Bin; Wang, Bing; Lv, Guo-Jun; Ma, Xiao-Jun

    2014-01-01

    Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections. PMID:25071326

  1. Strategies for drug delivery to the central nervous system by systemic route.

    PubMed

    Kasinathan, Narayanan; Jagani, Hitesh V; Alex, Angel Treasa; Volety, Subrahmanyam M; Rao, J Venkata

    2015-05-01

    Delivery of a drug into the central nervous system (CNS) is considered difficult. Most of the drugs discovered over the past decade are biological, which are high in molecular weight and polar in nature. The delivery of such drugs across the blood-brain barrier presents problems. This review discusses some of the options available to reach the CNS by systemic route. The focus is mainly on the recent developments in systemic delivery of a drug to the CNS. Databases such as Scopus, Google scholar, Science Direct, SciFinder and online journals were referred for preparing this article including 89 references. There are at least nine strategies that could be adopted to achieve the required drug concentration in the CNS. The recent developments in drug delivery are very promising to deliver biologicals into the CNS.

  2. High content analysis platform for optimization of lipid mediated CRISPR-Cas9 delivery strategies in human cells.

    PubMed

    Steyer, Benjamin; Carlson-Stevermer, Jared; Angenent-Mari, Nicolas; Khalil, Andrew; Harkness, Ty; Saha, Krishanu

    2016-04-01

    in the human genome and precisely suture in therapeutic sequences. Biomaterials based delivery strategies could help transition these technologies to the clinic. The design space for materials based delivery strategies is vast and optimization is essential to ensuring the safety and efficacy of these treatments. Therefore, new methods are required to rapidly and systematically screen gene-editing efficacy in human cells. This work utilizes an innovative platform to generate and screen many formulations of synthetic biomaterials and components of the CRISPR-Cas9 system in parallel. On this platform, we watch genome surgery in action using high content image analysis. These capabilities enabled us to identify formulation parameters for Cas9-material complexes that can optimize gene-editing in a specific human cell type. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Novel treatment strategies for brain tumors and metastases

    PubMed Central

    El-Habashy, Salma E.; Nazief, Alaa M.; Adkins, Chris E.; Wen, Ming Ming; El-Kamel, Amal H.; Hamdan, Ahmed M.; Hanafy, Amira S.; Terrell, Tori O.; Mohammad, Afroz S.; Lockman, Paul R.; Nounou, Mohamed Ismail

    2015-01-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood–brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  4. Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

    PubMed Central

    Khalin, Igor; Alyautdin, Renad; Kocherga, Ganna; Bakar, Muhamad Abu

    2015-01-01

    Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration. PMID:25995632

  5. Treatment planning for SBRT using automated field delivery: A case study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ritter, Timothy A., E-mail: timritte@med.umich.edu; Department of Radiation Oncology, Veterans Affairs Ann Arbor Health Care System, Ann Arbor, MI; Owen, Dawn

    Stereotactic body radiation therapy (SBRT) treatment planning and delivery can be accomplished using a variety of techniques that achieve highly conformal dose distributions. Herein, we describe a template-based automated treatment field approach that enables rapid delivery of more than 20 coplanar fields. A case study is presented to demonstrate how modest adaptations to traditional SBRT planning can be implemented to take clinical advantage of this technology. Treatment was planned for a left-sided lung lesion adjacent to the chest wall using 25 coplanar treatment fields spaced at 11° intervals. The plan spares the contralateral lung and is in compliance with themore » conformality standards set forth in Radiation Therapy and Oncology Group protocol 0915, and the dose tolerances found in the report of the American Association of Physicists in Medicine Task Group 101. Using a standard template, treatment planning was accomplished in less than 20 minutes, and each 10 Gy fraction was delivered in approximately 5.4 minutes. For those centers equipped with linear accelerators capable of automated treatment field delivery, the use of more than 20 coplanar fields is a viable SBRT planning approach and yields excellent conformality and quality combined with rapid planning and treatment delivery. Although the case study discusses a laterally located lung lesion, this technique can be applied to centrally located tumors with similar results.« less

  6. Racial and Ethnic Differences in Utilization of Labor Management Strategies Intended to Reduce Cesarean Delivery Rates.

    PubMed

    Yee, Lynn M; Costantine, Maged M; Rice, Madeline Murguia; Bailit, Jennifer; Reddy, Uma M; Wapner, Ronald J; Varner, Michael W; Thorp, John M; Caritis, Steve N; Prasad, Mona; Tita, Alan T N; Sorokin, Yoram; Rouse, Dwight J; Blackwell, Sean C; Tolosa, Jorge E

    2017-12-01

    To examine whether racial and ethnic differences exist in the frequency of and indications for cesarean delivery and to assess whether application of labor management strategies intended to reduce cesarean delivery rates is associated with patient's race and ethnicity. This is a secondary analysis of a multicenter observational obstetric cohort. Trained research personnel abstracted maternal and neonatal records of greater than 115,000 pregnant women from 25 hospitals (2008-2011). Women at term with singleton, nonanomalous, vertex, liveborn neonates were included in two cohorts: 1) nulliparous women (n=35,529); and 2) multiparous women with prior vaginal deliveries only (n=39,871). Women were grouped as non-Hispanic black, non-Hispanic white, Hispanic, and Asian. Multivariable logistic regression was used to evaluate the following outcomes: overall cesarean delivery frequency, indications for cesarean delivery, and utilization of labor management strategies intended to safely reduce cesarean delivery. A total of 75,400 women were eligible for inclusion, of whom 47% (n=35,529) were in the nulliparous cohort and 53% (n=39,871) were in the multiparous cohort. The frequencies of cesarean delivery were 25.8% among nulliparous women and 6.0% among multiparous women. For nulliparous women, the unadjusted cesarean delivery frequencies were 25.0%, 28.3%, 28.7%, and 24.0% for non-Hispanic white, non-Hispanic black, Asian, and Hispanic women, respectively. Among nulliparous women, the adjusted odds of cesarean delivery were higher in all racial and ethnic groups compared with non-Hispanic white women (non-Hispanic black adjusted odds ratio [OR] 1.47, 95% CI 1.36-1.59; Asian adjusted OR 1.26, 95% CI 1.14-1.40; Hispanic adjusted OR 1.17, 95% CI 1.07-1.27) as a result of greater odds of cesarean delivery both for nonreassuring fetal status and labor dystocia. Nonapplication of labor management strategies regarding failed induction, arrest of dilation, arrest of descent, or

  7. Peptide and protein delivery using new drug delivery systems.

    PubMed

    Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

  8. Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

    PubMed Central

    Kydd, Janel; Jadia, Rahul; Velpurisiva, Praveena; Gad, Aniket; Paliwal, Shailee; Rai, Prakash

    2017-01-01

    Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines. PMID:29036899

  9. Identifying Service Delivery Strategies for Ethnically Diverse Users of a Wildland-Urban Recreation Site

    Treesearch

    John M. Baas

    1992-01-01

    Service delivery has become an increasingly important part of managing public lands for recreation. The range of preferences held by ethnically diverse users of recreation sites may warrant the development of more than one service delivery strategy. Two questions were examined: (1) Are there differences in site perceptions that can be identified on the basis on...

  10. University Educational Service Delivery Strategy in a Changing World: Implications for Ethical Values and Leadership Integrity in Nigeria

    ERIC Educational Resources Information Center

    Akintayo, D. I.

    2008-01-01

    This paper examined university educational service delivery strategy in a changing world as it affects ethical values and leadership integrity in Nigeria. This was for the purpose of determining appropriate strategies for improving the quality of service delivery system in Nigerian universities. The paper submits that the quality and quantity of…

  11. Nanomedicine as a potential approach to empower the new strategies for the treatment of preeclampsia.

    PubMed

    Valero, Lucie; Alhareth, Khair; Gil, Sophie; Lecarpentier, Edouard; Tsatsaris, Vassilis; Mignet, Nathalie; Fournier, Thierry; Andrieux, Karine

    2018-01-31

    Preeclampsia is a serious pregnancy disorder characterized by the onset of high blood pressure and proteinuria. Although the understanding of the disease is increasing, it remains without treatment, other than the delivery of the baby and the placenta. This review sets out to discuss some new developments and strategies in the treatment of preeclampsia. We briefly review the current knowledge on the preeclamptic pathophysiology. We then examine the recent trends in preeclampsia treatment and, in particular, the tracks of potential therapeutic targets. Finally, we focus on the possibilities nanocarriers could offer in the management of preeclampsia. Indeed, nanocarriers could help to prevent transplacental passage and promote placental-specific drug delivery, thereby enhancing efficacy and improving safety. Tendencies are then drawn from the available studies on the optimal characteristics of a nanocarrier to deliver drugs to the placenta. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Quality control procedures for dynamic treatment delivery techniques involving couch motion.

    PubMed

    Yu, Victoria Y; Fahimian, Benjamin P; Xing, Lei; Hristov, Dimitre H

    2014-08-01

    In this study, the authors introduce and demonstrate quality control procedures for evaluating the geometric and dosimetric fidelity of dynamic treatment delivery techniques involving treatment couch motion synchronous with gantry and multileaf collimator (MLC). Tests were designed to evaluate positional accuracy, velocity constancy and accuracy for dynamic couch motion under a realistic weight load. A test evaluating the geometric accuracy of the system in delivering treatments over complex dynamic trajectories was also devised. Custom XML scripts that control the Varian TrueBeam™ STx (Serial #3) axes in Developer Mode were written to implement the delivery sequences for the tests. Delivered dose patterns were captured with radiographic film or the electronic portal imaging device. The couch translational accuracy in dynamic treatment mode was 0.01 cm. Rotational accuracy was within 0.3°, with 0.04 cm displacement of the rotational axis. Dose intensity profiles capturing the velocity constancy and accuracy for translations and rotation exhibited standard deviation and maximum deviations below 3%. For complex delivery involving MLC and couch motions, the overall translational accuracy for reproducing programmed patterns was within 0.06 cm. The authors conclude that in Developer Mode, TrueBeam™ is capable of delivering dynamic treatment delivery techniques involving couch motion with good geometric and dosimetric fidelity.

  13. Mucin-mediated nanocarrier disassembly for triggered uptake of oligonucleotides as a delivery strategy for the potential treatment of mucosal tumours

    NASA Astrophysics Data System (ADS)

    Martirosyan, A.; Olesen, M. J.; Fenton, R. A.; Kjems, J.; Howard, K. A.

    2016-06-01

    This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites.This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal

  14. Recent Advances in Delivery of Drug-Nucleic Acid Combinations for Cancer Treatment

    PubMed Central

    Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

    2013-01-01

    Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. PMID:23624358

  15. Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

    PubMed

    Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

    2013-12-10

    Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Five focus strategies to organize health care delivery.

    PubMed

    Peltokorpi, Antti; Linna, Miika; Malmström, Tomi; Torkki, Paulus; Lillrank, Paul Martin

    2016-01-01

    The focused factory is one of the concepts that decision-makers have adopted for improving health care delivery. However, disorganized definitions of focus have led to findings that cannot be utilized systematically. The purpose of this paper is to discuss strategic options to focus health care operations. First the literature on focus in health care is reviewed revealing conceptual challenges. Second, a definition of focus in terms of demand and requisite variety is defined, and the mechanisms of focus are explicated. A classification of five focus strategies that follow the original idea to reduce variety in products and markets is presented. Finally, the paper examines managerial possibilities linked to the focus strategies. The paper proposes a framework of five customer-oriented focus strategies which aim at reducing variety in different characteristics of care pathways: population; urgency and severity; illnesses and symptoms; care practices and processes; and care outcomes. Empirical research is needed to evaluate the costs and benefits of the five strategies and about system-level effects of focused units on competition and coordination. Focus is an enabling condition that needs to be exploited using specific demand and supply management practices. It is essential to understand how focus mechanisms differ between strategies, and to select focus that fits with organization's strategy and key performance indicators. Compared to previous more resource-oriented approaches, this study provides theoretically solid and practically relevant customer-oriented framework for focusing in health care.

  17. A system for EPID-based real-time treatment delivery verification during dynamic IMRT treatment.

    PubMed

    Fuangrod, Todsaporn; Woodruff, Henry C; van Uytven, Eric; McCurdy, Boyd M C; Kuncic, Zdenka; O'Connor, Daryl J; Greer, Peter B

    2013-09-01

    To design and develop a real-time electronic portal imaging device (EPID)-based delivery verification system for dynamic intensity modulated radiation therapy (IMRT) which enables detection of gross treatment delivery errors before delivery of substantial radiation to the patient. The system utilizes a comprehensive physics-based model to generate a series of predicted transit EPID image frames as a reference dataset and compares these to measured EPID frames acquired during treatment. The two datasets are using MLC aperture comparison and cumulative signal checking techniques. The system operation in real-time was simulated offline using previously acquired images for 19 IMRT patient deliveries with both frame-by-frame comparison and cumulative frame comparison. Simulated error case studies were used to demonstrate the system sensitivity and performance. The accuracy of the synchronization method was shown to agree within two control points which corresponds to approximately ∼1% of the total MU to be delivered for dynamic IMRT. The system achieved mean real-time gamma results for frame-by-frame analysis of 86.6% and 89.0% for 3%, 3 mm and 4%, 4 mm criteria, respectively, and 97.9% and 98.6% for cumulative gamma analysis. The system can detect a 10% MU error using 3%, 3 mm criteria within approximately 10 s. The EPID-based real-time delivery verification system successfully detected simulated gross errors introduced into patient plan deliveries in near real-time (within 0.1 s). A real-time radiation delivery verification system for dynamic IMRT has been demonstrated that is designed to prevent major mistreatments in modern radiation therapy.

  18. Nanotechnology-Based Strategies for siRNA Brain Delivery for Disease Therapy.

    PubMed

    Zheng, Meng; Tao, Wei; Zou, Yan; Farokhzad, Omid C; Shi, Bingyang

    2018-05-01

    Small interfering RNA (siRNA)-based gene silencing technology has demonstrated significant potential for treating brain-associated diseases. However, effective and safe systemic delivery of siRNA into the brain remains challenging because of biological barriers such as enzymatic degradation, short circulation lifetime, the blood-brain barrier (BBB), insufficient tissue penetration, cell endocytosis, and cytosolic transport. Nanotechnology offers intriguing potential for addressing these challenges in siRNA brain delivery in conjunction with chemical and biological modification strategies. In this review, we outline the challenges of systemic delivery of siRNA-based therapy for brain diseases, highlight recent advances in the development and engineering of siRNA nanomedicines for various brain diseases, and discuss our perspectives on this exciting research field for siRNA-based therapy towards more effective brain disease therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review.

    PubMed

    Guzman-Aranguez, Ana; Fonseca, Begoña; Carracedo, Gonzalo; Martin-Gil, Alba; Martinez-Aguila, Alejandro; Pintor, Jesús

    2016-09-01

    Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses.

  20. Modeling Test and Treatment Strategies for Presymptomatic Alzheimer Disease

    PubMed Central

    Burke, James F.; Langa, Kenneth M.; Hayward, Rodney A.; Albin, Roger L.

    2014-01-01

    Objectives In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. Methods Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. Findings In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. Conclusions Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment. PMID:25474698

  1. Characterization of the pH and Temperature in the Rabbit, Pig, and Monkey Eye: Key Parameters for the Development of Long-Acting Delivery Ocular Strategies.

    PubMed

    Lorget, Florence; Parenteau, Audrey; Carrier, Michel; Lambert, Daniel; Gueorguieva, Ana; Schuetz, Chris; Bantseev, Vlad; Thackaberry, Evan

    2016-09-06

    Many long-acting delivery strategies for ocular indications rely on pH- and/or temperature-driven release of the therapeutic agent and degradation of the drug carrier. Yet, these physiological parameters are poorly characterized in ocular animal models. These strategies aim at reducing the frequency of dosing, which is of particular interest for the treatment of chronic disorders affecting the posterior segment of the eye, such as macular degeneration that warrants monthly or every other month intravitreal injections. We used anesthetized white New Zealand rabbits, Yucatan mini pigs, and cynomolgus monkeys to characterize pH and temperature in several vitreous locations and the central aqueous location. We also established post mortem pH changes in the vitreous. Our data showed regional and species differences, which need to be factored into strategies for developing biodegradable long-acting delivery systems.

  2. Experiences of operational costs of HPV vaccine delivery strategies in Gavi-supported demonstration projects

    PubMed Central

    Holroyd, Taylor; Nanda, Shreya; Bloem, Paul; Griffiths, Ulla K.; Sidibe, Anissa; Hutubessy, Raymond C. W.

    2017-01-01

    From 2012 to 2016, Gavi, the Vaccine Alliance, provided support for countries to conduct small-scale demonstration projects for the introduction of the human papillomavirus vaccine, with the aim of determining which human papillomavirus vaccine delivery strategies might be effective and sustainable upon national scale-up. This study reports on the operational costs and cost determinants of different vaccination delivery strategies within these projects across twelve countries using a standardized micro-costing tool. The World Health Organization Cervical Cancer Prevention and Control Costing Tool was used to collect costing data, which were then aggregated and analyzed to assess the costs and cost determinants of vaccination. Across the one-year demonstration projects, the average economic and financial costs per dose amounted to US$19.98 (standard deviation ±12.5) and US$8.74 (standard deviation ±5.8), respectively. The greatest activities representing the greatest share of financial costs were social mobilization at approximately 30% (range, 6–67%) and service delivery at about 25% (range, 3–46%). Districts implemented varying combinations of school-based, facility-based, or outreach delivery strategies and experienced wide variation in vaccine coverage, drop-out rates, and service delivery costs, including transportation costs and per diems. Size of target population, number of students per school, and average length of time to reach an outreach post influenced cost per dose. Although the operational costs from demonstration projects are much higher than those of other routine vaccine immunization programs, findings from our analysis suggest that HPV vaccination operational costs will decrease substantially for national introduction. Vaccination costs may be decreased further by annual vaccination, high initial investment in social mobilization, or introducing/strengthening school health programs. Our analysis shows that drivers of cost are dependent on

  3. Experiences of operational costs of HPV vaccine delivery strategies in Gavi-supported demonstration projects.

    PubMed

    Botwright, Siobhan; Holroyd, Taylor; Nanda, Shreya; Bloem, Paul; Griffiths, Ulla K; Sidibe, Anissa; Hutubessy, Raymond C W

    2017-01-01

    From 2012 to 2016, Gavi, the Vaccine Alliance, provided support for countries to conduct small-scale demonstration projects for the introduction of the human papillomavirus vaccine, with the aim of determining which human papillomavirus vaccine delivery strategies might be effective and sustainable upon national scale-up. This study reports on the operational costs and cost determinants of different vaccination delivery strategies within these projects across twelve countries using a standardized micro-costing tool. The World Health Organization Cervical Cancer Prevention and Control Costing Tool was used to collect costing data, which were then aggregated and analyzed to assess the costs and cost determinants of vaccination. Across the one-year demonstration projects, the average economic and financial costs per dose amounted to US$19.98 (standard deviation ±12.5) and US$8.74 (standard deviation ±5.8), respectively. The greatest activities representing the greatest share of financial costs were social mobilization at approximately 30% (range, 6-67%) and service delivery at about 25% (range, 3-46%). Districts implemented varying combinations of school-based, facility-based, or outreach delivery strategies and experienced wide variation in vaccine coverage, drop-out rates, and service delivery costs, including transportation costs and per diems. Size of target population, number of students per school, and average length of time to reach an outreach post influenced cost per dose. Although the operational costs from demonstration projects are much higher than those of other routine vaccine immunization programs, findings from our analysis suggest that HPV vaccination operational costs will decrease substantially for national introduction. Vaccination costs may be decreased further by annual vaccination, high initial investment in social mobilization, or introducing/strengthening school health programs. Our analysis shows that drivers of cost are dependent on

  4. External triggering and triggered targeting strategies for drug delivery

    NASA Astrophysics Data System (ADS)

    Wang, Yanfei; Kohane, Daniel S.

    2017-06-01

    Drug delivery systems that are externally triggered to release drugs and/or target tissues hold considerable promise for improving the treatment of many diseases by minimizing nonspecific toxicity and enhancing the efficacy of therapy. These drug delivery systems are constructed from materials that are sensitive to a wide range of external stimuli, including light, ultrasound, electrical and magnetic fields, and specific molecules. The responsiveness conferred by these materials allows the release of therapeutics to be triggered on demand and remotely by a physician or patient. In this Review, we describe the rationales for such systems and the types of stimuli that can be deployed, and provide an outlook for the field.

  5. Nanocarriers for cancer-targeted drug delivery.

    PubMed

    Kumari, Preeti; Ghosh, Balaram; Biswas, Swati

    2016-01-01

    Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.

  6. From Molecular to Nanotechnology Strategies for Delivery of Neurotrophins: Emphasis on Brain-Derived Neurotrophic Factor (BDNF)

    PubMed Central

    Géral, Claire; Angelova, Angelina; Lesieur, Sylviane

    2013-01-01

    Neurodegenerative diseases represent a major public health problem, but beneficial clinical treatment with neurotrophic factors has not been established yet. The therapeutic use of neurotrophins has been restrained by their instability and rapid degradation in biological medium. A variety of strategies has been proposed for the administration of these leading therapeutic candidates, which are essential for the development, survival and function of human neurons. In this review, we describe the existing approaches for delivery of brain-derived neurotrophic factor (BDNF), which is the most abundant neurotrophin in the mammalian central nervous system (CNS). Biomimetic peptides of BDNF have emerged as a promising therapy against neurodegenerative disorders. Polymer-based carriers have provided sustained neurotrophin delivery, whereas lipid-based particles have contributed also to potentiation of the BDNF action. Nanotechnology offers new possibilities for the design of vehicles for neuroprotection and neuroregeneration. Recent developments in nanoscale carriers for encapsulation and transport of BDNF are highlighted. PMID:24300402

  7. Drug Delivery in Cancer Therapy, Quo Vadis?

    PubMed

    Lu, Zheng-Rong; Qiao, Peter

    2018-03-22

    The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody-drug conjugates, liposomes, polymer-drug conjugates, polymer implants, micelles, and nanoparticles. The clinical outcomes of these delivery systems from various phases of clinical trials are summarized. The success and limitations of the drug delivery strategies are discussed based on the clinical observations. In addition, the challenges in applying drug delivery for efficacious cancer therapy, including physical barriers, tumor heterogeneity, drug resistance, and metastasis, are discussed along with future perspectives of drug delivery in cancer therapy. In doing so, we intend to underscore that efficient delivery of cancer therapeutics to solid malignancies remains a major challenge in cancer therapy, and requires a multidisciplinary approach that integrates knowledge from the diverse fields of chemistry, biology, engineering, and medicine. The overall objective of this review is to improve our understanding of the clinical fate of commonly investigated drug delivery strategies, and to identify the limitations that must be addressed in future drug delivery strategies, toward the pursuit of curative therapies for cancer.

  8. Engaging Foster Parents in Treatment: A Randomized Trial of Supplementing Trauma-focused Cognitive Behavioral Therapy with Evidence-based Engagement Strategies

    PubMed Central

    Pullmann, Michael D.; Berliner, Lucy; Koschmann, Elizabeth; McKay, Mary; Deblinger, Esther

    2014-01-01

    The goal of this study was to examine the impact of supplementing Trauma-focused Cognitive Behavioral Therapy (TF-CBT; Cohen, Mannarino, & Deblinger, 2006) with evidence-based engagement strategies on foster parent and foster youth engagement in treatment, given challenges engaging foster parents in treatment. A randomized controlled trial of TF-CBT standard delivery compared to TF-CBT plus evidence-based engagement strategies was conducted with 47 children and adolescents in foster care and one of their foster parents. Attendence, engagement, and clinical outcomes were assessed 1 month into treatment, end of treatment, and 3 months post-treatment. Youth and foster parents who received TF-CBT plus evidence-based engagement strategies were more likely to be retained in treatment through four sessions and were less likely to drop out of treatment prematurely. The engagement strategies did not appear to have an effect on the number of cancelled or no-show sessions or on treatment satisfaction. Clinical outcomes did not differ by study condition, but exploratory analyses suggest that youth had significant improvements with treatment. Strategies that specifically target engagement may hold promise for increasing access to evidence-based practices and for increasing likelihood of treatment completion. PMID:24791605

  9. Convection-enhanced delivery for the treatment of glioblastoma

    PubMed Central

    Vogelbaum, Michael A.; Aghi, Manish K.

    2015-01-01

    Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low–positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique. PMID:25746090

  10. Non-coding RNAs: Therapeutic Strategies and Delivery Systems.

    PubMed

    Ling, Hui

    The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer.

  11. The delivery of medical services in a retail shopping mall: a strategy for growth.

    PubMed

    Hayden, K R

    1989-01-01

    The successful medical practice of the future will continually search for growth strategies. This writer believes the location of a primary care medical clinic in a retail shopping mall, with a full menu of primary services, is one strategy for growth. It is an effective method of health care delivery to a community.

  12. Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy.

    PubMed

    Suzuki, Kazumichi; Gillin, Michael T; Sahoo, Narayan; Zhu, X Ronald; Lee, Andrew K; Lippy, Denise

    2011-07-01

    To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 +/- 35 patients. This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies

  13. Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine

    PubMed Central

    Nguyen, Minh Khanh; Alsberg, Eben

    2014-01-01

    Polymer hydrogels have been widely explored as therapeutic delivery matrices because of their ability to present sustained, localized and controlled release of bioactive factors. Bioactive factor delivery from injectable biopolymer hydrogels provides a versatile approach to treat a wide variety of diseases, to direct cell function and to enhance tissue regeneration. The innovative development and modification of both natural-(e.g., alginate (ALG), chitosan, hyaluronic acid (HA), gelatin, heparin (HEP), etc.) and synthetic-(e.g., polyesters, polyethyleneimine (PEI), etc.) based polymers has resulted in a variety of approaches to design drug delivery hydrogel systems from which loaded therapeutics are released. This review presents the state-of-the-art in a wide range of hydrogels that are formed though self-assembly of polymers and peptides, chemical crosslinking, ionic crosslinking and biomolecule recognition. Hydrogel design for bioactive factor delivery is the focus of the first section. The second section then thoroughly discusses release strategies of payloads from hydrogels for therapeutic medicine, such as physical incorporation, covalent tethering, affinity interactions, on demand release and/or use of hybrid polymer scaffolds, with an emphasis on the last 5 years. PMID:25242831

  14. An effective tumor-targeting strategy utilizing hypoxia-sensitive siRNA delivery system for improved anti-tumor outcome.

    PubMed

    Kang, Lin; Fan, Bo; Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Gao, Zhonggao

    2016-10-15

    Hypoxia is a feature of most solid tumors, targeting hypoxia is considered as the best validated yet not extensively exploited strategy in cancer therapy. Here, we reported a novel tumor-targeting strategy using a hypoxia-sensitive siRNA delivery system. In the study, 2-nitroimidazole (NI), a hydrophobic component that can be converted to hydrophilic 2-aminoimidazole (AI) through bioreduction under hypoxic conditions, was conjugated to the alkylated polyethyleneimine (bPEI1.8k-C6) to form amphiphilic bPEI1.8k-C6-NI polycations. bPEI1.8k-C6-NI could self-assemble into micelle-like aggregations in aqueous, which contributed to the improved stability of the bPEI1.8k-C6-NI/siRNA polyplexes, resulted in increased cellular uptake. After being transported into the hypoxic tumor cells, the selective nitro-to-amino reduction would cause structural change and elicit a relatively loose structure to facilitate the siRNA dissociation in the cytoplasm, for enhanced gene silencing efficiency ultimately. Therefore, the conflict between the extracellular stability and the intracellular siRNA release ability of the polyplexes was solved by introducing the hypoxia-responsive unit. Consequently, the survivin-targeted siRNA loaded polyplexes shown remarkable anti-tumor effect not only in hypoxic cells, but also in tumor spheroids and tumor-bearing mice, indicating that the hypoxia-sensitive siRNA delivery system had great potential for tumor-targeted therapy. Hypoxia is one of the most remarkable features of most solid tumors, and targeting hypoxia is considered as the best validated strategy in cancer therapy. However, in the past decades, there were few reports about using this strategy in the drug delivery system, especially in siRNA delivery system. Therefore, we constructed a hypoxia-sensitive siRNA delivery system utilizing a hypoxia-responsive unit, 2-nitroimidazole, by which the unavoidable conflict between improved extracellular stability and promoted intracellular si

  15. Bioengineering Strategies for Designing Targeted Cancer Therapies

    PubMed Central

    Wen, Xuejun

    2014-01-01

    The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

  16. Ultrasound-mediated drug delivery for cardiovascular disease

    PubMed Central

    Sutton, Jonathan T; Haworth, Kevin J; Pyne-Geithman, Gail; Holland, Christy K

    2014-01-01

    Introduction Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery. Areas covered The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies. Expert opinion These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and less-invasive treatments. PMID:23448121

  17. Bolstering cholesteryl ester hydrolysis in liver: A hepatocyte-targeting gene delivery strategy for potential alleviation of atherosclerosis

    PubMed Central

    He, Hongliang; Lancina, Michael G.; Wang, Jing; Korzun, William J.; Yang, Hu; Ghosh, Shobha

    2017-01-01

    Current atherosclerosis treatment strategies primarily focus on limiting further cholesteryl esters (CE) accumulation by reducing endogenous synthesis of cholesterol in the liver. No therapy is currently available to enhance the removal of CE, a crucial step to reduce the burden of the existing disease. Given a central role of hepatic cholesteryl ester hydrolase (CEH) in intrahepatic hydrolysis of CE and subsequent removal of the resulting free cholesterol, in this work, we applied galactose-functionalized polyamidoamine (PAMAM) dendrimer G5 (Gal-G5) for hepatocyte-specific delivery of CEH expression vector. The data presented herein show increased specific uptake of Gal-G5 by the hepatocytes in vitro and in vivo. Furthermore, the upregulated CEH expression in the hepatocytes significantly enhanced intracellular hydrolysis of HDL-CE and subsequent conversion/secretion of hydrolyzed free cholesterol (FC) as bile acids. Increased CEH expression in the liver significantly increased the flux of HDL-CE to biliary as well as fecal FC and bile acids. Meanwhile, Gal-G5 did not induce hepatic or renal toxicity. It was not immunotoxic. Because of these encouraging pre-clinical testing results, using this safe and highly efficient hepatocyte-specific gene delivery platform to enhance the hepatic processes involved in cholesterol elimination is a promising strategy for alleviation of atherosclerosis. PMID:28349866

  18. A drug-delivery strategy for overcoming drug resistance in breast cancer through targeting of oncofetal fibronectin.

    PubMed

    Saw, Phei Er; Park, Jinho; Jon, Sangyong; Farokhzad, Omid C

    2017-02-01

    A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers. We constructed EDB-specific aptide (APT EDB )-conjugated liposome to simultaneously deliver siRNA(siMDR1) and Dox to drug-resistant breast cancer cells. APT EDB -LS(Dox,siMDR1) led to enhanced delivery of payloads into MCF7/ADR cells and showed significantly higher accumulation and retention in the tumors. While either APT EDB -LS(Dox) or APT EDB -LS(siMDR1) did not lead to appreciable tumor retardation in MCF7/ADR orthotropic model, APT EDB -LS(Dox,siMDR1) treatment resulted in significant reduction of the drug-resistant breast tumor. Taken together, this study provides a new strategy of drug delivery for drug-resistant cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. A software tool to automatically assure and report daily treatment deliveries by a cobalt‐60 radiation therapy device

    PubMed Central

    Wooten, H. Omar; Green, Olga; Li, Harold H.; Liu, Shi; Li, Xiaoling; Rodriguez, Vivian; Mutic, Sasa; Kashani, Rojano

    2016-01-01

    The aims of this study were to develop a method for automatic and immediate verification of treatment delivery after each treatment fraction in order to detect and correct errors, and to develop a comprehensive daily report which includes delivery verification results, daily image‐guided radiation therapy (IGRT) review, and information for weekly physics reviews. After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a commercial MRI‐guided radiotherapy treatment machine, we designed a procedure to use 1) treatment plan files, 2) delivery log files, and 3) beam output information to verify the accuracy and completeness of each daily treatment delivery. The procedure verifies the correctness of delivered treatment plan parameters including beams, beam segments and, for each segment, the beam‐on time and MLC leaf positions. For each beam, composite primary fluence maps are calculated from the MLC leaf positions and segment beam‐on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. A daily treatment delivery report is designed to include all required information for IGRT and weekly physics reviews including the plan and treatment fraction information, daily beam output information, and the treatment delivery verification results. A computer program was developed to implement the proposed procedure of the automatic delivery verification and daily report generation for an MRI guided radiation therapy system. The program was clinically commissioned. Sensitivity was measured with simulated errors. The final version has been integrated into the commercial version of the treatment delivery system. The method automatically verifies the EBRT treatment deliveries and generates the daily treatment reports. Already in clinical use for over one year, it is useful to facilitate delivery error detection, and to expedite physician daily IGRT

  20. Advances in systemic delivery of anti-cancer agents for the treatment of metastatic cancer.

    PubMed

    Grundy, Megan; Coussios, Constantin; Carlisle, Robert

    2016-07-01

    The successful treatment of metastatic cancer is refractory to strategies employed to treat confined, primary lesions, such as surgical resection and radiation therapy, and thus must be addressed by systemic delivery of anti-cancer agents. Conventional systemically administered chemotherapeutics are often ineffective and come with severe dose-limiting toxicities. This review focuses on the recent developments in systemic therapy for metastatic cancer. Firstly, the strategies employed to improve the efficacy of conventional chemotherapeutics by 'passively' and 'actively' targeting them to tumors are discussed. Secondly, recent advances in the use of biologics to better target cancer and to instigate anti-tumor immunity are reviewed. Under the label of 'biologics', antibody-therapies, T cell engaging therapies, oncolytic virotherapies and cell-based therapies are examined and evaluated. Improving specificity of action, and engaging the immune system appear to be key goals in the development of novel or reformulated anti-cancer agents for the treatment of metastatic cancer. One of the largest areas of opportunity in this field will be the identification of robust predictive biomarkers for use in conjunction with these agents. Treatment regimens that combine an agent to elicit an immune response (such as an oncolytic virus), and an agent to potentiate/mediate that immune response (such as immune checkpoint inhibitors) are predicted to be more effective than treatment with either agent alone.

  1. Engaging foster parents in treatment: a randomized trial of supplementing trauma-focused cognitive behavioral therapy with evidence-based engagement strategies.

    PubMed

    Dorsey, Shannon; Pullmann, Michael D; Berliner, Lucy; Koschmann, Elizabeth; McKay, Mary; Deblinger, Esther

    2014-09-01

    The goal of this study was to examine the impact of supplementing Trauma-focused Cognitive Behavioral Therapy (TF-CBT; Cohen et al., 2006) with evidence-based engagement strategies on foster parent and foster youth engagement in treatment, given challenges engaging foster parents in treatment. A randomized controlled trial of TF-CBT standard delivery compared to TF-CBT plus evidence-based engagement strategies was conducted with 47 children and adolescents in foster care and one of their foster parents. Attendance, engagement, and clinical outcomes were assessed 1 month into treatment, end of treatment, and 3 months post-treatment. Youth and foster parents who received TF-CBT plus evidence-based engagement strategies were more likely to be retained in treatment through four sessions and were less likely to drop out of treatment prematurely. The engagement strategies did not appear to have an effect on the number of canceled or no-show sessions or on treatment satisfaction. Clinical outcomes did not differ by study condition, but exploratory analyses suggest that youth had significant improvements with treatment. Strategies that specifically target engagement may hold promise for increasing access to evidence-based treatments and for increasing likelihood of treatment completion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.

    PubMed

    Faustino, Célia; Rijo, Patrícia; Reis, Catarina Pinto

    2017-06-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Anaemia: can we define haemoglobin thresholds for impaired oxygen homeostasis and suggest new strategies for treatment?

    PubMed

    Hare, Gregory M T; Tsui, Albert K Y; Ozawa, Sherri; Shander, Aryeh

    2013-03-01

    Observational clinical studies in perioperative medicine have defined a progressive increase in mortality that is proportional to both chronic preoperative anaemia and acute interpretative reductions in haemoglobin concentration (Hb). However, this knowledge has not yet helped to define the critical Hb threshold for organ injury and mortality in specific patient populations or in individual patients. Nor has this knowledge enabled us to develop effective treatment strategies for anaemia, as evident from the lack of a demonstrable improvement in survival in patients randomised to higher Hb levels by various treatment strategies including allogeneic red blood cell transfusion, erythropoiesis-stimulating agents (ESAs) and haemoglobin-based oxygen carriers (HBOCs). These findings emphasise the need for a clearer understanding of the mechanism of anaemia-induced mortality. Towards achieving this goal, experimental studies have defined adaptive mechanism by which oxygen homeostasis is maintained during acute anaemia. The mechanisms include: (1) effective sensing of anaemia-induced tissue hypoxia; (2) adaptive cardiovascular responses to maintain adequate tissue oxygen delivery; (3) heterogeneity of organ-specific oxygen delivery to preferentially sustain vital organs which are essential for acute survival (heart and brain); (4) evidence of increased vital organ injury with interruption of cardiovascular responses to anaemia and (5) evidence of activation of adaptive cellular responses to maintain oxygen homeostasis and support survival during acute anaemia. Understanding these mechanisms may allow us to define treatment thresholds and novel treatment strategies for acute anaemia based on biological markers of tissue hypoxia. The overall goal of these approaches is to improve patient outcomes, including event-free perioperative survival. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Treatment Strategies for Hypopigmentation in the Context of Burn Hypertrophic Scars

    PubMed Central

    Carney, Bonnie C.; McKesey, Jacqueline P.; Rosenthal, Dean S.

    2018-01-01

    Dyspigmentation in burn scars can contribute to the development of psychosocial complications after injury and can be detrimental to social reintegration and quality of life for burn survivors. Although treatments for skin lightening to treat hyperpigmentation have been well reviewed in the literature, skin-darkening strategies to treat hypopigmentation have not. The following potential treatment options in the context of burn hypertrophic scar will be discussed: use of the melanocyte-keratinocyte transplantation procedure, use of ectopic synthetic analogues of alpha-melanocyte stimulating hormone to initiate melanogenesis, and use of FK506 to induce melanogenesis. A proposed future direction of research in laser-assisted drug delivery of inducers of local melanin production, with the hope of developing a targeted, effective approach to dyspigmentation in hypertrophic scar is also discussed. PMID:29464168

  5. FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY

    PubMed Central

    Liu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan

    2010-01-01

    Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized. PMID:22473061

  6. Patient Perceptions of Treatment Delivery Platforms for Cognitive Behavioral Therapy for Insomnia.

    PubMed

    Cheung, Janet M Y; Bartlett, Delwyn J; Armour, Carol L; Laba, Tracey-Lea; Saini, Bandana

    2017-03-21

    Stepped care has given rise to the proliferation of abbreviated CBT-I programs and delivery formats. This includes interventions delivered by allied health professionals and those delivered electronically through the Internet. This article aims to explore patient perceptions between electronic and face-to-face (FTF) delivery platforms for (abbreviated) CBT-I. Patients with insomnia from specialist sleep or psychology clinics and those from the general community in Sydney, Australia. Semistructured interviews were conducted with patients with insomnia, guided by a schedule of questions and a choice task to explore patient perceptions of the different CBT-I treatment delivery platforms (e.g., perceived advantages and disadvantages or willingness to engage with either platform). Interviews were transcribed verbatim and analyzed using Framework Analysis. Participants also completed a battery of clinical mood and insomnia measures. Fifty-one interviews were conducted with patients with insomnia from specialist sleep or psychology clinics (n = 22) and the general community (n = 29). Synthesis of the qualitative data set revealed three themes pertinent to the patients' perspective toward electronic and FTF CBT-I delivery: Concepts of Efficacy, Concerns About Treatment, and Treatment on My Terms. Participants' choice to engage with either platform was also informed by diverse factors including perceived efficacy of treatment, personal commitments, lifestyle, and beliefs about sleep and insomnia. Clarifying patient treatment priorities and allaying potential concerns about engaging with an electronic treatment platform represent important steps for disseminating eCBT-I into mainstream practice.

  7. Predisposing factors for bacterial vaginosis, treatment efficacy and pregnancy outcome among term deliveries; results from a preterm delivery study.

    PubMed

    Larsson, P-G; Fåhraeus, Lars; Carlsson, Bodil; Jakobsson, Tell; Forsum, Urban

    2007-10-22

    Bacterial vaginosis (BV) during pregnancy is associated with an increased risk of preterm delivery but little is known about factors that could predict BV. We have analyzed if it is possible to identify a category of pregnant women that should be screened for BV, and if BV would alter the pregnancy outcome at term; we have also studied the treatment efficacy of clindamycin. Prospective BV screening and treatment study of 9025 women in a geographically defined region in southeast Sweden. BV was defined as a modified Nugent score of 6 and above. Data was collected from the Swedish Medical Birth Register. Women allocated to treatment were supplied with vaginal clindamycin cream. The main outcome goals were to identify factors that could predict BV. Vaginal smears were consistent with BV criteria in 9.3%. Logistic regression indicates a significant correlation between smoking and BV (p < 0.001) and a greater prevalence of BV in the lower age groups (p < 0.001). We found no correlation between BV and history of preterm deliveries, previous miscarriages, extra-uterine pregnancies, infertility problems or reported history of urinary tract infections-factors that earlier have been associated with BV. Treatment with clindamycin cream showed a cure rate of 77%. Less than 1% of women with a normal vaginal smear in early pregnancy will develop BV during the pregnancy. There was no association between BV and the obstetric outcome among women who delivered at term. Women with BV, both treated patients and nontreated, had the same obstetric outcome at term as women with normal vaginal flora. BV is more than twice as common among smokers, and there is a higher prevalence in the younger age group. However these two markers for BV do not suffice as a tool for screening, and considering the lack of other risk factors associated with BV, screening of all pregnant women might be a strategy to follow in a program intended to reduce the number of preterm births.

  8. Nanoparticle-based drug delivery to the vagina: a review

    PubMed Central

    Ensign, Laura M.; Cone, Richard; Hanes, Justin

    2014-01-01

    Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

  9. Recent Advances of Cocktail Chemotherapy by Combination Drug Delivery Systems

    PubMed Central

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-01-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end. PMID:26546751

  10. PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery

    PubMed Central

    Das, Sreemanti; Khuda-Bukhsh, Anisur Rahman

    2016-01-01

    Current treatment methods for melanoma have some limitations such as less target-specific action, severe side effects and resistance to drugs. Significant progress has been made in exploring novel drug delivery systems based on suitable biochemical mechanisms using nanoparticles ranging from 10 to 400 nm for drug delivery and imaging, utilizing their enhanced penetration and retention properties. Poly-lactide-co-glycolide (PLGA), a copolymer of poly-lactic acid and poly-glycolic acid, provides an ideally suited performance-based design for better penetration into skin cells, thereby having a greater potential for the treatment of melanoma. Moreover, encapsulation protects the drug from deactivation by biological reactions and interactions with biomolecules, ensuring successful delivery and bioavailability for effective treatment. Controlled and sustained delivery of drugs across the skin barrier that otherwise prohibits entry of larger molecules can be successfully made with adequately stable biocompatible nanocarriers such as PLGA for taking drugs through the small cutaneous pores permitting targeted deposition and prolonged drug action. PLGA is now being extensively used in photodynamic therapy and targeted therapy through modulation of signal proteins and drug-DNA interactions. Recent advances made on these nanomedicines and their advantages in the treatment of skin melanoma are highlighted and discussed in this review. PMID:27934796

  11. [Strategies of treatment for febrile neutropenia].

    PubMed

    Terui, Yasuhito

    2013-06-01

    The guideline on febrile neutropenia(FN)was published by the Japanese Society of Medical Oncology(JSMO)in 2012. Based on this guideline, the treatment strategy for febrile neutropenia that is discussed in this paper includes empiric treatment strategies, methicillin-resistant Staphylococcus aureus antibiotics in the initial treatment, treatment for severe FN, treatment for outpatients, duration of FN treatment, treatment after recovery from fever associated with neutropenia, and empiric treatment with anti-fungal drugs in patients with prolonged FN.

  12. A population based evaluation of the mode of delivery in association with infertility treatment from 1990-2012.

    PubMed

    Reichelt, J; Kyvernitakis, I; Misselwitz, B; Hadji, P; Schmidt, S; Kalder, M

    2015-02-01

    This study refers to population based data and investigates the development of the mode of delivery associated with infertility treatment over the last 23 years. All 1 202,557 deliveries in Hesse, Germany, between 1990 and 2012 were assessed. 2.2% of the study population, 26,761, had a delivery subsequent to infertility treatment based on the Hessian Perinatal Registry (HEPE). An evaluation in this subgroup was performed investigating the associations between the mode of delivery and the gestational week and the mother's age. A continuous and significant (p<0.01) increase of cesarean section (CS) rates subsequent to infertility treatment (1990: 41,3%; 2012: 55,9%) as well as a conversely also significant (p<0.01) reduction of vaginal operative and spontaneous deliveries associated with infertility treatment between 1990 and 2012 was found. Furthermore, the preterm delivery rate and the proportion of deliveries of parturients older than 35 years of age in association with infertility treatment raised over the last years. Rates of full-term deliveries and deliveries of women younger than 35 years remained stable during the observation period. The rate of cesarean section is continuously rising over the last 23 years with regard to parturients subsequent to infertility treatment. The CS rate is significantly higher compared to women with a spontaneous pregnancy and in comparison to the data from 20 years ago. Most recently, the number of CS (51,2%) exceeded the number of vaginal deliveries (48,8%) in Hesse subsequent to infertility treatment for the first time. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Convection-enhanced delivery for the treatment of glioblastoma.

    PubMed

    Vogelbaum, Michael A; Aghi, Manish K

    2015-03-01

    Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low-positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. A coordinated control strategy for insulin and glucagon delivery in type 1 diabetes.

    PubMed

    Herrero, Pau; Bondia, Jorge; Oliver, Nick; Georgiou, Pantelis

    2017-10-01

    Type 1 diabetes is an autoimmune condition characterised by a pancreatic insulin secretion deficit, resulting in high blood glucose concentrations, which can lead to micro- and macrovascular complications. Type 1 diabetes also leads to impaired glucagon production by the pancreatic α-cells, which acts as a counter-regulatory hormone to insulin. A closed-loop system for automatic insulin and glucagon delivery, also referred to as an artificial pancreas, has the potential to reduce the self-management burden of type 1 diabetes and reduce the risk of hypo- and hyperglycemia. To date, bihormonal closed-loop systems for glucagon and insulin delivery have been based on two independent controllers. However, in physiology, the secretion of insulin and glucagon in the body is closely interconnected by paracrine and endocrine associations. In this work, we present a novel biologically-inspired glucose control strategy that accounts for such coordination. An in silico study using an FDA-accepted type 1 simulator was performed to evaluate the proposed coordinated control strategy compared to its non-coordinated counterpart, as well as an insulin-only version of the controller. The proposed coordinated strategy achieves a reduction of hyperglycemia without increasing hypoglycemia, when compared to its non-coordinated counterpart.

  15. Inulin based glutathione-responsive delivery system for colon cancer treatment.

    PubMed

    Wang, Dongdong; Sun, Feifei; Lu, Chunbo; Chen, Peng; Wang, Zhaojie; Qiu, Yuanhao; Mu, Haibo; Miao, Zehong; Duan, Jinyou

    2018-05-01

    Colorectal cancer is one of the most common types of tumor in the world. Here we developed a lipoic acid esterified polysaccharide (inulin) delivery system for tanshinone IIA to treat colorectal cancer in vitro. The release of tanshinone IIA in the system was highly responsive to glutathione, which is commonly abundant in cancer cells. In addition, this drug delivery system was proliferative to Bifidobacterium longum, the common inhabitant of human intestine. Thus, this strategy might be useful to improve colon cancer therapy efficacy of anticancer drugs and meanwhile promote the growth of beneficial commensal flora in the gut. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Permeation enhancer strategies in transdermal drug delivery.

    PubMed

    Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

  17. Targeted Vascular Drug Delivery in Cerebral Cancer.

    PubMed

    Humle, Nanna; Johnsen, Kasper Bendix; Arendt, Gitte Abildgaard; Nielsen, Rikke Paludan; Moos, Torben; Thomsen, Louiza Bohn

    2016-01-01

    This review presents the present-day literature on the anatomy and physiological mechanisms of the blood-brain barrier and the problematic of cerebral drug delivery in relation to malignant brain tumors. First step in treatment of malignant brain tumors is resection, but there is a high risk of single remnant infiltrative tumor cells in the outer zone of the brain tumor. These infiltrative single-cells will be supplied by capillaries with an intact BBB as opposed to the partly leaky BBB found in the tumor tissue before resection. Even though BBB penetrance of a chemotherapeutic agent is considered irrelevant though the limited success rate for chemotherapeutic treatability of GBM tumors indicate otherwise. Therefore drug delivery strategies to cerebral cancer after resection should be tailored to being able to both penetrate the intact BBB and target the cancer cells. In this review the intact bloodbrain barrier and cerebral cancer with main focus on glioblastoma multiforme (GBM) is introduced. The GBM induced formation of a blood-tumor barrier and the consequences hereof is described and discussed with emphasis on the impact these changes of the BBB has on drug delivery to GBM. The most commonly used drug carriers for drug delivery to GBM is described and the current drug delivery strategies for glioblastoma multiforme including possible routes through the BBB and epitopes, which can be targeted on the GBM cells is outlined. Overall, this review aims to address targeted drug delivery in GBM treatment when taking the differing permeability of the BBB into consideration.

  18. Optimal routes of administration, vehicles and timing of progesterone treatment for inhibition of delivery during pregnancy.

    PubMed

    Fang, Dajun; Moreno, Mario; Garfield, Robert E; Kuon, Ruben; Xia, Huimin

    2017-09-01

    Progestins, notably progesterone (P4) and 17 alpha hydroxyprogesterone caproate, are presently used to treat pregnant women at risk of preterm birth. The aim of this study was to assess the optimal treatment options for progesterone (P4) to delay delivery using a sensitive bioassay for progesterone. Pregnant rats, known to be highly sensitive to progestins, were treated with P4, including Prochieve ® (also known as Crinone ® ), in various vehicles from day 13 of gestation and in late gestation, days 19 to 22, and delivery times noted. Various routes of administration of P4 and various treatment periods were studied. Use of micronized P4 by rectal, subcutaneous injection (sc) and topical (transdermal) administration in various oils all significantly (P<0.05-<0.001) delay delivery, but vaginal Prochieve ® did not. Administration of P4 in late gestation also prevented (P<0.001) delivery even when given 8h before delivery. Prochieve ® possesses little biological activity to suppress delivery in a sensitive bioassay system and suggests that this preparation may be of little value in prevention and inhibition of preterm birth. Further, this study shows: 1) Inhibition of delivery is increased with P4 treatments when given subcutaneously or topically. 2) P4 in fish oil provides the best vehicle for topical treatment and may be an effective treatment of preterm birth. 3) P4 in fish oil also delays delivery even when treatment begins just prior to normal delivery. 4) To prevent preterm birth in pregnant women, randomized controlled studies are needed with a potent progestin using better formulations and routes of administration. Copyright © 2017. Published by Elsevier B.V.

  19. Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers.

    PubMed

    Islam, Nazrul; Richard, Derek

    2018-05-24

    Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Doxorubicin-loaded platelets conjugated with anti-CD22 mAbs: a novel targeted delivery system for lymphoma treatment with cardiopulmonary avoidance

    PubMed Central

    Zhou, Rongfu; Wang, Fan; Liu, Xu; Ouyang, Jian; Chen, Bing

    2017-01-01

    B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX–platelet–CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs. Anti-CD22 mAb-labeled platelets can precisely deliver DOX to tumor cells. Our in vitro and in vivo experiments showed the enhanced antitumor activity and attenuated cardiotoxicity of DOX when delivered as DOX–platelet–CD22. Compared with other delivery systems, the uptake of DOX–platelet–CD22 by macrophage-like cells decreased. Moreover, DOX–platelet–CD22 showed platelet properties, such as tumor cell-induced platelet aggregation. Therefore, targeted chemotherapy that is mediated by DOX–platelet–CD22 is a promising option for lymphoma treatment. PMID:28938559

  1. Doxorubicin-loaded platelets conjugated with anti-CD22 mAbs: a novel targeted delivery system for lymphoma treatment with cardiopulmonary avoidance.

    PubMed

    Xu, Peipei; Zuo, Huaqin; Zhou, Rongfu; Wang, Fan; Liu, Xu; Ouyang, Jian; Chen, Bing

    2017-08-29

    B-cell lymphoma accounts for approximately 85% of all adult non-Hodgkin's lymphoma cases. Doxorubicin (DOX) is an indispensable drug for the treatment of non-Hodgkin's lymphoma. However, DOX causes severe cardiotoxicity, which limits its use in conventional treatment strategies. In this study, we developed a novel drug delivery system for lymphoma treatment: DOX-loaded platelets that were conjugated with anti-CD22 monoclonal antibodies (mAbs) (DOX-platelet-CD22). Platelets are bio- and immune-compatible drug carriers that can prolong the circulation time of drugs. Anti-CD22 mAb-labeled platelets can precisely deliver DOX to tumor cells. Our in vitro and in vivo experiments showed the enhanced antitumor activity and attenuated cardiotoxicity of DOX when delivered as DOX-platelet-CD22. Compared with other delivery systems, the uptake of DOX-platelet-CD22 by macrophage-like cells decreased. Moreover, DOX-platelet-CD22 showed platelet properties, such as tumor cell-induced platelet aggregation. Therefore, targeted chemotherapy that is mediated by DOX-platelet-CD22 is a promising option for lymphoma treatment.

  2. siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery.

    PubMed

    Gomes, Maria João; Martins, Susana; Sarmento, Bruno

    2015-05-01

    As the population ages, brain pathologies such as neurodegenerative diseases and brain cancer increase their incidence, being the need to find successful treatments of upmost importance. Drug delivery to the central nervous system (CNS) is required in order to reach diseases causes and treat them. However, biological barriers, mainly blood-brain barrier (BBB), are the key obstacles that prevent the effectiveness of possible treatments due to their ability to strongly limit the perfusion of compounds into the brain. Over the past decades, new approaches towards overcoming BBB and its efflux transporters had been proposed. One of these approaches here reviewed is through small interfering RNA (siRNA), which is capable to specifically target one gene and silence it in a post-transcriptional way. There are different possible functional proteins at the BBB, as the ones responsible for transport or just for its tightness, which could be a siRNA target. As important as the effective silence is the way to delivery siRNA to its anatomical site of action. This is where nanotechnology-based systems may help, by protecting siRNA circulation and providing cell/tissue-targeting and intracellular siRNA delivery. After an initial overview on incidence of brain diseases and basic features of the CNS, BBB and its efflux pumps, this review focuses on recent strategies to reach brain based on siRNA, and how to specifically target these approaches in order to treat brain diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Delivery Strategies in Behavioral Obesity Treatment: Comparing Type and Degree of Therapist Contact in Treating the Obese.

    ERIC Educational Resources Information Center

    Balch, Philip; And Others

    Relative to other treatment modalities for obesity, behavioral strategies, particularly self-control, have been established as effective means of weight loss and control. While most of the early research reported the presence of live professional therapists treating individuals or groups, more recent interest has focused on programs using little…

  4. Stimuli-responsive nanomaterials for therapeutic protein delivery.

    PubMed

    Lu, Yue; Sun, Wujin; Gu, Zhen

    2014-11-28

    Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Stimuli-Responsive Nanomaterials for Therapeutic Protein Delivery

    PubMed Central

    Lu, Yue; Sun, Wujin; Gu, Zhen

    2014-01-01

    Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. PMID:25151983

  6. Development of small RNA delivery systems for lung cancer therapy.

    PubMed

    Fujita, Yu; Kuwano, Kazuyoshi; Ochiya, Takahiro

    2015-03-06

    RNA interference (RNAi) has emerged as a powerful tool for studying target identification and holds promise for the development of therapeutic gene silencing. Recent advances in RNAi delivery and target selection provide remarkable opportunities for translational medical research. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications. Lung cancer is still the leading cause of cancer death worldwide, for which novel therapeutic strategies are critically needed. Recently, we have reported a novel platform (PnkRNA™ and nkRNA®) to promote naked RNAi approaches through inhalation without delivery vehicles in lung cancer xenograft models. We suggest that a new class of RNAi therapeutic agent and local drug delivery system could also offer a promising RNAi-based strategy for clinical applications in cancer therapy. In this article, we show recent strategies for an RNAi delivery system and suggest the possible clinical usefulness of RNAi-based therapeutics for lung cancer treatment.

  7. Literacy and Communication Technologies: Distance Education Strategies for Literacy Delivery

    NASA Astrophysics Data System (ADS)

    Aderinoye, Rashid

    2008-11-01

    This article examines the promotion of literacy through information and communication technologies (ICTs) and through various modes of distance learning. After a general discussion of these approaches, the article focuses on efforts towards reducing illiteracy in Nigeria through integrated strategies for literacy delivery and especially through distance learning. After highlighting the strengths and weaknesses of these measures, the author makes some suggestions on how to maximize their effectiveness in helping Nigeria to achieve the targets of the Education for All agenda and the Millennium Development Goals.

  8. [Oligometastasized colorectal cancer-modern treatment strategies].

    PubMed

    Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P

    2018-06-05

    The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.

  9. Biomaterials for the Treatment of Alzheimer's Disease.

    PubMed

    Hadavi, Darya; Poot, André A

    2016-01-01

    Alzheimer's disease (AD) as a progressive and fatal neurodegenerative disease represents a huge unmet need for treatment. The low efficacy of current treatment methods is not only due to low drug potency but also due to the presence of various obstacles in the delivery routes. One of the main barriers is the blood-brain barrier. The increasing prevalence of AD and the low efficacy of current therapies have increased the amount of research on unraveling of disease pathways and development of treatment strategies. One of the interesting areas for the latter subject is biomaterials and their applications. This interest originates from the fact that biomaterials are very useful for the delivery of therapeutic agents, such as drugs, proteins, and/or cells, in order to treat diseases and regenerate tissues. Recently, manufacturing of nano-sized delivery systems has increased the efficacy and delivery potential of biomaterials. In this article, we review the latest developments with regard to the use of biomaterials for the treatment of AD, including nanoparticles and liposomes for delivery of therapeutic compounds and scaffolds for cell delivery strategies.

  10. Current Strategies in the Modification of PLGA-based Gene Delivery System.

    PubMed

    Ramezani, Mohammad; Ebrahimian, Mahboubeh; Hashemi, Maryam

    2017-01-01

    Successful gene therapy has been limited by safe and efficient delivery of nucleic acid to the target cells. Poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are able to deliver drugs and genes efficiently. This formulation has several advantages in comparison with other formulations including improvement in solubility, stability, controlling of degradation and release of the entrapped agents. For application of PLGA as a gene carrier, there exist many challenges. PLGA NPs could protect the encapsulated DNA from in vivo degradation but the DNA release is slow and the negative charge acts as a barrier to DNA incorporation and delivery. Also, during the preparation process, DNA could be exposed to high shear stress and organic solvents which could result in its inactivation. Moreover, PLGA NPs could be modified with different agents to reduce cytotoxicity, to enhance delivery efficiency and to target specific tissues/cells. This review summarizes different methods used for the preparation of PLGA NPs as gene carriers and recent strategies for the modification of PLGA particles applied in gene therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases

    PubMed Central

    Zhang, Zheng; Tsai, Pei-Chin; Ramezanli, Tannaz; Michniak-Kohn, Bozena B.

    2013-01-01

    Human skin not only functions as a permeation barrier (mainly due to the stratum corneum layer), but also provides a unique delivery pathway for therapeutic and other active agents. These compounds penetrate via intercellular, intracellular and transappendageal routes, resulting in topical delivery (into skin strata) and transdermal delivery (to subcutaneous tissues and into the systemic circulation). Passive and active permeation enhancement methods have been widely applied to increase the cutaneous penetration. The pathology, pathogenesis and topical treatment approaches of dermatological diseases, such as psoriasis, contact dermatitis, and skin cancer, are then discussed. Recent literature has demonstrated that nanoparticles-based topical delivery systems can be successful in treating these skin conditions. The studies are reviewed starting with the nanoparticles based on natural polymers specially chitosan, followed by those made of synthetic, degradable (aliphatic polyesters) and non-degradable (polyarylates) polymers; emphasis is given to nanospheres made of polymers derived from naturally occurring metabolites, the tyrosine-derived nanospheres (TyroSpheres™). In summary, the nanoparticles-based topical delivery systems combine the advantages of both the nano-sized drug carriers and the topical approach, and are promising for the treatment of skin diseases. For the perspectives, the penetration of ultra-small nanoparticles (size smaller than 40 nm) into skin strata, the targeted delivery of the encapsulated drugs to hair follicle stem cells, and the combination of nanoparticles and microneedle array technologies for special applications such as vaccine delivery are discussed. PMID:23386536

  12. TH-C-12A-02: Comparison of Two RapidArc Delivery Strategies in Stereotactic Body Radiotherapy of Stage I and II Peripheral Lung Tumors with Unflattened Beams

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huang, B; Lu, J; Chen, J

    2014-06-15

    Purpose: The full arcs strategy used in SBRT with RapidArc and unflattened (FFF) beams in large and heterogeneous peripheral non-smallcell lung cancer (NSCLC) appears to be suboptimal as it increases the disadvantageous dose to the contralateral lung, which potentially increases the toxicity to surrounding tissues. In this study, we investigated, for the first time, the dose delivery strategies using partial arcs (PA) and the fully rotational arcs with avoidance sectors (FAAS) for SBRT with FFF beams in peripheral NSCLC patients. Methods: Eighteen patients with NSCLC (stage I and II) were selected for this study. Nine patients with a GTV <=more » 10cc were designated as the small tumor group. The remaining nine patients with a GTV between 10 cc and 44 cc were assigned to the large tumor group. The treatment plans were generated in eighteen patients using PA and FAAS, respectively, and delivered with a Varian TrueBeam Linac. Dosimetry of the target and organs at risk (OAR), total MU, out-of-field dose, and delivery time were analyzed. Delta4 and Portal dosimetry were employed to evaluate the delivery accuracy. Results: or the small tumor group, the FAAS plans significantly achieved a better conformity index, the lower total MU and out-of-field dose, a shorter treatment time, and the reduced doses to cord, heart, and lung (p < 0.05). But the target doses were slightly higher than that delivered by PA plans. For the large tumor group, the PA plans significantly attained a better conformity index and a shorter treatment time (p < 0.05). Furthermore, all plans achieved a high pass rate, with all the gamma indices greater than 97% at the Γ{sub 3mm,} {sub 3%} threshold. Conclusion: This study suggests that FAAS strategy is more beneficial for small tumor patients undergoing lung SBRT with FFF beams. However, for large tumor patients, PA strategy is recommended. NIH/NIGMS grant U54 GM104944, Lincy Endowed Assistant Professorship.« less

  13. Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.

    PubMed

    Yang, Qi; Parker, Christina L; McCallen, Justin D; Lai, Samuel K

    2015-12-28

    Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. The development of accurate and high quality radiotherapy treatment delivery

    NASA Astrophysics Data System (ADS)

    Griffiths, Susan E.

    Accurate radiotherapy delivery is required for curing cancer. Historical radiotherapy accuracy studies at Leeds (1983-1991) are discussed in context of when radiographers were not involved in practice design. The seminal research was unique in being led by a radiographer practitioner, and in prospectively studying the accuracy of different techniques within one department. The viability of alignment of treatment beams with marks painted on a patient's skin varied daily, and, using film I showed that the alignment of treatment on anatomy varied. I then led 6 sequential studies with collaborating oncologists. Unique outcomes were in identifying the origins of treatment inaccuracies, implementing and evidencing changes in multi-disciplinary practice, thus improving accuracy and reproducibility generally and achieving accuracy for the pelvis to within current norms. Innovations included: discontinuation of painted skin marks and developing whole-body patient positioning using lasers, tattoos, and standardised supports; unification of set-up conditions through planning and treatment; planning normal tissue margins round target tissue to allow for inaccuracies (1985); improved manual shielding methods, changed equipment usage, its quality assurance and design; influenced the development of portal imaging and image analysis. Consequences and current implications. The research, still cited internationally, contributed to clinical management of lymphoma, and critically underpins contemporary practice. It led to my becoming the first radiographer invited into multi-disciplinary collaborative work, to advise in the first multi-centre clinical trials to consider treatment delivery accuracy, contribute to books written from within other disciplines and inform guidelines for good practice so helping to improve practices, with recent publications. I thus led my profession into research activity. Later work included development of a national staffing formula for radiotherapy

  15. Ocular drug delivery systems: An overview

    PubMed Central

    Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

    2014-01-01

    The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

  16. Ocular drug delivery systems: An overview.

    PubMed

    Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

    The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

  17. Nanotechnology for protein delivery: Overview and perspectives.

    PubMed

    Yu, Mikyung; Wu, Jun; Shi, Jinjun; Farokhzad, Omid C

    2016-10-28

    Protein-based therapeutics have made a significant impact in the treatment of a variety of important human diseases. However, given their intrinsically vulnerable structure and susceptibility to enzymatic degradation, many therapeutic proteins such as enzymes, growth factors, hormones, and cytokines suffer from poor physicochemical/biological stability and immunogenicity that may limit their potential benefits, and in some cases limit their utility. Furthermore, when protein therapeutics are developed for intracellular targets, their internalization and biological activity may be limited by inefficient membrane permeability and/or endosomal escape. Development of effective protein delivery strategies is therefore essential to further enhance therapeutic outcomes to enable widespread medical applications. This review discusses the advantages and limitations of marketed and developmental-stage protein delivery strategies, and provides a focused overview of recent advances in nanotechnology platforms for the systemic delivery of therapeutic proteins. In addition, we also highlight nanoparticle-mediated non-invasive administration approaches (e.g., oral, nasal, pulmonary, and transdermal routes) for protein delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Simultaneous delivery time and aperture shape optimization for the volumetric-modulated arc therapy (VMAT) treatment planning problem

    NASA Astrophysics Data System (ADS)

    Mahnam, Mehdi; Gendreau, Michel; Lahrichi, Nadia; Rousseau, Louis-Martin

    2017-07-01

    In this paper, we propose a novel heuristic algorithm for the volumetric-modulated arc therapy treatment planning problem, optimizing the trade-off between delivery time and treatment quality. We present a new mixed integer programming model in which the multi-leaf collimator leaf positions, gantry speed, and dose rate are determined simultaneously. Our heuristic is based on column generation; the aperture configuration is modeled in the columns and the dose distribution and time restriction in the rows. To reduce the number of voxels and increase the efficiency of the master model, we aggregate similar voxels using a clustering technique. The efficiency of the algorithm and the treatment quality are evaluated on a benchmark clinical prostate cancer case. The computational results show that a high-quality treatment is achievable using a four-thread CPU. Finally, we analyze the effects of the various parameters and two leaf-motion strategies.

  19. Sub-optimal delivery of intermittent preventive treatment for malaria in pregnancy in Nigeria: influence of provider factors.

    PubMed

    Onoka, Chima A; Onwujekwe, Obinna E; Hanson, Kara; Uzochukwu, Benjamin S

    2012-09-07

    The level of access to intermittent preventive treatment for malaria in pregnancy (IPTp) in Nigeria is still low despite relatively high antenatal care coverage in the study area. This paper presents information on provider factors that affect the delivery of IPTp in Nigeria. Data were collected from heads of maternal health units of 28 public and six private health facilities offering antenatal care (ANC) services in two districts in Enugu State, south-east Nigeria. Provider knowledge of guidelines for IPTp was assessed with regard to four components: the drug used for IPTp, time of first dose administration, of second dose administration, and the strategy for sulphadoxine-pyrimethamine (SP) administration (directly observed treatment, DOT). Provider practices regarding IPTp and facility-related factors that may explain observations such as availability of SP and water were also examined. Only five (14.7%) of all 34 providers had correct knowledge of all four recommendations for provision of IPTp. None of them was a private provider. DOT strategy was practiced in only one and six private and public providers respectively. Overall, 22 providers supplied women with SP in the facility and women were allowed to take it at home. The most common reason for doing so amongst public providers was that women were required to come for antenatal care on empty stomachs to enhance the validity of manual fundal height estimation. Two private providers did not think it was necessary to use the DOT strategy because they assumed that women would take their drugs at home. Availability of SP and water in the facility, and concerns about side effects were not considered impediments to delivery of IPTp. There was low level of knowledge of the guidelines for implementation of IPTp by all providers, especially those in the private sector. This had negative effects such as non-practice of DOT strategy by most of the providers, which can lead to low levels of adherence to IPTp and

  20. Convection-enhanced delivery for the treatment of brain tumors

    PubMed Central

    Debinski, Waldemar; Tatter, Stephen B

    2013-01-01

    The brain is highly accessible for nutrients and oxygen, however delivery of drugs to malignant brain tumors is a very challenging task. Convection-enhanced delivery (CED) has been designed to overcome some of the difficulties so that pharmacological agents that would not normally cross the BBB can be used for treatment. Drugs are delivered through one to several catheters placed stereotactically directly within the tumor mass or around the tumor or the resection cavity. Several classes of drugs are amenable to this technology including standard chemotherapeutics or novel experimental targeted drugs. The first Phase III trial for CED-delivered, molecularly targeted cytotoxin in the treatment of recurrent glioblastoma multiforme has been accomplished and demonstrated objective clinical efficacy. The lessons learned from more than a decade of attempts at exploiting CED for brain cancer treatment weigh critically for its future clinical applications. The main issues center around the type of catheters used, number of catheters and their exact placement; pharmacological formulation of drugs, prescreening patients undergoing treatment and monitoring the distribution of drugs in tumors and the tumor-infiltrated brain. It is expected that optimizing CED will make this technology a permanent addition to clinical management of brain malignancies. PMID:19831841

  1. Recent Progress of Nano-drug Delivery System for Liver Cancer Treatment.

    PubMed

    Zhou, Feilong; Teng, Fangfang; Deng, Peizong; Meng, Ning; Song, Zhimei; Feng, Runliang

    2018-02-07

    Liver cancer is one of serious diseases which threaten human life and health. Studies on the treatment of liver cancer have attracted widespread attention. Application of nano-drug delivery system (NDDS) can not only improve selective drug delivery to liver tissue and improve the bioavailability of drug, but also can reduce the side effects of drugs when it is specially modified in the respects of structure modification or specific target molecules decoration. This review will address the latest development of liver-targeted drug delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. The application of prodrug-based nano-drug delivery strategy in cancer combination therapy.

    PubMed

    Ge, Yanxiu; Ma, Yakun; Li, Lingbing

    2016-10-01

    Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Cell-Mediated Drugs Delivery

    PubMed Central

    Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

    2011-01-01

    INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

  4. [Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain].

    PubMed

    Domínguez, Alazne; Álvarez, Antonia; Suárez-Merino, Blanca; Goñi-de-Cerio, Felipe

    2014-03-01

    The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents' entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases.

  5. Unintended Consequences of Evidence-Based Treatment Policy Reform: Is Implementation the Goal or the Strategy for Higher Quality Care?

    PubMed

    Park, Alayna L; Tsai, Katherine H; Guan, Karen; Chorpita, Bruce F

    2018-02-14

    This study examined patterns of evidence-based treatment (EBT) delivery following a county-wide EBT reform initiative. Data were gathered from 60 youth and their 21 providers, who were instructed to deliver therapy as they normally would under the EBT initiative. Results showed limited applicability of county-supported EBTs to this service sample, and that most youth did not receive traditional delivery of EBTs. Findings suggest that it may be unrealistic to expect providers to deliver EBTs with fidelity with all clients, and that EBT implementation may be best thought of as a strategy for improving mental health services rather than a goal.

  6. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

    Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems.

  7. Non-viral gene delivery strategies for gene therapy: a "ménage à trois" among nucleic acids, materials, and the biological environment. Stimuli-responsive gene delivery vectors

    NASA Astrophysics Data System (ADS)

    Pezzoli, Daniele; Candiani, Gabriele

    2013-03-01

    Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription-translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.

  8. Anterior eye segment drug delivery systems: current treatments and future challenges.

    PubMed

    Molokhia, Sarah A; Thomas, Samuel C; Garff, Kevin J; Mandell, Kenneth J; Wirostko, Barbara M

    2013-03-01

    New technologies for delivery of drugs, such as small molecules and biologics, are of growing interest among clinical and pharmaceutical researchers for use in treating anterior segment eye disease. The challenge is to deliver effective drugs at therapeutic concentrations to the targeted ocular tissue with minimal side effects. To achieve this, a better understanding of the unmet needs, what is required of the various methods of delivery to achieve successful delivery, and the potential challenges of anterior segment drug delivery is necessary and the primarily aim of this review. This review covers the various physiological and anatomical barriers that exist for effective delivery to the targeted tissue of the eye, the pathological conditions of the anterior segment, and the unmet needs for treatment of these ocular diseases. Second, it reviews the novel delivery technologies that have the potential to maintain and/or improve the drug's therapeutic index and improving both patient adherence for chronic therapy and potential patient outcomes. This review bridges the pharmaceutical and clinical research/challenges and provides a detailed overview of anterior segment drug delivery accomplishments thus far, for researchers and clinicians.

  9. Bolstering cholesteryl ester hydrolysis in liver: A hepatocyte-targeting gene delivery strategy for potential alleviation of atherosclerosis.

    PubMed

    He, Hongliang; Lancina, Michael G; Wang, Jing; Korzun, William J; Yang, Hu; Ghosh, Shobha

    2017-06-01

    Current atherosclerosis treatment strategies primarily focus on limiting further cholesteryl esters (CE) accumulation by reducing endogenous synthesis of cholesterol in the liver. No therapy is currently available to enhance the removal of CE, a crucial step to reduce the burden of the existing disease. Given the central role of hepatic cholesteryl ester hydrolase (CEH) in the intrahepatic hydrolysis of CE and subsequent removal of the resulting free cholesterol (FC), in this work, we applied galactose-functionalized polyamidoamine (PAMAM) dendrimer generation 5 (Gal-G5) for hepatocyte-specific delivery of CEH expression vector. The data presented herein show the increased specific uptake of Gal-G5/CEH expression vector complexes (simply Gal-G5/CEH) by hepatocytes in vitro and in vivo. Furthermore, the upregulated CEH expression in the hepatocytes significantly enhanced the intracellular hydrolysis of high density lipoprotein-associated CE (HDL-CE) and subsequent conversion/secretion of hydrolyzed FC as bile acids (BA). The increased CEH expression in the liver significantly increased the flux of HDL-CE to biliary as well as fecal FC and BA. Meanwhile, Gal-G5 did not induce hepatic or renal toxicity. It was also not immunotoxic. Because of these encouraging pre-clinical testing results, using this safe and highly efficient hepatocyte-specific gene delivery platform to enhance the hepatic processes involved in cholesterol elimination is a promising strategy for the alleviation of atherosclerosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

    PubMed

    Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; Lőbenberg, Raimar; Doschak, Michael R

    2015-12-01

    Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation. In the following review, we evaluate transdermal drug delivery systems, with a particular focus on delivering therapeutic agents to treat superficial bone pain, notably stress fractures. We further introduce and discuss several small peptide hormones active in bone (such as calcitonins and parathyroid hormone) that have shown potential for transdermal delivery, often under the added augmentation of transdermal drug delivery systems that employ lipo/hydrophilicity, electric charge, and/or microprojection facilitation across the skin barrier.

  11. Commissioning of an integrated platform for time-resolved treatment delivery in scanned ion beam therapy by means of optical motion monitoring.

    PubMed

    Fattori, G; Saito, N; Seregni, M; Kaderka, R; Pella, A; Constantinescu, A; Riboldi, M; Steidl, P; Cerveri, P; Bert, C; Durante, M; Baroni, G

    2014-12-01

    The integrated use of optical technologies for patient monitoring is addressed in the framework of time-resolved treatment delivery for scanned ion beam therapy. A software application has been designed to provide the therapy control system (TCS) with a continuous geometrical feedback by processing the external surrogates tridimensional data, detected in real-time via optical tracking. Conventional procedures for phase-based respiratory phase detection were implemented, as well as the interface to patient specific correlation models, in order to estimate internal tumor motion from surface markers. In this paper, particular attention is dedicated to the quantification of time delays resulting from system integration and its compensation by means of polynomial interpolation in the time domain. Dedicated tests to assess the separate delay contributions due to optical signal processing, digital data transfer to the TCS and passive beam energy modulation actuation have been performed. We report the system technological commissioning activities reporting dose distribution errors in a phantom study, where the treatment of a lung lesion was simulated, with both lateral and range beam position compensation. The zero-delay systems integration with a specific active scanning delivery machine was achieved by tuning the amount of time prediction applied to lateral (14.61 ± 0.98 ms) and depth (34.1 ± 6.29 ms) beam position correction signals, featuring sub-millimeter accuracy in forward estimation. Direct optical target observation and motion phase (MPh) based tumor motion discretization strategies were tested, resulting in 20.3(2.3)% and 21.2(9.3)% median (IQR) percentual relative dose difference with respect to static irradiation, respectively. Results confirm the technical feasibility of the implemented strategy towards 4D treatment delivery, with negligible percentual dose deviations with respect to static irradiation.

  12. Implantable and transdermal polymeric drug delivery technologies for the treatment of central nervous system disorders.

    PubMed

    Govender, Thiresen; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

    2017-06-01

    The complexity of the brain and the membranous blood-brain barrier (BBB) has proved to be a significant limitation to the systemic delivery of pharmaceuticals to the brain rendering them sub-therapeutic and ineffective in the treatment of neurological diseases. Apart from this, lack of innovation in product development to counteract the problem is also a major contributing factor to a poor therapeutic outcome. Various innovative strategies show potential in treating some of the neurological disorders; however, drug delivery remains the most popular. To attain therapeutic drug levels in the central nervous system, large, intolerable systemic doses are generally administered. The major factors responsible for the success maintenance therapy of neurological diseases included controlled and sustained release of neurotherapeutics, reduced frequency of administration, higher bioavailability, and patient compliances. Conventional oral or injectable formulations cannot satisfy all the requirements in many circumstances. This article reviews the therapeutic implantable polymeric and transdermal devices employed in an attempt to effectively achieve therapeutic quantities of drug across the BBB over a prolonged period, to improve patient disease prognosis.

  13. Strategies for maximizing clinical effectiveness in the treatment of schizophrenia.

    PubMed

    Tandon, Rajiv; Targum, Steven D; Nasrallah, Henry A; Ross, Ruth

    2006-11-01

    The ultimate clinical objective in the treatment of schizophrenia is to enable affected individuals to lead maximally productive and personally meaningful lives. As with other chronic diseases that lack a definitive cure, the individual's service/recovery plan must include treatment interventions directed towards decreasing manifestations of the illness, rehabilitative services directed towards enhancing adaptive skills, and social support mobilization aimed at optimizing function and quality of life. In this review, we provide a conceptual framework for considering approaches for maximizing the effectiveness of the array of treatments and other services towards promoting recovery of persons with schizophrenia. We discuss pharmacological, psychological, and social strategies that decrease the burden of the disease of schizophrenia on affected individuals and their families while adding the least possible burden of treatment. In view of the multitude of treatments necessary to optimize outcomes for individuals with schizophrenia, effective coordination of these services is essential. In addition to providing best possible clinical assessment and pharmacological treatment, the psychiatrist must function as an effective leader of the treatment team. To do so, however, the psychiatrist must be knowledgeable about the range of available services, must have skills in clinical-administrative leadership, and must accept the responsibility of coordinating the planning and delivery of this multidimensional array of treatments and services. Finally, the effectiveness of providing optimal individualized treatment/rehabilitation is best gauged by measuring progress on multiple effectiveness domains. Approaches for efficient and reliable assessment are discussed.

  14. Coping with changing conditions: alternative strategies for the delivery of maternal and child health and family planning services in Dhaka, Bangladesh.

    PubMed Central

    Routh, S.; el Arifeen, S.; Jahan, S. A.; Begum, A.; Thwin, A. A.; Baqui, A. H.

    2001-01-01

    The door-to-door distribution of contraceptives and information on maternal and child health and family planning (MCH-FP) services, through bimonthly visits to eligible couples by trained fieldworkers, has been instrumental in increasing the contraceptive prevalence rate and immunization coverage in Bangladesh. The doorstep delivery strategy, however, is labour-intensive and costly. More cost-effective service delivery strategies are needed, not only for family planning services but also for a broader package of reproductive and other essential health services. Against this backdrop, operations research was conducted by the Centre for Health and Population Research at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) from January 1996 to May 1997, in collaboration with government agencies and a leading national nongovernmental organization, with a view to developing and field-testing alternative approaches to the delivery of MCH-FP services in urban areas. Two alternative strategies featuring the withdrawal of home-based distribution and the delivery of basic health care from fixed-site facilities were tested in two areas of Dhaka. The clinic-based service delivery strategy was found to be a feasible alternative to the resource-intensive doorstep system in urban Dhaka. It did not adversely affect programme performance and it allowed the needs of clients to be addressed holistically through a package of essential health and family planning services. PMID:11242821

  15. Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Sengbusch, Evan R.

    Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing

  16. Investigation of pulsed IMRT and VMAT for re-irradiation treatments: dosimetric and delivery feasibilities

    NASA Astrophysics Data System (ADS)

    Lin, Mu-Han; Price, Robert A., Jr.; Li, Jinsheng; Kang, Shengwei; Li, Jie; Ma, C.-M.

    2013-11-01

    Many tumor cells demonstrate hyperradiosensitivity at doses below ˜50 cGy. Together with the increased normal tissue repair under low dose rate, the pulsed low dose rate radiotherapy (PLDR), which separates a daily fractional dose of 200 cGy into 10 pulses with 3 min interval between pulses (˜20 cGy/pulse and effective dose rate 6.7 cGy min-1), potentially reduces late normal tissue toxicity while still providing significant tumor control for re-irradiation treatments. This work investigates the dosimetric and technical feasibilities of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT)-based PLDR treatments using Varian Linacs. Twenty one cases (12 real re-irradiation cases) including treatment sites of pancreas, prostate, pelvis, lung, head-and-neck, and breast were recruited for this study. The lowest machine operation dose rate (100 MU min-1) was employed in the plan delivery. Ten-field step-and-shoot IMRT and dual-arc VMAT plans were generated using the Eclipse TPS with routine planning strategies. The dual-arc plans were delivered five times to achieve a 200 cGy daily dose (˜20 cGy arc-1). The resulting plan quality was evaluated according to the heterogeneity and conformity indexes (HI and CI) of the planning target volume (PTV). The dosimetric feasibility of retaining the hyperradiosensitivity for PLDR was assessed based on the minimum and maximum dose in the target volume from each pulse. The delivery accuracy of VMAT and IMRT at the 100 MU min-1 machine operation dose rate was verified using a 2D diode array and ion chamber measurements. The delivery reproducibility was further investigated by analyzing the Dynalog files of repeated deliveries. A comparable plan quality was achieved by the IMRT (CI 1.10-1.38 HI 1.04-1.10) and the VMAT (CI 1.08-1.26 HI 1.05-1.10) techniques. The minimum/maximum PTV dose per pulse is 7.9 ± 5.1 cGy/33.7 ± 6.9 cGy for the IMRT and 12.3 ± 4.1 cGy/29.2 ± 4.7 cGy for the VMAT. Six out of

  17. Covalent nano delivery systems for selective imaging and treatment of brain tumors.

    PubMed

    Ljubimova, Julia Y; Sun, Tao; Mashouf, Leila; Ljubimov, Alexander V; Israel, Liron L; Ljubimov, Vladimir A; Falahatian, Vida; Holler, Eggehard

    2017-04-01

    Nanomedicine is a rapidly evolving form of therapy that holds a great promise for superior drug delivery efficiency and therapeutic efficacy than conventional cancer treatment. In this review, we attempt to cover the benefits and the limitations of current nanomedicines with special attention to covalent nano conjugates for imaging and drug delivery in the brain. The improvement in brain tumor treatment remains dismal despite decades of efforts in drug development and patient care. One of the major obstacles in brain cancer treatment is the poor drug delivery efficiency owing to the unique blood-brain barrier (BBB) in the CNS. Although various anti-cancer agents are available to treat tumors outside of the CNS, the majority fails to cross the BBB. In this regard, nanomedicines have increasingly drawn attention due to their multi-functionality and versatility. Nano drugs can penetrate BBB and other biological barriers, and selectively accumulate in tumor cells, while concurrently decreasing systemic toxicity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

    NASA Astrophysics Data System (ADS)

    Bhise, Nupura S.

    Gene therapy involves the delivery of deoxyribonucleic acid (DNA) into cells to override or replace a malfunctioning gene for treating debilitating genetic diseases, including cancer and neurodegenerative diseases. In addition to its use as a therapeutic, it can also serve as a technology to enable regenerative medicine strategies. The central challenge of the gene therapy research arena is developing a safe and effective delivery agent. Since viral vectors have critical immunogenic and tumorogenic safety issues that limit their clinical use, recent efforts have focused on developing non-viral biomaterial based delivery vectors. Cationic polymers are an attractive class of gene delivery vectors due to their structural versatility, ease of synthesis, biodegradability, ability to self-complex into nanoparticles with negatively charged DNA, capacity to carry large cargo, cellular uptake and endosomal escape capacity. In this thesis, we hypothesized that developing a biomaterial library of poly(betaamino esters) (PBAE), a newer class of cationic polymers consisting of biodegradable ester groups, would allow investigating vector design parameters and formulating effective non-viral gene delivery strategies for cancer drug delivery, tissue engineering and stem cell engineering. Consequently, a high-throughput transfection assay was developed to screen the PBAE-based nanoparticles in hard to transfect fibroblast cell lines. To gain mechanistic insights into the nanoparticle formulation process, biophysical properties of the vectors were characterized in terms of molecular weight (MW), nanoparticle size, zeta potential and plasmid per particle count. We report a novel assay developed for quantifying the plasmid per nanoparticle count and studying its implications for co-delivery of multiple genes. The MW of the polymers ranged from 10 kDa to 100 kDa, nanoparticle size was about 150 run, zeta potential was about 30 mV in sodium acetate buffer (25 mM, pH 5) and 30 to 100

  19. Bicellar systems as a new colloidal delivery strategy for skin.

    PubMed

    Rubio, L; Rodríguez, G; Barbosa-Barros, L; Alonso, C; Cócera, M; de la Maza, A; Parra, J L; López, O

    2012-04-01

    The presented work evaluates the use of bicellar systems as new delivery vectors for controlled release of compounds through the skin. Two different active principles were introduced into the bicellar systems: diclofenac diethylamine (DDEA) and flufenamic acid (Ffa). Bicellar systems are discoidal aggregates formed by long and short alkyl chain phospholipids. Characterization of the bicellar systems by dynamic light scattering (DLS) and cryogenic transmission electron microscopy (Cryo-TEM) showed that particle size decreased when DDEA was encapsulated and increased when Ffa was included in the bicellar systems. Percutaneous absorption studies demonstrated a lower penetration of DDEA and Ffa through the skin when the drugs were included in the bicellar systems than when the drugs were applied in an aqueous solution (DDEA) and in an ethanolic solution (Ffa); the reduction in penetration was more pronounced with Ffa. These bicellar systems may have retardant effects on percutaneous absorption, which result in a promising strategy for future drug or cosmetic delivery applications. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. The health maintenance organization strategy: a corporate takeover of health services delivery.

    PubMed

    Salmon, J W

    1975-01-01

    This paper presents a political economic framework for viewing the social organization of the delivery of health care servies and predicting a qualitatively different institutional configuration involving the health maintenance organization. The principal forces impacting American capitalism today are leading to a fundamental restructuring for increased social efficiency of the entire social welfare sector, including the health services industry. The method to achieve this restructuring involves health policy directed at raising the contribution to the social surplus from the delivery of health care services and eventual corporate domination. The health maintenance organization conceptualization is examined with suggestions as to how the HMO strategy promoted by the state leads to this corporate takeover. The mechanism and extent of the present corporate involvement are examined and implications of health services as a social control mechanism are presented.

  1. Delivery of multiple siRNAs using lipid-coated PLGA nanoparticles for treatment of prostate cancer.

    PubMed

    Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha; Dunn, Stuart S; Enlow, Elizabeth M; Luft, J Christopher; Tian, Shaomin; Napier, Mary E; Pohlhaus, Patrick D; Rolland, Jason P; DeSimone, Joseph M

    2012-01-11

    Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called Particle Replication In Nonwetting Templates (PRINT). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32-46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer. © 2011 American Chemical Society

  2. Household coping strategies for delivery and related healthcare cost: findings from rural Bangladesh.

    PubMed

    Hoque, Mohammad Enamul; Dasgupta, Sushil Kanta; Naznin, Eva; Al Mamun, Abdullah

    2015-10-01

    This study aims to measure the economic costs of maternal complication and to understand household coping strategies for financing maternal healthcare cost. A household survey of the 706 women with maternal complication, of whom 483 had normal delivery, was conducted to collect data at 6 weeks and 6 months post-partum. Data were collected on socio-economic information of the household, expenditure during delivery and post-partum, coping strategies adopted by households and other related information. Despite the high cost of health care associated with maternal complications, the majority of families were capable of protecting consumption on non-health items. Around one-third of households spent more than 20% of their annual household expenditure on maternal health care. Almost 50% were able to avoid catastrophic spending because of the coping strategies that they relied on. In general, households appeared resilient to short-term economic consequences of maternal health shocks, due to the availability of informal credit, donations from relatives and selling assets. While richer households fund a greater portion of the cost of maternal health care from income and savings, the poorer households with severe maternal complication resorted to borrowing from local moneylenders at high interest, which may leave them vulnerable to financial difficulties. Financial protection, especially for the poor, may benefit households against economic consequences of maternal complication. © 2015 John Wiley & Sons Ltd.

  3. Drug delivery strategies for chemoprevention of UVB-induced skin cancer: A review.

    PubMed

    Bagde, Arvind; Mondal, Arindam; Singh, Mandip

    2018-01-01

    Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast, and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed toward improvements in terms of delivery modes, therapeutic agents, and site-specificity of therapeutics delivery. The effective chemoprevention activity achieved is based on the efficiency of the delivery system used and the amount of the therapeutic molecule deposited in the skin. In this article, we have discussed different studies performed specifically for the chemoprevention of UVB-induced skin cancer. Ultra-flexible nanocarriers, transethosomes nanocarriers, silica nanoparticles, silver nanoparticles, nanocapsule suspensions, microemulsion, nanoemulsion, and polymeric nanoparticles which have been used so far to deliver the desired drug molecule for preventing the UVB-induced skin cancer. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Liposome-based drug co-delivery systems in cancer cells.

    PubMed

    Zununi Vahed, Sepideh; Salehi, Roya; Davaran, Soodabeh; Sharifi, Simin

    2017-02-01

    Combination therapy and nanotechnology offer a promising therapeutic method in cancer treatment. By improving drug's pharmacokinetics, nanoparticulate systems increase the drug's therapeutic effects while decreasing its adverse side effects related to high dosage. Liposomes are extensively used as drug delivery systems and several liposomal nanomedicines have been approved for clinical applications. In this regard, liposome-based combination chemotherapy (LCC) opens a novel avenue in drug delivery research and has increasingly become a significant approach in clinical cancer treatment. This review paper focuses on LCC strategies including co-delivery of: two chemotherapeutic drugs, chemotherapeutic agent with anti-cancer metals, and chemotherapeutic agent with gene agents and ligand-targeted liposome for co-delivery of chemotherapeutic agents. Definitely, the multidisciplinary method may help improve the efficacy of cancer therapy. An extensive literature review was performed mainly using PubMed. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. A non-covalent peptide-based strategy for ex vivo and in vivo oligonucleotide delivery.

    PubMed

    Crombez, Laurence; Morris, May C; Heitz, Frederic; Divita, Gilles

    2011-01-01

    The dramatic acceleration in identification of new nucleic acid-based therapeutic molecules such as short interfering RNA (siRNA) and peptide-nucleic acid (PNA) analogues has provided new perspectives for therapeutic targeting of specific genes responsible for pathological disorders. However, the poor cellular uptake of nucleic acids together with the low permeability of the cell membrane to negatively charged molecules remain major obstacles to their clinical development. Several non-viral strategies have been proposed to improve the delivery of synthetic short oligonucleotides both in cultured cells and in vivo. Cell-penetrating peptides constitute very promising tools for non-invasive cellular import of oligonucleotides and analogs. We recently described a non-covalent strategy based on short amphiphatic peptides (MPG8/PEP3) that have been successfully applied ex vivo and in vivo for the delivery of therapeutic siRNA and PNA molecules. PEP3 and MPG8 form stable nanoparticles with PNA analogues and siRNA, respectively, and promote their efficient cellular uptake, independently of the endosomal pathway, into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. This chapter describes easy-to-handle protocols for the use of MPG-8 or PEP-3-nanoparticle technologies for PNA and siRNA delivery into adherent and suspension cell lines as well as in vivo into cancer mouse models.

  6. Transepidermal drug delivery: a new treatment option for areata alopecia?

    PubMed

    Issa, Maria Claudia Almeida; Pires, Marianna; Silveira, Priscilla; Xavier de Brito, Esther; Sasajima, Cristiane

    2015-02-01

    Transepidermal drug delivery (TED) is a new potential method in dermatology. Permeability alterations induced by ablative fractional resurfacing have been described with the aim to increasing the delivery of different substances into the skin. To evaluate clinical response and side effects of TED in areata alopecia (AA) treatment using ablative fractional methods associated with acoustic pressure ultrasound (US) to deliver triamcinolone solution into the skin. Five cases of AA underwent treatment which comprised of 3 steps: 1) Ablative fractioned RF or CO2 laser 2) topical application of triamcinolone 3) acoustic pressure wave US. The number of sessions varied according to the clinical response, ranging from one to six sessions. All patients had complete recovery of the area treated. Two of them treated with ablative fractional RF + triamcinolone + US had complete response after three and six sessions. The other two treated with ablative fractional CO2 + triamcinolone + US had complete response after one session. Fractioned ablative resurfacing associated with acoustic pressure wave US is a new option to areata alopecia treatment with good clinical result and low incidence of side effects.

  7. Quality assurance for online adapted treatment plans: benchmarking and delivery monitoring simulation.

    PubMed

    Li, Taoran; Wu, Qiuwen; Yang, Yun; Rodrigues, Anna; Yin, Fang-Fang; Jackie Wu, Q

    2015-01-01

    An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system was designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system's performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Online adapted plans were

  8. Robotic path-finding in inverse treatment planning for stereotactic radiosurgery with continuous dose delivery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vandewouw, Marlee M., E-mail: marleev@mie.utoronto

    Purpose: Continuous dose delivery in radiation therapy treatments has been shown to decrease total treatment time while improving the dose conformity and distribution homogeneity over the conventional step-and-shoot approach. The authors develop an inverse treatment planning method for Gamma Knife® Perfexion™ that continuously delivers dose along a path in the target. Methods: The authors’ method is comprised of two steps: find a path within the target, then solve a mixed integer optimization model to find the optimal collimator configurations and durations along the selected path. Robotic path-finding techniques, specifically, simultaneous localization and mapping (SLAM) using an extended Kalman filter, aremore » used to obtain a path that travels sufficiently close to selected isocentre locations. SLAM is novelly extended to explore a 3D, discrete environment, which is the target discretized into voxels. Further novel extensions are incorporated into the steering mechanism to account for target geometry. Results: The SLAM method was tested on seven clinical cases and compared to clinical, Hamiltonian path continuous delivery, and inverse step-and-shoot treatment plans. The SLAM approach improved dose metrics compared to the clinical plans and Hamiltonian path continuous delivery plans. Beam-on times improved over clinical plans, and had mixed performance compared to Hamiltonian path continuous plans. The SLAM method is also shown to be robust to path selection inaccuracies, isocentre selection, and dose distribution. Conclusions: The SLAM method for continuous delivery provides decreased total treatment time and increased treatment quality compared to both clinical and inverse step-and-shoot plans, and outperforms existing path methods in treatment quality. It also accounts for uncertainty in treatment planning by accommodating inaccuracies.« less

  9. Advancing drug delivery systems for the treatment of multiple sclerosis.

    PubMed

    Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

    2015-12-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

  10. Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

    PubMed Central

    Zhang, Bo; Hu, Yu; Pang, Zhiqing

    2017-01-01

    Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

  11. Prodrug Strategy for PSMA-targeted Delivery of TGX-221 to Prostate Cancer Cells

    PubMed Central

    Zhao, Yunqi; Duan, Shaofeng; Zeng, Xing; Liu, Chunjing; Davies, Neal M.; Li, Benyi; Forrest, M. Laird

    2013-01-01

    TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit. Recent studies showed that TGX-221 has anti-proliferative activity against PTEN-deficient tumor cell lines including prostate cancers. The objective of this study was to develop an encapsulation system for parenterally delivering TGX-221 to the target tissue through a prostate-specific membrane aptamer (PSMAa10) with little or no side effects. In this study, PEG-PCL micelles were formulated to encapsulate the drug, and a prodrug strategy was pursued to improve the stability of the carrier system. Fluorescence imaging studies demonstrated that the cellular uptake of both drug and nanoparticles were significantly improved by targeted micelles in a PSMA positive cell line. The area under the plasma concentration time curve of the micelle formulation in nude mice was 2.27-fold greater than the naked drug, and the drug clearance rate was 17.5-fold slower. These findings suggest a novel formulation approach for improving site-specific drug delivery of a molecular-targeted prostate cancer treatment. PMID:22494444

  12. Laser-assisted topical corticosteroid delivery for the treatment of keloids.

    PubMed

    Park, Ji Hye; Chun, Ji Young; Lee, Jong Hee

    2017-04-01

    Laser-assisted drug delivery has generated intense interest. The objectives of this study are to evaluate the clinical benefit of laser-assisted corticosteroid delivery and to compare this technique to corticosteroid intralesional injection, a standard treatment for keloids. Patients with keloids on the left shoulder after BCG vaccination were enrolled in this study. The entire lesion was first treated with an ablative fractional erbium-YAG laser. After this treatment, the lesion was divided into two halves. The first half received an intralesional injection of corticosteroid, whereas the second half received topical application of corticosteroids that were occluded for 3 hours. Four treatment sessions were conducted, with treatments occurring once every 6 weeks. Treatment outcomes were evaluated using the Vancouver Scar Scale (VSS). Pain was self-assessed by the patient during the procedure. The mean keloid VSS score before treatment was 8.59 ± 1.23 for the corticosteroid injection site and 8.31 ± 2.09 for the topical site. After treatment, the mean keloid VSS score was decreased on both sides (4.56 ± 1.09 vs 5.02 ± 0.87, respectively, P > 0.05). Patients rated their satisfaction level as "moderate" on both sides. However, the mean pain score was 1.1 out of 10 on the topical side versus 6.1 on the corticosteroid injection site. The combination of ablative fractional laser treatment and topical corticosteroid application is a promising modality for the treatment of keloids. Moreover, this procedure was not associated with any serious adverse reactions or unbearable pain.

  13. Development of an intradermal DNA vaccine delivery strategy to achieve single-dose immunity against respiratory syncytial virus.

    PubMed

    Smith, Trevor R F; Schultheis, Katherine; Morrow, Matthew P; Kraynyak, Kimberly A; McCoy, Jay R; Yim, Kevin C; Muthumani, Karuppiah; Humeau, Laurent; Weiner, David B; Sardesai, Niranjan Y; Broderick, Kate E

    2017-05-15

    Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, and an effective, safe RSV vaccine remains an unmet need. Here we assess a novel vaccination strategy based on the intradermal delivery of a SynCon® DNA-based vaccine encoding engineered RSV-F antigen using a surface electroporation device (SEP) to target epidermal cells, in clinically relevant experimental models. We demonstrate the ability of this strategy to elicit robust immune responses. Importantly we demonstrate complete resistance to pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A challenge model. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine, there was no enhanced lung inflammation upon virus challenge after DNA vaccination. In summary the data presented outline the pre-clinical development of a highly efficacious, tolerable and safe non-replicating vaccine delivery strategy. Copyright © 2017. Published by Elsevier Ltd.

  14. Intrathecal Drug Delivery and Spinal Cord Stimulation for the Treatment of Cancer Pain.

    PubMed

    Xing, Fangfang; Yong, R Jason; Kaye, Alan David; Urman, Richard D

    2018-02-05

    The purpose of the present investigation is to summarize the body and quality of evidence including the most recent studies in support of intrathecal drug delivery systems and spinal cord stimulation for the treatment of cancer-related pain. In the past 3 years, a number of prospective studies have been published supporting intrathecal drug delivery systems for cancer pain. Additional investigation with adjuvants to morphine-based analgesia including dexmedetomidine and ziconotide support drug-induced benefits of patient-controlled intrathecal analgesia. A study has also been recently published regarding cost-savings for intrathecal drug delivery system compared to pharmacologic management, but an analysis in the Ontario, Canada healthcare system projects additional financial costs. Finally, the Polyanalgesic Consensus Committee has updated its recommendations regarding clinical guidelines for intrathecal drug delivery systems to include new information on dosing, trialing, safety, and systemic opioid reduction. There is still a paucity of clinical evidence for spinal cord stimulation in the treatment of cancer pain. There are new intrathecal drugs under investigation including various conopeptides and AYX1. Large, prospective, modern, randomized controlled studies are still needed to support the use of both intrathecal drug delivery systems as well as spinal cord stimulation for cancer pain populations. There are multiple prospective and small randomized controlled studies that highlight a potential promising future for these interventional modalities. Related to the challenge and urgency of cancer pain, the pain practitioner community is moving toward a multimodal approach that includes discussions regarding the role of intrathecal therapies and spinal cord stimulation to the individualized treatment of patients.

  15. Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Able, Charles M., E-mail: cable@wfubmc.edu; Bright, Megan; Frizzell, Bart

    Purpose: Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. Methods and Materials: A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles withmore » 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. Results: There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. Conclusions: SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.« less

  16. Nanotechnology for the Prevention and Treatment of Cataract.

    PubMed

    Cetinel, Sibel; Montemagno, Carlo

    2015-01-01

    The purpose of this article was to review recent advances in the applications of nanotechnology in cataract treatment and prevention strategies. A literature review on the use of nanotechnology for the prevention and treatment of cataract was done. Research articles about nanotechnology-based treatments and prevention technologies for cataract were searched on Web of Science, and the most recent advances were reported. Nonsteroid anti-inflammatory drugs, natural antioxidants, biologic and chemical chaperones, and chaperones such as molecules have found great application in preventing and treating cataracts. Current scientific research on new treatment strategies, which focuses on the biochemical basis of the disease, will likely result in new anticataract agents. However, none of the drug formulations will be approved for use unless efficient delivery is promised. Nanoparticle engineering together with biomimetic strategies enable the development of next-generation, more efficient, less complex, and personalized treatments. The only currently available treatment for cataracts, surgical replacement of the opacified lens, is not an easily accessible option in developing countries. New treatment strategies based on topical drugs would enable treatment to reach massive populations facing the threat of blindness and more effectively deal with the postsurgical complications. Nanotechnology plays a key role in improving drug delivery systems with enhanced controlled release, targeted delivery, and bioavailability to overcome diffusion limitations in the eye.

  17. Quality assurance for online adapted treatment plans: Benchmarking and delivery monitoring simulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Taoran, E-mail: taoran.li.duke@gmail.com; Wu, Qiuwen; Yang, Yun

    Purpose: An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. Methods: The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system wasmore » designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system’s performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT

  18. Vascular-targeted nanocarriers: design considerations and strategies for successful treatment of atherosclerosis and other vascular diseases.

    PubMed

    Kelley, William J; Safari, Hanieh; Lopez-Cazares, Genesis; Eniola-Adefeso, Omolola

    2016-11-01

    Vascular-targeted nanocarriers are an attractive option for the treatment of a number of cardiovascular diseases, as they allow for more specific delivery and increased efficacy of many small molecule drugs. However, immune clearance, limited cellular uptake, and particle-cell dynamics in blood flow can hinder nanocarrier efficacy in many applications. This review aims to investigate successful strategies for the use of vascular-targeted nanocarriers in the treatment of cardiovascular diseases such as atherosclerosis. In particular, the review will highlight strategies employed for actively targeting the components of the atherosclerotic plaque, including endothelial cells, macrophages, and platelets and passive targeting via endothelial permeability, as well as design specifications (such as size, shape, and density) aimed at enhancing the ability of nanocarriers to reach the vascular wall. WIREs Nanomed Nanobiotechnol 2016, 8:909-926. doi: 10.1002/wnan.1414 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  19. Improving Care for Depression & Suicide Risk in Adolescents: Innovative Strategies for Bringing Treatments to Community Settings

    PubMed Central

    Asarnow, Joan Rosenbaum; Miranda, Jeanne

    2015-01-01

    This article reviews the literature on interventions and services for depression and suicide prevention among adolescents, with the goals of placing this science within the context of current changing health care environments and highlighting innovative models for improving health and mental health. We examine the: challenges and opportunities offered by new initiatives and legislation designed to transform the U.S. health and mental healthcare systems; summarize knowledge regarding the treatment of depression and suicidality/self-harm in adolescents; and describe innovative models for partnering with health systems and communities. This review demonstrates that treatment models and service delivery strategies are currently available for increasing evidence-based care, particularly for depression, and concludes with recommendations for future research and quality improvement initiatives aimed at inspiring additional efforts to put science to work, bridge science and community practice, and develop strategies for partnering with communities to improve care, mental health, and well-being among adolescents. PMID:24437432

  20. Radiation dose delivery verification in the treatment of carcinoma-cervix

    NASA Astrophysics Data System (ADS)

    Shrotriya, D.; Kumar, S.; Srivastava, R. N. L.

    2015-06-01

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  1. Delivery of peptide and protein drugs over the blood-brain barrier.

    PubMed

    Brasnjevic, Ivona; Steinbusch, Harry W M; Schmitz, Christoph; Martinez-Martinez, Pilar

    2009-04-01

    Peptide and protein (P/P) drugs have been identified as showing great promises for the treatment of various neurodegenerative diseases. A major challenge in this regard, however, is the delivery of P/P drugs over the blood-brain barrier (BBB). Intense research over the last 25 years has enabled a better understanding of the cellular and molecular transport mechanisms at the BBB, and several strategies for enhanced P/P drug delivery over the BBB have been developed and tested in preclinical and clinical-experimental research. Among them, technology-based approaches (comprising functionalized nanocarriers and liposomes) and pharmacological strategies (such as the use of carrier systems and chimeric peptide technology) appear to be the most promising ones. This review combines a comprehensive overview on the current understanding of the transport mechanisms at the BBB with promising selected strategies published so far that can be applied to facilitate enhanced P/P drug delivery over the BBB.

  2. Controlled Bioactive Molecules Delivery Strategies for Tendon and Ligament Tissue Engineering using Polymeric Nanofibers.

    PubMed

    Hiong Teh, Thomas Kok; Hong Goh, James Cho; Toh, Siew Lok

    2015-01-01

    The interest in polymeric nanofibers has escalated over the past decade given its promise as tissue engineering scaffolds that can mimic the nanoscale structure of the native extracellular matrix. With functionalization of the polymeric nanofibers using bioactive molecules, localized signaling moieties can be established for the attached cells, to stimulate desired biological effects and direct cellular or tissue response. The inherently high surface area per unit mass of polymeric nanofibers can enhance cell adhesion, bioactive molecules loading and release efficiencies, and mass transfer properties. In this review article, the application of polymeric nanofibers for controlled bioactive molecules delivery will be discussed, with a focus on tendon and ligament tissue engineering. Various polymeric materials of different mechanical and degradation properties will be presented along with the nanofiber fabrication techniques explored. The bioactive molecules of interest for tendon and ligament tissue engineering, including growth factors and small molecules, will also be reviewed and compared in terms of their nanofiber incorporation strategies and release profiles. This article will also highlight and compare various innovative strategies to control the release of bioactive molecules spatiotemporally and explore an emerging tissue engineering strategy involving controlled multiple bioactive molecules sequential release. Finally, the review article concludes with challenges and future trends in the innovation and development of bioactive molecules delivery using polymeric nanofibers for tendon and ligament tissue engineering.

  3. Recent in vivo advances in cell-penetrating peptide-assisted drug delivery.

    PubMed

    Kurrikoff, Kaido; Gestin, Maxime; Langel, Ülo

    2016-01-01

    Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment. In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP-cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA). Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.

  4. Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment.

    PubMed

    Zhou, Zhiping; Singh, Ranjodh; Souweidane, Mark M

    2017-01-01

    Convection-enhanced delivery (CED) is a technique designed to deliver drugs directly into the brain or tumors. Its ability to bypass the blood-brain barrier (BBB), one of the major hurdles in delivering drugs to the brain, has made it a promising drug delivery method for the treatment of primary brain tumors. A number of clinical trials utilizing CED of various therapeutic agents have been conducted to treat patients with supratentorial high-grade gliomas. Significant responses have been observed in certain patients in all of these trials. However, the insufficient ability to monitor drug distribution and pharmacokinetics hampers CED from achieving its potentials on a larger scale. Brainstem CED for diffuse intrinsic pontine glioma (DIPG) treatment is appealing because this tumor is compact and has no definitive treatment. The safety of brainstem CED has been established in small and large animals, and recently in early stage clinical trials. There are a few current clinical trials of brainstem CED in treating DIPG patients using targeted macromolecules such as antibodies and immunotoxins. Future advances for CED in DIPG treatment will come from several directions including: choosing the right agents for infusion; developing better agents and regimen for DIPG infusion; improving instruments and technique for easier and accurate surgical targeting and for allowing multisession or prolonged infusion to implement optimal time sequence; and better understanding and control of drug distribution, clearance and time sequence. CED-based therapies for DIPG will continue to evolve with new understanding of the technique and the disease.

  5. Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment

    PubMed Central

    Zhou, Zhiping; Singh, Ranjodh; Souweidane, Mark M.

    2017-01-01

    Convection-enhanced delivery (CED) is a technique designed to deliver drugs directly into the brain or tumors. Its ability to bypass the blood-brain barrier (BBB), one of the major hurdles in delivering drugs to the brain, has made it a promising drug delivery method for the treatment of primary brain tumors. A number of clinical trials utilizing CED of various therapeutic agents have been conducted to treat patients with supratentorial high-grade gliomas. Significant responses have been observed in certain patients in all of these trials. However, the insufficient ability to monitor drug distribution and pharmacokinetics hampers CED from achieving its potentials on a larger scale. Brainstem CED for diffuse intrinsic pontine glioma (DIPG) treatment is appealing because this tumor is compact and has no definitive treatment. The safety of brainstem CED has been established in small and large animals, and recently in early stage clinical trials. There are a few current clinical trials of brainstem CED in treating DIPG patients using targeted macromolecules such as antibodies and immunotoxins. Future advances for CED in DIPG treatment will come from several directions including: choosing the right agents for infusion; developing better agents and regimen for DIPG infusion; improving instruments and technique for easier and accurate surgical targeting and for allowing multisession or prolonged infusion to implement optimal time sequence; and better understanding and control of drug distribution, clearance and time sequence. CED-based therapies for DIPG will continue to evolve with new understanding of the technique and the disease. PMID:27306036

  6. Gene delivery strategies for the treatment of mucopolysaccharidoses.

    PubMed

    Baldo, Guilherme; Giugliani, Roberto; Matte, Ursula

    2014-03-01

    Mucopolysaccharidosis (MPS) disorders are genetic diseases caused by deficiencies in the lysosomal enzymes responsible for the degradation of glycosaminoglycans. Current treatments are not able to correct all disease symptoms and are not available for all MPS types, which makes gene therapy especially relevant. Multiple gene therapy approaches have been tested for different types of MPS, and our aim in this study is to critically analyze each of them. In this review, we have included the major studies that describe the use of adeno-associated retroviral and lentiviral vectors, as well as relevant non-viral approaches for MPS disorders. Some protocols such as the use of adeno-associated vectors and lentiviral vectors are approaching the clinic for these disorders and, along with combined approaches, seem to be the future of gene therapy for MPS.

  7. Telepsychiatrists' Medication Treatment Strategies in the Children's Attention-Deficit/Hyperactivity Disorder Telemental Health Treatment Study

    PubMed Central

    Tse, Yuet Juhn; Fesinmeyer, Megan D.; Garcia, Jessica; Myers, Kathleen

    2016-01-01

    Abstract Objective: The purpose of this study was to examine the prescribing strategies that telepsychiatrists used to provide pharmacologic treatment in the Children's Attention-Deficit/Hyperactivity Disorder (ADHD) Telemental Health Treatment Study (CATTS). Methods: CATTS was a randomized controlled trial that demonstrated the superiority of a telehealth service delivery model for the treatment of ADHD with combined pharmacotherapy and behavior training (n=111), compared with management in primary care augmented with a telepsychiatry consultation (n=112). A diagnosis of ADHD was established with the Computerized Diagnostic Interview Schedule for Children (CDISC), and comorbidity for oppositional defiant disorder (ODD) and anxiety disorders (AD) was established using the CDISC and the Child Behavior Checklist. Telepsychiatrists used the Texas Children's Medication Algorithm Project (TCMAP) for ADHD to guide pharmacotherapy and the treat-to-target model to encourage their assertive medication management to a predetermined goal of 50% reduction in ADHD-related symptoms. We assessed whether telepsychiatrists' decision making about making medication changes was associated with baseline ADHD symptom severity, comorbidity, and attainment of the treat-to-target goal. Results: Telepsychiatrists showed high fidelity (91%) to their chosen algorithms in medication management. At the end of the trial, the CATTS intervention showed 46.0% attainment of the treat-to-target goal compared with 13.6% for the augmented primary care condition, and significantly greater attainment of the goal by comorbidity status for the ADHD with one and ADHD with two comorbidities groups. Telepsychiatrists' were more likely to decide to make medication adjustments for youth with higher baseline ADHD severity and the presence of disorders comorbid with ADHD. Multiple mixed methods regression analyses controlling for baseline ADHD severity and comorbidity status indicated that the telepsychiatrists

  8. Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders.

    PubMed

    Ong, Wei-Yi; Shalini, Suku-Maran; Costantino, Luca

    2014-01-01

    Many potential drugs for the treatment of neurological diseases are unable to reach the brain in sufficient enough concentrations to be therapeutic because of the blood brain barrier. On the other hand, direct delivery of drugs to the brain provides the possibility of a greater therapeutic-toxic ratio than with systemic drug delivery. The use of intranasal delivery of therapeutic agents to the brain provides a means of bypassing the blood brain barrier in a non-invasive manner. In this respect, nanosized drug carriers were shown to enhance the delivery of drugs to CNS compared to equivalent drug solution formulations. Neurological conditions that have been studied in animal models that could benefit from nose-to-brain delivery of nanotherapeutics include pain, epilepsy, neurodegenerative disease and infectious diseases. The delivery of drugs to the brain via the nose-to-brain route holds great promise, on the basis of preclinical research by means of drug delivery systems such as polymeric nanoparticles and clinical data related to intranasal delivery to CNS of large molecular weight biologics administered in solution, but safety issues about toxicity on nasal mucosa, Np transport into the brain, delivery only to specific brain regions and variability in the adsorbed dose still represent research topics that need to be considered, with a view of clinical translation of these delivery systems.

  9. Interventions That Target Criminogenic Needs for Justice-Involved Persons With Serious Mental Illnesses: A Targeted Service Delivery Approach.

    PubMed

    Wilson, Amy Blank; Farkas, Kathleen; Bonfine, Natalie; Duda-Banwar, Janelle

    2018-05-01

    This research describes the development of a targeted service delivery approach that tailors the delivery of interventions that target criminogenic needs to the specific learning and treatment needs of justice-involved people with serious mental illnesses (SMIs). This targeted service delivery approach includes five service delivery strategies: repetition and summarizing, amplification, active coaching, low-demand practice, and maximizing participation. Examples of how to apply each strategy in session are provided, as well as recommendations on when to use each strategy during the delivery of interventions that target criminogenic needs. This targeted service delivery approach makes an important contribution to the development of interventions for justice-involved people with SMI by increasing the chances that people with SMI can participate fully in and benefit from these interventions that target criminogenic needs. These developments come at a critical time in the field as the next generation of services for justice-involved people with SMI are being developed.

  10. Ultrasound-assisted drug delivery for treatment of venous thrombosis: a case study.

    PubMed

    Marchiondo, Kathleen; Frink, Amber

    2008-01-01

    Ultrasound-assisted drug delivery is a relatively new medical intervention that combines low-intensity ultrasound waves with infusion of a thrombolytic agent directly into a thrombosed vein. Studies have demonstrated that clots are eradicated faster, more completely, and with fewer bleeding events with the use of ultrasound-assisted drug delivery for treatment of deep vein thrombosis compared to that of traditional therapies. Critical care nurses are responsible for preprocedure assessment and teaching and continuous monitoring of the patient during therapy for effectiveness and potential complications. An advantage of this technology from a nursing perspective is the minimal amount of time required for monitoring the drug delivery system, allowing greater focus on patient assessment and care.

  11. The importance of nonstop treatment after delivery for pregnant women with type 2 diabetes.

    PubMed

    Omori, Yasue; Yanagisawa, Keiko; Sato, Asako; Uchigata, Yasuko

    2017-03-01

    There are no reports of very long follow-up studies of pregnant women with type 2 diabetes after delivery. Here we describe cases of Japanese women whom we treated for 20 to 50 years after deliveries to investigate the relationship between blood glucose control and diabetic complications. In Japan, the prevalence of type 1 diabetes is very low, and we have very few long-term follow-up cases with type 1 diabetes. Therefore, we chose to describe subjects with type 2 diabetes only. We present data on a total of 80 deliveries, 68 cases, treated by one of us (Y.O.) for more than a 50-year period. They are divided into 4 groups based on duration of treatment after delivery: more than 50 years (1 delivery, 1 patient), 40 to 49 years (13 deliveries, 11 patients), 30 to 39 years (19 deliveries, 16 patients), and 20 to 29 years (47 deliveries, 40 patients). Their present average ages in these 4 groups are 77, 72.4, 65.9, and 55.5 years, respectively. Their average HbA1c levels at last visit, in May 2014, are 8.2%, 7.6%.,7.2%, and 8.3%, respectively. Despite elevated HbA1c levels, they had relatively few complications: 40% (no retinopathy), 43.8% (simple retinopathy), and 12.5% (treated with photocoagulation); 67.5% (no albuminuria), 26.3% (albuminuria), and 6.3% (treated with renal transplantation or hemodialysis). Therefore, even if glycemic control is not ideal, nonstop treatment of Japanese women for type 2 diabetes after deliveries is effective to prevent diabetic complications. Long-term attention to care of diabetes after pregnancy may be preventive of diabetic complications in other populations as well. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer

    NASA Astrophysics Data System (ADS)

    Zhang, Li; Yang, Xin; Lv, Yaqi; Xin, Xiaofei; Qin, Chao; Han, Xiaopeng; Yang, Lei; He, Wei; Yin, Lifang

    2017-04-01

    Co-delivery of microRNAs and chemotherapeutic drugs into tumor cells is an attractive strategy for synergetic breast cancer therapy due to their complementary mechanisms. In this work, a core-shell nanocarrier coated by cationic albumin was developed to simultaneously deliver miRNA-34a and docetaxel (DTX) into breast cancer cells for improved therapeutic effect. The co-delivery nanocarriers showed a spherical morphology with an average particle size of 183.9 nm, and they efficiently protected miRNA-34a from degradation by RNase and serum. Importantly, the nanocarriers entered the cytosol via a caveolae-mediated pathway without entrapment in endosomes/lysosomes, thus improving the utilization of the cargo. In vitro, the co-delivery nanocarriers suppressed the expression of anti-apoptosis gene Bcl-2 at both transcription and protein levels, inhibited tumor cell migration and efficiently induced cell apoptosis and cytotoxicity. In vivo, the co-delivery nanocarriers prolonged the blood circulation of DTX, enhanced tumor accumulation of the cargo and significantly inhibited tumor growth and metastasis in 4T1-tumor bearing mice models. Taken together, the present nanocarrier co-loading with DTX and miRNA-34a is a new nanoplatform for the combination of insoluble drugs and gene/protein drugs and provides a promising strategy for the treatment of metastatic breast cancer.

  13. SU-E-T-106: An Institutional Review of Using Commercially Available Software to Evaluate Treatment Plan Quality for Various Treatment Sites and Beam Deliveries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Esquivel, C; Patton, L; Walker, S

    Purpose: Use Sun Nuclear Quality Reports™ with PlanIQ™ to evaluate different treatment delivery techniques for various treatment sites. Methods: Fifteen random patients with different treatment sites were evaluated. These include the Head/Neck, prostate, pelvis, lung, esophagus, axilla, bladder and abdomen. Initially, these sites were planned on the Pinnacle {sup 3} V9.6 treatment planning system and utilized nine 6MV step-n-shoot IMRT fields. The RT plan, dose and structure sets were sent to Quality Reports™ where a DVH was recreated and the plans were compared to a unique Plan Algorithm for each treatment site. Each algorithm has its own plan quality metricsmore » and objectives, which include the PTV coverage, PTV maximum dose, the prescription dose outside the target, doses to the critical structures, and the global maximum dose and its location. Each plan was scored base on meeting each objective. Plans may have been reoptimized and reevaluated with Quality Reports™ based on the initial score. PlanIQ™ was used to evaluate if any objective not met was achievable or difficult to obtain. A second plan using VMAT delivery was created for each patient and scored with Quality Reports™. Results: There were a wide range of scores for the different treatment sites with some scoring better for IMRT plans and some better for the VMAT deliveries. The variation in the scores could be attributed to the treatment site, location, and shape of the target. Most deliveries were chosen for the VMAT due to the short treatment times and quick patient throughput with acceptable plan scores. Conclusion: The tools are provided for both physician and dosimetrist to objectively evaluate the use of VMAT delivery versus the step-n-shoot IMRT delivery for various sites. PlanIQ validates if objectives can be met. For the physicist, a concise pass/fail report is created for plan evaluation.« less

  14. Enterprise networks. Strategies for integrated delivery systems.

    PubMed

    Siwicki, B

    1997-02-01

    More integrated delivery systems are making progress toward building computer networks that link all their care delivery sites so they can efficiently and economically coordinate care. A growing number of these systems are turning to intranets--private computer networks that use Internet-derived protocols and technologies--to move information that's essential to managing scare health care resources.

  15. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-06-01

    Particle therapy is a field in remarkable development, with the goal of increasing the number of indications which could benefit from such treatments and the access to the therapy. The therapeutic usage of a particle beam defines the technical requirements of all the elements of the therapy chain: we summarize the main characteristics of accelerators, the beam line, the treatment room, the integrated therapy and imaging systems used in particle therapy. Aiming at a higher flexibility in the choice of treatments, an increasing number of centers around the world have chosen to equip their treatment rooms with gantries, rotating beam line structures that allow a complete flexibility in the choice of the treatment angle. We review the current designs. A particle therapy gantry though is a quite expensive structure, and future development will increasingly consider reducing the cost and the footprint. Increasing the number of indications also means development in the delivery techniques and solving some of the issues which traditionally affected particle therapy, for example the precision of the delivery in presence of motion and the large penumbras for low depths. We show the current strategies in these fields, focusing on pencil beam scanning (PBS), and give some hints about future developments.

  16. [Fundamental strategies to address the problem of public health service delivery insufficiency of disease prevention and control system of China].

    PubMed

    Shao, Jing-jing; Yu, Jing-jin; Yu, Ming-zhu; Duan, Yong; Gong, Xiangguang; Chen, Zheng; Wang, Hua; Shi, Peiwu; Liang, Zhankai; Yang, Feng; Wang, Dunzhi; Yue, Jianning; Luo, Shi; Luo, Li; Wang, Weicheng; Wang, Ying; Sun, Mei; Su, Zhongxin; Ma, Ning; Xie, Hongbin; Hao, Mo

    2005-03-01

    To develop and demonstrate the strategies to solve the problem of public health service delivery insufficiency of disease prevention and control system of China. 205 literatures in 8 national academic journals concerning health service management have been reviewed. The method of boundary analysis has been employed to conclude the various reform strategies. Based on the causes and mechanism of public health service delivery insufficiency of disease prevention and control system, the logic analysis has been employed to develop fundamental strategies, which has been demonstrated by 154 CDC using intention questionnaires. There are fundamental strategies to which the agreeing rate for sampling CDC was over 95%: to make sure government should afford the financing function of disease prevention and control and secure the feasible investment for centers of disease prevention and control. Meanwhile, the working efficiency of CDC should be improved through strengthening management and reforming government investing manner.

  17. Short-peptide-based molecular hydrogels: novel gelation strategies and applications for tissue engineering and drug delivery

    NASA Astrophysics Data System (ADS)

    Wang, Huaimin; Yang, Zhimou

    2012-08-01

    Molecular hydrogels hold big potential for tissue engineering and controlled drug delivery. Our lab focuses on short-peptide-based molecular hydrogels formed by biocompatible methods and their applications in tissue engineering (especially, 3D cell culture) and controlled drug delivery. This feature article firstly describes our recent progresses of the development of novel methods to form hydrogels, including the strategy of disulfide bond reduction and assistance with specific protein-peptide interactions. We then introduce the applications of our hydrogels in fields of controlled stem cell differentiation, cell culture, surface modifications of polyester materials by molecular self-assembly, and anti-degradation of recombinant complex proteins. A novel molecular hydrogel system of hydrophobic compounds that are only formed by hydrolysis processes was also included in this article. The hydrogels of hydrophobic compounds, especially those of hydrophobic therapeutic agents, may be developed into a carrier-free delivery system for long term delivery of therapeutic agents. With the efforts in this field, we believe that molecular hydrogels formed by short peptides and hydrophobic therapeutic agents can be practically applied for 3D cell culture and long term drug delivery in near future, respectively.

  18. Targeted Delivery of Therapeutic Oligonucleotides for the Treatment of Prostate Cancer

    DTIC Science & Technology

    2004-05-01

    AD Award Number: DAMD17-01-1-0090 TITLE: Targeted Delivery of Therapeutic Oligonucleotides for the Treatment of Prostate Cancer PRINCIPAL...independence and chemoresistance are the major obstacles in the treatment of patients with advanced prostate cancer (Denis & Murphy, 1993; Oh & Kantoff...independence and chemoresistance in prostate cancer (McDonnell et al., 1992; Colombel et al., 1993; Berchem et al., 1995; Raffo et al., 1995; Bauer et al

  19. Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier

    PubMed Central

    Strazielle, Nathalie; Ghersi-Egea, Jean-François

    2016-01-01

    The blood-brain interfaces restrict the cerebral bioavailability of pharmacological compounds. Various drug delivery strategies have been developed to improve drug penetration into the brain. Most strategies target the microvascular endothelium forming the blood-brain barrier proper. Targeting the blood-cerebrospinal fluid (CSF) barrier formed by the epithelium of the choroid plexuses in addition to the blood-brain barrier may offer added-value for the treatment of central nervous system diseases. For instance, targeting the CSF spaces, adjacent tissue, or the choroid plexuses themselves is of interest for the treatment of neuroinflammatory and infectious diseases, cerebral amyloid angiopathy, selected brain tumors, hydrocephalus or neurohumoral dysregulation. Selected CSF-borne materials seem to reach deep cerebral structures by mechanisms that need to be understood in the context of chronic CSF delivery. Drug delivery through both barriers can reduce CSF sink action towards parenchymal drugs. Finally, targeting the choroid plexus-CSF system can be especially relevant in the context of neonatal and pediatric diseases of the central nervous system. Transcytosis appears the most promising mechanism to target in order to improve drug delivery through brain barriers. The choroid plexus epithelium displays strong vesicular trafficking and secretory activities that deserve to be explored in the context of cerebral drug delivery. Folate transport and exosome release into the CSF, plasma protein transport, and various receptor-mediated endocytosis pathways may prove useful mechanisms to exploit for efficient drug delivery into the CSF. This calls for a clear evaluation of transcytosis mechanisms at the blood-CSF barrier, and a thorough evaluation of CSF drug delivery rates. PMID:27464721

  20. Peptide and low molecular weight proteins based kidney targeted drug delivery systems.

    PubMed

    Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei

    2018-05-30

    Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Various drug delivery approaches to the central nervous system.

    PubMed

    Pasha, Santosh; Gupta, Kshitij

    2010-01-01

    The presence of the blood-brain barrier (BBB), an insurmountable obstacle, in particular, and other barriers in brain and periphery contribute to hindrance of the successful diagnosis and treatment of a myriad of central nervous system pathologies. This review discusses several strategies adopted to define a rational drug delivery approach to the CNS along with a short description of the strategies implemented by the authors' group to enhance the analgesic activity, a CNS property, of chimeric peptide of Met-enkephalin and FMRFa (YGGFMKKKFMRFa-YFa). Various approaches for drug delivery to the CNS with their beneficial and non-beneficial aspects, supported by an extensive literature survey published recently, up to August 2009. The reader will have the privilege of gaining an understanding of previous as well as recent approaches to breaching the CNS barriers. Among the various strategies discussed, the potential for efficacious CNS drug targeting in future lies either with the non-invasively administered multifunctional nanosystems or these nanosystems without characterstics such as long systemic circulating capability and avoiding reticuloendothelial system scavenging system of the body, endogenous transporters and efflux inhibitors administered by convection-enhanced delivery.

  2. Advances in the psychosocial treatment of addiction: the role of technology in the delivery of evidence-based psychosocial treatment.

    PubMed

    Marsch, Lisa A; Dallery, Jesse

    2012-06-01

    The clinical community has a growing array of psychosocial interventions with a strong evidence base available for the treatment of SUDs. Considerable opportunity exists for leveraging technology in the delivery of evidence-based interventions to promote widespread reach and impact of evidence-based care. Data from this line of research to date are promising, and underscore the potential public health impact of technology-based therapeutic tools. To fully realize the potential of technology-delivered interventions, several areas of inquiry remain important. First, scientifically sound strategies should be explored to ensure technology-based interventions are optimally designed to produce maximal behavior change. Second, efficient and effective methods should be identified to integrate technology-based interventions into systems of care in a manner that is most responsive to the needs of individual users. Third, payment, privacy, and regulatory systems should be refined and extended to go beyond electronic medical records and telehealth/distance care models, and support the deployment of technology-based systems to enhance the quality, efficiency and cost-effectiveness of care. Fourth, the mechanisms underlying behavior change derived from technology-based treatments should be explicated, including new mechanisms that may be tapped via novel, technology-based tools. Such work will be critical in isolating mechanisms that are useful in predicting treatment response, and in ensuring that key ingredients are present in technology-based interventions as they are made widely available.

  3. Advances in bioresponsive closed-loop drug delivery systems.

    PubMed

    Yu, Jicheng; Zhang, Yuqi; Yan, Junjie; Kahkoska, Anna R; Gu, Zhen

    2017-11-27

    Controlled drug delivery systems are able to improve efficacy and safety of therapeutics by optimizing the duration and kinetics of release. Among them, closed-loop delivery strategies, also known as self-regulated administration, have proven to be a practical tool for homeostatic regulation, by tuning drug release as a function of biosignals relevant to physiological and pathological processes. A typical example is glucose-responsive insulin delivery system, which can mimic the pancreatic beta cells to release insulin with a proper dose at a proper time point by responding to plasma glucose levels. Similar self-regulated systems are also important in the treatment of other diseases including thrombosis and bacterial infection. In this review, we survey the recent advances in bioresponsive closed-loop drug delivery systems, including glucose-responsive, enzyme-activated, and other biosignal-mediated delivery systems. We also discuss the future opportunities and challenges in this field. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery

    PubMed Central

    An, Fei-Fei; Zhang, Xiao-Hong

    2017-01-01

    Biosafety is the primary concern in clinical translation of nanomedicine. As an intrinsic ingredient of human blood without immunogenicity and encouraged by its successful clinical application in Abraxane, albumin has been regarded as a promising material to produce nanoparticles for bioimaging and drug delivery. The strategies for synthesizing albumin-based nanoparticles could be generally categorized into five classes: template, nanocarrier, scaffold, stabilizer and albumin-polymer conjugate. This review introduces approaches utilizing albumin in the preparation of nanoparticles and thereby provides scientists with knowledge of goal-driven design on albumin-based nanomedicine. PMID:29109768

  5. Self-management toolkit and delivery strategy for end-of-life pain: the mixed-methods feasibility study.

    PubMed

    Bennett, Michael I; Mulvey, Matthew R; Campling, Natasha; Latter, Sue; Richardson, Alison; Bekker, Hilary; Blenkinsopp, Alison; Carder, Paul; Closs, Jose; Farrin, Amanda; Flemming, Kate; Gallagher, Jean; Meads, David; Morley, Stephen; O'Dwyer, John; Wright-Hughes, Alexandra; Hartley, Suzanne

    2017-12-01

    Pain affects most people approaching the end of life and can be severe for some. Opioid analgesia is effective, but evidence is needed about how best to support patients in managing these medicines. To develop a self-management support toolkit (SMST) and delivery strategy and to test the feasibility of evaluating this intervention in a future definitive trial. Phase I - evidence synthesis and qualitative interviews with patients and carers. Phase II - qualitative semistructured focus groups and interviews with patients, carers and specialist palliative care health professionals. Phase III - multicentre mixed-methods single-arm pre-post observational feasibility study. Phase I - six patients and carers. Phase II - 15 patients, four carers and 19 professionals. Phase III - 19 patients recruited to intervention that experienced pain, living at home and were treated with strong opioid analgesia. Process evaluation interviews with 13 patients, seven carers and 11 study nurses. Self-Management of Analgesia and Related Treatments at the end of life (SMART) intervention comprising a SMST and a four-step educational delivery approach by clinical nurse specialists in palliative care over 6 weeks. Recruitment rate, treatment fidelity, treatment acceptability, patient-reported outcomes (such as scores on the Brief Pain Inventory, Self-Efficacy for Managing Chronic Disease Scale, Edmonton Symptom Assessment Scale, EuroQol-5 Dimensions, Satisfaction with Information about Medicines Scale, and feasibility of collecting data on health-care resource use for economic evaluation). Phase I - key themes on supported self-management were identified from evidence synthesis and qualitative interviews. Phase II - the SMST was developed and refined. The delivery approach was nested within a nurse-patient consultation. Phase III - intervention was delivered to 17 (89%) patients, follow-up data at 6 weeks were available on 15 patients. Overall, the intervention was viewed as acceptable and

  6. Drug self-delivery systems for cancer therapy.

    PubMed

    Qin, Si-Yong; Zhang, Ai-Qing; Cheng, Si-Xue; Rong, Lei; Zhang, Xian-Zheng

    2017-01-01

    Carrier-assistant drug delivery systems (DDSs) have been rapidly established for cancer therapy and great strides have been made in recent years. However, further development of DDSs is retarded by the aspects such as the low drug carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. Drug self-delivery systems (DSDSs), in which active drugs exhibit nanoscale characteristic to realize intracellular delivery by themselves without the help of nanocarriers, have been rapidly developed to address these issues. In this review, we present a comprehensive summary of the recent advances in DSDSs for cancer therapy. After a brief introduction to the major types of DSDSs and their fabrication strategies, we emphatically discuss some representative achievements of these DSDSs for passive or/and positive targeting therapy, combinational therapy as well as theranostics. The design principle is explained and justified, which can cast a new light on developing drug delivery systems for cancer treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Receptor-Mediated Drug Delivery Systems Targeting to Glioma

    PubMed Central

    Wang, Shanshan; Meng, Ying; Li, Chengyi; Qian, Min; Huang, Rongqin

    2015-01-01

    Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications. PMID:28344260

  8. Medical capsule robots: A renaissance for diagnostics, drug delivery and surgical treatment.

    PubMed

    Mapara, Sanyat S; Patravale, Vandana B

    2017-09-10

    The advancements in electronics and the progress in nanotechnology have resulted in path breaking development that will transform the way diagnosis and treatment are carried out currently. This development is Medical Capsule Robots, which has emerged from the science fiction idea of robots travelling inside the body to diagnose and cure disorders. The first marketed capsule robot was a capsule endoscope developed to capture images of the gastrointestinal tract. Today, varieties of capsule endoscopes are available in the market. They are slightly larger than regular oral capsules, made up of a biocompatible case and have electronic circuitry and mechanisms to capture and transmit images. In addition, robots with diagnostic features such as in vivo body temperature detection and pH monitoring have also been launched in the market. However, a multi-functional unit that will diagnose and cure diseases inside the body has not yet been realized. A remote controlled capsule that will undertake drug delivery and surgical treatment has not been successfully launched in the market. High cost, inadequate power supply, lack of control over drug release, limited space for drug storage on the capsule, inadequate safety and no mechanisms for active locomotion and anchoring have prevented their entry in the market. The capsule robots can revolutionize the current way of diagnosis and treatment. This paper discusses in detail the applications of medical capsule robots in diagnostics, drug delivery and surgical treatment. In diagnostics, detailed analysis has been presented on wireless capsule endoscopes, issues associated with the marketed versions and their corresponding solutions in literature. Moreover, an assessment has been made of the existing state of remote controlled capsules for targeted drug delivery and surgical treatment and their future impact is predicted. Besides the need for multi-functional capsule robots and the areas for further research have also been

  9. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.

    PubMed

    Hua, Susan; Marks, Ellen; Schneider, Jennifer J; Keely, Simon

    2015-07-01

    Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. PROMOTE Study: Safety of Osteopathic Manipulative Treatment During the Third Trimester by Labor and Delivery Outcomes.

    PubMed

    Hensel, Kendi L; Roane, Brandy M; Chaphekar, Anita Vikas; Smith-Barbaro, Peggy

    2016-11-01

    Few quality data exist on the safety of osteopathic manipulative treatment (OMT) during pregnancy. The Pregnancy Research on Osteopathic Manipulation Optimizing Treatment Effects (PROMOTE) study was a randomized controlled clinical trial that studied the application of an OMT protocol to manage pain and dysfunction in pregnant patients during their third trimester. To evaluate the safety of an OMT protocol applied during the third trimester of pregnancy by analyzing incidence of high-risk status and labor and delivery outcomes. In the PROMOTE study, 400 pregnant patients were randomly assigned to 1 of 3 study groups: usual care plus OMT (OMT), usual care plus placebo ultrasound treatment (PUT), or usual care only (UCO). The incidence of high-risk status of participants and outcomes of labor and delivery, including length of labor, fever in mother during labor, operative vaginal delivery, conversion to cesarean delivery, need for forceps or vacuum device, need for episiotomy, incidence of perineal laceration, meconium-stained amniotic fluid, and infants' Apgar scores, were analyzed. Data from 380 participants were studied. High-risk status was less likely to develop in participants who received OMT (95% CI, 0.16-0.91; P=.03). The OMT protocol also did not increase risk of precipitous labor, operative vaginal delivery, conversion to cesarean delivery, need for forceps or vacuum device, need for episiotomy, incidence of perineal laceration, or meconium-stained amniotic fluid when compared with participants in the other 2 groups (P>.05). Of all other maternal outcomes examined, no difference was reported among the 3 treatment groups with the exception of incidence of prolonged labor in the OMT group. Participants receiving OMT had longer durations of labor than participants in the other groups (P=.002). These results suggest that the OMT protocol given during the third trimester of pregnancy as applied in the PROMOTE study is safe with regard to labor and delivery

  11. Clinical evaluation of 4D PET motion compensation strategies for treatment verification in ion beam therapy

    NASA Astrophysics Data System (ADS)

    Gianoli, Chiara; Kurz, Christopher; Riboldi, Marco; Bauer, Julia; Fontana, Giulia; Baroni, Guido; Debus, Jürgen; Parodi, Katia

    2016-06-01

    A clinical trial named PROMETHEUS is currently ongoing for inoperable hepatocellular carcinoma (HCC) at the Heidelberg Ion Beam Therapy Center (HIT, Germany). In this framework, 4D PET-CT datasets are acquired shortly after the therapeutic treatment to compare the irradiation induced PET image with a Monte Carlo PET prediction resulting from the simulation of treatment delivery. The extremely low count statistics of this measured PET image represents a major limitation of this technique, especially in presence of target motion. The purpose of the study is to investigate two different 4D PET motion compensation strategies towards the recovery of the whole count statistics for improved image quality of the 4D PET-CT datasets for PET-based treatment verification. The well-known 4D-MLEM reconstruction algorithm, embedding the motion compensation in the reconstruction process of 4D PET sinograms, was compared to a recently proposed pre-reconstruction motion compensation strategy, which operates in sinogram domain by applying the motion compensation to the 4D PET sinograms. With reference to phantom and patient datasets, advantages and drawbacks of the two 4D PET motion compensation strategies were identified. The 4D-MLEM algorithm was strongly affected by inverse inconsistency of the motion model but demonstrated the capability to mitigate the noise-break-up effects. Conversely, the pre-reconstruction warping showed less sensitivity to inverse inconsistency but also more noise in the reconstructed images. The comparison was performed by relying on quantification of PET activity and ion range difference, typically yielding similar results. The study demonstrated that treatment verification of moving targets could be accomplished by relying on the whole count statistics image quality, as obtained from the application of 4D PET motion compensation strategies. In particular, the pre-reconstruction warping was shown to represent a promising choice when combined with intra

  12. A clinical information systems strategy for a large integrated delivery network.

    PubMed Central

    Kuperman, G. J.; Spurr, C.; Flammini, S.; Bates, D.; Glaser, J.

    2000-01-01

    Integrated delivery networks (IDNs) are an emerging class of health care institutions. IDNs are formed from the affiliation of individual health care institutions and are intended to be more efficient in the current fiscal health care environment. To realize efficiencies and support their strategic visions, IDNs rely critically on excellent information technology (IT). Because of its importance to the mission of the IDN, strategic decisions about IT are made by the top leadership of the IDN. At Partners HealthCare System, a large IDN in Boston, MA, a clinical information systems strategy has been created to support the Partners clinical vision. In this paper, we discuss the Partners' structure, clinical vision, and current IT initiatives in place to address the clinical vision. The initiatives are: a clinical data repository, inpatient process support, electronic medical records, a portal strategy, referral applications, knowledge resources, support for product lines, patient computing, confidentiality, and clinical decision support. We address several of the issues encountered in trying to bring excellent information technology to a large IDN. PMID:11079921

  13. The effect of delivery mechanisms on the uptake of bed net re-impregnation in Kilifi District, Kenya.

    PubMed

    Snow, R W; McCabe, E; Mbogo, C N; Molyneux, C S; Some, E S; Mung'ala, V O; Nevill, C G

    1999-03-01

    The results of recently completed trials in Africa of insecticide-treated bed nets (ITBN) offer new possibilities for malaria control. These experimental trials aimed for high ITBN coverage combined with high re-treatment rates. Whilst necessary to understand protective efficacy, the approaches used to deliver the intervention provide few indications of what coverage of net re-treatment would be under operational conditions. Varied delivery and financing strategies have been proposed for the sustainable delivery of ITBNs and re-treatment programmes. Following the completion of a randomized, controlled trial on the Kenyan coast, a series of suitable delivery strategies were used to continue net re-treatment in the area. The trial adopted a bi-annual, house-to-house re-treatment schedule free of charge using research project staff and resulted in over 95% coverage of nets issued to children. During the year following the trial, sentinel dipping stations were situated throughout the community and household members informed of their position and opening times. This free re-treatment service achieved between 61-67% coverage of nets used by children for three years. In 1997 a social marketing approach, that introduced cost-retrieval, was used to deliver the net re-treatment services. The immediate result of this transition was that significantly fewer of the mothers who had used the previous re-treatment services adopted this revised approach and coverage declined to 7%. The future of new delivery services and their financing are discussed in the context of their likely impact upon previously defined protective efficacy and cost-effectiveness estimates.

  14. Assuring high quality treatment delivery in clinical trials - Results from the Trans-Tasman Radiation Oncology Group (TROG) study 03.04 "RADAR" set-up accuracy study.

    PubMed

    Haworth, Annette; Kearvell, Rachel; Greer, Peter B; Hooton, Ben; Denham, James W; Lamb, David; Duchesne, Gillian; Murray, Judy; Joseph, David

    2009-03-01

    A multi-centre clinical trial for prostate cancer patients provided an opportunity to introduce conformal radiotherapy with dose escalation. To verify adequate treatment accuracy prior to patient recruitment, centres submitted details of a set-up accuracy study (SUAS). We report the results of the SUAS, the variation in clinical practice and the strategies used to help centres improve treatment accuracy. The SUAS required each of the 24 participating centres to collect data on at least 10 pelvic patients imaged on a minimum of 20 occasions. Software was provided for data collection and analysis. Support to centres was provided through educational lectures, the trial quality assurance team and an information booklet. Only two centres had recently carried out a SUAS prior to the trial opening. Systematic errors were generally smaller than those previously reported in the literature. The questionnaire identified many differences in patient set-up protocols. As a result of participating in this QA activity more than 65% of centres improved their treatment delivery accuracy. Conducting a pre-trial SUAS has led to improvement in treatment delivery accuracy in many centres. Treatment techniques and set-up accuracy varied greatly, demonstrating a need to ensure an on-going awareness for such studies in future trials and with the introduction of dose escalation or new technologies.

  15. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention

    PubMed Central

    Holpuch, Andrew S.; Phelps, Maynard P.; Desai, Kashappa-Goud H.; Chen, Wei; Koutras, George M.; Han, Byungdo B.; Warner, Blake M.; Pei, Ping; Seghi, Garrett A.; Tong, Meng; Border, Michael B.; Fields, Henry W.; Stoner, Gary D.; Larsen, Peter E.; Liu, Zhongfa; Schwendeman, Steven P.; Mallery, Susan R.

    2012-01-01

    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1—TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1—UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4—CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR’s preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to

  16. Evaluation of a mucoadhesive fenretinide patch for local intraoral delivery: a strategy to reintroduce fenretinide for oral cancer chemoprevention.

    PubMed

    Holpuch, Andrew S; Phelps, Maynard P; Desai, Kashappa-Goud H; Chen, Wei; Koutras, George M; Han, Byungdo B; Warner, Blake M; Pei, Ping; Seghi, Garrett A; Tong, Meng; Border, Michael B; Fields, Henry W; Stoner, Gary D; Larsen, Peter E; Liu, Zhongfa; Schwendeman, Steven P; Mallery, Susan R

    2012-05-01

    Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and subtherapeutic intraoral drug levels. Local drug delivery, however, provides site-specific therapeutically relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal mucosa. Fenretinide and blank-control patches were placed on right/left buccal mucosa, respectively, in eight rabbits (30 min, q.d., 10 days). No clinical or histological deleterious effects occurred. LC-MS/MS analyses of post-treatment samples revealed a delivery gradient with highest fenretinide levels achieved at the patch-mucosal interface (no metabolites), pharmacologically active levels in fenretinide-treated oral mucosa (mean: 5.65 μM; trace amounts of 4-oxo-4-HPR) and undetectable sera levels. Epithelial markers for cell proliferation (Ki-67), terminal differentiation (transglutaminase 1-TGase1) and glucuronidation (UDP-glucuronosyltransferase1A1-UGT1A1) exhibited fenretinide concentration-specific relationships (elevated TGase1 and UGT1A1 levels <5 μM, reduced Ki-67 indices >5 μM) relative to blank-treated epithelium. All fenretinide-treated tissues showed significantly increased intraepithelial apoptosis (TUNEL) positivity, implying activation of intersecting apoptotic and differentiation pathways. Human oral mucosal correlative studies showed substantial interdonor variations in levels of the enzyme (cytochrome P450 3A4-CYP3A4) responsible for conversion of fenretinide to its highly active metabolite, 4-oxo-4-HPR. Complementary in vitro assays in human oral keratinocytes revealed fenretinide and 4-oxo-4-HPR's preferential suppression of DNA synthesis in dysplastic as opposed to normal oral keratinocytes. Collectively, these data showed that mucoadhesive patch-mediated fenretinide delivery is a viable strategy to reintroduce

  17. Current treatment options and drug delivery systems as potential therapeutic agents for ovarian cancer: a review.

    PubMed

    Ye, Hongye; Karim, Anis Abdul; Loh, Xian Jun

    2014-12-01

    Ovarian cancer is one of the most common and deadliest gynecologic cancer with about 75% of the patients presenting in advanced stages. The introduction of intraperitoneal chemotherapy in 2006 had led to a 16 month improvement in the overall survival. However, catheter-related complication and the complexity of the procedure had deterred intraperitoneal route as the preferred route of treatment. Other alternative treatments had been developed by incorporating other FDA-approved agents or procedures such as pegylated liposomal doxorubicin (PLD), hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and the administration of bevacizumab. Various clinical trials were conducted on these alternatives as both the first-line treatment and second- or third-line therapy for the recurrent disease. The outcome of these studies were summarized and discussed. A prospective improvement in the treatment of ovarian cancer could be done through the use of a drug delivery system. Selected promising recent developments in ovarian cancer drug delivery systems using different delivery vehicles, surface modifications, materials and drugs were also reviewed. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Innovations in gene and growth factor delivery systems for diabetic wound healing

    PubMed Central

    Laiva, Ashang Luwang; O'Brien, Fergal J.

    2017-01-01

    Abstract The rise in lower extremity amputations due to nonhealing of foot ulcers in diabetic patients calls for rapid improvement in effective treatment regimens. Administration of growth factors (GFs) are thought to offer an off‐the‐shelf treatment; however, the dose‐ and time‐dependent efficacy of the GFs together with the hostile environment of diabetic wound beds impose a major hindrance in the selection of an ideal route for GF delivery. As an alternative, the delivery of therapeutic genes using viral and nonviral vectors, capable of transiently expressing the genes until the recovery of the wounded tissue offers promise. The development of implantable biomaterial dressings capable of modulating the release of either single or combinatorial GFs/genes may offer solutions to this overgrowing problem. This article reviews the state of the art on gene and protein delivery and the strategic optimization of clinically adopted delivery strategies for the healing of diabetic wounds. PMID:28482114

  19. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  20. Influence of delivery strategy on message-processing mechanisms and future adherence to a Dutch computer-tailored smoking cessation intervention.

    PubMed

    Stanczyk, Nicola Esther; Crutzen, Rik; Bolman, Catherine; Muris, Jean; de Vries, Hein

    2013-02-06

    Smoking tobacco is one of the most preventable causes of illness and death. Web-based tailored smoking cessation interventions have shown to be effective. Although these interventions have the potential to reach a large number of smokers, they often face high attrition rates, especially among lower educated smokers. A possible reason for the high attrition rates in the latter group is that computer-tailored smoking cessation interventions may not be attractive enough as they are mainly text-based. Video-based messages might be more effective in attracting attention and stimulating comprehension in people with a lower educational level and could therefore reduce attrition rates. The objective of the present study was to investigate whether differences exist in message-processing mechanisms (attention, comprehension, self-reference, appreciation, processing) and future adherence (intention to visit/use the website again, recommend the website to others), according to delivery strategy (video or text based messages) and educational level, to a Dutch computer-tailored smoking cessation program. Smokers who were motivated to quit within the following 6 months and who were aged over 16 were included in the program. Participants were randomly assigned to one of two conditions (video/text CT). The sample was stratified into 2 categories: lower and higher educated participants. In total, 139 participants completed the first session of the web-based tailored intervention and were subsequently asked to fill out a questionnaire assessing message-processing mechanisms and future adherence. ANOVAs and regression analyses were conducted to investigate the differences in message-processing mechanisms and future adherence with regard to delivery strategy and education. No interaction effects were found between delivery strategy (video vs text) and educational level on message-processing mechanisms and future adherence. Delivery strategy had no effect on future adherence and

  1. Influence of Delivery Strategy on Message-Processing Mechanisms and Future Adherence to a Dutch Computer-Tailored Smoking Cessation Intervention

    PubMed Central

    Crutzen, Rik; Bolman, Catherine; Muris, Jean; de Vries, Hein

    2013-01-01

    Background Smoking tobacco is one of the most preventable causes of illness and death. Web-based tailored smoking cessation interventions have shown to be effective. Although these interventions have the potential to reach a large number of smokers, they often face high attrition rates, especially among lower educated smokers. A possible reason for the high attrition rates in the latter group is that computer-tailored smoking cessation interventions may not be attractive enough as they are mainly text-based. Video-based messages might be more effective in attracting attention and stimulating comprehension in people with a lower educational level and could therefore reduce attrition rates. Objective The objective of the present study was to investigate whether differences exist in message-processing mechanisms (attention, comprehension, self-reference, appreciation, processing) and future adherence (intention to visit/use the website again, recommend the website to others), according to delivery strategy (video or text based messages) and educational level, to a Dutch computer-tailored smoking cessation program. Methods Smokers who were motivated to quit within the following 6 months and who were aged over 16 were included in the program. Participants were randomly assigned to one of two conditions (video/text CT). The sample was stratified into 2 categories: lower and higher educated participants. In total, 139 participants completed the first session of the web-based tailored intervention and were subsequently asked to fill out a questionnaire assessing message-processing mechanisms and future adherence. ANOVAs and regression analyses were conducted to investigate the differences in message-processing mechanisms and future adherence with regard to delivery strategy and education. Results No interaction effects were found between delivery strategy (video vs text) and educational level on message-processing mechanisms and future adherence. Delivery strategy had no

  2. Virosome, a hybrid vehicle for efficient and safe drug delivery and its emerging application in cancer treatment.

    PubMed

    Liu, Hanqing; Tu, Zhigang; Feng, Fan; Shi, Haifeng; Chen, Keping; Xu, Ximing

    2015-06-01

    A virosome is an innovative hybrid drug delivery system with advantages of both viral and non-viral vectors. Studies have shown that a virosome can carry various biologically active molecules, such as nucleic acids, peptides, proteins and small organic molecules. Targeted drug delivery using virosome-based systems can be achieved through surface modifications of virosomes. A number of virosome-based prophylactic and therapeutic products with high safety profiles are currently available in the market. Cancer treatment is a big battlefield for virosome-based drug delivery systems. This review provides an overview of the general concept, preparation procedures, working mechanisms, preclinical studies and clinical applications of virosomes in cancer treatment.

  3. The study of marketed and experimental formulation approaches enabling site-specific delivery of mesalamine in patients with inflammatory bowel disease.

    PubMed

    Kadiyala, Irina; Jacobs, Dylan

    2014-04-01

    This patent review focuses exclusively on the oral delivery of mesalamine (5-ASA) and excludes oral mesalamine pro-drug and rectal delivery formulations. The formulation strategies of marketed formulations (Apriso(®), Asacol(®), Lialda(®) and Pentasa(®)) and non-marketed formulations are reviewed and explained by decoding formulation specifics that enable the site specific delivery for the treatment of inflammatory bowel disease.

  4. Nanotechnology-Based Drug Delivery Systems for Treatment of Tuberculosis--A Review.

    PubMed

    da Silva, Patricia Bento; de Freitas, Eduardo Sinésio; Bernegossi, Jessica; Gonçalez, Maíra Lima; Sato, Mariana Rillo; Leite, Clarice Queico Fujimura; Pavan, Fernando Rogério; Chorilli, Marlus

    2016-02-01

    Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t₁/₂ (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB.

  5. A facile construction strategy of stable lipid nanoparticles for drug delivery using a hydrogel-thickened microemulsion system

    NASA Astrophysics Data System (ADS)

    Chen, Huabing; Xiao, Ling; Du, Danrong; Mou, Dongsheng; Xu, Huibi; Yang, Xiangliang

    2010-01-01

    We report a novel facile method for preparing stable nanoparticles with inner spherical solid spheres and an outer hydrogel matrix using a hot O/W hydrogel-thickened microemulsion with spontaneous stability. The nanoparticles with average diameters of about 30.0 nm and 100.0 nm were constructed by cooling the hot hydrogel-thickened microemulsion at different temperatures, respectively. We explained the application of these nanoparticles by actualizing the cutaneous delivery of drug-loaded nanoparticles. The in vitro skin permeation studies showed that the nanoparticles could significantly reduce the penetration of model drugs through skin and resulted in their dermal uptakes in skin. The sol-gel process of TEOS was furthermore used in the template of HTM to regulate the particle size of nanoparticles. The coating of silica on the surface of nanoparticles could regulate the penetration of drug into skin from dermal delivery to transdermal delivery. This strategy provides a facile method to produce nanoparticles with long-term stability and ease of manufacture, which might have a promising application in drug delivery.

  6. Buccal drug delivery technologies for patient-centred treatment of radiation-induced xerostomia (dry mouth).

    PubMed

    Malallah, Osamah S; Garcia, Cristina M Aller; Proctor, Gordon B; Forbes, Ben; Royall, Paul G

    2018-04-25

    Radiotherapy is a life-saving treatment for head and neck cancers, but almost 100% of patients develop dry mouth (xerostomia) because of radiation-induced damage to their salivary glands. Patients with xerostomia suffer symptoms that severely affect their health as well as physical, social and emotional aspects of their life. The current management of xerostomia is the application of saliva substitutes or systemic delivery of saliva-stimulating cholinergic agents, including pilocarpine, cevimeline or bethanechol tablets. It is almost impossible for substitutes to replicate all the functional and sensory facets of natural saliva. Salivary stimulants are a better treatment option than saliva substitutes as the former induce the secretion of natural saliva from undamaged glands; typically, these are the minor salivary glands. However, patients taking cholinergic agents systemically experience pharmacology-related side effects including sweating, excessive lacrimation and gastrointestinal tract distresses. Local delivery direct to the buccal mucosa has the potential to provide rapid onset of drug action, i.e. activation of minor salivary glands within the buccal mucosa, while sparing systemic drug exposure and off-target effects. This critical review of the technologies for the local delivery of saliva-stimulating agents includes oral disintegrating tablets (ODTs), oral disintegrating films, medicated chewing gums and implantable drug delivery devices. Our analysis makes a strong case for the development of ODTs for the buccal delivery of cholinergic agents: these must be patient-friendly delivery platforms with variable loading capacities that release the drug rapidly in fluid volumes typical of residual saliva in xerostomia (0.05-0.1 mL). Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Intracellular delivery of proteins by nanocarriers.

    PubMed

    Ray, Moumita; Lee, Yi-Wei; Scaletti, Federica; Yu, Ruijin; Rotello, Vincent M

    2017-04-01

    Intracellular delivery of proteins is potentially a game-changing approach for therapeutics. However, for most applications, the protein needs to access the cytosol to be effective. A wide variety of strategies have been developed for protein delivery, however access of delivered protein to the cytosol without acute cytotoxicity remains a critical issue. In this review we discuss recent trends in protein delivery using nanocarriers, focusing on the ability of these strategies to deliver protein into the cytosol.

  8. Recent Advances in Carrier Mediated Nose-to-Brain Delivery of Pharmaceutics.

    PubMed

    Bourganis, Vassilis; Kammona, Olga; Alexopoulos, Aleck; Kiparissides, Costas

    2018-05-04

    Central nervous system (CNS) disorders (e.g., multiple sclerosis, Alzheimer's disease, etc.) represent a growing public health issue, primarily due to the increased life expectancy and the aging population. The treatment of such disorders is notably elaborate and requires the delivery of therapeutics to the brain in appropriate amounts to elicit a pharmacological response. However, despite the major advances both in neuroscience and drug delivery research, the administration of drugs to the CNS still remains elusive. It is commonly accepted that effectiveness-related issues arise due to the inability of parenterally administered macromolecules to cross the Blood-Brain Barrier (BBB) in order to access the CNS, thus impeding their successful delivery to brain tissues. As a result, the direct Nose-to-Brain delivery has emerged as a powerful strategy to circumvent the BBB and deliver drugs to the brain. The present review article attempts to highlight the different experimental and computational approaches pursued so far to attain and enhance the direct delivery of therapeutic agents to the brain and shed some light on the underlying mechanisms involved in the pathogenesis and treatment of neurological disorders. Copyright © 2018. Published by Elsevier B.V.

  9. High-intensity focused ultrasound treatment of placenta accreta after vaginal delivery: a preliminary study.

    PubMed

    Bai, Y; Luo, X; Li, Q; Yin, N; Fu, X; Zhang, H; Qi, H

    2016-04-01

    To evaluate the safety and efficiency of high-intensity focused ultrasound (HIFU) in the treatment of placenta accreta after vaginal delivery. Enrolled into this study between September 2011 and September 2013 were 12 patients who had been diagnosed with placenta accreta following vaginal delivery and who had stable vital signs. All patients were treated using an ultrasound-guided HIFU treatment system. As indication of the effectiveness of the treatment we considered decreased vascular index on color Doppler imaging, decrease in size of residual placenta compared with pretreatment size on assessment by three-dimensional ultrasound with Virtual Organ Computer-aided Analysis, reduced signal intensity and degree of enhancement on magnetic resonance imaging and avoidance of hysterectomy following treatment. To assess the safety of HIFU treatment, we recorded side effects, hemorrhage, infection, sex steroid levels, return of menses and subsequent pregnancy. Patients were followed up in this preliminary study until December 2013. The 12 patients receiving HIFU treatment had an average postpartum hospital stay of 6.8 days and an average period of residual placental involution of 36.9 days. HIFU treatment did not apparently increase the risk of infection or hemorrhage and no patient required hysterectomy. In all patients menstruation recommenced after an average of 80.2 days, and sex steroid levels during the middle luteal phase of the second menstrual cycle were normal. Two patients became pregnant again during the follow-up period. This preliminary study suggests that ultrasound-guided HIFU is a safe and effective non-invasive method to treat placenta accreta patients after vaginal delivery who have stable vital signs and desire to preserve fertility. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  10. Nanocarrier-mediated drugs targeting cancer stem cells: an emerging delivery approach.

    PubMed

    Malhi, Sarandeep; Gu, Xiaochen

    2015-07-01

    Cancer stem cells (CSCs) play an important role in the development of drug resistance, metastasis and recurrence. Current conventional therapies do not commonly target CSCs. Nanocarrier-based delivery systems targeting cancer cells have entered a new era of treatment, where specific targeting to CSCs may offer superior outcomes to efficient cancer therapies. This review discusses the involvement of CSCs in tumor progression and relevant mechanisms associated with CSCs resistance to conventional chemo- and radio-therapies. It highlights CSCs-targeted strategies that are either under evaluation or could be explored in the near future, with a focus on various nanocarrier-based delivery systems of drugs and nucleic acids to CSCs. Novel nanocarriers targeting CSCs are presented in a cancer-specific way to provide a current perspective on anti-CSCs therapeutics. The field of CSCs-targeted therapeutics is still emerging with a few small molecules and macromolecules currently proving efficacy in clinical trials. However considering the complexities of CSCs and existing delivery difficulties in conventional anticancer therapies, CSC-specific delivery systems would face tremendous technical and clinical challenges. Nanocarrier-based approaches have demonstrated significant potential in specific drug delivery and targeting; their success in CSCs-targeted drug delivery would not only significantly enhance anticancer treatment but also address current difficulties associated with cancer resistance, metastasis and recurrence.

  11. The suprachoroidal pathway: a new drug delivery route to the back of the eye.

    PubMed

    Rai, Uma Do J P; Young, Simon A; Thrimawithana, Thilini R; Abdelkader, Hamdy; Alani, Adam W G; Pierscionek, Barbara; Alany, Raid G

    2015-04-01

    The development of safe and convenient drug delivery strategies for treatment of posterior segment eye diseases is challenging. Although intravitreal injection has wide acceptance amongst clinicians, its use is associated with serious side-effects. Recently, the suprachoroidal space (SCS) has attracted the attention of ophthalmologists and pharmaceutical formulators as a potential site for drug administration and delivery to the posterior segment of the eye. This review highlights the major constraints of drug delivery to the posterior eye segment, key anatomical and physiological features of the SCS and drug delivery applications of this route with emphasis on microneedles along with future perspectives. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Examining leadership as a strategy to enhance health care service delivery in regional hospitals in South Africa.

    PubMed

    Govender, Sagaren; Gerwel Proches, Cecile N; Kader, Abdulla

    2018-01-01

    Four public hospitals in South Africa, which render both specialized and nonspecialized services to thousands of patients, were examined to determine the impact of leadership on health care service delivery. These hospitals were inundated by various problems that were impacting negatively on health care service delivery. This research study aimed to gain a comprehensive understanding of the challenges, complexities and constraints facing public health care in KwaZulu-Natal (KZN) and to examine leadership as a strategy to enhance healthcare service delivery with a particular focus on four regional hospitals in the KZN Province. The mixed-method research approach was utilized. Purposive sampling and stratified random sampling were employed in the research setting, and in-depth, semistructured interviews and questionnaires were used to collect data. Data were analyzed using the Nvivo computer software package for in-depth interviews and the Statistical Package for the Social Sciences (SPSS) software for the quantitative analysis. The research findings showed that the current leadership framework adopted by the health care leaders in regional hospitals in KZN is weak and is contributing to poor health care service delivery. This study, therefore, aimed to address the current challenges and weaknesses that are impacting negatively on health care service delivery in regional hospitals in the KZN Province and made recommendations for improvement.

  13. Oral Insulin Delivery: How Far Are We?

    PubMed Central

    Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

    2013-01-01

    Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

  14. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

    Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

  15. Local delivery of sirolimus nanoparticles for the treatment of in-stent restenosis.

    PubMed

    Zago, Alexandre C; Raudales, José C; Attizzani, Guilherme; Matte, Bruno S; Yamamoto, German I; Balvedi, Julise A; Nascimento, Ludmila; Kosachenco, Beatriz G; Centeno, Paulo R; Zago, Alcides J

    2013-02-01

    To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model. Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high. Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment. There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1. PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans. Copyright © 2012 Wiley Periodicals, Inc.

  16. Surface-Modified Nanocarriers for Nose-to-Brain Delivery: From Bioadhesion to Targeting

    PubMed Central

    Clementino, Adryana; Buttini, Francesca; Colombo, Gaia; Pescina, Silvia; Stanisçuaski Guterres, Silvia; Nicoli, Sara

    2018-01-01

    In the field of nasal drug delivery, nose-to-brain delivery is among the most fascinating applications, directly targeting the central nervous system, bypassing the blood brain barrier. Its benefits include dose lowering and direct brain distribution of potent drugs, ultimately reducing systemic side effects. Recently, nasal administration of insulin showed promising results in clinical trials for the treatment of Alzheimer’s disease. Nanomedicines could further contribute to making nose-to-brain delivery a reality. While not disregarding the need for devices enabling a formulation deposition in the nose’s upper part, surface modification of nanomedicines appears the key strategy to optimize drug delivery from the nasal cavity to the brain. In this review, nanomedicine delivery based on particle engineering exploiting surface electrostatic charges, mucoadhesive polymers, or chemical moieties targeting the nasal epithelium will be discussed and critically evaluated in relation to nose-to-brain delivery. PMID:29543755

  17. A continuous arc delivery optimization algorithm for CyberKnife m6.

    PubMed

    Kearney, Vasant; Descovich, Martina; Sudhyadhom, Atchar; Cheung, Joey P; McGuinness, Christopher; Solberg, Timothy D

    2018-06-01

    This study aims to reduce the delivery time of CyberKnife m6 treatments by allowing for noncoplanar continuous arc delivery. To achieve this, a novel noncoplanar continuous arc delivery optimization algorithm was developed for the CyberKnife m6 treatment system (CyberArc-m6). CyberArc-m6 uses a five-step overarching strategy, in which an initial set of beam geometries is determined, the robotic delivery path is calculated, direct aperture optimization is conducted, intermediate MLC configurations are extracted, and the final beam weights are computed for the continuous arc radiation source model. This algorithm was implemented on five prostate and three brain patients, previously planned using a conventional step-and-shoot CyberKnife m6 delivery technique. The dosimetric quality of the CyberArc-m6 plans was assessed using locally confined mutual information (LCMI), conformity index (CI), heterogeneity index (HI), and a variety of common clinical dosimetric objectives. Using conservative optimization tuning parameters, CyberArc-m6 plans were able to achieve an average CI difference of 0.036 ± 0.025, an average HI difference of 0.046 ± 0.038, and an average LCMI of 0.920 ± 0.030 compared with the original CyberKnife m6 plans. Including a 5 s per minute image alignment time and a 5-min setup time, conservative CyberArc-m6 plans achieved an average treatment delivery speed up of 1.545x ± 0.305x compared with step-and-shoot plans. The CyberArc-m6 algorithm was able to achieve dosimetrically similar plans compared to their step-and-shoot CyberKnife m6 counterparts, while simultaneously reducing treatment delivery times. © 2018 American Association of Physicists in Medicine.

  18. Microneedles for intradermal and transdermal delivery

    PubMed Central

    Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

    2014-01-01

    The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

  19. Cost Effective Delivery Strategies in Rural Areas: Programs for Young Handicapped Children. Vol. I. Making It Work in Rural Communities. A Rural Network Monograph.

    ERIC Educational Resources Information Center

    Black, Talbot, Ed.; Hutinger, Patricia, Ed.

    Using a common format outlining program settings, agencies, children/families served, staff, services, delivery strategies, and program costs, descriptions of four cost-effective rural service delivery programs for young handicapped children provide evidence that good rural programs are affordable. The Early Lifestyle Program at King's Daughters'…

  20. Magnetic nanoparticles-based drug and gene delivery systems for the treatment of pulmonary diseases.

    PubMed

    El-Sherbiny, Ibrahim M; Elbaz, Nancy M; Sedki, Mohammed; Elgammal, Abdulaziz; Yacoub, Magdi H

    2017-02-01

    Magnetic nanoparticles (MNPs) have gained much attention due to their unique properties such as biocompatibility and biodegradability as well as magnetic and heat-medicated characteristics. Due to these inherent properties, MNPs have been widely used in various biomedical applications including targeted drug delivery and hyperthermia-based therapy. Hyperthermia is a promising approach for the thermal activation therapy of several diseases, including pulmonary diseases. Additionally, due to their large loading capacity and controlled release ability, several MNP-based drug delivery systems have been emerged for treatment of cystic fibrosis and lung cancer. This review provides an overview on the unique properties of MNPs and magnetic-mediated hyperthermia with emphasis on the recent biomedical applications of MNPs in treatment of both lung cancer and cystic fibrosis.

  1. The role of treatment delivery factors in exposure-based cognitive behavioral therapy for panic disorder with agoraphobia.

    PubMed

    Weck, Florian; Grikscheit, Florian; Höfling, Volkmar; Kordt, Anne; Hamm, Alfons O; Gerlach, Alexander L; Alpers, Georg W; Arolt, Volker; Kircher, Tilo; Pauli, Paul; Rief, Winfried; Lang, Thomas

    2016-08-01

    Treatment delivery factors (i.e., therapist adherence, therapist competence, and therapeutic alliance) are considered to be important for cognitive behavioral therapy (CBT) for panic disorder and agoraphobia (PD/AG). In the current study, four independent raters conducted process evaluations based on 168 two-hour videotapes of 84 patients with PD/AG treated with exposure-based CBT. Two raters evaluated patients' interpersonal behavior in Session 1. Two raters evaluated treatment delivery factors in Session 6, in which therapists provided the rationale for conducting exposure exercises. At the 6-month follow-up, therapists' adherence (r=0.54) and therapeutic alliance (r=0.31) were significant predictors of changes in agoraphobic avoidance behavior; therapist competence was not associated with treatment outcomes. Patients' interpersonal behavior in Session 1 was a significant predictor of the therapeutic alliance in Session 6 (r=0.17). The findings demonstrate that treatment delivery factors, particularly therapist adherence, are relevant to the long-term success of CBT for PD/AG. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance

    PubMed Central

    Yadav, Narayan Prasad; Jain, Sanyog; Arora, Sumit

    2013-01-01

    Liver is a vital organ responsible for plethora of functions including detoxification, protein synthesis, and the production of biochemicals necessary for the sustenance of life. Therefore, patients with chronic liver diseases such as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate attention to sustain life and as a result are often exposed to the prolonged treatment with drugs/herbal medications. Lack of site-specific delivery of these medications to the hepatocytes/nonparenchymal cells and adverse effects associated with their off-target interactions limit their continuous use. This calls for the development and fabrication of targeted delivery systems which can deliver the drug payload at the desired site of action for defined period of time. The primary aim of drug targeting is to manipulate the whole body distribution of drugs, that is, to prevent distribution to non-target cells and concomitantly increase the drug concentration at the targeted site. Carrier molecules are designed for their selective cellular uptake, taking advantage of specific receptors or binding sites present on the surface membrane of the target cell. In this review, various aspects of liver targeting of drug molecules and herbal medications have been discussed which elucidate the importance of delivering the drugs/herbal medications at their desired site of action. PMID:24286077

  3. Gene Delivery in Neuro-Oncology.

    PubMed

    Dixit, Karan; Kumthekar, Priya

    2017-09-02

    Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a dismal prognosis despite aggressive multimodal management thus novel treatments are urgently needed. Gene therapy is a versatile treatment strategy being investigated in multiple cancers including GBM. In gene therapy, a variety of vectors or "carriers" are used to deliver genes designed for different anti-tumoral effects. Gene delivery vehicles and approaches to treatment will be addressed in this review. The most commonly studied vectors are viral based, however, driven by advances in biomedical engineering, mesenchymal and neural stem cells, as well as multiple different types of nanoparticles have been developed to improve tumor tropism and also increase gene transfer into tumor cells. Different genes have been studied including suicide genes, which convert non-toxic prodrug into cytotoxic drug; immunomodulatory genes, which stimulate the immune system; and tumor suppressor genes which repair the defect that allow cells to divide unchecked. Gene therapy may be a promising treatment strategy in neuro-oncology as it is versatile and flexible due to the ability to tailor vectors and genes for specific therapeutic activity. Pre-clinical studies and clinical trials have demonstrated feasibility and safety of gene therapy; however, further studies are required to determine efficacy.

  4. In vitro and ex vivo strategies for intracellular delivery

    NASA Astrophysics Data System (ADS)

    Stewart, Martin P.; Sharei, Armon; Ding, Xiaoyun; Sahay, Gaurav; Langer, Robert; Jensen, Klavs F.

    2016-10-01

    Intracellular delivery of materials has become a critical component of genome-editing approaches, ex vivo cell-based therapies, and a diversity of fundamental research applications. Limitations of current technologies motivate development of next-generation systems that can deliver a broad variety of cargo to diverse cell types. Here we review in vitro and ex vivo intracellular delivery approaches with a focus on mechanisms, challenges and opportunities. In particular, we emphasize membrane-disruption-based delivery methods and the transformative role of nanotechnology, microfluidics and laboratory-on-chip technology in advancing the field.

  5. Treatment-resistant Schizophrenia: Evidence-based Strategies

    PubMed Central

    Englisch, Susanne; Zink, Mathias

    2012-01-01

    Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy. PMID:22654380

  6. Osteogenesis imperfecta in childhood: treatment strategies.

    PubMed

    Engelbert, R H; Pruijs, H E; Beemer, F A; Helders, P J

    1998-12-01

    Osteogenesis imperfecta (OI) is a skeletal disorder of remarkable clinical variability characterized by bone fragility, osteopenia, variable degrees of short stature, and progressive skeletal deformities. Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint laxity, and maturity onset deafness are described in the literature. OI occurs in about 1 in 20,000 births and is caused by quantitative and qualitative defects in the synthesis of collagen I. Depending on the severity of the disease, a large impact on motor development, range of joint motion, muscle strength, and functional ability may occur. Treatment strategies should primarily focus on the improvement of functional ability and the adoption of compensatory strategies, rather than merely improving range of joint motion and muscle strength. Surgical treatment of the extremities may be indicated to stabilize the long bones to optimize functional ability and walking capacity. Surgical treatment of the spine may be indicated in patients with progressive spinal deformity and in those with symptomatic basilar impression.

  7. Stabilization and delivery approaches for protein and peptide pharmaceuticals: an extensive review of patents.

    PubMed

    Swain, Suryakanta; Mondal, Debanik; Beg, Sarwar; Patra, Chinam Niranjan; Dinda, Subas Chandra; Sruti, Jammula; Rao, Muddana Eswara Bhanoji

    2013-04-01

    Proteins and peptides are the building blocks of human body and act as the arsenal to combat against the invading pathogenic organisms for treatment and management of diseases. Majority of such biomacromolecules are synthesized by the human body itself. However, entry of disease causing pathogens causes misleading in the synthesis of desired proteins for antibody formation. In such alarming situations, the delivery of requisite protein and peptide from external source helps in augmenting the body's immunity. The major drawbacks underlying poor biopharmaceutical performance of high molecular weight protein and peptide drugs are due to poor oral absorption, formulation stability, degradation in the gastric milieu, susceptible to presystemic metabolism. Numerous literature recounts the application of myriad drug delivery strategies for the effective delivery of protein and peptides viz. parentral, oral, transdermal, nasal, pulmonary, rectal, buccal and ocular drug delivery systems. There are many reviews on various delivery strategies for protein and peptide pharmaceuticals, but the present review article provides a bird's eye view on various novel drug delivery systems used for enhanced delivery of protein and peptide pharmaceuticals in the light of patent literature. Apart from this, the present manuscript endeavor provides idea on possible causes and major degradation pathways responsible for poor stability of protein and peptide drugs along with recent market instances on them utilizing novel drug delivery systems.

  8. Combined use of monopolar radiofrequency and transdermal drug delivery in the treatment of melasma.

    PubMed

    Cameli, Norma; Abril, Elva; Mariano, Maria; Berardesca, Enzo

    2014-07-01

    Melasma is a common acquired pigmentary disorder that has a considerable psychological impact on the patient. The recurrent and refractory nature of this condition makes it difficult for treatment. We aim to evaluate the efficacy and safety of a combined system that simultaneously uses monopolar radiofrequency (RF) and transdermal drug delivery of phytocomplex containing 1% kojic acid in the treatment of melasma. Fifty patients affected by melasma underwent 6 sessions of treatment at 1-week intervals. The outcome was evaluated before treatment (T0) and 1 month (T1) and 6 months (T2) after treatment using the Melasma Area and Severity Index score, a Mexameter, and Visioface devices for digital and ultraviolet computerized image analysis of skin color. The image analysis showed that hyperpigmentation was significantly reduced at T1 and T2 compared with baseline. Melasma Area and Severity Index score, the average melanin score, and the average erythema values showed a significant reduction. No side effects were observed or reported. This study describes the first report of improvement in melasma through the combined use of monopolar RF with transdermal delivery of depigmenting agents. This could be a safe, tolerable, and effective alternative tool for the treatment of melasma.

  9. Examining leadership as a strategy to enhance health care service delivery in regional hospitals in South Africa

    PubMed Central

    Govender, Sagaren; Gerwel Proches, Cecile N; Kader, Abdulla

    2018-01-01

    Background Four public hospitals in South Africa, which render both specialized and nonspecialized services to thousands of patients, were examined to determine the impact of leadership on health care service delivery. These hospitals were inundated by various problems that were impacting negatively on health care service delivery. Purpose This research study aimed to gain a comprehensive understanding of the challenges, complexities and constraints facing public health care in KwaZulu-Natal (KZN) and to examine leadership as a strategy to enhance healthcare service delivery with a particular focus on four regional hospitals in the KZN Province. Methods The mixed-method research approach was utilized. Purposive sampling and stratified random sampling were employed in the research setting, and in-depth, semistructured interviews and questionnaires were used to collect data. Data were analyzed using the Nvivo computer software package for in-depth interviews and the Statistical Package for the Social Sciences (SPSS) software for the quantitative analysis. Results The research findings showed that the current leadership framework adopted by the health care leaders in regional hospitals in KZN is weak and is contributing to poor health care service delivery. Conclusion This study, therefore, aimed to address the current challenges and weaknesses that are impacting negatively on health care service delivery in regional hospitals in the KZN Province and made recommendations for improvement. PMID:29535529

  10. Nanotechnology-Based Drug Delivery Systems for Photodynamic Therapy of Cancer: A Review.

    PubMed

    Calixto, Giovana Maria Fioramonti; Bernegossi, Jéssica; de Freitas, Laura Marise; Fontana, Carla Raquel; Chorilli, Marlus

    2016-03-11

    Photodynamic therapy (PDT) is a promising alternative approach for improved cancer treatment. In PDT, a photosensitizer (PS) is administered that can be activated by light of a specific wavelength, which causes selective damage to the tumor and its surrounding vasculature. The success of PDT is limited by the difficulty in administering photosensitizers (PSs) with low water solubility, which compromises the clinical use of several molecules. Incorporation of PSs in nanostructured drug delivery systems, such as polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), gold nanoparticles (AuNPs), hydrogels, liposomes, liquid crystals, dendrimers, and cyclodextrin is a potential strategy to overcome this difficulty. Additionally, nanotechnology-based drug delivery systems may improve the transcytosis of a PS across epithelial and endothelial barriers and afford the simultaneous co-delivery of two or more drugs. Based on this, the application of nanotechnology in medicine may offer numerous exciting possibilities in cancer treatment and improve the efficacy of available therapeutics. Therefore, the aim of this paper is to review nanotechnology-based drug delivery systems for photodynamic therapy of cancer.

  11. Cancer Nanotechnology: Recent Trends and Developments in Strategies for Targeting Cancer Cells to Improve Cancer Imaging and Treatment.

    PubMed

    Xu, Jingyao; Zhou, Xiaoling; Li, Yifei; Tian, Yudan

    2017-01-01

    Nanotechnology is a multidisciplinary field, which have the potential to cover applications in many subjects such as biology, chemistry and physics. The combined efforts of these subjects can lead to the successful engineering of nanodevices and nanovectors for targeted delivery and sensing/detection of cancer cells/tissues. The modulation of nanomaterials at surface and bulk level further adds value to this technology and develop strategies for early detection of precancerous and malignant cells from biological fluids. Furthermore, the novel nanotechnology-based imaging modalities have the prospects to offer non-invasive cancer imaging and treatment response study in real-time. This review covers the advantages of nanotechnology, which have been exploited for effective and targeted delivery of anti-cancer agents. Moreover, the initiatives taken by National Cancer Laboratory, USA to improve the clinical success of nanomedicines and nanovectors have also been comprehensively summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Treatment of Acute Massive Pulmonary Embolism by Streptokinase during Labour and Delivery

    PubMed Central

    Hall, R. J. C.; Young, C.; Sutton, G. C.; Cambell, S.

    1972-01-01

    A 29-year-old woman sustained an acute massive pulmonary embolism in the 32nd week of pregnancy. Rapid clinical improvement followed the use of streptokinase. Treatment was continued for 41 hours, including labour and the first three hours after delivery. There was slow but severe postpartum haemorrhage. Partial uterine atony occurred, and may have been due, at least in part, to fibrin degradation products arising from thrombolysis. No adverse effects were noted in the baby. Our experience suggests that streptokinase may be given during labour but that an oxytocic agent may be needed; and that reversal of fibrinolysis before delivery is best achieved by the use of aprotinin (Trasylol) rather than aminocaproic acid. Imagesp647-a PMID:4539533

  13. Treatment of acute massive pulmonary embolism by streptokinase during labour and delivery.

    PubMed

    Hall, R J; Young, C; Sutton, G C; Cambell, S

    1972-12-16

    A 29-year-old woman sustained an acute massive pulmonary embolism in the 32nd week of pregnancy. Rapid clinical improvement followed the use of streptokinase. Treatment was continued for 41 hours, including labour and the first three hours after delivery. There was slow but severe postpartum haemorrhage. Partial uterine atony occurred, and may have been due, at least in part, to fibrin degradation products arising from thrombolysis. No adverse effects were noted in the baby.Our experience suggests that streptokinase may be given during labour but that an oxytocic agent may be needed; and that reversal of fibrinolysis before delivery is best achieved by the use of aprotinin (Trasylol) rather than aminocaproic acid.

  14. Vitamin A supplementation in Tanzania: the impact of a change in programmatic delivery strategy on coverage.

    PubMed

    Masanja, Honorati; Schellenberg, Joanna Armstrong; Mshinda, Hassan M; Shekar, Meera; Mugyabuso, Joseph K L; Ndossi, Godwin D; de Savigny, Don

    2006-11-01

    Efficient delivery strategies for health interventions are essential for high and sustainable coverage. We report impact of a change in programmatic delivery strategy from routine delivery through the Expanded Programme on Immunization (EPI+) approach to twice-yearly mass distribution campaigns on coverage of vitamin A supplementation in Tanzania We investigated disparities in age, sex, socio-economic status, nutritional status and maternal education within vitamin A coverage in children between 1 and 2 years of age from two independent household level child health surveys conducted (1) during a continuous universal targeting scheme based on routine EPI contacts for children aged 9, 15 and 21 months (1999); and (2) three years later after the introduction of twice-yearly vitamin A supplementation campaigns for children aged 6 months to 5 years, a 6-monthly universal targeting scheme (2002). A representative cluster sample of approximately 2,400 rural households was obtained from Rufiji, Morogoro Rural, Kilombero and Ulanga districts. A modular questionnaire about the health of all children under the age of five was administered to consenting heads of households and caretakers of children. Information on the use of child health interventions including vitamin A was asked. Coverage of vitamin A supplementation among 1-2 year old children increased from 13% [95% CI 10-18%] in 1999 to 76% [95%CI 72-81%] in 2002. In 2002 knowledge of two or more child health danger signs was negatively associated with vitamin A supplementation coverage (80% versus 70%) (p = 0.04). Nevertheless, we did not find any disparities in coverage of vitamin A by district, gender, socio-economic status and DPT vaccinations. Change in programmatic delivery of vitamin A supplementation was associated with a major improvement in coverage in Tanzania that was been sustained by repeated campaigns for at least three years. There is a need to monitor the effect of such campaigns on the routine health

  15. Social workers and delivery of evidence-based psychosocial treatments for substance use disorders.

    PubMed

    Wells, Elizabeth A; Kristman-Valente, Allison N; Peavy, K Michelle; Jackson, T Ron

    2013-01-01

    Social workers encounter individuals with substance use disorders (SUDs) in a variety of settings. With changes in health care policy and a movement toward integration of health and behavioral health services, social workers will play an increased role vis-á-vis SUD. As direct service providers, administrators, care managers, and policy makers, they will select, deliver, or advocate for delivery of evidence-based SUD treatment practices. This article provides an overview of effective psychosocial SUD treatment approaches. In addition to describing the treatments, the article discusses empirical support, populations for whom the treatments are known to be efficacious, and implementation issues.

  16. SU-E-J-17: Intra-Fractional Prostate Movement Correction During Treatment Delivery Period for Prostate Cancer Using the Intra-Fractional Orthogonal KV-MV Image Pairs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, J; Azawi, S; Cho-Lim, J

    Purpose: To evaluate the intra-fractional prostate movement range during the beam delivery and implement new IGRT method to correct the prostate movement during the hypofractionated prostate treatment delivery. Methods: To evaluate the prostate internal motion range during the beam delivery, 11 conventional treatments were utilized. Two-arc RapidArc plans were used for the treatment delivery. Orthogonal KV imaging is performed in the middle of the treatment to correct intra-fractional prostate movement. However, it takes gantry-mounted on-board imaging system relative long time to finish the orthogonal KV imaging because of gantry rotation. To avoid gantry movement and accelerate the IGRT processing time,more » orthogonal KV-MV image pair is tested using the OBI daily QA Cube phantom. Results: The average prostate movement between two orthogonal KV image pairs was 0.38cm (0.20cm ∼ 0.85cm). And the interval time between them was 6.71 min (4.64min ∼ 9.22 min). 2-arc beam delivery time is within 3 minutes for conventional RapidArc treatment delivery. Hypofractionated treatment or SBRT need 4 partial arc and possible non-coplanar technology, which need much longer beam delivery time. Therefore prostate movement might be larger. New orthogonal KV-MV image pair is a new method to correct the prostate movement in the middle of the beam delivery if real time tracking method is not available. Orthogonal KV-MV image pair doesn’t need gantry rotation. Images were acquired quickly which minimized possible new prostate movement. Therefore orthogonal KV-MV image pair is feasible for IGRT. Conclusion: Hypofractionated prostate treatment with less PTV margin always needs longer beam delivery time. Therefore prostate movement correction during the treatment delivery is critical. Orthogonal KV-MV imaging pair is efficient and accurate to correct the prostate movement during treatment beam delivery. Due to limited fraction number and high dose per fraction, the MV imaging

  17. Localized Hyperthermia for Enhanced Targeted Delivery of Polymer Therapeutics

    NASA Astrophysics Data System (ADS)

    Frazier, Nicholas

    It is estimated that in 2016, more than 848,000 new cases of cancer will be diagnosed in men with more than a quarter being prostate cancer and more than 26,000 deaths attributed to this disease. Prostate cancer poses a limited risk when detected at an early stage and treatment of stages II-III has a 5-year survival rate of almost 100%. However, these early-stage cancers can eventually progress and develop into stage IV, dramatically dropping the 5-year survival rate to 28%. Thus, development of a new therapy is needed to fully eliminate these tumors. Combination of heat and chemotherapy improves therapeutic efficacy while allowing for reduced dosing of drugs and limiting side effects. Localized hyperthermia has been used to enhance the delivery of polymer therapeutics to prostate tumors through increased blood flow, vascular permeability, and incorporation of heat shock targeting. This strategy has been shown to increase the delivery and retention of polymer-drug conjugates leading to enhanced efficacy. Although much work has been done using this strategy, the effects of different thermal dosing on polymer accumulation are unknown. The first aim of this research is to examine how altering heating parameters influences polymer tumor accumulation. The hypothesis for this aim is that there is an optimal thermal treatment that leads to the maximal amount of polymer accumulation in the tumors. Additionally, the previously used heating method of plasmonic photothermal therapy (PPTT) can result in long-term accumulation of gold nanoparticles in healthy organs, potentially limiting clinical applicability. The second aim of this proposal will be focused on investigating the alternative method of high intensity focused ultrasound (HIFU) for selective heating of tumors and enhancing macromolecular delivery. HIFU has shown the capability for precise, noninvasive heating of specific regions within the prostate through magnetic resonance imaging (MRI) guidance. The hypothesis

  18. LHRH-Targeted Drug Delivery Systems for Cancer Therapy.

    PubMed

    Li, Xiaoning; Taratula, Oleh; Taratula, Olena; Schumann, Canan; Minko, Tamara

    2017-01-01

    Targeted delivery of therapeutic and diagnostic agents to cancer sites has significant potential to improve the therapeutic outcome of treatment while minimizing severe side effects. It is widely accepted that decoration of the drug delivery systems with targeting ligands that bind specifically to the receptors on the cancer cells is a promising strategy that may substantially enhance accumulation of anticancer agents in the tumors. Due to the transformed cellular nature, cancer cells exhibit a variety of overexpressed cell surface receptors for peptides, hormones, and essential nutrients, providing a significant number of target candidates for selective drug delivery. Among others, luteinizing hormonereleasing hormone (LHRH) receptors are overexpressed in the majority of cancers, while their expression in healthy tissues, apart from pituitary cells, is limited. The recent studies indicate that LHRH peptides can be employed to efficiently guide anticancer and imaging agents directly to cancerous cells, thereby increasing the amount of these substances in tumor tissue and preventing normal cells from unnecessary exposure. This manuscript provides an overview of the targeted drug delivery platforms that take advantage of the LHRH receptors overexpression by cancer cells.

  19. First line fertility treatment strategies regarding IUI and IVF require clinical evidence.

    PubMed

    Bahadur, G; Homburg, R; Muneer, A; Racich, P; Alangaden, T; Al-Habib, A; Okolo, S

    2016-06-01

    The advent of intracytoplasmic sperm injection (ICSI) has contributed to a significant growth in the delivery of assisted conception technique, such that IVF/ICSI procedures are now recommended over other interventions. Even the UK National Institute for Health Care Excellence (NICE) guidelines controversially recommends against intrauterine insemination (IUI) procedures in favour of IVF. We reflect on some of the clinical, economic, financial and ethical realities that have been used to selectively promote IVF over IUI, which is less intrusive and more patient friendly, obviates the need for embryo storage and has a global application. The evidence strongly favours IUI over IVF in selected couples and national funding strategies should include IUI treatment options. IUI, practised optimally as a first line treatment in up to six cycles, would also ease the pressures on public funds to allow the provision of up to three IVF cycles for couple who need it. Fertility clinics should also strive towards ISO15189 accreditation standards for basic semen diagnosis for male infertility used to triage ICSI treatment, to reduce the over-diagnosis of severe male factor infertility. Importantly, there is a need to develop global guidelines on inclusion policies for IVF/ICSI procedures. These suggestions are an ethically sound basis for constructing the provision of publicly funded fertility treatments. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Design strategies and applications of circulating cell-mediated drug delivery systems.

    PubMed

    Su, Yixue; Xie, Zhiwei; Kim, Gloria B; Dong, Cheng; Yang, Jian

    2015-01-01

    Drug delivery systems, particularly nanomaterial-based drug delivery systems, possess a tremendous amount of potential to improve diagnostic and therapeutic effects of drugs. Controlled drug delivery targeted to a specific disease is designed to significantly improve the pharmaceutical effects of drugs and reduce their side effects. Unfortunately, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even with the development of numerous surface markers and targeting modalities. Thus, alternative drug and nanomedicine targeting approaches are desired. Circulating cells, such as erythrocytes, leukocytes, and stem cells, present innate disease sensing and homing properties. Hence, using living cells as drug delivery carriers has gained increasing interest in recent years. This review highlights the recent advances in the design of cell-mediated drug delivery systems and targeting mechanisms. The approaches of drug encapsulation/conjugation to cell-carriers, cell-mediated targeting mechanisms, and the methods of controlled drug release are elaborated here. Cell-based "live" targeting and delivery could be used to facilitate a more specific, robust, and smart payload distribution for the next-generation drug delivery systems.

  1. Innovative vaccine delivery strategies in response to a cholera outbreak in the challenging context of Lake Chilwa. A rapid qualitative assessment.

    PubMed

    Heyerdahl, Leonard W; Ngwira, Bagrey; Demolis, Rachel; Nyirenda, Gabriel; Mwesawina, Maurice; Rafael, Florentina; Cavailler, Philippe; Bernard Le Gargasson, Jean; Mengel, Martin A; Gessner, Bradford D; Guillermet, Elise

    2017-11-07

    A reactive campaign using two doses of Shanchol Oral Cholera Vaccine (OCV) was implemented in 2016 in the Lake Chilwa Region (Malawi) targeting fish dependent communities. Three strategies for the second vaccine dose delivery (including delivery by a community leader and self-administration) were used to facilitate vaccine access. This assessment collected vaccine perceptions and opinions about the OCV campaign of 313 study participants, including: fishermen, fish traders, farmers, community leaders, and one health and one NGO officer. Socio-demographic surveys were conducted, In Depth Interviews and Focus Group Discussions were conducted before and during the campaign. Some fishermen perceived the traditional delivery strategy as reliable but less practical. Delivery by traditional leaders was acceptable for some participants while others worried about traditional leaders not being trained to deliver vaccines or beneficiaries taking doses on their own. A slight majority of beneficiaries considered the self-administration strategy practical while some beneficiaries worried about storing vials outside of the cold chain or losing vials. During the campaign, a majority of participants preferred receiving oral vaccines instead of injections given ease of intake and lack of pain. OCV was perceived as efficacious and safe. However, a lack of information on how sero-protection may be delayed and the degree of sero-protection led to loss of trust in vaccine potency among some participants who witnessed cholera cases among vaccinated individuals. OCV campaign implementation requires accompanying communication on protective levels, less than 100% vaccine efficacy, delays in onset of sero-protection, and out of cold chain storage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. A dual strategy to improve the penetration and treatment of breast cancer by combining shrinking nanoparticles with collagen depletion by losartan.

    PubMed

    Cun, Xingli; Ruan, Shaobo; Chen, Jiantao; Zhang, Li; Li, Jianping; He, Qin; Gao, Huile

    2016-02-01

    Although development of nanomedicines has been a promising direction in tumor treatment, the therapeutic outcome of current nanomedicines is unsatisfying, partly because of the poor retention and penetration in tumors. Recently, a kind of tumor microenvironment sensitive size shrinkable nanoparticles (DOX-AuNPs-GNPs) has been developed by our lab, which could enhance the tumor penetration and retention depending on the size shrinking. However, the further enhancement is still restricted by dense collagen network in tumors. Thus in this study, we combined DOX-AuNPs-GNPs with losartan to deplete tumor collagen (constituted up to 90% of extracellular matrix) to further improve tumor penetration. In vitro, DOX-AuNPs-GNPs can shrink from over 117.8nm to less than 50.0nm and release DOX-AuNPs under the triggering of tumor overexpressed matrix metalloproteinases-2 (MMP-2). In vivo, pretreatment with losartan significantly decrease the collagen level and improve the tumor penetration. In combination, losartan combined with DOX-AuNPs-GNPs showed the best drug delivery efficiency, striking penetration efficiency and best 4T1 breast tumor inhibition effect. In conclusion, this study provided a promising synergetic strategy to improve the tumor treatment efficiency of nanomedicines. We have developed a dual strategy for deep tumor penetration through combining size shrinkable DOX-AuNPs-GNPs with depleting tumor collagen by losartan. Additionally, we demonstrate therapeutic efficacy in breast tumor bearing mouse model. DOX-AuNPs-GNPs co-administration with losartan is a novel and highly attractive strategy for anti-tumor drug delivery with the potential for broad applications in clinic. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.

    PubMed

    Bhaskar, Sonu; Tian, Furong; Stoeger, Tobias; Kreyling, Wolfgang; de la Fuente, Jesús M; Grazú, Valeria; Borm, Paul; Estrada, Giovani; Ntziachristos, Vasilis; Razansky, Daniel

    2010-03-03

    Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as

  4. Treatment delivery software for a new clinical grade ultrasound system for thermoradiotherapy.

    PubMed

    Novák, Petr; Moros, Eduardo G; Straube, William L; Myerson, Robert J

    2005-11-01

    A detailed description of a clinical grade Scanning Ultrasound Reflector Linear Array System (SURLAS) applicator was given in a previous paper [Med. Phys. 32, 230-240 (2005)]. In this paper we concentrate on the design, development, and testing of the personal computer (PC) based treatment delivery software that runs the therapy system. The SURLAS requires the coordinated interaction between the therapy applicator and several peripheral devices for its proper and safe operation. One of the most important tasks was the coordination of the input power sequences for the elements of two parallel opposed ultrasound arrays (eight 1.5 cm x 2 cm elements/array, array 1 and 2 operate at 1.9 and 4.9 MHz, respectively) in coordination with the position of a dual-face scanning acoustic reflector. To achieve this, the treatment delivery software can divide the applicator's treatment window in up to 64 sectors (minimum size of 2 cm x 2 cm), and control the power to each sector independently by adjusting the power output levels from the channels of a 16-channel radio-frequency generator. The software coordinates the generator outputs with the position of the reflector as it scans back and forth between the arrays. Individual sector control and dual frequency operation allows the SURLAS to adjust power deposition in three dimensions to superficial targets coupled to its treatment window. The treatment delivery software also monitors and logs several parameters such as temperatures acquired using a 16-channel thermocouple thermometry unit. Safety (in particular to patients) was the paramount concern and design criterion. Failure mode and effects analysis (FMEA) was applied to the applicator as well as to the entire therapy system in order to identify safety issues and rank their relative importance. This analysis led to the implementation of several safety mechanisms and a software structure where each device communicates with the controlling PC independently of the others. In case

  5. Treatment Strategy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

    PubMed

    Nakamura, Shotaro; Matsumoto, Takayuki

    2015-09-01

    Recent trends and current knowledge on the diagnosis and treatment strategy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are reviewed. Helicobacter pylori infection plays the causative role in the pathogenesis, and H pylori eradication is the first-line treatment of this disease, which leads to complete remission in 60% to 90% of cases. A Japanese multicenter study confirmed that the long-term outcome of gastric MALT lymphoma after H pylori eradication is excellent. Treatment strategies for patients not responding to H pylori eradication including "watch and wait" strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and combination of these should be tailored in consideration of the disease extent in each patient. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. pH-sensitive nano-systems for drug delivery in cancer therapy.

    PubMed

    Liu, Juan; Huang, Yuran; Kumar, Anil; Tan, Aaron; Jin, Shubin; Mozhi, Anbu; Liang, Xing-Jie

    2014-01-01

    Nanotechnology has been widely used in the development of new strategies for drug delivery and cancer therapy. Compared to traditional drug delivery systems, nano-based drug delivery system have greater potential in a variety of areas, such as multiple targeting functionalization, in vivo imaging, combined drug delivery, extended circulation time, and systemic control release. Nano-systems incorporating stimulus-responsive materials have remarkable properties which allow them to bypass biological barriers and achieve targeted intracellular drug delivery. As a result of the active metabolism of tumor cells, the tumor microenvironment (TME) is highly acidic compared to normal tissues. pH-Sensitive nano-systems have now been developed in which drug release is specifically triggered by the acidic tumor environment. Studies have demonstrated that novel pH-sensitive drug delivery systems are capable of improving the efficiency of cancer treatment. A number of these have been translated from bench to clinical application and have been approved by the Food and Drug Administration (FDA) for treatment of various cancerous diseases. Herein, this review mainly focuses on pH-sensitive nano-systems, including advances in drug delivery, mechanisms of drug release, and possible improvements in drug absorption, with the emphasis on recent research in this field. With deeper understanding of the difference between normal and tumor tissues, it might be possible to design ever more promising pH-responsive nano-systems for drug delivery and cancer therapy in the near future. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  7. Hyperthermia in bone generated with MR imaging-controlled focused ultrasound: control strategies and drug delivery.

    PubMed

    Staruch, Robert; Chopra, Rajiv; Hynynen, Kullervo

    2012-04-01

    To evaluate the feasibility of achieving image-guided drug delivery in bone by using magnetic resonance (MR) imaging-controlled focused ultrasound hyperthermia and temperature-sensitive liposomes. Experiments were approved by the institutional animal care committee. Hyperthermia (43°C, 20 minutes) was generated in 10-mm-diameter regions at a muscle-bone interface in nine rabbit thighs by using focused ultrasound under closed-loop temperature control with MR thermometry. Thermosensitive liposomal doxorubicin was administered systemically during heating. Heating uniformity and drug delivery were evaluated for control strategies with the temperature control image centered 10 mm (four rabbits) or 0 mm (five rabbits) from the bone. Simulations estimated temperature elevations in bone. Drug delivery was quantified by using the fluorescence of doxorubicin extracted from bone marrow and muscle and was compared between treated and untreated thighs by using the one-sided Wilcoxon signed rank test. With ultrasound focus and MR temperature control plane 0 mm and 10 mm from the bone interface, average target region temperatures were 43.1°C and 43.3°C, respectively; numerically estimated bone temperatures were 46.8°C and 78.1°C. The 10-mm offset resulted in thermal ablation; numerically estimated muscle temperature was 66.1°C at the bone interface. Significant increases in doxorubicin concentration occurred in heated versus unheated marrow (8.2-fold, P = .002) and muscle (16.8-fold, P = .002). Enhancement occurred for 0- and 10-mm offsets, which suggests localized drug delivery in bone is possible with both hyperthermia and thermal ablation. MR imaging-controlled focused ultrasound can achieve localized hyperthermia in bone for image-guided drug delivery in bone with temperature-sensitive drug carriers. © RSNA, 2012.

  8. Physico-chemical strategies to enhance stability and drug retention of polymeric micelles for tumor-targeted drug delivery

    PubMed Central

    Shi, Yang; Lammers, Twan; Storm, Gert; Hennink, Wim E.

    2017-01-01

    Polymeric micelles (PM) have been extensively used for tumor-targeted delivery of hydrophobic anti-cancer drugs. The lipophilic core of PM is naturally suitable for loading hydrophobic drugs and the hydrophilic shell endows them with colloidal stability and stealth properties. Decades of research on PM have resulted in tremendous numbers of PM-forming amphiphilic polymers, and approximately a dozen micellar nanomedicines have entered the clinic. The first generation of PM can be considered solubilizers of hydrophobic drugs, with short circulation times resulting from poor micelle stability and unstable drug entrapment. To more optimally exploit the potential of PM for targeted drug delivery, several physical (e.g. π-π stacking, stereocomplexation, hydrogen bonding, host-guest complexation and coordination interaction) and chemical (e.g. free radical polymerization, click chemistry, disulfide and hydrazone bonding) strategies have been developed to improve micelle stability and drug retention. In this review, we describe the most promising physico-chemical approaches to enhance micelle stability and drug retention, and we summarize how these strategies have resulted in systems with promising therapeutic efficacy in animal models, paving the way for clinical translation. PMID:27413999

  9. Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson's disease treatment.

    PubMed

    Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

    Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.

  10. Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma.

    PubMed

    Hall, Justin; Prabhakar, Shilpa; Balaj, Leonora; Lai, Charles P; Cerione, Richard A; Breakefield, Xandra O

    2016-04-01

    Extracellular vesicles present an attractive delivery vehicle for therapeutic proteins. They intrinsically contain many proteins which can provide information to other cells. Advantages include reduced immune reactivity, especially if derived from the same host, stability in biologic fluids, and ability to target uptake. Those from mesenchymal stem cells appear to be intrinsically therapeutic, while those from cancer cells promote tumor progression. Therapeutic proteins can be loaded into vesicles by overexpression in the donor cell, with oligomerization and membrane sequences increasing their loading. Examples of protein delivery for therapeutic benefit in pre-clinical models include delivery of: catalase for Parkinson's disease to reduce oxidative stress and thus help neurons to survive; prodrug activating enzymes which can convert a prodrug which crosses the blood-brain barrier into a toxic chemotherapeutic drug for schwannomas and gliomas; and the apoptosis-inducing enzyme, caspase-1 under a Schwann cell specific promoter for schwannoma. This therapeutic delivery strategy is novel and being explored for a number of diseases.

  11. Recent pharmacological advances in the treatment of preterm membrane rupture, labour and delivery.

    PubMed

    Doggrell, Sheila A

    2004-09-01

    Preterm delivery (before 37 completed weeks of gestation) is the major determinant of infant mortality. In women with a previous preterm birth associated with bacterial vaginosis, prophylactic antibiotics (e.g., metronidazole) reduce the risk of preterm birth and low birth weight. Trichomonas vaginalis increases the risk of preterm delivery, but metronidazole is not beneficial for this and may even be detrimental. Antibiotic use (e.g., erythromycin) prolongs pregnancy in late premature rupture and has health benefits for the neonate. However, antibiotics are probably not useful in preterm labour. Intramuscular 17alpha-progesterone and vaginal progesterone reduce the rate of preterm labour in high-risk pregnancies, including previous spontaneous preterm delivery. Magnesium sulfate, beta2-adrenoceptor agonists and the oxytocin-receptor antagonist, atosiban, are effective in reducing uterine contractions short-term, but there is little evidence that this leads to improved outcomes for the neonate. However, tocolysis with calcium-channel blockers does seem to lead to better outcomes for the neonate. Fetal side effects, such as ductus arteriosus constriction and impaired renal function, are associated with the inhibition of prostaglandin synthesis with indomethacin. New approaches and more effective drugs are required in the treatment of preterm delivery.

  12. Needle-free nasal delivery of glucagon for treatment of diabetes-related severe hypoglycemia: toxicology of polypropylene resin used in delivery device.

    PubMed

    Reno, Frederick E; Edwards, C Nicholas; Bendix Jensen, Morten; Török-Bathó, Magdolna; Esdaile, David J; Piché, Claude; Triest, Myriam; Carballo, Dolorès

    2016-09-01

    The intranasal route is a promising route of administration for several emergency rescue drugs including naloxone and glucagon. Glucagon nasal powder (GNP) is a novel, needle-free delivery system for intranasal administration of glucagon for the treatment of severe hypoglycemia, an infrequent but serious complication of insulin use in patients with diabetes. The GNP delivery device is a compact, highly portable, single-use nasal powder dosing device constructed of polypropylene that allows for simple, single-step administration. To evaluate the toxicological profile of the polypropylene resin used in the actuator part of the delivery device that will contact skin and nasal mucosal membranes of the patient, we performed an in vitro cytotoxicity study, a skin sensitization study and an irritation (intracutaneous reactivity) study in animal models. Extracts of the actuator of the GNP device were generated from HAM F12 medium with 10% fetal bovine serum, 0.9% sodium chloride (NaCl) or sesame oil. The in vitro cytotoxicity test was performed in cultured L929 mouse fibroblasts. Skin sensitization analysis was performed in 10 guinea pigs according to the Magnusson-Kligman method, using a maximization method with Freund's Complete Adjuvant. Irritation following intracutaneous/intradermal treatment with device extracts (NaCl and sesame oil extractants) was assessed in three New Zealand White rabbits. In vitro cytotoxicity test: Both undiluted and diluted extract showed no toxicity (i.e. no abnormal morphology, cell death or cell lysis) toward L929 fibroblasts (cytotoxicity grade 0). Sensitization test in guinea pigs: Challenge with device extracts did not evoke positive responses in test animals previously induced with device extracts. The net response value represented an incidence rate of 0% and a net dermal irritation score value of 0.00. Irritation (intracutaneous/intradermal) test in New Zealand White rabbits: Device extracts and corresponding vehicle controls caused

  13. Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain

    PubMed Central

    Goins, WF; Goss, JR; Chancellor, MB; de Groat, WC; Glorioso, JC; Yoshimura, N

    2009-01-01

    Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder. PMID:19242523

  14. Polydopamine-Functionalized CA-(PCL-ran-PLA) Nanoparticles for Target Delivery of Docetaxel and Chemo-photothermal Therapy of Breast Cancer

    PubMed Central

    Kong, Na; Deng, Mei; Sun, Xiu-Na; Chen, Yi-Ding; Sui, Xin-Bing

    2018-01-01

    Current limitations of cancer therapy include the lack of effective strategy for target delivery of chemotherapeutic drugs, and the difficulty of achieving significant efficacy by single treatment. Herein, we reported a synergistic chemo-photothermal strategy based on aptamer (Apt)-polydopamine (pD) functionalized CA-(PCL-ran-PLA) nanoparticles (NPs) for effective delivery of docetaxel (DTX) and enhanced therapeutic effect. The developed DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs achieved promising advantages, such as (i) improved drug loading content (LC) and encapsulation efficiency (EE) initiated by star-shaped copolymer CA-(PCL-ran-PLA); (ii) effective target delivery of drugs to tumor sites by incorporating AS1411 aptamers; (iii) significant therapeutic efficacy caused by synergistic chemo-photothermal treatment. In addition, the pD coating strategy with simple procedures could address the contradiction between targeting modification and maintaining formerly excellent bio-properties. Therefore, with excellent bio-properties and simple preparation procedures, the DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs effectively increased the local drug concentration in tumor sites, minimized side effects, and significantly eliminated tumors, indicating the promising application of these NPs for cancer therapy. PMID:29527167

  15. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review.

    PubMed

    Kanamala, Manju; Wilson, William R; Yang, Mimi; Palmer, Brian D; Wu, Zimei

    2016-04-01

    As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

    PubMed

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

  17. Lipid and polymeric carrier-mediated nucleic acid delivery

    PubMed Central

    Zhu, Lin; Mahato, Ram I

    2010-01-01

    Importance of the field Nucleic acids such as plasmid DNA, antisense oligonucleotide, and RNA interference (RNAi) molecules, have a great potential to be used as therapeutics for the treatment of various genetic and acquired diseases. To design a successful nucleic acid delivery system, the pharmacological effect of nucleic acids, the physiological condition of the subjects or sites, and the physicochemical properties of nucleic acid and carriers have to be thoroughly examined. Areas covered in this review The commonly used lipids, polymers and corresponding delivery systems are reviewed in terms of their characteristics, applications, advantages and limitations. What the reader will gain This article aims to provide an overview of biological barriers and strategies to overcome these barriers by properly designing effective synthetic carriers for nucleic acid delivery. Take home message A thorough understanding of biological barriers and the structure–activity relationship of lipid and polymeric carriers is the key for effective nucleic acid therapy. PMID:20836625

  18. Modelling outcomes of complex treatment strategies following a clinical guideline for treatment decisions in patients with rheumatoid arthritis.

    PubMed

    Tran-Duy, An; Boonen, Annelies; Kievit, Wietske; van Riel, Piet L C M; van de Laar, Mart A F J; Severens, Johan L

    2014-10-01

    Management of rheumatoid arthritis (RA) is characterised by a sequence of disease-modifying antirheumatic drugs (DMARDs) and biological response modifiers (BRMs). In most of the Western countries, the drug sequences are determined based on disease activity and treatment history of the patients. A model for realistic patient outcomes should reflect the treatment pathways relevant for patients with specific characteristics. This study aimed at developing a model that could simulate long-term patient outcomes and cost effectiveness of treatment strategies with and without inclusion of BRMs following a clinical guideline for treatment decisions. Discrete event simulation taking into account patient characteristics and treatment history was used for model development. Treatment effect on disease activity, costs, health utilities and times to events were estimated using Dutch observational studies. Long-term progression of physical functioning was quantified using a linear mixed-effects model. Costs and health utilities were estimated using two-part models. The treatment strategy recommended by the Dutch Society for Rheumatology where both DMARDs and BRMs were available (Strategy 2) was compared with the treatment strategy without BRMs (Strategy 1). Ten thousand theoretical patients were tracked individually until death. In the probabilistic sensitivity analysis, Monte Carlo simulations were performed with 1,000 sets of parameters sampled from appropriate probability distributions. The simulated changes over time in disease activity and physical functioning were plausible. The incremental cost per quality-adjusted life-year gained of Strategy 2 compared with Strategy 1 was 124,011. At a willingness-to-pay threshold higher than 119,167, Strategy 2 dominated Strategy 1 in terms of cost effectiveness but the probability that the Strategy 2 is cost effective never exceeded 0.87. It is possible to model the outcomes of complex treatment strategies based on a

  19. Stepped Care: A Promising Treatment Strategy for Mandated Students

    ERIC Educational Resources Information Center

    Borsari, Brian; Tevyaw, Tracy O'Leary

    2005-01-01

    Over the past decade, there has been a steady increase in the number of mandated students who have been referred to campus alcohol programs for violating campus alcohol policies. However, the severity of alcohol use and problems varies widely in mandated students, indicating that a "one size fits all" delivery of treatment may be inappropriate.…

  20. Factors that influence treatment strategies in advanced colorectal cancer.

    PubMed

    Nesbitt, C; Glendinning, R J; Byrne, C; Poston, G J

    2007-12-01

    This review focuses on the factors that now influence our treatment strategies designed to increase the pool of patients with colorectal liver metastases for whom curative treatment may be possible. These strategies include improved preoperative staging techniques, new standards for surgical resection, novel surgical strategies, the application of modern systemic chemotherapy in a neoadjuvant setting, an emerging role for ablative therapies and an emphasis on the collaborative, a reappraisal of staging advanced disease, multidisciplinary management, and defining the role of the patient in managing their disease. It is now clear that an aggressive multi-disciplinary approach to the management of this problem will lead to nearly one third of these patients being considered for treatment that even if not achieving complete cure, offers significant long-term survival.

  1. Strategies for transporting nanoparticles across the blood-brain barrier.

    PubMed

    Zhang, Tian-Tian; Li, Wen; Meng, Guanmin; Wang, Pei; Liao, Wenzhen

    2016-02-01

    The existence of blood-brain barrier (BBB) hampers the effective treatment of central nervous system (CNS) diseases. Almost all macromolecular drugs and more than 98% of small molecule drugs cannot pass the BBB. Therefore, the BBB remains a big challenge for delivery of therapeutics to the central nervous system. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now possible to design delivery systems that could cross the BBB effectively. Because of their advantageous properties, nanoparticles have been widely deployed for brain-targeted delivery. This review paper presents the current understanding of the BBB under physiological and pathological conditions, and summarizes strategies and systems for BBB crossing with a focus on nanoparticle-based drug delivery systems. In summary, with wider applications and broader prospection the treatment of brain targeted therapy, nano-medicines have proved to be more potent, more specific and less toxic than traditional drug therapy.

  2. Strategies for treatment of dystonia.

    PubMed

    Dressler, Dirk; Altenmueller, Eckart; Bhidayasiri, Roongroj; Bohlega, Saeed; Chana, Pedro; Chung, Tae Mo; Frucht, Steven; Garcia-Ruiz, Pedro J; Kaelin, Alain; Kaji, Ryuji; Kanovsky, Petr; Laskawi, Rainer; Micheli, Federico; Orlova, Olga; Relja, Maja; Rosales, Raymond; Slawek, Jaroslaw; Timerbaeva, Sofia; Warner, Thomas T; Saberi, Fereshte Adib

    2016-03-01

    Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

  3. MO-C-BRF-01: Pediatric Treatment Planning I: Overview of Planning Strategies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Olch, A; Hua, C

    Most Medical Physicists working in radiotherapy departments see few pediatric patients. This is because, fortunately, children get cancer at a rate nearly 100 times lower than adults. Children have not smoked, abused alcohol, or been exposed to environmental carcinogens for decades, and of course, have not fallen victim to the aging process. Children get very different cancers than adults. Breast or prostate cancers, typical in adults, are rarely seen in children but instead a variety of tumors occur in children that are rarely seen in adults; examples are germinomas, ependymomas and primitive neuroectodermal tumors, which require treatment of the child'smore » brain or neuroblastoma, requiring treatment in the abdomen. The treatment of children with cancer using radiation therapy is one of the most challenging planning and delivery problems facing the physicist. This is because bones, brain, breast tissue, and other organs are more sensitive to radiation in children than in adults. Because most therapy departments treat mostly adults, when the rare 8 year-old patient comes to the department for treatment, the physicist may not understand the clinical issues of his disease which drive the planning and delivery decisions. Additionally, children are more prone than adults to developing secondary cancers after radiation. This fact has important implications for the choice of delivery techniques, especially when considering IMRT. For bilateral retinoblastoma for example, an irradiated child has a 50% chance of developing a second cancer by age 50. In the first presentation, an overview of childhood cancers and their corresponding treatment techniques will be given. These can be some of the most complex treatments that are delivered in the radiation therapy department. These cancers include leukemia treated with total body irradiation, medulloblastoma, treated with craniospinal irradiation plus a conformal boost to the posterior fossa, neuroblastoma, requiring focal

  4. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein.

    PubMed

    Kessler, P D; Podsakoff, G M; Chen, X; McQuiston, S A; Colosi, P C; Matelis, L A; Kurtzman, G J; Byrne, B J

    1996-11-26

    Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence that current methods of gene delivery can practically achieve this goal. In this study, we demonstrate that, following a single intramuscular administration of a recombinant adeno-associated virus (rAAV) vector containing the beta-galactosidase (AAV-lacZ) gene into adult BALB/c mice, protein expression was detected in myofibers for at least 32 weeks. A single intramuscular administration of an AAV vector containing a gene for human erythropoietin (AAV-Epo) into mice resulted in dose-dependent secretion of erythropoietin and corresponding increases in red blood cell production that persisted for up to 40 weeks. Primary human myotubes transduced in vitro with the AAV-Epo vector also showed dose-dependent production of Epo. These results demonstrate that rAAV vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single intramuscular administration. Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherited and acquired protein deficiencies.

  5. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein

    PubMed Central

    Kessler, Paul D.; Podsakoff, Gregory M.; Chen, Xiaojuan; McQuiston, Susan A.; Colosi, Peter C.; Matelis, Laura A.; Kurtzman, Gary J.; Byrne, Barry J.

    1996-01-01

    Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence that current methods of gene delivery can practically achieve this goal. In this study, we demonstrate that, following a single intramuscular administration of a recombinant adeno-associated virus (rAAV) vector containing the β-galactosidase (AAV-lacZ) gene into adult BALB/c mice, protein expression was detected in myofibers for at least 32 weeks. A single intramuscular administration of an AAV vector containing a gene for human erythropoietin (AAV-Epo) into mice resulted in dose-dependent secretion of erythropoietin and corresponding increases in red blood cell production that persisted for up to 40 weeks. Primary human myotubes transduced in vitro with the AAV-Epo vector also showed dose-dependent production of Epo. These results demonstrate that rAAV vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single intramuscular administration. Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherited and acquired protein deficiencies. PMID:8943064

  6. Strategies for improving transportation project delivery performance.

    DOT National Transportation Integrated Search

    2016-09-01

    project delivery performance for the various contracting methods that are : applicable for CTDOTs use. The report is structured in two parts. Part A covers overall : project deliverability and Part B is focused on environmental review processes an...

  7. Biomimetic nanoparticles for siRNA delivery in the treatment of leukaemia.

    PubMed

    Guo, Jianfeng; Cahill, Mary R; McKenna, Sharon L; O'Driscoll, Caitriona M

    2014-12-01

    Leukaemia is a bone marrow cancer occurring in acute and chronic subtypes. Acute leukaemia is a rapidly fatal cancer potentially causing death within a few weeks, if untreated. Leukaemia arises as a result of disruption to haematopoietic precursors, caused either by acquired gene fusions, gene mutations or inappropriate expression of the relevant oncogenes. Current treatment options have made significant progress, but the 5 year survival for acute leukaemia remains under 10% in elderly patients, and less than 50% for some types of acute leukaemia in younger adults. For chronic leukaemias longer survival is generally expected and for chronic myeloid leukaemia patients on tyrosine kinase inhibitors the median survival is not yet reached and is expected to exceed 10 years. Chemotherapy and haematopoietic stem cell transplantation (HSCT) for acute leukaemia provide the mainstay of therapy for patients under 65 and both carry significant morbidity and mortality. Alternative and superior therapeutic strategies for acute leukaemias are urgently required. Recent molecular-based knowledge of recurring chromosome rearrangements, in particular translocations and inversions, has resulted in significant advances in understanding the molecular pathogenesis of leukaemia. Identification of a number of unique fusion genes has facilitated the development of highly specific small interfering RNAs (siRNA). Although delivery of siRNA using multifunctional nanoparticles has been investigated to treat solid cancers, the application of this approach to blood cancers is at an early stage. This review describes current treatments for leukaemia and highlights the potential of leukaemic fusion genes as therapeutic targets for RNA interference (RNAi). In addition, the design of biomimetic nanoparticles which are capable of responding to the physiological environment of leukaemia and their potential to advance RNAi therapeutics to the clinic will be critically evaluated. Copyright © 2014

  8. An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus).

    PubMed

    Munang'andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

    2016-12-13

    Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia ( Niloticus oreochromis ) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy.

  9. An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus)

    PubMed Central

    Munang’andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

    2016-01-01

    Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy. PMID:27983591

  10. Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis.

    PubMed

    Ford, Caleb A; Cassat, James E

    2017-09-01

    Osteomyelitis, a common and debilitating invasive infection of bone, is a frequent complication following orthopedic surgery and causes pathologic destruction of skeletal tissues. Bone destruction during osteomyelitis results in necrotic tissue, which is poorly penetrated by antibiotics and can serve as a nidus for relapsing infection. Osteomyelitis therefore frequently necessitates surgical debridement procedures, which provide a unique opportunity for targeted delivery of antimicrobial and adjunctive therapies. Areas covered: Following surgical debridement, tissue voids require implanted materials to facilitate the healing process. Antibiotic-loaded, non-biodegradable implants have been the standard of care. However, a new generation of biodegradable, osteoconductive materials are being developed. Additionally, in the face of widespread antimicrobial resistance, alternative therapies to traditional antibiotic regimens are being investigated, including bone targeting compounds, antimicrobial surface modifications of orthopedic implants, and anti-virulence strategies. Expert commentary: Recent advances in biodegradable drug delivery scaffolds make this technology an attractive alternative to traditional techniques for orthopedic infection that require secondary operations for removal. Advances in novel treatment methods are expanding the arsenal of viable antimicrobial treatment strategies in the face of widespread drug resistance. Despite a need for large scale clinical investigations, these strategies offer hope for future treatment of this difficult invasive disease.

  11. Advances in the Local and Targeted Delivery of Anti-infective Agents for Management of Osteomyelitis

    PubMed Central

    Ford, Caleb A.; Cassat, James E.

    2018-01-01

    Structured Abstract Introduction Osteomyelitis, a common and debilitating invasive infection of bone, is a frequent complication following orthopedic surgery and causes pathologic destruction of skeletal tissues. Bone destruction during osteomyelitis results in necrotic tissue, which is poorly penetrated by antibiotics and can serve as a nidus for relapsing infection. Osteomyelitis therefore frequently necessitates surgical debridement procedures, which provide a unique opportunity for targeted delivery of antimicrobial and adjunctive therapies. Areas Covered Following surgical debridement, tissue voids require implanted materials to facilitate the healing process. Antibiotic-loaded, non-biodegradable implants have been the standard of care. However, a new generation of biodegradable, osteoconductive materials are being developed. Additionally, in the face of widespread antimicrobial resistance, alternative therapies to traditional antibiotic regimens are being investigated, including bone targeting compounds, antimicrobial surface modifications of orthopedic implants, and anti-virulence strategies. Expert Commentary Recent advances in biodegradable drug delivery scaffolds make this technology an attractive alternative to traditional techniques for orthopedic infection that require secondary operations for removal. Advances in novel treatment methods are expanding the arsenal of viable antimicrobial treatment strategies in the face of widespread drug resistance. Despite a need for large scale clinical investigations, these strategies offer hope for future treatment of this difficult invasive disease. PMID:28837368

  12. Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis.

    PubMed

    Konijeti, Gauree G; Sauk, Jenny; Shrime, Mark G; Gupta, Meera; Ananthakrishnan, Ashwin N

    2014-06-01

    Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.

  13. Oral delivery of insulin for treatment of diabetes: status quo, challenges and opportunities.

    PubMed

    Wong, Chun Y; Martinez, Jorge; Dass, Crispin R

    2016-09-01

    Diabetes mellitus is characterised by progressive β-cell destruction and loss of function, or loss of ability of tissues to respond to insulin. Daily subcutaneous insulin injection is standard management for people with diabetes, although patient compliance is hard to achieve due to the inconvenience of injections, so other forms of delivery are being tested, including oral administration. This review summarises the developments in oral insulin administration. The PubMed database was consulted to compile this review comparing conventional subcutaneous injection of insulin to the desired oral delivery. Oral administration of insulin has potential benefits in reducing pain and chances of skin infection, improving the portal levels of insulin and avoiding side effects such as hyperinsulinemia, weight gain and hypoglycaemia. Although oral delivery of insulin is an ideal administration route for patients with diabetes, several physiological barriers have to be overcome. An expected low oral bioavailability can be attributed to its high molecular weight, susceptibility to enzymatic proteolysis and low diffusion rate across the mucin barrier. Strategies for increasing the bioavailability of oral insulin include the use of enzyme inhibitors, absorption enhancers, mucoadhesive polymers and chemical modification for endogenous receptor-mediated absorption. These may help significantly increase patient compliance and disease management. © 2016 Royal Pharmaceutical Society.

  14. Nanoparticles for the delivery of therapeutic antibodies: Dogma or promising strategy?

    PubMed

    Sousa, Flávia; Castro, Pedro; Fonte, Pedro; Kennedy, Patrick J; Neves-Petersen, Maria Teresa; Sarmento, Bruno

    2017-10-01

    Over the past two decades, therapeutic antibodies have demonstrated promising results in the treatment of a wide array of diseases. However, the application of antibody-based therapy implies multiple administrations and a high cost of antibody production, resulting in costly therapy. Another disadvantage inherent to antibody-based therapy is the limited stability of antibodies and the low level of tissue penetration. The use of nanoparticles as delivery systems for antibodies allows for a reduction in antibody dosing and may represent a suitable alternative to increase antibody stability Areas covered: We discuss different nanocarriers intended for the delivery of antibodies as well as the corresponding encapsulation methods. Recent developments in antibody nanoencapsulation, particularly the possible toxicity issues that may arise from entrapment of antibodies into nanocarriers, are also assessed. In addition, this review will discuss the alterations in antibody structure and bioactivity that occur with nanoencapsulation. Expert opinion: Nanocarriers can protect antibodies from degradation, ensuring superior bioavailability. Encapsulation of therapeutic antibodies may offer some advantages, including potential targeting, reduced immunogenicity and controlled release. Furthermore, antibody nanoencapsulation may aid in the incorporation of the antibodies into the cells, if intracellular components (e.g. intracellular enzymes, oncogenic proteins, transcription factors) are to be targeted.

  15. Oxygen delivery using engineered microparticles

    PubMed Central

    Seekell, Raymond P.; Lock, Andrew T.; Peng, Yifeng; Cole, Alexis R.; Perry, Dorothy A.; Kheir, John N.; Polizzotti, Brian D.

    2016-01-01

    A continuous supply of oxygen to tissues is vital to life and interruptions in its delivery are poorly tolerated. The treatment of low-blood oxygen tensions requires restoration of functional airways and lungs. Unfortunately, severe oxygen deprivation carries a high mortality rate and can make otherwise-survivable illnesses unsurvivable. Thus, an effective and rapid treatment for hypoxemia would be revolutionary. The i.v. injection of oxygen bubbles has recently emerged as a potential strategy to rapidly raise arterial oxygen tensions. In this report, we describe the fabrication of a polymer-based intravascular oxygen delivery agent. Polymer hollow microparticles (PHMs) are thin-walled, hollow polymer microcapsules with tunable nanoporous shells. We show that PHMs are easily charged with oxygen gas and that they release their oxygen payload only when exposed to desaturated blood. We demonstrate that oxygen release from PHMs is diffusion-controlled, that they deliver approximately five times more oxygen gas than human red blood cells (per gram), and that they are safe and effective when injected in vivo. Finally, we show that PHMs can be stored at room temperature under dry ambient conditions for at least 2 mo without any effect on particle size distribution or gas carrying capacity. PMID:27791101

  16. SU-E-T-268: Differences in Treatment Plan Quality and Delivery Between Two Commercial Treatment Planning Systems for Volumetric Arc-Based Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, S; Zhang, H; Zhang, B

    2015-06-15

    Purpose: To clinically evaluate the differences in volumetric modulated arc therapy (VMAT) treatment plan and delivery between two commercial treatment planning systems. Methods: Two commercial VMAT treatment planning systems with different VMAT optimization algorithms and delivery approaches were evaluated. This study included 16 clinical VMAT plans performed with the first system: 2 spine, 4 head and neck (HN), 2 brain, 4 pancreas, and 4 pelvis plans. These 16 plans were then re-optimized with the same number of arcs using the second treatment planning system. Planning goals were invariant between the two systems. Gantry speed, dose rate modulation, MLC modulation, planmore » quality, number of monitor units (MUs), VMAT quality assurance (QA) results, and treatment delivery time were compared between the 2 systems. VMAT QA results were performed using Mapcheck2 and analyzed with gamma analysis (3mm/3% and 2mm/2%). Results: Similar plan quality was achieved with each VMAT optimization algorithm, and the difference in delivery time was minimal. Algorithm 1 achieved planning goals by highly modulating the MLC (total distance traveled by leaves (TL) = 193 cm average over control points per plan), while maintaining a relatively constant dose rate (dose-rate change <100 MU/min). Algorithm 2 involved less MLC modulation (TL = 143 cm per plan), but greater dose-rate modulation (range = 0-600 MU/min). The average number of MUs was 20% less for algorithm 2 (ratio of MUs for algorithms 2 and 1 ranged from 0.5-1). VMAT QA results were similar for all disease sites except HN plans. For HN plans, the average gamma passing rates were 88.5% (2mm/2%) and 96.9% (3mm/3%) for algorithm 1 and 97.9% (2mm/2%) and 99.6% (3mm/3%) for algorithm 2. Conclusion: Both VMAT optimization algorithms achieved comparable plan quality; however, fewer MUs were needed and QA results were more robust for Algorithm 2, which more highly modulated dose rate.« less

  17. Mectizan(®) procurement and delivery for onchocerciasis mass drug administration programmes.

    PubMed

    Ogoussan, Kisito T; Hopkins, Adrian

    2011-09-01

    The discovery of Mectizan has engendered a safe onchocerciasis chemoprevention tool. To make the drug available promptly to people at risk of onchocerciasis, a procurement and delivery mechanism has been put in place around the Mectizan Donation Program, which oversees the Merck donation of Mectizan. The number of yearly approved treatment doses has increased rapidly since 1988 from 255,000 to more than 80 million in 2007 and 2008. Cumulatively, from 1987 to 2008 more than 697 million treatment doses have been approved corresponding to 1.5 billion Mectizan tablets shipped. Although the current demand for treatment is met, the ultimate goal is to cover all people at risk. A comprehensive drug policy from recipient countries is still needed to back up the current efficient procurement and delivery mechanism in order to attain the ultimate to goal, and is equally important for scaling up mass drug administration as part of national neglected tropical disease control/elimination strategies. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment.

    PubMed

    Liu, Jia; Qi, Chao; Tao, Kaixiong; Zhang, Jinxiang; Zhang, Jian; Xu, Luming; Jiang, Xulin; Zhang, Yunti; Huang, Lei; Li, Qilin; Xie, Hongjian; Gao, Jinbo; Shuai, Xiaoming; Wang, Guobin; Wang, Zheng; Wang, Lin

    2016-03-01

    Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross-linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericin's photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems.

  19. PLGA-Chitosan nanoparticle-mediated gene delivery for oral cancer treatment: A brief review

    NASA Astrophysics Data System (ADS)

    Bakar, L. M.; Abdullah, M. Z.; Doolaanea, A. A.; Ichwan, S. J. A.

    2017-08-01

    Cancer becomes a serious issue on society with increasing of their growth and proliferation, either in well economic developed countries or not. Recent years, oral cancer is one of the most threatening diseases impairing the quality of life of the patient. Scientists have emphasised on application of gene therapy for oral cancer by using nanoparticle as transportation vectors as a new alternative platform in order to overcome the limitations of conventional approaches. In modern medicine, nanotechnologies’ application, such as nanoparticles-mediated gene delivery, is one of promising tool for therapeutic devices. The objective of this article is to present a brief review summarizes on the current progress of nanotechnology-based gene delivery treatment system targeted for oral cancer.

  20. Ultrasound-stimulated drug delivery for treatment of residual disease after incomplete resection of head and neck cancer.

    PubMed

    Sorace, Anna G; Korb, Melissa; Warram, Jason M; Umphrey, Heidi; Zinn, Kurt R; Rosenthal, Eben; Hoyt, Kenneth

    2014-04-01

    Microbubbles triggered with localized ultrasound (US) can improve tumor drug delivery and retention. Termed US-stimulated drug delivery, this strategy was applied to head and neck cancer (HNC) in a post-surgical tumor resection model. Luciferase-positive HNC squamous cell carcinoma (SCC) was implanted in the flanks of nude athymic mice (N = 24) that underwent various degrees of surgical tumor resection (0%, 50% or 100%). After surgery, animals received adjuvant therapy with cetuximab-IRDye alone, or cetuximab-IRDye in combination with US-stimulated drug delivery or saline injections (control) on days 4, 7 and 10. Tumor drug delivery was assessed on days 0, 4, 7, 10, 14 and 17 with an in vivo fluorescence imaging system, and tumor viability was evaluated at the same times with in vivo bioluminescence imaging. Tumor caliper measurements occurred two times per week for 24 d. Optical imaging revealed that in the 50% tumor resection group, US-stimulated drug delivery resulted in a significant increase in cetuximab delivery compared with administration of drug alone on day 10 (day of peak fluorescence) (p = 0.03). Tumor viability decreased in all groups that received cetuximab-IRDye in combination with US-stimulated drug delivery, compared with the group that received only the drug. After various degrees of surgical resection, this novel study reports positive improvements in drug uptake in the residual cancer cells when drug delivery is stimulated with US. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  1. Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors

    NASA Astrophysics Data System (ADS)

    Zhu, Yu

    Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo

  2. Advancing Cancer Treatment Delivery - Role of Physics

    NASA Astrophysics Data System (ADS)

    Bortfeld, Thomas

    Radiation treatment of localized tumors has evolved rapidly in recent decades, allowing radiation oncologists to deliver more focused treatments with significantly reduced side effects. One of the disruptive innovations led by physicists has been the development of intensity-modulated and image-guided radiation therapy (IMRT and IGRT), which has become the state of the art in radiation therapy with photons. At the next stage of the development, there is now growing interest in treating tumors with protons or heavier particles, which have the added physical benefit of the Bragg peak. However, proton and heavier particle therapy is available to fewer than 1% of the patients. The first reason for that is the higher cost and bigger size of particle therapy facilities. The second reason is uncertainty of the treatment delivery, which limits its accuracy and precision. To address the first point (higher cost), physicists are involved in developments to make the equipment much more compact and cheaper. Examples include superconducting accelerators, laser-accelerated accelerators, more compact ``gantries'' that rotate the beam around the patient, as well as other solutions to treat the patients form multiple directions of incidence. The uncertainties in positioning the Bragg peak in the patient are being addressed by in-vivo measurements of dose deposition, or surrogates thereof. Examples include the measurement of prompt gamma radiation produced by the proton beam as it traverses the patient. Positron-Emission-Tomography (PET) scans have also been used to measure the tissue activation by the proton beam. Finally, the measurement of sound waves produced by pulsed proton beams leading to rapid expansions of the irradiated tissue has recently been successfully pursued. After resolving the issue of aiming a treatment beam with high precision and low cost, such that the majority of the patients will benefit from it, one of the next challenges for physicists in medicine is to

  3. Physical Methods for Intracellular Delivery: Practical Aspects from Laboratory Use to Industrial-Scale Processing

    PubMed Central

    Meacham, J. Mark; Durvasula, Kiranmai; Degertekin, F. Levent; Fedorov, Andrei G.

    2015-01-01

    Effective intracellular delivery is a significant impediment to research and therapeutic applications at all processing scales. Physical delivery methods have long demonstrated the ability to deliver cargo molecules directly to the cytoplasm or nucleus, and the mechanisms underlying the most common approaches (microinjection, electroporation, and sonoporation) have been extensively investigated. In this review, we discuss established approaches, as well as emerging techniques (magnetofection, optoinjection, and combined modalities). In addition to operating principles and implementation strategies, we address applicability and limitations of various in vitro, ex vivo, and in vivo platforms. Importantly, we perform critical assessments regarding (1) treatment efficacy with diverse cell types and delivered cargo molecules, (2) suitability to different processing scales (from single cell to large populations), (3) suitability for automation/integration with existing workflows, and (4) multiplexing potential and flexibility/adaptability to enable rapid changeover between treatments of varied cell types. Existing techniques typically fall short in one or more of these criteria; however, introduction of micro-/nanotechnology concepts, as well as synergistic coupling of complementary method(s), can improve performance and applicability of a particular approach, overcoming barriers to practical implementation. For this reason, we emphasize these strategies in examining recent advances in development of delivery systems. PMID:23813915

  4. Physical and Chemical Strategies for Therapeutic Delivery by Using Polymeric Nanoparticles

    PubMed Central

    Morachis, José M.; Mahmoud, Enas A.

    2012-01-01

    A significant challenge that most therapeutic agents face is their inability to be delivered effectively. Nanotechnology offers a solution to allow for safe, high-dose, specific delivery of pharmaceuticals to the target tissue. Nanoparticles composed of biodegradable polymers can be designed and engineered with various layers of complexity to achieve drug targeting that was unimaginable years ago by offering multiple mechanisms to encapsulate and strategically deliver drugs, proteins, nucleic acids, or vaccines while improving their therapeutic index. Targeting of nanoparticles to diseased tissue and cells assumes two strategies: physical and chemical targeting. Physical targeting is a strategy enabled by nanoparticle fabrication techniques. It includes using size, shape, charge, and stiffness among other parameters to influence tissue accumulation, adhesion, and cell uptake. New methods to measure size, shape, and polydispersity will enable this field to grow and more thorough comparisons to be made. Physical targeting can be more economically viable when certain fabrication techniques are used. Chemical targeting can employ molecular recognition units to decorate the surface of particles or molecular units responsive to diseased environments or remote stimuli. In this review, we describe sophisticated nanoparticles designed for tissue-specific chemical targeting that use conjugation chemistry to attach targeting moieties. Furthermore, we describe chemical targeting using stimuli responsive nanoparticles that can respond to changes in pH, heat, and light. PMID:22544864

  5. Maximizing cost-effectiveness by adjusting treatment strategy according to glaucoma severity

    PubMed Central

    Guedes, Ricardo Augusto Paletta; Guedes, Vanessa Maria Paletta; Gomes, Carlos Eduardo de Mello; Chaoubah, Alfredo

    2016-01-01

    Abstract Background: The aim of this study is to determine the most cost-effective strategy for the treatment of primary open-angle glaucoma (POAG) in Brazil, from the payer's perspective (Brazilian Public Health System) in the setting of the Glaucoma Referral Centers. Methods: Study design was a cost-effectiveness analysis of different treatment strategies for POAG. We developed 3 Markov models (one for each glaucoma stage: early, moderate and advanced), using a hypothetical cohort of POAG patients, from the perspective of the Brazilian Public Health System (SUS) and a horizon of the average life expectancy of the Brazilian population. Different strategies were tested according to disease severity. For early glaucoma, we compared observation, laser and medications. For moderate glaucoma, medications, laser and surgery. For advanced glaucoma, medications and surgery. Main outcome measures were ICER (incremental cost-effectiveness ratio), medical direct costs and QALY (quality-adjusted life year). Results: In early glaucoma, both laser and medical treatment were cost-effective (ICERs of initial laser and initial medical treatment over observation only, were R$ 2,811.39/QALY and R$ 3,450.47/QALY). Compared to observation strategy, the two alternatives have provided significant gains in quality of life. In moderate glaucoma population, medical treatment presented the highest costs among treatment strategies. Both laser and surgery were highly cost-effective in this group. For advanced glaucoma, both tested strategies were cost-effective. Starting age had a great impact on results in all studied groups. Initiating glaucoma therapy using laser or surgery were more cost-effective, the younger the patient. Conclusion: All tested treatment strategies for glaucoma provided real gains in quality of life and were cost-effective. However, according to the disease severity, not all strategies provided the same cost-effectiveness profile. Based on our findings, there should be a

  6. The application of carbon nanotubes in target drug delivery systems for cancer therapies

    NASA Astrophysics Data System (ADS)

    Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

    2011-10-01

    Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

  7. Chemically controlled closed-loop insulin delivery.

    PubMed

    Ravaine, Valérie; Ancla, Christophe; Catargi, Bogdan

    2008-11-24

    Alternative treatments for diabetes are currently being investigated to improve both patient comfort and avoid complications due to hyperglycaemia episodes. In the absence of a cure like pancreas or beta-islets transplants, the ideal method would be an artificial "closed-loop" system able to mimic pancreas activity. This would operate continuously and automatically, causing appropriate response to losses and gains in glucose levels. Chemically controlled closed-loop insulin delivery has been explored by two main strategies. The first one consists in delivering insulin with a glucose-responsive matrix. Polymeric hydrogels that swell or shrink according to the glucose concentration allow delivering insulin doses adapted to the glucose concentration. The second strategy consists in modifying insulin itself with glucose-sensitive functional groups that trigger its activity. Recent developments made in these areas represent significant progress in terms of biocompatibility, selectivity, pharmacokinetics, and easiness of administration, as required for in vivo applications. Although some issues still have to be overcome, this field of research is promising as a possible alternative to other approaches for diabetes treatment.

  8. Advances in the delivery of buprenorphine for opioid dependence.

    PubMed

    Rosenthal, Richard N; Goradia, Viral V

    2017-01-01

    Opioid use disorders (OUDs) have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD.

  9. TU-FG-201-03: Automatic Pre-Delivery Verification Using Statistical Analysis of Consistencies in Treatment Plan Parameters by the Treatment Site and Modality

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, S; Wu, Y; Chang, X

    Purpose: A novel computer software system, namely APDV (Automatic Pre-Delivery Verification), has been developed for verifying patient treatment plan parameters right prior to treatment deliveries in order to automatically detect and prevent catastrophic errors. Methods: APDV is designed to continuously monitor new DICOM plan files on the TMS computer at the treatment console. When new plans to be delivered are detected, APDV checks the consistencies of plan parameters and high-level plan statistics using underlying rules and statistical properties based on given treatment site, technique and modality. These rules were quantitatively derived by retrospectively analyzing all the EBRT treatment plans ofmore » the past 8 years at authors’ institution. Therapists and physicists will be notified with a warning message displayed on the TMS computer if any critical errors are detected, and check results, confirmation, together with dismissal actions will be saved into database for further review. Results: APDV was implemented as a stand-alone program using C# to ensure required real time performance. Mean values and standard deviations were quantitatively derived for various plan parameters including MLC usage, MU/cGy radio, beam SSD, beam weighting, and the beam gantry angles (only for lateral targets) per treatment site, technique and modality. 2D-based rules of combined MU/cGy ratio and averaged SSD values were also derived using joint probabilities of confidence error ellipses. The statistics of these major treatment plan parameters quantitatively evaluate the consistency of any treatment plans which facilitates automatic APDV checking procedures. Conclusion: APDV could be useful in detecting and preventing catastrophic errors immediately before treatment deliveries. Future plan including automatic patient identify and patient setup checks after patient daily images are acquired by the machine and become available on the TMS computer. This project is supported by

  10. Routes for Drug Translocation Across the Blood-Brain Barrier: Exploiting Peptides as Delivery Vectors.

    PubMed

    Kristensen, Mie; Brodin, Birger

    2017-09-01

    A number of potent drugs for the treatment of brain diseases are available. However, in order for them to reach their target site of action, they must pass the blood-brain barrier (BBB). The capillary endothelium comprises the major barrier of the BBB and allows only passive permeation of some small lipophilic molecules. Brain delivery of the larger biopharmaceuticals, which today includes an increasing number of novel drug entities, is therefore restricted, both due to their molecular size and their hydrophilic nature. Thus, the development of novel drug entities intended for the treatment of brain diseases such as neurodegenerative diseases or brain cancers require a delivery strategy for overcoming the BBB before reaching its final target within the brain. Peptide-based delivery vector is an emerging tool as shuttles for drug delivery across the BBB and one may explore receptor-mediated transcytosis, adsorptive-mediated transcytosis, and the paracellular route. The latter, however, being controversial due to the risk of co-delivery of blood-borne potential harmful substances. On the other hand, a number of studies report on drug delivery across the BBB exploiting receptor-mediated transcytosis and adsorptive-mediated transcytosis, indicating that peptides and peptide vectors may be of use in a central nervous system delivery context. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Effect of a community-based delivery of intermittent preventive treatment of malaria in pregnancy on treatment seeking for malaria at health units in Uganda.

    PubMed

    Mbonye, A K; Schultz Hansen, K; Bygbjerg, I C; Magnussen, P

    2008-05-01

    The impact of intermittent preventive treatment (IPTp) on malaria in pregnancy is well known. However, in countries where this policy is implemented, poor access and low compliance have been widely reported. Novel approaches are needed to deliver this intervention. To assess whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilizers can administer IPTp with sulphadoxine-pyrimethamine (SP) to pregnant women, reach those at greatest risk of malaria, and increase access and compliance with IPTp. An intervention study compared the delivery of IPTp in the community with routine delivery of IPTp at health units. The primary outcome measures were the proportion of adolescents and primigravidae accessed, and the proportion of women who received two doses of SP. The study also assessed the effect of the intervention on access to malaria treatment, antenatal care, other services and related costs. More women (67.5%) received two doses of SP through the community approach compared with health units (39.9%; P<0.0001). Women who accessed IPTp in the community were at an earlier stage of pregnancy (21.0 weeks of gestation) than women who accessed IPTp at health units (23.1 weeks of gestation; P<0.0001). However, health units were visited by a higher proportion of primigravidae (23.6% vs 20.0%; P<0.04) and adolescents (28.4% vs 25.0%; P<0.03). Generally, women who accessed IPTp at health units made more visits for malaria treatment (2.6 (1.0-4.7) vs 1.8 (1.4-2.2); P<0.03). At recruitment, more women who accessed IPTp at health units sought malaria treatment compared with those who accessed IPTp in the community (56.9% vs 49.2%). However, at delivery, a high proportion of women who accessed IPTp in the community had sought malaria treatment (70.3%), suggesting the possibility that the novel approach had a positive impact on care seeking for malaria. Similarly, utilization of antenatal care, insecticide-treated nets

  12. Hydrogels for Atopic Dermatitis and Wound Management: A Superior Drug Delivery Vehicle.

    PubMed

    Harrison, Ian P; Spada, Fabrizio

    2018-06-14

    Wound management, in addition to presenting a significant burden to patients and their families, also contributes significantly to a country’s healthcare costs. Treatment strategies are numerous, but in most cases not ideal. Hydrogels, three-dimensional polymeric materials that can withstand a great degree of swelling without losing structural integrity, are drawing great attention for their use as topical wound management solutions in the form of films and as vehicles for drug delivery, due to their unique properties of high water content, biocompatibility, and flexibility. Hydrogels, both naturally and synthetically derived, can be tuned to respond to specific stimuli such as pH, temperature and light and they are ideally suited as drug delivery vehicles. Here we provide a brief overview of the history and characteristics of hydrogels, assess their uses in wound management and drug delivery, and compare them with other types of common drug delivery vehicle.

  13. Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment

    PubMed Central

    Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

    2016-01-01

    Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. PMID:27994458

  14. Recent perspectives on the delivery of biologics to back of the eye

    PubMed Central

    Joseph, Mary; Trinh, Hoang M.; Cholkar, Kishore; Pal, Dhananjay; Mitra, Ashim K.

    2017-01-01

    Introduction Biologics are generally macromolecules, large in size with poor stability in biological environments. Delivery of biologics to tissues at the back of the eye remains a challenge. To overcome these challenges and treat posterior ocular diseases, several novel approaches have been developed. Nanotechnology-based delivery systems, like drug encapsulation technology, macromolecule implants and gene delivery are under investigation. We provide an overview of emerging technologies for biologics delivery to back of the eye tissues. Moreover, new biologic drugs currently in clinical trials for ocular neovascular diseases have been discussed. Areas Covered Anatomy of the eye, posterior segment disease and diagnosis, barriers to biologic delivery, ocular pharmacokinetic, novel biologic delivery system Expert Opinion Anti-VEGF therapy represents a significant advance in developing biologics for the treatment of ocular neovascular diseases. Various strategies for biologic delivery to posterior ocular tissues are under development with some in early or late stages of clinical trials. Despite significant progress in the delivery of biologics, there is unmet need to develop sustained delivery of biologics with nearly zero-order release kinetics to the back of the eye tissues. In addition, elevated intraocular pressure associated with frequent intravitreal injections of macromolecules is another concern that needs to be addressed. PMID:27573097

  15. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    NASA Astrophysics Data System (ADS)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  16. Treatment Strategies for Intracranial Mirror Aneurysms.

    PubMed

    Wang, Wen-Xin; Xue, Zhe; Li, Lin; Wu, Chen; Zhang, Yan-Yang; Lou, Xin; Ma, Lin; Sun, Zheng-Hui

    2017-04-01

    Intracranial mirror aneurysms are clinically rare and uncommonly reported in the literature. Therefore, the present study evaluated a series of mirror aneurysm cases with respect to the clinical features of the patients and the treatment strategies that were used. This study retrospectively reviewed and systematically analyzed the clinical features, imaging data, treatment methods, and treatment outcomes of 68 cases of mirror aneurysms (a total of 70 pairs) in patients who were admitted to our department between November 2007 and May 2016. The patient population included 24 male and 44 female patients, with a mean age of 52 years. The mirror aneurysms were primarily located in posterior communicating artery and middle cerebral artery and 65 of the aneurysms were large or giant (≧10 mm). Of the 68 patients, 28 were treated by the clipping or embolization of all aneurysms in one stage, 16 were treated in 2 stages, 16 were treated by treating part of the aneurysms, and 8 were observed. The modified Rankin Scale scores of the 60 patients that were treated indicated that 52 had a good recovery (modified Rankin Scale score ≦2; 86.7%), and 1 patient died. Treatment strategies for mirror aneurysms should be determined individually according to the location, size, and morphology of the aneurysm, as well as the clinical manifestations of each patient. Furthermore, the responsible ruptured aneurysm should be given treatment priority, whereas the contralateral unruptured aneurysm should be observed or treated in either 1 or 2 stages. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Fluvastatin as a micropore lifetime enhancer for sustained delivery across microneedle-treated skin.

    PubMed

    Ghosh, Priyanka; Brogden, Nicole K; Stinchcomb, Audra L

    2014-02-01

    Microneedles (MNs), a physical skin permeation enhancement technique, facilitate drug delivery across the skin, thus enhancing the number of drugs that can be delivered transdermally in therapeutically relevant concentrations. The micropores created in the skin by MNs reseal because of normal healing processes of the skin, thus limiting the duration of the drug delivery window. Pore lifetime enhancement strategies can increase the effectiveness of MNs as a drug delivery mechanism by prolonging the delivery window. Fluvastatin (FLU), a HMGCoA reductase inhibitor, was used in this study to enhance the pore lifetime by inhibiting the synthesis of cholesterol, a major component of the stratum corneum lipids. The study showed that using FLU as a pretreatment it is possible to enhance the pore lifetime of MN-treated skin and thus allow for sustained drug delivery. The skin recovered within a 30-45-min time period following the removal of occlusion, and there was no significant irritation observed due to the treatment compared to the control sites. Thus, it can be concluded that localized skin treatment with FLU can be used to extend micropore lifetime and deliver drugs for up to 7 days across MN-treated skin. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  18. CONFLICT IN EASTERN UKRAINE: STRATEGY FOR TUBERCULOSIS.

    PubMed

    Kuchuloria, T; Akhvlediani, T; Akhvlediani, N

    2016-09-01

    This root cause analysis concerns the conflict in the Eastern Ukraine and its impact on healthcare delivery in the context of treating internally displaced persons (IDPs). Inadequate treatment of tuberculosis (TB) was selected as a major topic for intervention planning in conflict areas in Ukraine. With respect to treating TB among IDPs, rapid diagnosis and adequate nutrition and shelter are important components of care and disease control. The DOT, supported by trained primary healthcare providers equipped with rapid MDR TB diagnostic capacities, need to provide appropriate shelter and nutrition to IDPs. In addition to active disease management, this paper discusses the important role of ongoing project monitoring and communicating evaluation findings with all the major stakeholders shaping the national TB strategy in Ukraine. A comprehensive strategy is essential for successful transitioning and re-structuring of TB healthcare delivery both during after conflict resolution.

  19. EMP-induced BBB-disruption enhances drug delivery to glioma and increases treatment efficacy in rats.

    PubMed

    Li, Kangchu; Zhang, Keying; Xu, Shenglong; Wang, Xiaowu; Zhou, Yongchun; Zhou, Yan; Gao, Peng; Lin, Jiajin; Ding, Guirong; Guo, Guozhen

    2018-01-01

    Chemotherapy on gliomas is not satisfactorily efficient because the presence of blood-brain barriers (BBB) leads to inadequate exposure of tumor cells to administered drugs. In order to facilitate chemotherapeutics to penetrate BBB and increase the treatment efficacy of gliomas, electromagnetic pulse (EMP) was applied and the 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU) lomustine concentration in tumor tissue, tumor size, tumor apoptosis, and side effects were measured in glioma-bearing rat model. The results showed that EMP exposure could enhance the delivery of CCNU to tumor tissue, facilitate tumor apoptosis, and inhibit tumor growth without obvious side effects. The data indicated that EMP-induced BBB disruption could enhance delivery of CCNU to glioblastoma multiforme and increase treatment efficacy in glioma-bearing rats. Bioelectromagnetics. 39:60-67, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Cognitive and neuropsychiatric impairments in Alzheimer's disease: current treatment strategies.

    PubMed

    Borisovskaya, Anna; Pascualy, Marcella; Borson, Soo

    2014-09-01

    This update on Alzheimer's disease (AD) discusses treatment strategies for cognitive and neuropsychiatric symptoms (such as agitation, psychosis, anxiety, and depression) common in this illness, emphasizing in particular nonpharmacologic strategies such as cognitive interventions, physical exercise, and psychotherapy. We provide an overview of cognitive enhancers and their combination strategies and medications commonly used for treatment of neuropsychiatric symptoms in AD. Finally, we give recommendations for providing support to caregivers and suggest how to identify caregiver/patient pairs most in need of intensive dementia care services.

  1. [Diagnostics and treatment strategies for multiple trauma patients].

    PubMed

    Pfeifer, R; Pape, H-C

    2016-02-01

    Severe trauma is still one of the leading causes of death worldwide. The initial treatment and diagnostics are of immense importance in polytraumatized patients. The initial approach mainly focuses on the advanced trauma life support (ATLS) concept. This includes the identification of life-threatening conditions and application of life-saving interventions. Depending on the physiological condition of the patient, the surgical treatment strategies of early total care (ETC) or damage control orthopedics (DCO) can be chosen. Appropriate surgical management can reduce the incidence of associated delayed systemic complications. This review summarizes the most commonly used definitions of polytrauma (including the Berlin polytrauma definition) and classification systems of severely injured patients. Moreover, the recently introduced treatment strategy of the safe definitive surgery concept for severely injured patients is also discussed in this article.

  2. SU-E-T-370: Evaluating Plan Quality and Dose Delivery Accuracy of Tomotherapy SBRT Treatments for Lung Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Blake, S; Thwaites, D; Hansen, C

    2015-06-15

    Purpose: This study evaluated the plan quality and dose delivery accuracy of stereotactic body radiotherapy (SBRT) helical Tomotherapy (HT) treatments for lung cancer. Results were compared with those previously reported by our group for flattening filter (FF) and flattening filter free (FFF) VMAT treatments. This work forms part of an ongoing multicentre and multisystem planning and dosimetry audit on FFF beams for lung SBRT. Methods: CT datasets and DICOM RT structures delineating the target volume and organs at risk for 6 lung cancer patients were selected. Treatment plans were generated using the HT treatment planning system. Tumour locations were classifiedmore » as near rib, near bronchial tree or in free lung with prescribed doses of 48Gy/4fr, 50Gy/5fr and 54Gy/3fr respectively. Dose constraints were specified by a modified RTOG0915 protocol used for an Australian SBRT phase II trial. Plan quality was evaluated using mean PTV dose, PTV volume receiving 100% of the prescribed dose (V100%), target conformity (CI=VD100%/VPTV) and low dose spillage (LDS=VD50%/VPTV). Planned dose distributions were compared to those measured using an ArcCheck phantom. Delivery accuracy was evaluated using a gamma-index pass rate of 95% with 3% (of max dose) and 3mm criteria. Results: Treatment plans for all patients were clinically acceptable in terms of quality and accuracy of dose delivery. The following DVH metrics are reported as averages (SD) of all plans investigated: mean PTV dose was 115.3(2.4)% of prescription, V100% was 98.8(0.9)%, CI was 1.14(0.03) and LDS was 5.02(0.37). The plans had an average gamma-index passing rate of 99.3(1.3)%. Conclusion: The results reported in this study for HT agree within 1 SD to those previously published by our group for VMAT FF and FFF lung SBRT treatments. This suggests that HT delivers lung SBRT treatments of comparable quality and delivery accuracy as VMAT using both FF and FFF beams.« less

  3. Cost-effectiveness of Competing Strategies for Management of Recurrent Clostridium difficile Infection: A Decision Analysis

    PubMed Central

    Konijeti, Gauree G.; Sauk, Jenny; Shrime, Mark G.; Gupta, Meera; Ananthakrishnan, Ashwin N.

    2014-01-01

    Background. Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. Methods. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. Results. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. Conclusions. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI. PMID:24692533

  4. Noninvasive ocular drug delivery: potential transcorneal and other alternative delivery routes for therapeutic molecules in glaucoma.

    PubMed

    Foldvari, Marianna

    2014-01-01

    Drug delivery to the eye is made difficult by multiple barriers (such as the tear film, cornea, and vitreous) between the surface of the eye and the treatment site. These barriers are difficult to surmount for the purposes of drug delivery without causing toxicity. Using nanotechnology tools to control, manipulate, and study delivery systems, new approaches to delivering drugs, genes, and antigens that are effective and safe can be developed. Topical administration to the ocular surface would be the safest method for delivery, as it is noninvasive and painless compared with other delivery methods. However, there is only limited success using topical delivery methods, especially for gene therapy. Current thinking on treatments of the future enabled by nanodelivery systems and the identification of target specificity parameters that require deeper understanding to develop successful topical delivery systems for glaucoma is highlighted.

  5. Nanodrug delivery systems in dentistry: a review on current status and future perspectives.

    PubMed

    Renugalakshmi, Apathsakayan; Vinothkumar, Thilla Sekar; Kandaswamy, Deivanayagam

    2011-09-01

    The present review provides an insight into various potential areas of dentistry that are being invaded by nanotechnology based drugs and drug delivery systems. Current treatments for diseases of dental and oral structures rely on the use of classical pharmacological agents which, in some cases are limited by low efficacy and lack of selectivity to target cells. However, various nanostructures in drug delivery and their challenges in the field of dentistry have not been reviewed so far in the literature. The different treatment opportunities of importance include caries control restorations, tooth remineralisation, management of dentinal hypersensitivity, dental caries vaccine, management of oral biofilm, root canal disinfection, local anaesthesia and periodontal infection. The authors have also identified few dental applications demanding extensive research to emerge as a promising therapeutic strategy. We conclude by claiming that dentistry should follow the trend of probing matter at nanoscale to achieve a predictable treatment outcome.

  6. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye. © 2016 S. Karger AG, Basel.

  7. Fundamentals of pulmonary drug delivery.

    PubMed

    Groneberg, D A; Witt, C; Wagner, U; Chung, K F; Fischer, A

    2003-04-01

    Aerosol administration of peptide-based drugs plays an important role in the treatment of pulmonary and systemic diseases and the unique cellular properties of airway epithelium offers a great potential to deliver new compounds. As the relative contributions from the large airways to the alveolar space are important to the local and systemic availability, the sites and mechanism of uptake and transport of different target compounds have to be characterized. Among the different respiratory cells, the ciliated epithelial cells of the larger and smaller airways and the type I and type II pneumocytes are the key players in pulmonary drug transport. With their diverse cellular characteristics, each of these cell types displays a unique uptake possibility. Next to the knowledge of these cellular aspects, the nature of aerosolized drugs, characteristics of delivery systems and the depositional and pulmonary clearance mechanisms display major targets to optimize pulmonary drug delivery. Based on the growing knowledge on pulmonary cell biology and pathophysiology due to modern methods of molecular biology, the future characterization of pulmonary drug transport pathways can lead to new strategies in aerosol drug therapy.

  8. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors

    PubMed Central

    Ullah, Izhar; Qureshi, Omer Salman; Mustapha, Omer; Shafique, Shumaila; Zeb, Alam

    2017-01-01

    Nanotechnology has recently gained increased attention for its capability to effectively diagnose and treat various tumors. Nanocarriers have been used to circumvent the problems associated with conventional antitumor drug delivery systems, including their nonspecificity, severe side effects, burst release and damaging the normal cells. Nanocarriers improve the bioavailability and therapeutic efficiency of antitumor drugs, while providing preferential accumulation at the target site. A number of nanocarriers have been developed; however, only a few of them are clinically approved for the delivery of antitumor drugs for their intended actions at the targeted sites. The present review is divided into three main parts: first part presents introduction of various nanocarriers and their relevance in the delivery of anticancer drugs, second part encompasses targeting mechanisms and surface functionalization on nanocarriers and third part covers the description of selected tumors, including breast, lungs, colorectal and pancreatic tumors, and applications of relative nanocarriers in these tumors. This review increases the understanding of tumor treatment with the promising use of nanotechnology. PMID:29042776

  9. Cost-effectiveness of screening and treatment for bacterial vaginosis in early pregnancy among women at low risk for preterm birth.

    PubMed

    Kekki, Minnamaija; Kurki, Tapio; Kotomäki, Teija; Sintonen, Harri; Paavonen, Jorma

    2004-01-01

    Bacterial vaginosis (BV) is an important risk factor for preterm birth. BV is detected in 10-30% of pregnant women and is often asymptomatic. Treatment of BV during pregnancy seems to reduce the risk of preterm delivery among high-risk women. We performed a cost-effectiveness analysis of screening and treatment for BV in early pregnancy among asymptomatic women at low risk for preterm delivery. A decision tree was built with two arms. For the screening (and treatment) arm the probabilities were derived from our earlier randomized trial on screening and treatment for BV, consisting of BV-positive women treated with intravaginal clindamycin cream or placebo and also of BV-negative pregnant women. The probabilities of outcomes among these women were collected from antenatal clinic records and hospital records, and for the no-screening arm mainly from the Finnish Perinatal Statistics. The outcomes considered were preterm delivery, mode of delivery, peripartum infections and postpartum complications. The unit costs associated with these outcomes were mainly based on disease-related groups (DRGs). No-screening was compared with two screening programs (one with clindamycin, the other with metronidazole treatment) and subjected to sensitivity analyses. There was no significant difference between screening and no-screening strategies in the costs and in the rate of preterm deliveries but the screening strategy produced significantly fewer peripartum infections and postpartum complications. Sensitivity analyses suggested that the screening strategy may become cost-saving if the rate of preterm deliveries exceeds 3%. Screening and treatment for BV in early pregnancy may not reduce costs compared to no-screening in a population at low risk for preterm birth but would produce, at the same cost, more health benefits in terms of fewer peripartum infections and postpartum complications. However, it may be cost-saving if the rate of preterm deliveries is higher than 3%.

  10. Corona-directed nucleic acid delivery into hepatic stellate cells for liver fibrosis therapy.

    PubMed

    Zhang, Zhengping; Wang, Chunming; Zha, Yinhe; Hu, Wei; Gao, Zhongfei; Zang, Yuhui; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

    2015-03-24

    Strategies to modify nanoparticles with biological ligands for targeted drug delivery in vivo have been widely studied but met with limited clinical success. A possible reason is that, in the blood circulation, serum proteins could rapidly form a layer of protein "corona" on the vehicle surface, which might block the modified ligands and hamper their targeting functions. We speculate that strategies for drug delivery can be designed based upon elegant control of the corona formation on the vehicle surfaces. In this study, we demonstrate a retinol-conjugated polyetherimine (RcP) nanoparticle system that selectively recruited the retinol binding protein 4 (RBP) in its corona components. RBP was found to bind retinol, and direct the antisense oligonucleotide (ASO)-laden RcP carrier to hepatic stellate cells (HSC), which play essential roles in the progression of hepatic fibrosis. In both mouse fibrosis models, induced by carbon tetrachloride (CCl4) and bile duct ligation (BDL), respectively, the ASO-laden RcP particles effectively suppressed the expression of type I collagen (collagen I), and consequently ameliorated hepatic fibrosis. Such findings suggest that this delivery system, designed to exploit the power of corona proteins, can serve as a promising tool for targeted delivery of therapeutic agents for the treatment of hepatic fibrosis.

  11. Targeted drug delivery nanosystems based on copolymer poly(lactide)-tocopheryl polyethylene glycol succinate for cancer treatment

    NASA Astrophysics Data System (ADS)

    Thu Ha, Phuong; Nguyen, Hoai Nam; Doan Do, Hai; Thong Phan, Quoc; Nguyet Tran Thi, Minh; Phuc Nguyen, Xuan; Nhung Hoang Thi, My; Huong Le, Mai; Nguyen, Linh Toan; Quang Bui, Thuc; Hieu Phan, Van

    2016-03-01

    Along with the development of nanotechnology, drug delivery nanosystems (DDNSs) have attracted a great deal of concern among scientists over the world, especially in cancer treatment. DDNSs not only improve water solubility of anticancer drugs but also increase therapeutic efficacy and minimize the side effects of treatment methods through targeting mechanisms including passive and active targeting. Passive targeting is based on the nano-size of drug delivery systems while active targeting is based on the specific bindings between targeting ligands attached on the drug delivery systems and the unique receptors on the cancer cell surface. In this article we present some of our results in the synthesis and testing of DDNSs prepared from copolymer poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS), which carry anticancer drugs including curcumin, paclitaxel and doxorubicin. In order to increase the targeting effect to cancer cells, active targeting ligand folate was attached to the DDNSs. The results showed copolymer PLA-TPGS to be an excellent carrier for loading hydrophobic drugs (curcumin and paclitaxel). The fabricated DDNSs had a very small size (50-100 nm) and enhanced the cellular uptake and cytotoxicity of drugs. Most notably, folate-decorated paclitaxel-loaded copolymer PLA-TPGS nanoparticles (Fol/PTX/PLA-TPGS NPs) were tested on tumor-bearing nude mice. During the treatment time, Fol/PTX/PLA-TPGS NPs always exhibited the best tumor growth inhibition compared to free paclitaxel and paclitaxel-loaded copolymer PLA-TPGS nanoparticles. All results evidenced the promising potential of copolymer PLA-TPGS in fabricating targeted DDNSs for cancer treatment.

  12. Ocular delivery of macromolecules

    PubMed Central

    Kim, Yoo-Chun; Chiang, Bryce; Wu, Xianggen; Prausnitz, Mark R.

    2014-01-01

    Biopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non--invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects. This review discusses the barriers to drug delivery via various ophthalmic routes of administration in the context of macromolecule delivery and discusses efforts to develop controlled-release systems for delivery of biopharmaceuticals to the eye. The growing number of macromolecular therapies in the eye needs improved drug delivery methods that increase drug efficacy, safety and patient compliance. PMID:24998941

  13. Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis.

    PubMed

    Gilger, B C; Wilkie, D A; Davidson, M G; Allen, J B

    2001-12-01

    To evaluate the use of an intravitreal sustained-release cyclosporine (CsA) delivery device for treatment of horses with naturally occurring recurrent uveitis. 16 horses with recurrent uveitis. Horses with frequent recurrent episodes of uveitis or with disease that was progressing despite appropriate medication were selected for this study. Additional inclusion criteria included adequate retinal function as determined by use of electroretinography, lack of severe cataract formation, and no vision-threatening ocular complications (eg, retinal detachment, severe retinal degeneration, and posterior synechia). Sustained-release CsA delivery devices (4 microg of CsA/d) were implanted into the vitreous through a sclerotomy at the pars plana. Reexaminations were performed 1, 3, 6, and 12 months after implantation, then continued annually. Ophthalmic changes, number of recurrent episodes of uveitis, and vision were recorded. The rate of recurrent episodes after device implantation (0.36 episodes/y) was less than prior to surgery (75 episodes/y). In addition, only 3 horses developed episodes of recurrent uveitis after surgery. Vision was detected in 14 of 16 affected eyes at a mean follow-up time of 13.8 months (range, 6 to 24 months). This intravitreal sustained-release CsA delivery device may be a safe and important tool for long-term treatment of horses with chronic recurrent uveitis.

  14. Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

    PubMed

    Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

    2014-12-01

    Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

  15. Optimization of a Nanomedicine-based Pc 4-PDT Strategy for Targeted Treatment of EGFR-Overexpressing Cancers

    PubMed Central

    Master, Alyssa M.; Livingston, Megan; Oleinick, Nancy L.; Gupta, Anirban Sen

    2012-01-01

    The current clinical mainstays for cancer treatment, namely, surgical resection, chemotherapy and radiotherapy, can cause significant trauma, systemic toxicity, and functional/cosmetic debilitation of tissue, especially if repetitive treatment becomes necessary due to tumor recurrence. Hence there is significant clinical interest in alternate treatment strategies like photodynamic therapy (PDT) which can effectively and selectively eradicate tumors and can be safely repeated if needed. We have previously demonstrated that the second-generation photosensitizer Pc 4 can be formulated within polymeric micelles, and these micelles can be specifically targeted to EGFR-overexpressing cancer cells using GE11 peptide ligands, to enhance cell-specific Pc 4 delivery and internalization. In the current study, we report on the in vitro optimization of the EGFR-targeting, Pc 4 loading of the micellar nanoformulation, along with optimization of the corresponding photoirradiation conditions to maximize Pc 4 delivery, internalization and subsequent PDT-induced cytotoxicity in EGFR-overexpressing cells in vitro. In our studies, absorption and fluorescence spectroscopy were used to monitor the cell-specific uptake of the GE11-decorated Pc 4-loaded micelles and the cytotoxic singlet oxygen production from the micelle-encapsulated Pc 4, to determine the optimum ligand density and Pc 4 loading. It was found that the micelle formulations bearing 10 mole% of GE11-modified polymer component resulted in the highest cellular uptake in EGFR-overexpressing A431 cells within the shortest incubation periods. Also, the loading of ~50 μg Pc 4 per mg of polymer in these micellar formulations resulted in the highest levels of singlet oxygen production. When formulations bearing these optimized parameters were tested in vitro on A431 cells for PDT effect, a formulation dose containing 400 nM Pc 4 and photoirradiation duration of 400 seconds at a fluence of 200 mJ/cm2 yielded close to 100% cell

  16. Self assembled materials: design strategies and drug delivery perspectives.

    PubMed

    Verma, Gunjan; Hassan, P A

    2013-10-28

    Self assembly of small molecules in complex supramolecular structures provides a new avenue in the development of materials for drug delivery applications. Owing to the low aqueous solubility of various drugs, an effective delivery system is often required to reach sufficient drug bioavailability and/or to facilitate clinical use. Micelles, amphiphilic gels, vesicles (liposomes), nanodisks, cubosomes, colloidosomes, tubules, microemulsions, lipid particles, polyelectrolyte capsules etc. are some of the intriguing structures formed via self assembly. As well as enabling improved solubilization, such materials can be tuned to offer a range of other advantages, including controlled or stimuli sensitive drug release, protection from drug hydrolysis and chemical or enzymatic degradation, a reduction in toxicity, improvement of drug availability, prevention of RES uptake or selective targeting to organelles etc. Such multiple functionalities can be brought together by self assembly of different functional molecules. This route offers a cost effective means of developing drug delivery carriers tailored to specific needs. Our current understanding of the microstructure evolution of self assembled materials will go a long way towards designing/selecting molecules to create well defined structures. We believe that most of the potential resources mentioned above are untapped and that there is a need to further strengthen research in this area to fully exploit their potential. Selective cross linking of core or shell, stimuli sensitive amphiphiles, prodrug amphiphiles, antibody coupled amphiphiles etc. are only some of the new approaches for the development of effective drug delivery systems via self assembly.

  17. Enhancing endosomal escape for nanoparticle mediated siRNA delivery

    NASA Astrophysics Data System (ADS)

    Ma, Da

    2014-05-01

    Gene therapy with siRNA is a promising biotechnology to treat cancer and other diseases. To realize siRNA-based gene therapy, a safe and efficient delivery method is essential. Nanoparticle mediated siRNA delivery is of great importance to overcome biological barriers for systemic delivery in vivo. Based on recent discoveries, endosomal escape is a critical biological barrier to be overcome for siRNA delivery. This feature article focuses on endosomal escape strategies used for nanoparticle mediated siRNA delivery, including cationic polymers, pH sensitive polymers, calcium phosphate, and cell penetrating peptides. Work has been done to develop different endosomal escape strategies based on nanoparticle types, administration routes, and target organ/cell types. Also, enhancement of endosomal escape has been considered along with other aspects of siRNA delivery to ensure target specific accumulation, high cell uptake, and low toxicity. By enhancing endosomal escape and overcoming other biological barriers, great progress has been achieved in nanoparticle mediated siRNA delivery.

  18. Alginate microparticles as oral colon drug delivery device: A review.

    PubMed

    Agüero, Lissette; Zaldivar-Silva, Dionisio; Peña, Luis; Dias, Marcos L

    2017-07-15

    The increase in the research interest on alginate microparticles in pharmaceutical and biomedical areas confirms its potential use as an effective matrix for drug and cell delivery. Among the well known alginate properties, pH sensitivity remains as an attractive option for targeting of drug in the colon region. This essential aspect is advantageous to enhance therapeutic efficacy of treatment of inflammatory bowel diseases, which require multi-drug administration frequently in a long period. As consequence, severe side effect appears leading to discontinuation of therapy and affecting quality of patient life. This review gives an overview of relevant properties of alginate as oral colon delivery systems and the recent innovative strategies of using alginate with other polymers as well as microencapsulation techniques. At the same time, it describes the several advantages of coating processes involving alginate over microparticles in order to design better material with sustained release characteristic for colon-targeted delivery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Intracellular Delivery System for Antibody–Peptide Drug Conjugates

    PubMed Central

    Berguig, Geoffrey Y; Convertine, Anthony J; Frayo, Shani; Kern, Hanna B; Procko, Erik; Roy, Debashish; Srinivasan, Selvi; Margineantu, Daciana H; Booth, Garrett; Palanca-Wessels, Maria Corinna; Baker, David; Hockenbery, David; Press, Oliver W; Stayton, Patrick S

    2015-01-01

    Antibodies armed with biologic drugs could greatly expand the therapeutic potential of antibody–drug conjugates for cancer therapy, broadening their application to disease targets currently limited by intracellular delivery barriers. Additional selectivity and new therapeutic approaches could be realized with intracellular protein drugs that more specifically target dysregulated pathways in hematologic cancers and other malignancies. A multifunctional polymeric delivery system for enhanced cytosolic delivery of protein drugs has been developed that incorporates endosomal-releasing activity, antibody targeting, and a biocompatible long-chain ethylene glycol component for optimized safety, pharmacokinetics, and tumor biodistribution. The pH-responsive polymeric micelle carrier, with an internalizing anti-CD22 monoclonal targeting antibody, effectively delivered a proapoptotic Bcl-2 interacting mediator (BIM) peptide drug that suppressed tumor growth for the duration of treatment and prolonged survival in a xenograft mouse model of human B-cell lymphoma. Antitumor drug activity was correlated with a mechanistic induction of the Bcl-2 pathway biomarker cleaved caspase-3 and a marked decrease in the Ki-67 proliferation biomarker. Broadening the intracellular target space by more effective delivery of protein/peptide drugs could expand the repertoire of antibody–drug conjugates to currently undruggable disease-specific targets and permit tailored drug strategies to stratified subpopulations and personalized medicines. PMID:25669432

  20. Satisfaction of patients with directly observed treatment strategy in Addis Ababa, Ethiopia: A mixed-methods study

    PubMed Central

    Getahun, Belete; Nkosi, Zethu Zerish

    2017-01-01

    Background Directly observed treatment, short course (DOTS) strategy has been a cornerstone for Tuberculosis (TB) control programs in developing countries. However, in Ethiopia satisfaction level of patients’ with TB with the this strategy is not well understood. Therefore, the study aimed to assess the satisfaction level of patients with TB with the DOTS. Method Explanatory sequential mixed method design was carried out in Addis Ababa, Ethiopia. Interviewer-administered questionnaire with 601 patients with TB who were on follow-up was employed in the quantitative approach. In the qualitative approach telephonic-interview with 25 persons lost to follow-up and focus group discussions with 23 TB experts were conducted. Result Sixty seven percent of respondent was satisfied with the DOTS. Rural residency (AOR = 3.4, 95% CI 1.6, 7.6), having TB symptoms (AOR = 0.6, 95% CI 0.4, 0.94) and treatment supporter (AOR = 4.3, 95%CI 2.7, 6.8) were associated with satisfaction with DOTS. In qualitative finding, all persons lost to follow-up were dissatisfied while TB experts enlightened lack of evidence to affirm the satisfaction level of patients with DOTS. Explored factors contributing to satisfaction include: on time availability of health care providers, DOTS service delivery process, general condition of health care facilities, nutritional support and transportation. Conclusion DOTS is limited to satisfy patients with TB and lacks a consistent system that determines the satisfaction level of patients with TB. Therefore, DOTS strategy needs to have a system to captures patients’ satisfaction level to respond on areas that need progress to improve DOTS service quality. PMID:28182754

  1. Advances in the delivery of buprenorphine for opioid dependence

    PubMed Central

    Rosenthal, Richard N; Goradia, Viral V

    2017-01-01

    Opioid use disorders (OUDs) have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD. PMID:28894357

  2. Curb Challenges of the “Trojan Horse” Approach: Smart Strategies in Achieving Effective yet Safe Cell-penetrating Peptide-based Drug Delivery

    PubMed Central

    Huang, Yongzhuo; Jiang, Yifan; Wang, Huiyuan; Wang, Jianxin; Shin, Meong Cheol; Byun, Youngro; He, Huining; Liang, Yanqin; Yang, Victor C.

    2013-01-01

    Cell-penetrating peptide (CPP)-mediated intracellular drug delivery system, often specifically termed as “the Trojan horse approach”, has become the “holy grail” in achieving effective delivery of macromolecular compounds such as proteins, DNA, siRNAs, and drug carriers. It is characterized by the unique cell- (or receptor-), temperature-, and payload-independent mechanisms, therefore offering potent means to improve poor cellular uptake of a variety of macromolecular drugs. Nevertheless, this “Trojan horse” approach also acts like a double-edged sword, causing serious safety and toxicity concerns to normal tissues or organs for in vivo application, due to lack of target selectivity of the powerful cell penetrating activity. To overcome this problem of potent yet non-selective penetration vs. targeting delivery, a number of “smart” strategies have been developed in recent years, including controllable CPP-based drug delivery systems based on various stimuli-responsive mechanisms. This review article provides a fundamental understanding of these smart systems, as well as a discussion of their real-time in vivo applicability. PMID:23369828

  3. Doxorubicin-loaded PLA/pearl electrospun nanofibrous scaffold for drug delivery and tumor cell treatment

    NASA Astrophysics Data System (ADS)

    Dai, Jiamu; Jin, Junhong; Yang, Shenglin; Li, Guang

    2017-07-01

    A drug-loaded implantable scaffold is a promising substitute for the treatment of tissue defects after a tumor resection operation. In this work, natural pearl powder with good biocompatibility and osteoconductivity was incorporated into polylactic (PLA) nanofibers via electrospinning, and doxorubicin hydrochloride (DOX) was also loaded in the PLA/pearl scaffold, resulting in a drug-loaded composite nanofibrous scaffold (DOX@PLA/pearl). In vitro drug delivery of DOX from a PLA/pearl composite scaffold was measured and in vitro anti-tumor efficacy was also examined, in particular the effect of the pearl content on both key properties were studied. The results showed that DOX was successfully loaded into PLA/pearl composite nanofibrous scaffolds with different pearl content. More importantly, the delivery rate of DOX kept rising as the pearl content increased, and the anti-tumor efficacy of the drug-loaded scaffold on HeLa cells was improved at an appropriate pearl powder concentration. Thus, we expect that the prepared DOX@PLA/pearl powder nanofibrous mat is a highly promising implantable scaffold that has great potential in postoperative cancer treatment.

  4. A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles.

    PubMed

    Sekerdag, Emine; Lüle, Sevda; Bozdağ Pehlivan, Sibel; Öztürk, Naile; Kara, Aslı; Kaffashi, Abbas; Vural, Imran; Işıkay, Ilkay; Yavuz, Burҫin; Oguz, Kader Karlı; Söylemezoğlu, Figen; Gürsoy-Özdemir, Yasemin; Mut, Melike

    2017-09-10

    New drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats. FTA loaded HNPs were prepared, characterized and evaluated for cytotoxicity. Rat glioma 2 (RG2) cells were implanted unilaterally into the right striatum of female Wistar rats. 10days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500μM freshly prepared FTA loaded HNPs via IN or intravenous (IV) application. Pre-treatment and post-treatment tumor sizes were determined with MRI. After a treatment period of 5days, IN applied FTA loaded HNPs achieved a significant decrease of 55.7% in tumor area, equal to IV applied FTA loaded HNPs. Herewith, we showed the potential utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Clinical experience with drug delivery systems as tools to decrease the toxicity of anticancer chemotherapeutic agents.

    PubMed

    Maranhão, Raul C; Vital, Carolina G; Tavoni, Thauany M; Graziani, Silvia R

    2017-10-01

    The toxicity of chemotherapeutic agents, resulting from their low pharmacological index, introduces considerable discomfort and risk to cancer patients. Among several strategies to reduce the toxicity of chemotherapeutic agents, targeted drug delivery is the most promising one. Areas covered: Liposomes, micelles, albumin-based, polymeric, dendritic and lipid core nanoparticles have been used as carriers to concentrate anticancer drugs in neoplastic tissues, and clinical studies of those preparations are reviewed. In most clinical studies, drug delivery systems reduced drug toxicity. Lipid core nanoparticles (LDE) that bind to cell lipoprotein receptors have the ability to concentrate in neoplastic tissues and were the first artificial non-liposomal system shown in in vivo studies to possess targeting properties. The toxicity reduction achieved by LDE as vehicle of carmustine, etoposide and paclitaxel was singularly strong. Expert opinion: The reduced toxicity offered by drug delivery systems has expanded treatment population that may benefit from chemotherapy including feeble, overtreated and elderly patients that would otherwise be offered palliative therapy. Drug delivery systems may either prolong the duration of treatments or allow increases in drug dose.

  6. Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fietkau, Rainer; Roedel, Claus; Hohenberger, Werner

    2007-03-15

    Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, andmore » delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.« less

  7. Impact of the Integration of Water Treatment, Hygiene, Nutrition, and Clean Delivery Interventions on Maternal Health Service Use

    PubMed Central

    O'Connor, Katherine; Kim, Sunkyung; Kelley, Maureen; Odhiambo, Aloyce; Faith, Sitnah; Otieno, Ronald; Nygren, Benjamin; Kamb, Mary; Quick, Robert

    2017-01-01

    Reducing barriers associated with maternal health service use, household water treatment, and improved hygiene is important for maternal and neonatal health outcomes. We surveyed a sample of 201 pregnant women who participated in a clinic-based intervention in Kenya to increase maternal health service use and improve household hygiene and nutrition through the distribution of water treatment products, soap, protein-fortified flour, and clean delivery kits. From multivariable logistic regression analyses, the adjusted odds of ≥ 4 antenatal care (ANC4+) visits (odds ratio [OR] = 3.0, 95% confidence interval [CI] = 1.9–4.5), health facility delivery (OR = 5.3, 95% CI = 3.4–8.3), and any postnatal care visit (OR = 2.8, 95% CI = 1.9–4.2) were higher at follow-up than at baseline, adjusting for demographic factors. Women who completed primary school had higher odds of ANC4+ visits (OR = 1.8, 95% CI = 1.1–2.9) and health facility delivery (OR = 4.2, 95% CI = 2.5–7.1) than women with less education. For women who lived ≤ 2.5 km from the health facility, the estimated odds of health facility delivery (OR = 2.4, 95% CI = 1.5–4.1) and postnatal care visit (OR = 1.6, 95% CI = 1.0–2.6) were higher than for those who lived > 2.5 km away. Compared with baseline, a higher percentage of survey participants at follow-up were able to demonstrate proper handwashing (P = 0.001); water treatment behavior did not change. This evaluation suggested that hygiene, nutritional, clean delivery incentives, higher education level, and geographical contiguity to health facility were associated with increased use of maternal health services by pregnant women. PMID:28193744

  8. PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive interface.

    PubMed

    Priyadarshini, Balasankar Meera; Mitali, Kakran; Lu, Thong Beng; Handral, Harish K; Dubey, Nileshkumar; Fawzy, Amr S

    2017-07-01

    To characterize and deliver fabricated CHX-loaded PLGA-nanoparticles inside micron-sized dentinal-tubules of demineralized dentin-substrates and resin-dentin interface. Nanoparticles fabricated by emulsion evaporation were assessed in-vitro by different techniques. Delivery of drug-loaded nanoparticles to demineralized dentin substrates, interaction with collagen matrix, and ex-vivo CHX-release profiles using extracted teeth connected to experimental setup simulating pulpal hydrostatic pressure were investigated. Furthermore, nanoparticles association/interaction with a commercial dentin-adhesive applied to demineralized dentin substrates were examined. The results showed that the formulated nanoparticles demonstrated attractive physicochemical properties, low cytotoxicity, potent antibacterial efficacy, and slow degradation and gradual CHX release profiles. Nanoparticles delivered efficiently inside dentinal-tubules structure to sufficient depth (>10μm) against the simulated upward pulpal hydrostatic-pressure, even after bonding-resins infiltration and were attached/retained on collagen-fibrils. These results verified the potential significance of this newly introduced drug-delivery therapeutic strategy for future clinical applications and promote for a new era of future dental research. This innovative drug-delivery strategy has proven to be a reliable method for delivering treatments that could be elaborated for other clinical applications in adhesive and restorative dentistry. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  9. SU-E-T-151: Breathing Synchronized Delivery (BSD) Planning for RapicArc Treatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lu, W; Chen, M; Jiang, S

    2015-06-15

    Purpose: To propose a workflow for breathing synchronized delivery (BSD) planning for RapicArc treatment. Methods: The workflow includes three stages: screening/simulation, planning, and delivery. In the screening/simulation stage, a 4D CT with the corresponding breathing pattern is acquired for each of the selected patients, who are able to follow their own breathing pattern. In the planning stage, one breathing phase is chosen as the reference, and contours are delineated on the reference image. Deformation maps to other phases are performed along with contour propagation. Based on the control points of the initial 3D plan for the reference phase and themore » respiration trace, the correlation with respiration phases, the leaf sequence and gantry angles is determined. The beamlet matrices are calculated with the corresponding breathing phase and deformed to the reference phase. Using the 4D dose evaluation tool and the original 3D plan DVHs criteria, the leaf sequence is further optimized to meet the planning objectives and the machine constraints. In the delivery stage, the patients are instructed to follow the programmed breathing patterns of their own, and all other parts are the same as the conventional Rapid-Arc delivery. Results: Our plan analysis is based on comparison of the 3D plan with a static target (SD), 3D plan with motion delivery (MD), and the BSD plan. Cyclic motion of range 0 cm to 3 cm was simulated for phantoms and lung CT. The gain of the BSD plan over MD is significant and concordant for both simulation and lung 4DCT, indicating the benefits of 4D planning. Conclusion: Our study shows that the BSD plan can approach the SD plan quality. However, such BSD scheme relies on the patient being able to follow the same breathing curve that is used in the planning stage during radiation delivery. Funded by Varian Medical Systems.« less

  10. Stabilization challenges and formulation strategies associated with oral biologic drug delivery systems.

    PubMed

    Truong-Le, Vu; Lovalenti, Phillip M; Abdul-Fattah, Ahmad M

    2015-10-01

    Delivery of proteins to mucosal tissues of GI tract typically utilize formulations which protect against proteolysis and target the mucosal tissues. Using case studies from literature and the authors' own work, the in-process stability and solid state storage stability of biopharmaceuticals formulated in delivery systems designed for oral delivery to the GI tract will be reviewed. Among the range of delivery systems, biodegradable polymer systems for protection and controlled release of proteins have been the most studied; hence these systems will be covered in greater depth. These delivery systems include polymeric biodegradable microspheres or nanospheres that contain proteins or vaccines, which are designed to reduce the number of administrations/inoculations and the total protein dose required to achieve the desired biological effect. Specifically, this review will include a landscape survey of the systems that have been studied, the manufacturing processes involved, stability through the manufacturing process, key pharmaceutical formulation parameters that impact stability of the encased proteins, and storage stability of the encapsulated proteins in these delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. MicroRNAs as therapeutics for future drug delivery systems in treatment of lung diseases.

    PubMed

    Dua, Kamal; Hansbro, Nicole G; Foster, Paul S; Hansbro, Philip M

    2017-02-01

    The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system. In this review, we have summarised the concept of miRNAs and different approaches which can be employed to deliver miRNAs effectively and safely to the target cells including the challenges associated with their development in particular emphasis on pulmonary diseases. Such approaches will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of miRNA delivery for pulmonary inflammatory diseases.

  12. Enhancing the Delivery of an Empirically-Supported Trauma-Focused Treatment for Adolescents: Providers' Views of the Role of Technology and Web-Based Resources.

    PubMed

    Orengo-Aguayo, Rosaura E; Hanson, Rochelle F; Moreland, Angela D; Jobe-Shields, Lisa; Adams, Zachary W

    2018-07-01

    This mixed-methods study assessed providers' views of the use of technology in the delivery of an empirically supported mental health treatment for adolescents (Trauma-Focused Cognitive Behavioral Therapy; TF-CBT). Thematic qualitative interviews were conducted with nine experienced providers. Emerging themes served as the basis for the creation of a quantitative web-based survey, completed by 56 TF-CBT experts, to assess the perceived helpfulness of the recommendations. Technology was perceived as a useful, appealing, and familiar tool that could greatly enhance the delivery of this treatment modality with adolescents. Main recommendations included the creation of a mobile application targeting all of the treatment components and a website with developmentally appropriate resources for providers, caregivers, and teens. Technology may be a useful tool for enhancing service delivery and promoting engagement among youth receiving trauma-focused mental health treatment.

  13. Nanostructured Platforms for the Sustained and Local Delivery of Antibiotics in the Treatment of Osteomyelitis

    PubMed Central

    Uskoković, Vuk

    2015-01-01

    This article provides a critical view of the current state of the development of nanoparticulate and other solid-state carriers for the local delivery of antibiotics in the treatment of osteomyelitis. Mentioned are the downsides of traditional means for treating bone infection, which involve systemic administration of antibiotics and surgical debridement, along with the rather imperfect local delivery options currently available in the clinic. Envisaged are more sophisticated carriers for the local and sustained delivery of antimicrobials, including bioresorbable polymeric, collagenous, liquid crystalline, and bioglass- and nanotube-based carriers, as well as those composed of calcium phosphate, the mineral component of bone and teeth. A special emphasis is placed on composite multifunctional antibiotic carriers of a nanoparticulate nature and on their ability to induce osteogenesis of hard tissues demineralized due to disease. An ideal carrier of this type would prevent the long-term, repetitive, and systemic administration of antibiotics and either minimize or completely eliminate the need for surgical debridement of necrotic tissue. Potential problems faced by even hypothetically “perfect” antibiotic delivery vehicles are mentioned too, including (i) intracellular bacterial colonies involved in recurrent, chronic osteomyelitis; (ii) the need for mechanical and release properties to be adjusted to the area of surgical placement; (iii) different environments in which in vitro and in vivo testings are carried out; (iv) unpredictable synergies between drug delivery system components; and (v) experimental sensitivity issues entailing the increasing subtlety of the design of nanoplatforms for the controlled delivery of therapeutics. PMID:25746204

  14. Agile delivery of protein therapeutics to CNS.

    PubMed

    Yi, Xiang; Manickam, Devika S; Brynskikh, Anna; Kabanov, Alexander V

    2014-09-28

    A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Agile Delivery of Protein Therapeutics to CNS

    PubMed Central

    Yi, Xiang; Manickam, Devika S.; Brynskikh, Anna; Kabanov, Alexander V.

    2014-01-01

    A variety of therapeutic proteins have shown potential to treat central nervous system (CNS) disorders. Challenge to deliver these protein molecules to the brain is well known. Proteins administered through parenteral routes are often excluded from the brain because of their poor bioavailability and the existence of the blood-brain barrier (BBB). Barriers also exist to proteins administered through non-parenteral routes that bypass the BBB. Several strategies have shown promise in delivering proteins to the brain. This review, first, describes the physiology and pathology of the BBB that underscore the rationale and needs of each strategy to be applied. Second, major classes of protein therapeutics along with some key factors that affect their delivery outcomes are presented. Third, different routes of protein administration (parenteral, central intracerebroventricular and intraparenchymal, intranasal and intrathecal) are discussed along with key barriers to CNS delivery associated with each route. Finally, current delivery strategies involving chemical modification of proteins and use of particle-based carriers are overviewed using examples from literature and our own work. Whereas most of these studies are in the early stage, some provide proof of mechanism of increased protein delivery to the brain in relevant models of CNS diseases, while in few cases proof of concept had been attained in clinical studies. This review will be useful to broad audience of students, academicians and industry professionals who consider critical issues of protein delivery to the brain and aim developing and studying effective brain delivery systems for protein therapeutics. PMID:24956489

  16. Successful Remote Delivery of a Treatment for Phonologic Alexia via Telerehab

    PubMed Central

    Sarah, Snider; David, Brennan; Rhonda, Friedman

    2015-01-01

    A growing body of literature supports the effectiveness of the remote delivery of rehabilitation services, i.e., telerehab. Aphasia treatment is particularly well suited for telerehab because of the verbal and visual nature of speech-language therapy, but scientific research investigating aphasia telerehab is in its infancy. No studies to date have evaluated whether treatment of acquired reading disorders by a live clinician can be feasibly, effectively, or efficiently conducted via telerehab. Here we address this gap in the literature by reporting our success remotely remediating the reading deficits of two participants with phonologic alexia. We adapted for the telerehab setting a previously validated treatment for phonologic alexia (Friedman, Sample, & Lott, 2002), which uses a paired-associate design to train reading of problematic words. Both telerehab participants significantly improved their reading of trained words in similar time frames as previous participants (Friedman et al., 2002; Kurland et al., 2008; Lott, Sample, Oliver, Lacey, & Friedman, 2008); furthermore, both participants reported high satisfaction with the telerehab setting. Although telerehab with alexic patients poses unique challenges, we conclude that treatment for alexia via telerehab is nevertheless feasible, may be equally effective as in-person treatment, and saves substantial resources for participants as well as clinicians. PMID:26018197

  17. Treatment 2.0: catalyzing the next phase of treatment, care and support.

    PubMed

    Duncombe, Chris; Ball, Andrew; Passarelli, Carlos; Hirnschall, Gottfried

    2013-01-01

    This review provides an update on the WHO/UNAIDS Treatment 2.0 strategy by reviewing the documents and technical updates issued under the initiative. Launched in 2010, this global initiative provides a framework for the continued scale-up of access to HIV care and treatment. WHO has prioritized once daily fixed-dose combination as the preferred antiretroviral (ARV) regimen to initiate HIV treatment, paving the way for programmatic simplification, with reduced toxicity and improved adherence. WHO also recommends the use of point-of-care diagnostics, with CD4 cell count technologies being implemented in the field and progress towards improving access to simplified viral load testing. The strategy also seeks mechanisms that can contribute to reducing treatment costs, such as pooled commodity procurement and public health-oriented licensing approaches. Improved service delivery, specifically through decentralization, task shifting, integration and community mobilization also has the potential to reduce costs and improve access. Support to countries has been provided through the timely release of a series of programmatic and technical updates on specific treatment-related topics. The Treatment 2.0 strategy articulates how innovation and greater efficiency can make HIV care and treatment more accessible and affordable, and guide treatment and prevention scale-up.

  18. A method for verification of treatment delivery in HDR prostate brachytherapy using a flat panel detector for both imaging and source tracking.

    PubMed

    Smith, Ryan L; Haworth, Annette; Panettieri, Vanessa; Millar, Jeremy L; Franich, Rick D

    2016-05-01

    Verification of high dose rate (HDR) brachytherapy treatment delivery is an important step, but is generally difficult to achieve. A technique is required to monitor the treatment as it is delivered, allowing comparison with the treatment plan and error detection. In this work, we demonstrate a method for monitoring the treatment as it is delivered and directly comparing the delivered treatment with the treatment plan in the clinical workspace. This treatment verification system is based on a flat panel detector (FPD) used for both pre-treatment imaging and source tracking. A phantom study was conducted to establish the resolution and precision of the system. A pretreatment radiograph of a phantom containing brachytherapy catheters is acquired and registration between the measurement and treatment planning system (TPS) is performed using implanted fiducial markers. The measured catheter paths immediately prior to treatment were then compared with the plan. During treatment delivery, the position of the (192)Ir source is determined at each dwell position by measuring the exit radiation with the FPD and directly compared to the planned source dwell positions. The registration between the two corresponding sets of fiducial markers in the TPS and radiograph yielded a registration error (residual) of 1.0 mm. The measured catheter paths agreed with the planned catheter paths on average to within 0.5 mm. The source positions measured with the FPD matched the planned source positions for all dwells on average within 0.6 mm (s.d. 0.3, min. 0.1, max. 1.4 mm). We have demonstrated a method for directly comparing the treatment plan with the delivered treatment that can be easily implemented in the clinical workspace. Pretreatment imaging was performed, enabling visualization of the implant before treatment delivery and identification of possible catheter displacement. Treatment delivery verification was performed by measuring the source position as each dwell was delivered

  19. A method for verification of treatment delivery in HDR prostate brachytherapy using a flat panel detector for both imaging and source tracking

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, Ryan L., E-mail: ryan.smith@wbrc.org.au; Millar, Jeremy L.; Franich, Rick D.

    Purpose: Verification of high dose rate (HDR) brachytherapy treatment delivery is an important step, but is generally difficult to achieve. A technique is required to monitor the treatment as it is delivered, allowing comparison with the treatment plan and error detection. In this work, we demonstrate a method for monitoring the treatment as it is delivered and directly comparing the delivered treatment with the treatment plan in the clinical workspace. This treatment verification system is based on a flat panel detector (FPD) used for both pre-treatment imaging and source tracking. Methods: A phantom study was conducted to establish the resolutionmore » and precision of the system. A pretreatment radiograph of a phantom containing brachytherapy catheters is acquired and registration between the measurement and treatment planning system (TPS) is performed using implanted fiducial markers. The measured catheter paths immediately prior to treatment were then compared with the plan. During treatment delivery, the position of the {sup 192}Ir source is determined at each dwell position by measuring the exit radiation with the FPD and directly compared to the planned source dwell positions. Results: The registration between the two corresponding sets of fiducial markers in the TPS and radiograph yielded a registration error (residual) of 1.0 mm. The measured catheter paths agreed with the planned catheter paths on average to within 0.5 mm. The source positions measured with the FPD matched the planned source positions for all dwells on average within 0.6 mm (s.d. 0.3, min. 0.1, max. 1.4 mm). Conclusions: We have demonstrated a method for directly comparing the treatment plan with the delivered treatment that can be easily implemented in the clinical workspace. Pretreatment imaging was performed, enabling visualization of the implant before treatment delivery and identification of possible catheter displacement. Treatment delivery verification was performed by measuring

  20. Optical treatment strategies to slow myopia progression: Effects of the visual extent of the optical treatment zone

    PubMed Central

    Smith, Earl L.

    2013-01-01

    In order to develop effective optical treatment strategies for myopia, it is important to understand how visual experience influences refractive development. Beginning with the discovery of the phenomenon of form deprivation myopia, research involving many animal species has demonstrated that refractive development is regulated by visual feedback. In particular, animal studies have shown that optically imposed myopic defocus slows axial elongation, that the effects of vision are dominated by local retinal mechanisms, and that peripheral vision can dominate central refractive development. In this review, the results obtained from clinical trials of traditional optical treatment strategies employed in efforts to slow myopia progression in children are interpreted in light of the results from animal studies and are compared to the emerging results from preliminary clinical studies of optical treatment strategies that manipulate the effective focus of the peripheral retina. Overall, the results suggest that imposed myopic defocus can slow myopia progression in children and that the effectiveness of an optical treatment strategy in reducing myopia progression is influenced by the extent of the visual field that is manipulated. PMID:23290590

  1. Filled carbon nanotubes in biomedical imaging and drug delivery.

    PubMed

    Martincic, Markus; Tobias, Gerard

    2015-04-01

    Carbon nanotubes have been advocated as promising candidates in the biomedical field in the areas of diagnosis and therapy. In terms of drug delivery, the use of carbon nanotubes can overcome some limitations of 'free' drugs by improving the formulation of poorly water-soluble drugs, allowing targeted delivery and even enabling the co-delivery of two or more drugs for combination therapy. Two different approaches are currently being explored for the delivery of diagnostic and therapeutic agents by carbon nanotubes, namely attachment of the payload to the external sidewalls or encapsulation into the inner cavities. Although less explored, the latter confers additional stability to the chosen diagnostic or therapeutic agents, and leaves the backbone structure of the nanotubes available for its functionalization with dispersing and targeting moieties. Several drug delivery systems and diagnostic agents have been developed in the last years employing the inner tubular cavities of carbon nanotubes. The research discussed in this review focuses on the use of carbon nanotubes that contain in their interior drug molecules and diagnosis-related compounds. The approaches employed for the development of such nanoscale vehicles along with targeting and releasing strategies are discussed. The encapsulation of both biomedical contrast agents and drugs inside carbon nanotubes is further expanding the possibilities to allow an early diagnosis and treatment of diseases.

  2. The Prevalence and Impact of Substance Use Disorder and Treatment on Maternal Obstetric Experiences and Birth Outcomes among Singleton Deliveries in Massachusetts

    PubMed Central

    Kotelchuck, Milton; Cheng, Erika R.; Belanoff, Candice; Cabral, Howard J.; Babakhanlou-Chase, Hermik; Derrington, Taletha M.; Diop, Hafsatou; Evans, Stephen R.; Bernstein, Judith

    2016-01-01

    Background Despite widely-known negative effects of substance use disorders (SUD) on women, children, and society, knowledge about population-based prevalence and impact of SUD and SUD treatment during the perinatal period is limited. Methods Population-based data from 375,851 singleton deliveries in Massachusetts 2003–2007 were drawn from a maternal-infant longitudinally-linked statewide dataset of vital statistics, hospital discharges (including emergency department (ED) visits), and SUD treatment records. Maternal SUD and SUD treatment were identified from one-year pre-conception through delivery. We determined (1) the prevalence of SUD and SUD treatment; (2) the association of SUD with women’s perinatal health service utilization, obstetric experiences, and birth outcomes; and (3) the association of SUD treatment with birth outcomes, using both bivariate and adjusted analyses. Principal Findings 5.5% of Massachusetts’s deliveries between 2003–2007 occurred in mothers with SUD, but only 66% of them received SUD treatment pre-delivery. Women with SUD were poorer, less educated and had more health problems; utilized less prenatal care but more antenatal ED visits and hospitalizations, and had worse obstetric and birth outcomes. In adjusted analyses, SUD was associated with higher risk of prematurity (AOR 1.35, 95% CI 1.28–1.41) and low birthweight (LBW) (AOR 1.73, 95%CI 1.64–1.82). Women receiving SUD treatment had lower odds of prematurity (AOR 0.61, 95%CI 0.55–0.68) and LBW (AOR 0.54, 95%CI 0.49–0.61). Conclusions SUD treatment may improve perinatal outcomes among pregnant women with SUD, but many who need treatment don’t receive it. Longitudinally-linked existing public health and programmatic records provide opportunities for states to monitor SUD identification and treatment. PMID:27832443

  3. Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

    PubMed

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2013-11-01

    Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Biodegradable nanoparticles for intracellular delivery of antimicrobial agents.

    PubMed

    Xie, Shuyu; Tao, Yanfei; Pan, Yuanhu; Qu, Wei; Cheng, Guyue; Huang, Lingli; Chen, Dongmei; Wang, Xu; Liu, Zhenli; Yuan, Zonghui

    2014-08-10

    Biodegradable nanoparticles have emerged as a promising strategy for ferrying antimicrobial agents into specific cells due to their unique properties. This review discusses the current progress and challenges of biodegradable nanoparticles for intracellular antimicrobial delivery to understand design principles for the development of ideal nanocarriers. The intracellular delivery performances of biodegradable nanoparticles for diverse antimicrobial agents are first summarized. Second, the cellular internalization and intracellular trafficking, degradation and release kinetics of nanoparticles as well as their relation with intracellular delivery of encapsulated antimicrobial agents are provided. Third, the influences of nanoparticle properties on the cellular internalization and intracellular fate of nanoparticles and their payload antimicrobial agents are discussed. Finally, the challenges and perspectives of nanoparticles for intracellular delivery of antimicrobial agents are addressed. The review will be helpful to the scientists who are interested in searching for more efficient nanosystem strategies for intracellular delivery of antimicrobial agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

    PubMed Central

    Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon

    2015-01-01

    Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy. PMID:26078967

  6. Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review.

    PubMed

    Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; Gonçalez, Maíra Lima; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon; Chorilli, Marlus

    2015-01-01

    Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

  7. Preconception care: delivery strategies and packages for care

    PubMed Central

    2014-01-01

    The notion of preconception care aims to target the existing risks before pregnancy, whereby resources may be used to improve reproductive health and optimize knowledge before conceiving. The preconception period provides an opportunity to intervene earlier to optimize the health of potential mothers (and fathers) and to prevent harmful exposures from affecting the developing fetus. These interventions include birth spacing and preventing teenage pregnancy, promotion of contraceptive use, optimization of weight and micronutrient status, prevention and management of infectious diseases, and screening for and managing chronic conditions. Given existing interventions and the need to organize services to optimize delivery of care in a logical and effective manner, interventions are frequently co-packaged or bundled together. This paper highlights packages of preconception interventions that can be combined and co-delivered to women through various delivery channels and provides a logical framework for development of such packages in varying contexts. PMID:25415178

  8. Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

    PubMed

    Barua, Neil U; Gill, Steven S; Love, Seth

    2014-03-01

    Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD). © 2013 International Society of Neuropathology.

  9. 'Smart' nanoparticles as drug delivery systems for applications in tumor therapy.

    PubMed

    Fang, Zhi; Wan, Lin-Yan; Chu, Liang-Yin; Zhang, Yan-Qiong; Wu, Jiang-Feng

    2015-01-01

    In the therapy of clinical diseases such as cancer, it is important to deliver drugs directly to tumor sites in order to maximize local drug concentration and reduce side effects. This objective may be realized by using 'smart' nanoparticles (NPs) as drug delivery systems, because they enable dramatic conformational changes in response to specific physical/chemical stimuli from the diseased cells for targeted and controlled drug release. In this review, we first briefly summarize the characteristics of 'smart' NPs as drug delivery systems in medical therapy, and then discuss their targeting transport, transmembrane and endosomal escape behaviors. Lastly, we focus on the applications of 'smart' NPs as drug delivery systems for tumor therapy. Biodegradable 'smart' NPs have the potential to achieve maximum efficacy and drug availability at the desired sites, and reduce the harmful side effects for healthy tissues in tumor therapy. It is necessary to select appropriate NPs and modify their characteristics according to treatment strategies of tumor therapy.

  10. Nanoengineered drug delivery systems for enhancing antibiotic therapy.

    PubMed

    Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

    2015-03-01

    Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Ionic liquids in drug delivery.

    PubMed

    Shamshina, Julia L; Barber, Patrick S; Rogers, Robin D

    2013-10-01

    To overcome potential problems with solid-state APIs, such as polymorphism, solubility and bioavailability, pure liquid salt (ionic liquid) forms of active pharmaceutical ingredients (API-ILs) are considered here as a design strategy. After a critical review of the current literature, the recent development of the API-ILs strategy is presented, with a particular focus on the liquefaction of drugs. A variety of IL tools for control over the liquid salt state of matter are discussed including choice of counterion to produce an IL from a given API; the concept of oligomeric ions that enables liquefaction of solid ILs by changing the stoichiometry or complexity of the ions; formation of 'liquid co-crystals' where hydrogen bonding is the driving force in the liquefaction of a neutral acid-base complex; combining an IL strategy with the prodrug strategy to improve the delivery of solid APIs; using ILs as delivery agents via trapping a drug in a micelle and finally ILs designed with tunable hydrophilic-lipophilic balance that matches the structural requirements needed to solubilize poorly water-soluble APIs. The authors believe that API-IL approaches may save failed lead candidates, extend the patent life of current APIs, lead to new delivery options or even new pharmaceutical action. They encourage the pharmaceutical industry to invest more research into the API-IL platform as it could lead to fast-tracked approval based on similarities to the APIs already approved.

  12. Development of antibody-modified chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier as a strategy for inhibiting HIV replication in astrocytes.

    PubMed

    Gu, Jijin; Al-Bayati, Karam; Ho, Emmanuel A

    2017-08-01

    RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands. In this study, chitosan nanoparticles (CS-NPs) were prepared by a complex coacervation method in the presence of siRNA, and antibody was chemically conjugated to the nanoparticles. The antibody-modified chitosan nanoparticles (Ab-CS-NPs) were spherical in shape, with an average particle size of 235.7 ± 10.2 nm and a zeta potential of 22.88 ± 1.78 mV. The therapeutic potential of the nanoparticles was evaluated based on their cellular uptake and gene silencing efficiency. Cellular accumulation and gene silencing efficiency of Ab-CS-NPs in astrocytes were significantly improved compared to non-modified CS-NPs and single-antibody-modified CS-NPs. These results suggest that the combination of anti-Tf antibody and anti-B2 antibody significantly increased the knockdown effect of siRNA-loaded nanoparticles. Thus, antibody-mediated dual-targeting nanoparticles are an efficient and promising delivery strategy for inhibiting HIV replication in astrocytes. Graphical abstract Graphic representation of dual-antibody-conjugated chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier (BBB) for inhibiting HIV replication in astrocytes. a Nanoparticle delivery to the BBB and penetration. b Tf

  13. Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

    PubMed Central

    Samorezov, Julia E.; Alsberg, Eben

    2015-01-01

    Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo. PMID:25445719

  14. Local Drug Delivery to Prevent Restenosis

    PubMed Central

    Seedial, Stephen M.; Ghosh, Soumojit; Saunders, R. Scott; Suwanabol, Pasithorn A.; Shi, Xudong; Liu, Bo; Kent, K. Craig

    2013-01-01

    Introduction Despite significant advances in vascular biology, bioengineering and pharmacology, restenosis remains a limitation to the overall efficacy of vascular reconstructions, both percutaneous and open. Although the pathophysiology of intimal hyperplasia is complex, a number of drugs and/or molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. In this article we provide a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis following vascular intervention. Methods A systematic electronic literature search using PubMed was performed for all accessible published articles through September 2012. In an effort to remain current, additional searches were performed for abstracts presented at relevant societal meetings, filed patents, clinical trials and funded NIH awards. Results The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents (DES). Until recently, however, DES were not found to be efficacious in the peripheral circulation. Further pursuit of intraluminal devices has led to the development of balloon-based technologies with a recent surge in trials involving drug-eluting balloons. Early data appears encouraging, particularly for treatment of lesions in the superficial femoral artery, with several devices having recently received the CE mark in Europe. Investigators have also explored periadventitial application of biomaterials containing anti-restenotic drugs, an approach that could be particularly useful for surgical bypass or endarterectomy. In the past systemic drug delivery has been unsuccessful, however, there has been recent exploration of intravenous delivery of drugs designed specifically to target injured or reconstructed arteries. Our review revealed a multitude of additional interesting

  15. Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates for targeted drug delivery.

    PubMed

    Xie, Xiangyang; Lin, Wen; Liu, Hui; Deng, Jianping; Chen, Ying; Liu, Hong; Fu, Xudong; Yang, Yang

    2016-10-01

    To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ∼200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.

  16. MicroRNA-targeted therapeutics for lung cancer treatment.

    PubMed

    Xue, Jing; Yang, Jiali; Luo, Meihui; Cho, William C; Liu, Xiaoming

    2017-02-01

    Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

  17. Strategy for a Sustained Quality Delivery Mode of ODL Programmes for Massive Enrollments and E-Learning: The Case for Zimbabwe Open University

    ERIC Educational Resources Information Center

    Kabanda, Gabriel

    2014-01-01

    The market dynamics in distance education has precipitated phenomenal growth opportunities in enrollments and e-learning. The purpose of the paper was to develop a strategy for sustained quality delivery mode of distance education progammes that precipitate massive enrollments and e-learning in an open and distance learning (ODL) institution using…

  18. Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice.

    PubMed

    Tehrani, A M; Hwang, S-K; Kim, T-H; Cho, C-S; Hua, J; Nah, W-S; Kwon, J-T; Kim, J-S; Chang, S-H; Yu, K-N; Park, S-J; Bhandari, D R; Lee, K-H; An, G-H; Beck, G R; Cho, M-H

    2007-03-01

    Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.

  19. Paclitaxel loaded phospholipid-based gel as a drug delivery system for local treatment of glioma.

    PubMed

    Chen, Tijia; Gong, Ting; Zhao, Ting; Liu, Xing; Fu, Yao; Zhang, Zhirong; Gong, Tao

    2017-08-07

    Paclitaxel (PTX) is a chemotherapeutic agent and has been widely used in clinic against human cancer. However, it has limited application in brain tumor treatment due to the poor penetration of blood brain barrier. Local delivery system is a promising carrier of PTX in the treatment of glioma. A biodegradable phospholipid-based gel (PG) system was developed for intratumoral injection and evaluated in brain glioma-bearing mice model. PTX loaded PG was composed of phospholipid, ethanol, medium chain triglyceride, triacetin and PTX. It was prepared by a very simple method. The system was a transparent solution with good fluidity, while turned into a gel after phase-transition when ethanol diffused. Both in vitro dissolution and in vivo imaging study proved the sustained release effect of PG system. In vivo tolerability study showed a better tolerability after mice treated with PTX PG compared with free PTX. The survival time of brain glioma-bearing mice after treatment with PTX PG was significantly prolonged compared with mice treated by free PTX (P<0.05). In conclusion, this study developed a novel PG based local PTX delivery system with simple preparation method, good tolerability and high therapeutic efficacy. It has a great potential to improve the clinical management of glioma. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Electroinduced Delivery of Hydrogel Nanoparticles in Colon 26 Cells, Visualized by Confocal Fluorescence System.

    PubMed

    Atanasova, Severina; Nikolova, Biliana; Murayama, Shuhei; Stoyanova, Elena; Tsoneva, Iana; Zhelev, Zhivko; Aoki, Ichio; Bakalova, Rumiana

    2016-09-01

    Nano-scale drug delivery systems (nano-DDS) are under intense investigation. Nano-platforms are developed for specific administration of small molecules, drugs, genes, contrast agents [quantum dots (QDs)] both in vivo and in vitro. Electroporation is a biophysical phenomenon which consists of the application of external electrical pulses across the cell membrane. The aim of this study was to research electro-assisted Colon 26 cell line internalization of QDs and QD-loaded nano-hydrogels (polymersomes) visualized by confocal microscopy and their influence on cell viability. The experiments were performed on the Colon 26 cancer cell line, using a confocal fluorescent imaging system and cell viability test. Electroporation facilitated the delivery of nanoparticles in vivo. We demonstrated increased voltage-dependent delivery of nanoparticles into cells after electrotreatment, without significant cell viability reduction. The delivery and retention of the polymersomes in vitro is a promising tool for future cancer treatment strategies and nanomedcine. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Strategies in treatment of suicidality: identification of common and treatment-specific interventions in empirically supported treatment manuals.

    PubMed

    Weinberg, Igor; Ronningstam, Elsa; Goldblatt, Mark J; Schechter, Mark; Wheelis, Joan; Maltsberger, John T

    2010-06-01

    Many reports of treatments for suicidal patients claim effectiveness in reducing suicidal behavior but fail to demonstrate which treatment interventions, or combinations thereof, diminish suicidality. In this study, treatment manuals for empirically supported psychological treatments for suicidal patients were examined to identify which interventions they had in common and which interventions were treatment-specific. Empirically supported treatments for suicidality were identified through a literature search of PsychLit and MEDLINE for the years 1970-2007, employing the following search strategy: [suicide OR parasuicide] AND [therapy OR psychotherapy OR treatment] AND [random OR randomized]. After identifying the reports on randomized controlled studies that tested effectiveness of different treatments, the reference list of each report was searched for further studies. Only reports published in English were included. To ensure that rated manuals actually correspond to the delivered and tested treatments, we included only treatment interventions with explicit adherence rating and scoring and with adequate adherence ratings in the published studies. Five manualized treatments demonstrating efficacy in reducing suicide risk were identified and were independently evaluated by raters using a list of treatment interventions. The common interventions included a clear treatment framework; a defined strategy for managing suicide crises; close attention to affect; an active, participatory therapist style; and use of exploratory and change-oriented interventions. Some treatments encouraged a multimodal approach and identification of suicidality as an explicit target behavior, and some concentrated on the patient-therapist relationship. Emphasis on interpretation and supportive interventions varied. Not all methods encouraged systematic support for therapists. This study identified candidate interventions for possible effectiveness in reducing suicidality. These interventions

  2. Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies

    PubMed Central

    Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F

    2017-01-01

    Abstract Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients’ psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. PMID:28498954

  3. Genital herpes and its treatment in relation to preterm delivery.

    PubMed

    Li, De-Kun; Raebel, Marsha A; Cheetham, T Craig; Hansen, Craig; Avalos, Lyndsay; Chen, Hong; Davis, Robert

    2014-12-01

    To examine the risks of genital herpes and antiherpes treatment during pregnancy in relation to preterm delivery (PTD), we conducted a multicenter, member-based cohort study within 4 Kaiser Permanente regions: northern and southern California, Colorado, and Georgia. The study included 662,913 mother-newborn pairs from 1997 to 2010. Pregnant women were classified into 3 groups based on genital herpes diagnosis and treatment: genital herpes without treatment, genital herpes with antiherpes treatment, and no herpes diagnosis or treatment (unexposed controls). After controlling for potential confounders, we found that compared with being unexposed, having untreated genital herpes during first or second trimester was associated with more than double the risk of PTD (odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.80, 2.76). The association was stronger for PTD due to premature rupture of membrane (OR = 3.57, 95% CI: 2.53, 5.06) and for early PTD (≤35 weeks gestation) (OR = 2.87, 95% CI: 2.22, 3.71). In contrast, undergoing antiherpes treatment during pregnancy was associated with a lower risk of PTD compared with not being treated, and the PTD risk was similar to that observed in the unexposed controls (OR = 1.11, 95% CI: 0.89, 1.38). The present study revealed increased risk of PTD associated with genital herpes infection if left untreated and a potential benefit of antiherpes medications in mitigating the effect of genital herpes infection on the risk of PTD. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Treatment strategy for a multidrug-resistant Klebsiella UTI.

    PubMed

    Fleming, Erin; Heil, Emily L; Hynicka, Lauren M

    2014-01-01

    To describe the management strategy for a multidrug-resistant (MDR) Klebsiella urinary tract infection (UTI). A 69-year-old Caucasian woman with a past medical history of recurrent UTIs and a right-lung transplant presented with fever to 101.4°F, chills, malaise, and cloudy, foul-smelling urine for approximately 1 week. She was found to have a MDR Klebsiella UTI that was sensitive to tigecycline and cefepime. To further evaluate the degree of resistance Etest minimum inhibitory concentrations were requested for cefepime, amikacin, meropenem, and ertapenem. The patient received a 14-day course of amikacin, which resulted in resolution of her symptoms. One month later, the patient's UTI symptoms returned. The urine culture again grew MDR Klebsiella, sensitive only to tigecycline. Fosfomycin was initiated and resulted in limited resolution of her symptoms. Colistin was started, however, therapy was discontinued on day 5 secondary to the development of acute kidney injury. Despite the short course of therapy, the patient's symptoms resolved. The case presented lends itself well to numerous discussion items that are important to consider when determining optimal treatment for MDR Gram-negative bacilli (GNBs). Susceptibility testing is an important tool for optimizing antibiotic therapy, however, automated systems may overestimate the susceptibility profile for a MDR GNB. Treatment strategies evaluated to treat MDR GNB, include combination therapy with a carbepenem and synergy using polymyxin. We have described the management strategy for a MDR Klebsiella UTI, the consequences of the initial management strategy, and potential strategies to manage these types of infections in future patients.

  5. Poster — Thur Eve — 33: The Influence of a Modeled Treatment Couch on Dose Distributions During IMRT and RapidArc Treatment Delivery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aldosary, Ghada; Nobah, Ahmad; Al-Zorkani, Faisal

    2014-08-15

    Treatment couches have been known to perturb dose delivery in patients. This effect is most pronounced in techniques such as IMRT and RapidArc. Although modern treatment planning systems (TPS) include data for a “default” treatment couch, actual couches are not manufactured identically. Thus, variations in their Hounsfield Unit (HU) values may exist. This study demonstrates a practical and simple method of acquiring reliable HU data for any treatment couch. We also investigate the effects of both the default and modeled treatment couches on absorbed dose. Experimental verifications show that by neglecting to incorporate the treatment couch in the TPS, dosemore » differences of up to 9.5% and 7.3% were present for 4 MV and 10 MV photon beams, respectively. Furthermore, a clinical study based on a cohort of 20 RapidArc and IMRT (brain, pelvis and abdominal) cases is performed. 2D dose distributions show that without the couch in the planning phase, differences ≤ 4.6% and 5.9% for RapidArc and IMRT cases are present for the same cases that the default couch was added to. Additionally, in comparison to the default couch, employing the modeled couch in the calculation process influences dose distributions by ≤ 2.7% and 8% for RapidArc and IMRT cases, respectively. This result was found to be site specific; where an accurate couch proves to be preferable for IMRT brain plans. As such, adding the couch during dose calculation decreases dose calculation errors, and a precisely modeled treatment couch offers higher dose delivery accuracy for brain treatment using IMRT.« less

  6. Feasibility study on the verification of actual beam delivery in a treatment room using EPID transit dosimetry.

    PubMed

    Baek, Tae Seong; Chung, Eun Ji; Son, Jaeman; Yoon, Myonggeun

    2014-12-04

    The aim of this study is to evaluate the ability of transit dosimetry using commercial treatment planning system (TPS) and an electronic portal imaging device (EPID) with simple calibration method to verify the beam delivery based on detection of large errors in treatment room. Twenty four fields of intensity modulated radiotherapy (IMRT) plans were selected from four lung cancer patients and used in the irradiation of an anthropomorphic phantom. The proposed method was evaluated by comparing the calculated dose map from TPS and EPID measurement on the same plane using a gamma index method with a 3% dose and 3 mm distance-to-dose agreement tolerance limit. In a simulation using a homogeneous plastic water phantom, performed to verify the effectiveness of the proposed method, the average passing rate of the transit dose based on gamma index was high enough, averaging 94.2% when there was no error during beam delivery. The passing rate of the transit dose for 24 IMRT fields was lower with the anthropomorphic phantom, averaging 86.8% ± 3.8%, a reduction partially due to the inaccuracy of TPS calculations for inhomogeneity. Compared with the TPS, the absolute value of the transit dose at the beam center differed by -0.38% ± 2.1%. The simulation study indicated that the passing rate of the gamma index was significantly reduced, to less than 40%, when a wrong field was erroneously irradiated to patient in the treatment room. This feasibility study suggested that transit dosimetry based on the calculation with commercial TPS and EPID measurement with simple calibration can provide information about large errors for treatment beam delivery.

  7. Insoluble drug delivery strategies: review of recent advances and business prospects

    PubMed Central

    Kalepu, Sandeep; Nekkanti, Vijaykumar

    2015-01-01

    The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects. PMID:26579474

  8. An Exploration of Service Delivery in India.

    ERIC Educational Resources Information Center

    McClam, Tricia; Woodside, Marianne

    2000-01-01

    Discusses visits to five social service agencies in Mumbai, India and interviews with human service providers and clients to better understand Indian human service delivery and its societal context. Identifies three Indian service delivery strategies to enrich teaching and add a global component to the curriculum: advocacy, the use of…

  9. Improving consistency and quality of service delivery: implications for the addiction treatment field.

    PubMed

    Knott, Anne Marie; Corredoira, Rafael; Kimberly, John

    2008-09-01

    Addiction treatment providers face serious problems in delivering consistent, high-quality services over time. Among those providers with multiple treatment sites, there is also intersite variability. This is a serious problem in the addiction field, likely to be made worse as new technologies are introduced and/or as there is industry consolidation (Corredoira, R., Kimberly, J. (2006) Industry evolution through consolidation: Implications for addiction treatment. Journal of Substance Abuse Treatment 31, 255-265.). Although serious, these problems in managing and monitoring to assure consistent service quality have been faced by many other industries. Here, we review evidence from research in other industries regarding three different forms of management (vertical integration, franchising, and licensing) across a chain of individual service providers. We show how each management form affects the level, consistency, and improvement of service delivery over time. In addition, we discuss how such performance advantages affect customer demand as well as regulatory endorsement of the consolidated firm and its approach.

  10. Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl; Kooy, Hanne M.; Heijmen, Ben J.M.

    2015-06-01

    Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases.more » Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.« less

  11. An Overview on Dry Eye Treatment: Approaches for Cyclosporin A Delivery

    PubMed Central

    Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2012-01-01

    Dry eye syndrome (DES, Keratoconjunctivitis sicca) is a common disorder of the tear film caused by decreased tear production or increased evaporation. Changes in tear composition also promote inflammation on the ocular surface by various mechanisms. Artificial tear drops, tear retention treatment, stimulation of tear secretion, or anti-inflammatory drugs may be used for dry eye treatment according to the severity of the disease. For untreated patients, the risk of ocular infection increases at considerable level and clinical course of the disease may proceed up to infection, corneal ulcer, and blindness. Artificial tears and/or punctual occlusions are used for tear replacement or preservation. New treatment approaches are designed to modify the underlying disease process. For the treatment of severe dry eye disease, cyclosporin A (CsA), the first one of the new generation immunomodulatory drugs, which has an anti-inflammatory effect, is frequently used. CsA has immunosuppressive effects following systemic application. Following local administration of CsA, it is expected to obtain effective drug concentration at the target area and to avoid the various side effects associated with systemic delivery. Microspheres, implants, and liposomes have been developed for administration of CsA subconjunctivally in order to enhance its efficiency. PMID:22619624

  12. Deformable Dose Reconstruction to Optimize the Planning and Delivery of Liver Cancer Radiotherapy

    NASA Astrophysics Data System (ADS)

    Velec, Michael

    The precise delivery of radiation to liver cancer patients results in improved control with higher tumor doses and minimized normal tissues doses. A margin of normal tissue around the tumor requires irradiation however to account for treatment delivery uncertainties. Daily image-guidance allows targeting of the liver, a surrogate for the tumor, to reduce geometric errors. However poor direct tumor visualization, anatomical deformation and breathing motion introduce uncertainties between the planned dose, calculated on a single pre-treatment computed tomography image, and the dose that is delivered. A novel deformable image registration algorithm based on tissue biomechanics was applied to previous liver cancer patients to track targets and surrounding organs during radiotherapy. Modeling these daily anatomic variations permitted dose accumulation, thereby improving calculations of the delivered doses. The accuracy of the algorithm to track dose was validated using imaging from a deformable, 3-dimensional dosimeter able to optically track absorbed dose. Reconstructing the delivered dose revealed that 70% of patients had substantial deviations from the initial planned dose. An alternative image-guidance technique using respiratory-correlated imaging was simulated, which reduced both the residual tumor targeting errors and the magnitude of the delivered dose deviations. A planning and delivery strategy for liver radiotherapy was then developed that minimizes the impact of breathing motion, and applied a margin to account for the impact of liver deformation during treatment. This margin is 38% smaller on average than the margin used clinically, and permitted an average dose-escalation to liver tumors of 9% for the same risk of toxicity. Simulating the delivered dose with deformable dose reconstruction demonstrated the plans with smaller margins were robust as 90% of patients' tumors received the intended dose. This strategy can be readily implemented with widely

  13. Drug delivery systems for ovarian cancer treatment: a systematic review and meta-analysis of animal studies

    PubMed Central

    Raavé, René; de Vries, Rob B.M.; Massuger, Leon F.; van Kuppevelt, Toin H.

    2015-01-01

    Current ovarian cancer treatment involves chemotherapy that has serious limitations, such as rapid clearance, unfavorable biodistribution and severe side effects. To overcome these limitations, drug delivery systems (DDS) have been developed to encapsulate chemotherapeutics for delivery to tumor cells. However, no systematic assessment of the efficacy of chemotherapy by DDS compared to free chemotherapy (not in a DDS) has been performed for animal studies. Here, we assess the efficacy of chemotherapy in DDS on survival and tumor growth inhibition in animal studies. We searched PubMed and EMBASE (via OvidSP) to systematically identify studies evaluating chemotherapeutics encapsulated in DDS for ovarian cancer treatment in animal studies. Studies were assessed for quality and risk of bias. Study characteristics were collected and outcome data (survival/hazard ratio or tumor growth inhibition) were extracted and used for meta-analyses. Meta-analysis was performed to identify and explore which characteristics of DDS influenced treatment efficacy. A total of 44 studies were included after thorough literature screening (2,735 studies found after initial search). The risk of bias was difficult to assess, mainly because of incomplete reporting. A total of 17 studies (377 animals) and 16 studies (259 animals) could be included in the meta-analysis for survival and tumor growth inhibition, respectively. In the majority of the included studies chemotherapeutics entrapped in a DDS significantly improved efficacy over free chemotherapeutics regarding both survival and tumor growth inhibition. Subgroup analyses, however, revealed that cisplatin entrapped in a DDS did not result in additional tumor growth inhibition compared to free cisplatin, although it did result in improved survival. Micelles did not show a significant tumor growth inhibition compared to free chemotherapeutics, which indicates that micelles may not be a suitable DDS for ovarian cancer treatment. Other

  14. Nanobiotechnology-based drug delivery in brain targeting.

    PubMed

    Dinda, Subas C; Pattnaik, Gurudutta

    2013-01-01

    Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity

  15. Engineering nanoparticle strategies for effective cancer immunotherapy.

    PubMed

    Yoon, Hong Yeol; Selvan, Subramanian Tamil; Yang, Yoosoo; Kim, Min Ju; Yi, Dong Kee; Kwon, Ick Chan; Kim, Kwangmeyung

    2018-03-21

    Cancer immunotherapy has been emerging in recent years, due to the inherent nature of the immune system. Although recent successes of immunotherapeutics in clinical application have attracted development of a novel immunotherapeutics, the off-target side effect and low immunogenicity of them remain challenges for the effective cancer immunotherapy. Theranostic nanoparticle system may one of key technology to address these issues by offering targeted delivery of various types of immunotherapeutics, resulting in significant improvements in the tumor immunotherapy. However, appropriate design or engineering of nanoparticles will be needed to improve delivery efficiency of antigen, adjuvant and therapeutics, resulting in eliciting antitumor immunity. Here, we review the current state of the art of cancer immunotherapeutic strategies, mainly based on nanoparticles (NPs). This includes NP-based antigen/adjuvant delivery vehicles to draining lymph nodes, and tumor antigen-specific T-lymphocytes for cancer immunotherapy. Several NP-based examples are shown for immune checkpoint modulation and immunogenic cell death. These overall studies demonstrate the great potential of NPs in cancer immunotherapy. Finally, engineering NP strategies will provide great opportunities to improve therapeutic effects as well as optimization of treatment processes, allowing to meet the individual needs in the cancer immunotherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

    PubMed Central

    Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus

    2016-01-01

    Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis. PMID:27540288

  17. Innovative Technology for the Assisted Delivery of Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson Disease

    ERIC Educational Resources Information Center

    Halpern, Angela E.; Ramig, Lorraine O.; Matos, Carlos E. C.; Petska-Cable, Jill A.; Spielman, Jennifer L.; Pogoda, Janice M.; Gilley, Phillip M.; Sapir, Shimon; Bennett, John K.; McFarland, David H.

    2012-01-01

    Purpose: To assess the feasibility and effectiveness of a newly developed assistive technology system, Lee Silverman Voice Treatment Companion (LSVT[R] Companion[TM], hereafter referred to as "Companion"), to support the delivery of LSVT[R]LOUD, an efficacious speech intervention for individuals with Parkinson disease (PD). Method: Sixteen…

  18. UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy

    PubMed Central

    Lin, Lizhou; Fan, Yu; Gao, Feng; Jin, Lifang; Li, Dan; Sun, Wenjie; Li, Fan; Qin, Peng; Shi, Qiusheng; Shi, Xiangyang; Du, Lianfang

    2018-01-01

    Conventional chemotherapy of pancreatic cancer (PaCa) suffers the problems of low drug permeability and inherent or acquired drug resistance. Development of new strategies for enhanced therapy still remains a great challenge. Herein, we report a new ultrasound-targeted microbubble destruction (UTMD)-promoted delivery system based on dendrimer-entrapped gold nanoparticles (Au DENPs) for co-delivery of gemcitabine (Gem) and miR-21 inhibitor (miR-21i). Methods: In this study, Gem-Au DENPs/miR-21i was designed and synthesized. The designed polyplexes were characterized via transmission electron microscopy (TEM), Gel retardation assay and dynamic light scattering (DLS). Then, the optimum exposure parameters were examined by an ultrasound exposure platform. The cellular uptake, cytotoxicity and anticancer effects in vitro were analyzed by confocal laser microscopy, spectra microplate reader, flow cytometry and a chemiluminescence imaging system. Lastly, the anticancer effects in vivo were evaluated by contrast-enhanced ultrasound (CEUS), hematoxylin and eosin (H&E) staining, TUNEL staining and comparison of tumor volume. Results: The results showed that the Gem-Au DENPs/miR-21i can be uptake by cancer cells and the cellular uptake was further facilitated by UTMD with an ultrasound power of 0.4 W/cm2 to enhance the cell permeability. Further, the co-delivery of Gem and miR-21i with or without UTMD treatment displayed 82-fold and 13-fold lower IC50 values than the free Gem, respectively. The UTMD-promoted co-delivery of Gem and miR-21i was further validated by in vivo treatment and showed a significant tumor volume reduction and an increase in blood perfusion of xenografted pancreatic tumors. Conclusion: The co-delivery of Gem and miR-21i using Au DENPs can be significantly promoted by UTMD technology, hence providing a promising strategy for effective pancreatic cancer treatments. PMID:29556365

  19. Nanoparticle-mediated growth factor delivery systems: A new way to treat Alzheimer's disease.

    PubMed

    Lauzon, Marc-Antoine; Daviau, Alex; Marcos, Bernard; Faucheux, Nathalie

    2015-05-28

    The number of people diagnosed with Alzheimer's disease (AD) is increasing steadily as the world population ages, thus creating a huge socio-economic burden. Current treatments have only transient effects and concentrate on a single aspect of AD. There is much evidence suggesting that growth factors (GFs) have a great therapeutic potential and can play on all AD hallmarks. Because GFs are prone to denaturation and clearance, a delivery system is required to ensure protection and a sustainable delivery. This review provides information about the latest advances in the development of GF delivery systems (GFDS) targeting the brain in terms of in vitro and in vivo effects in the context of AD and discusses new strategies designed to increase the availability and the specificity of GFs to the brain. This paper also discusses, on a mechanistic level, the different delivery hurdles encountered by the carrier or the GF itself from its injection site up to the brain tissue. The major mass transport phenomena influencing the delivery systems targeting the brain are addressed and insights are given about how mechanistic mathematical frameworks can be developed to use and optimize them. Copyright © 2015. Published by Elsevier B.V.

  20. Nanocrystal: a novel approach to overcome skin barriers for improved topical drug delivery.

    PubMed

    Patel, Viral; Sharma, Om Prakash; Mehta, Tejal

    2018-04-01

    Skin is an important route of drug delivery for the treatment of various dermatological conditions. The advent of nanotechnology is paving the roadmaps for topical drug delivery by providing sustained release as well as maintaining a localized effect, outweighing the toxicity concern. Area covered: This review highlighted the morphology of skin, its barrier nature as well as drug penetration pathways after topical application of formulations. The existing methods to improve topical drug delivery, by infringing or permeating the skin barriers, are discussed. This context concretes the foundation to accentuate the need for the development of nanocrystal-based topical formulation. The mechanism of drug release, immediate as well as sustained release, after topical administration of drug nanocrystals is also elaborated. The special emphasis is given on the breakthrough achieved, in topical drug delivery using drug nanocrystals, so far in the plethora of literature, patents, and products, under clinical trial as well as in the market. Expert opinion: The current research on nanocrystals for topical drug delivery is highlighting the breakthroughs achieved so far. The output of these research envisages that topical nanocrystals based formulations can be a novel strategy for the drugs which are facing solubility, bioavailability and toxicity concerns.

  1. Natural extracellular nanovesicles and photodynamic molecules: is there a future for drug delivery?

    PubMed

    Kusuzaki, Katsuyuki; Matsubara, Takao; Murata, Hiroaki; Logozzi, Mariantonia; Iessi, Elisabetta; Di Raimo, Rossella; Carta, Fabrizio; Supuran, Claudiu T; Fais, Stefano

    2017-12-01

    Photodynamic molecules represent an alternative approach for cancer therapy for their property (i) to be photo-reactive; (ii) to be not-toxic for target cells in absence of light; (iii) to accumulate specifically into tumour tissues; (iv) to be activable by a light beam only at the tumour site and (v) to exert cytotoxic activity against tumour cells. However, to date their clinical use is limited by the side effects elicited by systemic administration. Extracellular vesicles are endogenous nanosized-carriers that have been recently introduced as a natural delivery system for therapeutic molecules. We have recently shown the ability of human exosomes to deliver photodynamic molecules. Therefore, this review focussed on extracellular vesicles as a novel strategy for the delivery of photodynamic molecules at cancer sites. This completely new approach may enhance the delivery and decrease the toxicity of photodynamic molecules, therefore, represent the future for photodynamic therapy for cancer treatment.

  2. Recent advances in therapeutics and drug delivery for the treatment of inner ear diseases: a patent review (2011-2015).

    PubMed

    Nguyen, Kim; Kempfle, Judith S; Jung, David H; McKenna, Charles E

    2017-02-01

    Inner ear disorders such as hearing loss, tinnitus, and Ménière's disease significantly impact the quality of life of affected individuals. Treatment of such disorders is an ongoing challenge. Current clinical approaches relieve symptoms but do not fully restore hearing, and the search for more effective therapeutic methods represents an area of urgent current interest. Areas covered: Thirty four patents and patent applications published from 2011 to 2015 were selected from the database of the U.S. Patent and Trademark Office (USPTO) and World Intellectual Property Organization (WIPO), covering new approaches for the treatment of inner ear disorders described in the patent literature: 1) identification of new therapeutic agents, 2) development of sustained release formulations, and 3) medical devices that facilitate delivery of such agents to the inner ear. Expert opinion: The search for effective treatments of inner ear disorders is ongoing. Increased understanding of the molecular mechanisms of hearing loss, Ménière's disease, and tinnitus is driving development of new therapeutic agents. However, delivery of these agents to the inner ear is a continuing challenge. At present, combination of a suitable drug with an appropriate mode of drug delivery is the key focus of innovative research to cure inner ear disorders.

  3. Rehabilitating antisocial personalities: treatment through self-governance strategies

    PubMed Central

    McRae, Leon

    2012-01-01

    Offenders with antisocial personality disorder (ASPD) are widely assumed to reject psychotherapeutic intervention. Some commentators, therefore, argue that those with the disorder are better managed in the criminal justice system, where, following the introduction of indeterminate sentences, engagement with psychological treatment is coercively linked to the achievement of parole. By comparison, National Institute of Clinical Excellence guidelines on the management and treatment of ASPD recommend that those who are treatment seeking should be considered for admission to specialist psychiatric hospitals. The rationale is that prison-based interventions are underresourced, and the treatment of ASPD is underprioritised. The justification is that offenders with ASPD can be rehabilitated, if they are motivated. One problem, however, is that little is known about why offenders with ASPD seek treatment or what effect subsequent treatment has on their self-understanding. The aim of this paper is to address these unresolved issues. It draws on the findings of Economic and Social Research Council (ESRC) funded qualitative study examining the experiences of sentenced male offenders admitted to a specialist personality disorder ward within the medium secure estate and the medical practitioners who treat them. The data are analysed with reference to Michel Foucault's work on governmentality and strategy in power relations. Two arguments are advanced: first, offenders with ASPD are motivated by legal coercive pressures to implement a variety of Foucauldian-type strategies to give the false impression of treatment progress. Second, and related, treatment does not result in changes in self-understanding in the resistive client with ASPD. This presupposes that, in respect of this group at least, Foucault was mistaken in his claim that resistive behaviours merely mask the effectiveness of treatment norms over time. Nevertheless, the paper concludes that specialist treatment in the

  4. Histone-Targeted Nucleic Acid Delivery for Tissue Regenerative Applications

    NASA Astrophysics Data System (ADS)

    Munsell, Erik V.

    enhanced expression enabled more robust levels of chondrogenesis in MSCs than treatments with equivalent amounts of recombinant growth factor protein. Additionally, nanocarrier design optimization provided effective pDNA condensation and controllable interactions with native histone effectors. Importantly, these optimized nanocarriers conferred stable nanoplex formation and maintained transfection efficiency under physiologically relevant conditions. Taken together, these advances may help drive the clinical translation of histone-targeted nucleic acid delivery strategies for the regeneration of damaged tissue following traumatic injury.

  5. Brain aging and Parkinson's disease: New therapeutic approaches using drug delivery systems.

    PubMed

    Rodríguez-Nogales, C; Garbayo, E; Carmona-Abellán, M M; Luquin, M R; Blanco-Prieto, M J

    2016-02-01

    The etiology and pathogenesis of Parkinson's disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alpha-synuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. WE-D-BRD-01: Innovation in Radiation Therapy Delivery: Advanced Digital Linac Features

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xing, L; Wong, J; Li, R

    2014-06-15

    Last few years has witnessed significant advances in linac technology and therapeutic dose delivery method. Digital linacs equipped with high dose rate FFF beams have been clinically implemented in a number of hospitals. Gated VMAT is becoming increasingly popular in treating tumors affected by respiratory motion. This session is devoted to update the audience with these technical advances and to present our experience in clinically implementing the new linacs and dose delivery methods. Topics to be covered include, technical features of new generation of linacs from different vendors, dosimetric characteristics and clinical need for FFF-beam based IMRT and VMAT, respiration-gatedmore » VMAT, the concept and implementation of station parameter optimized radiation therapy (SPORT), beam level imaging and onboard image guidance tools. Emphasis will be on providing fundamental understanding of the new treatment delivery and image guidance strategies, control systems, and the associated dosimetric characteristics. Commissioning and acceptance experience on these new treatment delivery technologies will be reported. Clinical experience and challenges encountered during the process of implementation of the new treatment techniques and future applications of the systems will also be highlighted. Learning Objectives: Present background knowledge of emerging digital linacs and summarize their key geometric and dosimetric features. SPORT as an emerging radiation therapy modality specifically designed to take advantage of digital linacs. Discuss issues related to the acceptance and commissioning of the digital linacs and FFF beams. Describe clinical utility of the new generation of digital linacs and their future applications.« less

  7. An electrospun scaffold integrating nucleic acid delivery for treatment of full thickness wounds

    PubMed Central

    Kobsa, Serge; Kristofik, Nina J.; Sawyer, Andrew J.; Bothwell, Alfred L.M.; Kyriakides, Themis R.; Saltzman, W. Mark

    2013-01-01

    We developed a multi-functional construct capable of controlled delivery of bioactive substances that can improve wound repair by supporting the intrinsic ability of the skin to heal. We synthesized electrospun scaffolds—composed of a blend of the degradable polymers poly(L-lactide) (PLA) or polycaprolactone (PCL)—that produce highly efficient non-viral in vivo gene delivery to cells in the wound bed, provide a protective barrier during early wound healing, and support cell migration and growth. This multi-functional material was tested for its influence on wound healing: scaffolds were loaded with plasmids encoding keratinocyte growth factor (KGF) and applied to full thickness wounds in mice. Compared to scaffolds with control plasmids, animals receiving the KGF plasmid-loaded scaffold produced significant enhancements in wound healing, which was quantified by improvements in the rate of wound re-epithelialization, keratinocyte proliferation, and granulation response. Further, we quantified the expression level of endogenous and plasmid-derived KGF in wound samples: qRT-PCR on wound sections revealed a correlation between the levels of plasmid-derived protein expression and histological analysis of wound healing, revealing an inverse relationship between the expression level of exogenous KGF and the size of the unhealed epithelial layer in wounds. Our findings suggest that engineered nanofiber PLA/PCL scaffolds are capable of highly efficient controlled DNA delivery and are promising materials for treatment of cutaneous wounds. PMID:23453058

  8. Clinical correlates of augmentation/combination treatment strategies in major depressive disorder.

    PubMed

    Dold, M; Bartova, L; Mendlewicz, J; Souery, D; Serretti, A; Porcelli, S; Zohar, J; Montgomery, S; Kasper, S

    2018-05-01

    This multicenter, multinational, cross-sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD). Sociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance (ancova), and Spearman's correlation analyses. 60.64% of all participants received augmentation and/or combination strategies with a mean number of 2.18 ± 1.22 simultaneously prescribed psychiatric drugs. We found male gender, older age, Caucasian descent, higher weight, low educational status, absence of occupation, psychotic symptoms, melancholic and atypical features, suicide risk, in-patient treatment, longer duration of hospitalization, some psychiatric comorbidities (panic disorder, agoraphobia, obsessive-compulsive disorder, and bulimia nervosa), comorbid somatic comorbidity in general and concurrent hypertension, thyroid dysfunction, diabetes, and heart disease in particular, higher current and retrospective Montgomery and Åsberg Depression Rating Scale total scores, treatment resistance, and higher antidepressant dosing to be significantly associated with augmentation/combination treatment. These findings were corroborated when examining the number of concurrently administered psychiatric drugs in the statistical analyses. Our findings suggest a clear association between augmentation/combination strategies and treatment-resistant/difficult-to-treat MDD conditions characterized by severe symptomatology and high amount of psychiatric and somatic comorbidities. © 2018 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

  9. Successful delivery of adjuvant external beam radiotherapy for ependymoma in a patient with Ondine's curse

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Choi, Mehee; Thoma, Miranda; Tolekidis, George

    Ondine's curse is a rare, potentially life-threatening disorder characterized by loss of automatic breathing during sleep and preserved voluntary breathing. It is seldom encountered in the radiotherapy clinic but can pose significant technical challenges and safety concerns in the delivery of a prescribed radiation course. We report a unique case of successful delivery of radiotherapy for ependymoma in a patient with Ondine's curse. A 53-year-old gentleman presented with vertigo when lying down. Brain magnetic resonance imaging revealed an enhancing mass in the floor of the fourth ventricle. He underwent maximal safe resection. Pathology revealed ependymoma. The patient was referred formore » radiotherapy. Computed tomography simulation was performed in supine position with 3-point thermoplastic mask immobilization. Sequential TomoTherapy plans were developed. At first scheduled treatment, shortly after mask placement, his arms went limp and he was unresponsive. Vitals showed oxygen saturation 83%, pulse 127, and blood pressure 172/97 mm Hg. He was diagnosed with Ondine's curse thought secondary to previous brainstem damage; the combination of lying flat and pressure from the mask was causing him to go into respiratory arrest. As supine positioning did not seem clinically advisable, he was simulated in prone position. A RapidArc plan and a back-up conformal plan were developed. Prescriptions were modified to meet conservative organs-at-risk constraints. Several strategies were used to minimize uncertainties in set-up reproducibility associated with prone positioning. He tolerated prone RapidArc treatments well. The report highlights the importance of applying practical patient safety and treatment planning/delivery strategies in the management of this challenging case.« less

  10. A global logrank test for adaptive treatment strategies based on observational studies.

    PubMed

    Li, Zhiguo; Valenstein, Marcia; Pfeiffer, Paul; Ganoczy, Dara

    2014-02-28

    In studying adaptive treatment strategies, a natural question that is of paramount interest is whether there is any significant difference among all possible treatment strategies. When the outcome variable of interest is time-to-event, we propose an inverse probability weighted logrank test for testing the equivalence of a fixed set of pre-specified adaptive treatment strategies based on data from an observational study. The weights take into account both the possible selection bias in an observational study and the fact that the same subject may be consistent with more than one treatment strategy. The asymptotic distribution of the weighted logrank statistic under the null hypothesis is obtained. We show that, in an observational study where the treatment selection probabilities need to be estimated, the estimation of these probabilities does not have an effect on the asymptotic distribution of the weighted logrank statistic, as long as the estimation of the parameters in the models for these probabilities is n-consistent. Finite sample performance of the test is assessed via a simulation study. We also show in the simulation that the test can be pretty robust to misspecification of the models for the probabilities of treatment selection. The method is applied to analyze data on antidepressant adherence time from an observational database maintained at the Department of Veterans Affairs' Serious Mental Illness Treatment Research and Evaluation Center. Copyright © 2013 John Wiley & Sons, Ltd.

  11. A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

    PubMed

    Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

    2018-03-24

    Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

  12. Evidence Base on Outpatient Behavioral Treatments for Adolescent Substance Use, 2014-2017: Outcomes, Treatment Delivery, and Promising Horizons.

    PubMed

    Hogue, Aaron; Henderson, Craig E; Becker, Sara J; Knight, Danica K

    2018-06-12

    This article updates the evidence base on outpatient behavioral treatments for adolescent substance use (ASU) since publication of the previous review completed for this journal by Hogue, Henderson, Ozechowski, and Robbins (2014). It first summarizes the Hogue et al. findings along with those from recent literature reviews and meta-analytic studies of ASU treatments. It then presents study design and methods criteria used to select 11 comparative studies subjected to Journal of Clinical Child and Adolescent Psychology level of support evaluation. These 11 studies are detailed in terms of their sample characteristics, methodological quality, and substance use outcomes. Cumulative level of support designations are then made for each identified treatment approach. These cumulative designations are virtually identical to those of the previous review: ecological family-based treatment, individual cognitive-behavioral therapy, and group cognitive-behavioral therapy remain well-established; behavioral family-based treatment and motivational interviewing remain probably efficacious; drug counseling remains possibly efficacious; and an updated total of 5 multicomponent treatments combining more than 1 approach (3 of which include contingency management) are deemed well-established or probably efficacious. Treatment delivery issues associated with evidence-based approaches are then reviewed, focusing on client engagement, fidelity and mediator, and predictor and moderator effects. Finally, to help accelerate innovation in ASU treatment science and practice, the article outlines promising horizons in improving youth identification and access, specifying and implementing pragmatic treatment in community settings, and leveraging emerging lessons from implementation science.

  13. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Strategies to Combat Antibiotic Resistance in the Wastewater Treatment Plants

    PubMed Central

    Barancheshme, Fateme; Munir, Mariya

    2018-01-01

    The main goal of this manuscript is to review different treatment strategies and mechanisms for combating the antibiotic resistant bacteria (ARB) and antibiotic resistant genes (ARGs) in the wastewater environment. The high amount of antibiotics is released into the wastewater that may promote selection of ARB and ARGs which find their way into natural environments. Emerging microbial pathogens and increasing antibiotic resistance among them is a global public health issue. The propagation and spread of ARB and ARGs in the environment may result in an increase of antibiotic resistant microbial pathogens which is a worldwide environmental and public health concern. A proper treatment of wastewater is essential before its discharge into rivers, lake, or sewage system to prevent the spread of ARB and ARGs into the environment. This review discusses various treatment options applied for combating the spread of ARB and ARGs in wastewater treatment plants (WWTPs). It was reported that low-energy anaerobic–aerobic treatment reactors, constructed wetlands, and disinfection processes have shown good removal efficiencies. Nanomaterials and biochar combined with other treatment methods and coagulation process are very recent strategies regarding ARB and ARGs removal and need more investigation and research. Based on current studies a wide-ranging removal efficiency of ARGs can be achieved depending on the type of genes present and treatment processes used, still, there are gaps that need to be further investigated. In order to find solutions to control dissemination of antibiotic resistance in the environment, it is important to (1) study innovative strategies in large scale and over a long time to reach an actual evaluation, (2) develop risk assessment studies to precisely understand occurrence and abundance of ARB/ARGs so that their potential risks to human health can be determined, and (3) consider operating and environmental factors that affect the efficiency of each

  15. Kawasaki Disease: Etiopathogenesis and Novel Treatment Strategies

    PubMed Central

    Agarwal, Shreya; Agrawal, Devendra K.

    2017-01-01

    Introduction Kawasaki disease is an acute febrile systemic vasculitis that predominantly occurs in children below five years of age. Its etiopathogenesis is still not clear, but it is thought to be a complex interplay of genetic factors, infections and immunity. Areas covered This review article discusses in detail Kawasaki disease, with particular emphasis on the recent updates on its pathogenesis and upcoming alternate treatment options. Though self-limiting in many cases, it can lead to severe complications like coronary artery aneurysms and thrombo-embolic occlusions, and hence requires early diagnosis and urgent attention to avoid them. Intravenous immunoglobulin (IVIG) with or without aspirin has remained the sole treatment option for these cases, but 10-15% cases develop resistance to this treatment. Expert Commentary There is a need to develop additional treatment strategies for children with Kawasaki disease. Targeting different steps of pathogenesis could provide us with alternate therapeutic options. PMID:27590181

  16. Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

    PubMed Central

    Goodman, S. B.; Gibon, E.; Pajarinen, J.; Lin, T.-H.; Keeney, M.; Ren, P.-G.; Nich, C.; Yao, Z.; Egashira, K.; Yang, F.; Konttinen, Y. T.

    2014-01-01

    Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 (pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-κB) by delivery of an NF-κB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants. PMID:24478281

  17. Amblyopia treatment strategies and new drug therapies.

    PubMed

    Pescosolido, Nicola; Stefanucci, Alessio; Buomprisco, Giuseppe; Fazio, Stefano

    2014-01-01

    Amblyopia is a unilateral or bilateral reduction of visual acuity secondary to abnormal visual experience during early childhood. It is one of the most common causes of vision loss and monocular blindness and is commonly associated with strabismus, anisometropia, and visual deprivation (in particular congenital cataract and ptosis). It is clinically defined as a two-line difference of best-corrected visual acuity between the eyes. The purpose of this study was to understand the neural mechanisms of amblyopia and summarize the current therapeutic strategies. In particular, the authors focused on the concept of brain plasticity and its implication for new treatment strategies for children and adults with amblyopia. Copyright 2014, SLACK Incorporated.

  18. Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.

    PubMed

    Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina Del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F; Vieta, Eduard

    2017-08-01

    Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients' psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  19. Development of Microemulsion Based Nabumetone Transdermal Delivery For Treatment of Arthritis.

    PubMed

    Jagdale, Swati; Deore, Gokul; Chabukswar, Anuruddha

    2018-02-26

    Background Nabumetone is biopharmaceutics classification system (BCS) class II drug, widely used in the treatment of osteoarthritis and rheumatoid arthritis. The most frequently reported adverse reactions for the drug involve disturbance in gastrointestinal tract , diarrhea, dyspepsia and abdominal pain. Microemulgel has advantages of microemulsion for improving solubility for hydrophobic drug. Patent literature had shown that the work for drug has been carried on spray chilling, enteric coated tablet, and topical formulation which gave idea for present research work for development of transdermal delivery. Objective Objective of the present research work was to optimize transdermal microemulgel delivery for Nabumetone for treatment of arthritis. Method Oil, surfactant and co-surfactant were selected based on solubility study for the drug. Gelling agents used were Carbopol 934 and HPMC K100M. Optimization was carried out using 32 factorial design. Characterization and evaluation were carried out for microemulsion and microemulsion based gel. Results Field emission-scanning electron microscopy (FE-SEM) study of the microemulsion revealed globules of 50-200 nm size . Zeta potential -9.50 mV indicated good stability of microemulsion. Globule size measured by dynamic light scattering (zetasizer) was 160 nm. Design expert gave optimized batch as F7 which contain 0.2% w/w drug, 4.3% w/w liquid paraffin, 0.71% w/w tween 80, 0.35% w/w propylene glycol, 0.124% w/w Carbopol 934, 0.187% w/w HPMC K100M and 11.68% w/w water. In-vitro diffusion study for F7 batch showed 99.16±2.10 % drug release through egg membrane and 99.15±2.73% drug release in ex-vivo study. Conclusion Nabumetone microemulgel exhibiting good in-vitro and ex-vivo controlled drug release was optimized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Interval From Imaging to Treatment Delivery in the Radiation Surgery Age: How Long Is Too Long?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seymour, Zachary A., E-mail: seymourz@radonc.ucsf.edu; Fogh, Shannon E.; Westcott, Sarah K.

    Purpose: The purpose of this study was to evaluate workflow and patient outcomes related to frameless stereotactic radiation surgery (SRS) for brain metastases. Methods and Materials: We reviewed all treatment demographics, clinical outcomes, and workflow timing, including time from magnetic resonance imaging (MRI), computed tomography (CT) simulation, insurance authorization, and consultation to the start of SRS for brain metastases. Results: A total of 82 patients with 151 brain metastases treated with SRS were evaluated. The median times from consultation, insurance authorization, CT simulation, and MRI for treatment planning were 15, 7, 6, and 11 days to SRS. Local freedom from progressionmore » (LFFP) was lower in metastases with MRI ≥14 days before treatment (P=.0003, log rank). The 6- and 12-month LFFP rate were 95% and 75% for metastasis with interval of <14 days from MRI to treatment compared to 56% and 34% for metastases with MRI ≥14 days before treatment. On multivariate analysis, LFFP remained significantly lower for lesions with MRI ≥14 days at SRS (P=.002, Cox proportional hazards; hazard ratio: 3.4, 95% confidence interval: 1.6-7.3). Conclusions: Delay from MRI to SRS treatment delivery for brain metastases appears to reduce local control. Future studies should monitor the timing from imaging acquisition to treatment delivery. Our experience suggests that the time from MRI to treatment should be <14 days.« less

  1. Strategies for Prevention and Treatment of Trichomonas vaginalis Infections.

    PubMed

    Bouchemal, Kawthar; Bories, Christian; Loiseau, Philippe M

    2017-07-01

    The last estimated annual incidence of Trichomonas vaginalis worldwide exceeds that of chlamydia and gonorrhea combined. This critical review updates the state of the art on advances in T. vaginalis diagnostics and strategies for treatment and prevention of trichomoniasis. In particular, new data on treatment outcomes for topical administration of formulations are reviewed and discussed. Copyright © 2017 American Society for Microbiology.

  2. Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment.

    PubMed

    Zhang, Wen; Li, Changzheng; Shen, Chengwu; Liu, Yuguo; Zhao, Xiaoting; Liu, Ying; Zou, Dongna; Gao, Zhenfa; Yue, Chunwen

    2016-09-01

    Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers. This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues. In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. The in vitro and in vivo anti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line. PTX/CBP NPs achieved the highest cytotoxic effect among all formulations in vitro, as compared with single drug delivery NPs. In vivo investigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity. The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy.

  3. Modulating the tumor microenvironment with RNA interference as a cancer treatment strategy.

    PubMed

    Zins, Karin; Sioud, Mouldy; Aharinejad, Seyedhossein; Lucas, Trevor; Abraham, Dietmar

    2015-01-01

    The tumor microenvironment is composed of accessory cells and immune cells in addition to extracellular matrix (ECM) components. The stromal compartment interacts with cancer cells in a complex crosstalk to support tumor development. Growth factors and cytokines produced by stromal cells support the growth of tumor cells and promote interaction with the vasculature to enhance tumor progression and invasion. The activation of autocrine and paracrine oncogenic signaling pathways by growth factors, cytokines, and proteases derived from both tumor cells and the stromal compartment is thought to play a major role in assisting tumor cells during metastasis. Consequently, targeting tumor-stroma interactions by RNA interference (RNAi)-based approaches is a promising strategy in the search for novel treatment modalities in human cancer. Recent advances in packaging technology including the use of polymers, peptides, liposomes, and nanoparticles to deliver small interfering RNAs (siRNAs) into target cells may overcome limitations associated with potential RNAi-based therapeutics. Newly developed nonviral gene delivery approaches have shown improved anticancer efficacy suggesting that RNAi-based therapeutics provide novel opportunities to elicit significant gene silencing and induce regression of tumor growth. This chapter summarizes our current understanding of the tumor microenvironment and highlights some potential targets for therapeutic intervention with RNAi-based cancer therapeutics.

  4. Interaction between behavioral and pharmacological treatment strategies to decrease cocaine choice in rhesus monkeys.

    PubMed

    Banks, Matthew L; Blough, Bruce E; Negus, S Stevens

    2013-02-01

    Behavioral and pharmacotherapeutic approaches constitute two prominent strategies for treating cocaine dependence. This study investigated interactions between behavioral and pharmacological strategies in a preclinical model of cocaine vs food choice. Six rhesus monkeys, implanted with a chronic indwelling double-lumen venous catheter, initially responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, FR 10 schedule) during continuous 7-day treatment periods with saline or the agonist medication phenmetrazine (0.032-0.1 mg/kg/h). Subsequently, the FR response requirement for cocaine or food was varied (food, FR 100; cocaine, FR 1-100; cocaine, FR 10; food, FR 10-300), and effects of phenmetrazine on cocaine vs food choice were redetermined. Decreases in the cocaine FR or increases in the food FR resulted in leftward shifts in the cocaine choice dose-effect curve, whereas increases in the cocaine FR or decreases in the food FR resulted in rightward shifts in the cocaine choice dose-effect curve. The efficacy of phenmetrazine to decrease cocaine choice varied systematically as a function of the prevailing response requirements, such that phenmetrazine efficacy was greatest when cocaine choice was maintained by relatively low unit cocaine doses. These results suggest that efficacy of pharmacotherapies to modulate cocaine use can be influenced by behavioral contingencies of cocaine availability. Agonist medications may be most effective under contingencies that engender choice of relatively low cocaine doses.

  5. Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

    PubMed

    Bernal, Giovanna M; LaRiviere, Michael J; Mansour, Nassir; Pytel, Peter; Cahill, Kirk E; Voce, David J; Kang, Shijun; Spretz, Ruben; Welp, Ulrich; Noriega, Sandra E; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

    2014-01-01

    A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles. © 2014.

  6. Transdermal Drug Delivery: Opportunities and Challenges for Controlled Delivery of Therapeutic Agents Using Nanocarriers.

    PubMed

    Kurmi, Balak Das; Tekchandani, Pawan; Paliwal, Rishi; Paliwal, Shivani Rai

    2017-01-01

    Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin. Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier. In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it. The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Antibiotic treatment of bacterial vaginosis in pregnancy: a meta-analysis.

    PubMed

    Leitich, Harald; Brunbauer, Mathias; Bodner-Adler, Barbara; Kaider, Alexandra; Egarter, Christian; Husslein, Peter

    2003-03-01

    The purpose of this study was to evaluate the effectiveness of antibiotic treatment of bacterial vaginosis in pregnancy to reduce preterm delivery. We performed a meta-analysis of published, English-language, randomized, placebo-controlled clinical trials of antibiotic treatment of bacterial vaginosis in pregnant women with intact amniotic membranes at <37 weeks of gestation. Primary outcomes included preterm delivery, perinatal or neonatal death, and neonatal morbidity. Ten studies with results for 3969 patients were included. In patients without preterm labor, antibiotic treatment did not significantly decrease preterm delivery at <37 weeks of gestation, in all patients combined (odds ratio, 0.83; 95% CI, 0.57-1.21) nor in high-risk patients with a previous preterm delivery (odds ratio, 0.50; 95% CI, 0.22-1.12). In both groups, significant statistical heterogeneity was observed. A significant reduction in preterm delivery and no statistical heterogeneity were observed in 338 high-risk patients who received oral regimens with treatment durations of > or =7 days (odds ratio, 0.42; 95% CI, 0.27-0.67). Nonsignificant effects and no statistical heterogeneity were observed in low-risk patients (odds ratio, 0.94; 95% CI, 0.71-1.25) and with vaginal regimens (odds ratio, 1.25; 95% CI: 0.86-1.81). In one study antibiotic treatment in patients with preterm labor led to a nonsignificant decrease in the rate of preterm deliveries (odds ratio, 0.31; 95% CI, 0.03-3.24). The screening of pregnant women who have bacterial vaginosis and who have had a previous preterm delivery and treatment with an oral regimen of longer duration can be justified on the basis of current evidence. More studies are needed to confirm the effectiveness of this strategy, both in high-risk patients without preterm labor and in patients with preterm labor.

  8. Designing a theory-informed, contextually appropriate intervention strategy to improve delivery of paediatric services in Kenyan hospitals

    PubMed Central

    2013-01-01

    Background District hospital services in Kenya and many low-income countries should deliver proven, effective interventions that could substantially reduce child and newborn mortality. However such services are often of poor quality. Researchers have therefore been challenged to identify intervention strategies that go beyond addressing knowledge, skill, or resource inadequacies to support health systems to deliver better services at scale. An effort to develop a system-oriented intervention tailored to local needs and context and drawing on theory is described. Methods An intervention was designed to improve district hospital services for children based on four main strategies: a reflective process to distill root causes for the observed problems with service delivery; developing a set of possible intervention approaches to address these problems; a search of literature for theory that provided the most appropriate basis for intervention design; and repeatedly moving backwards and forwards between identified causes, proposed interventions, identified theory, and knowledge of the existing context to develop an overarching intervention that seemed feasible and likely to be acceptable and potentially sustainable. Results and discussion In addition to human and resource constraints key problems included failures of relevant professionals to take responsibility for or ownership of the challenge of pediatric service delivery; inadequately prepared, poorly supported leaders of service units (mid-level managers) who are often professionally and geographically isolated and an almost complete lack of useful information for routinely monitoring or understanding service delivery practice or outcomes. A system-oriented intervention recognizing the pivotal role of leaders of service units but addressing the outer and inner setting of hospitals was designed to help shape and support an appropriate role for these professionals. It aims to foster a sense of ownership while

  9. Designing a theory-informed, contextually appropriate intervention strategy to improve delivery of paediatric services in Kenyan hospitals.

    PubMed

    English, Mike

    2013-03-28

    District hospital services in Kenya and many low-income countries should deliver proven, effective interventions that could substantially reduce child and newborn mortality. However such services are often of poor quality. Researchers have therefore been challenged to identify intervention strategies that go beyond addressing knowledge, skill, or resource inadequacies to support health systems to deliver better services at scale. An effort to develop a system-oriented intervention tailored to local needs and context and drawing on theory is described. An intervention was designed to improve district hospital services for children based on four main strategies: a reflective process to distill root causes for the observed problems with service delivery; developing a set of possible intervention approaches to address these problems; a search of literature for theory that provided the most appropriate basis for intervention design; and repeatedly moving backwards and forwards between identified causes, proposed interventions, identified theory, and knowledge of the existing context to develop an overarching intervention that seemed feasible and likely to be acceptable and potentially sustainable. In addition to human and resource constraints key problems included failures of relevant professionals to take responsibility for or ownership of the challenge of pediatric service delivery; inadequately prepared, poorly supported leaders of service units (mid-level managers) who are often professionally and geographically isolated and an almost complete lack of useful information for routinely monitoring or understanding service delivery practice or outcomes. A system-oriented intervention recognizing the pivotal role of leaders of service units but addressing the outer and inner setting of hospitals was designed to help shape and support an appropriate role for these professionals. It aims to foster a sense of ownership while providing the necessary understanding, knowledge

  10. Developments in drug delivery of bioactive alkaloids derived from traditional Chinese medicine.

    PubMed

    Zheng, Xiao; Wu, Fei; Lin, Xiao; Shen, Lan; Feng, Yi

    2018-11-01

    The bioactive alkaloids (e.g. vincristine, hydroxycamptothecin, ligustrazine, and so on) from traditional Chinese medicine (TCM) have exerted potent efficacies (e.g. anti-tumor, anti-inflammation, immunosuppression, etc.). However, a series of undesirable physicochemical properties (like low solubility and weak stability) and baneful pharmacokinetic (PK) profiles (e.g. low bioavailability, short half time, rapid clearance, etc.) have severely restricted their applications in clinic. In addition, some side effects (like cumulative toxicities caused by high-frequency administration and their own toxicities) have recently been reported and also confined their clinical uses. Therefore, developments in drug delivery of such alkaloids are of significance in improving their drug-like properties and, thus, treatment efficiencies in clinic. Strategies, including (i) specific delivery via liposomes; (ii) sustained delivery via nanoparticles, gels, and emulsions; and (iii) transdermal delivery via ethosomes, solid lipid nanoparticles, and penetrating enhancers, have been reported to improve the pharmacokinetic and physicochemical characters of problematic TCM alkaloids, decline their adverse effects, and thus, boost their curative efficacies. In this review, the recent reports in this field were comprehensively summarized with the aim of providing an informative reference for relevant readers.

  11. Polymeric Carriers for Gene Delivery: Chitosan and Poly(amidoamine) Dendrimers

    PubMed Central

    Xu, Qingxing; Wang, Chi-Hwa; Pack, Daniel Wayne

    2012-01-01

    Gene therapy is a potential medical solution that promises new treatments and may hold the cure for many different types of diseases and disorders of the human race. However, gene therapy is still a growing medical field and the technology is still in its infancy. The main challenge for gene therapy is to find safe and effective vectors that are able to deliver genes to the specific cells and get them to express inside the cells. Due to safety concerns, synthetic delivery systems, rather than viral vectors, are preferred for gene delivery and significant efforts have been focused on the development of this field. However, we are faced with problems like low gene transfer efficiency, cytotoxicity and lack of cell-targeting capability for these synthetic delivery systems. Over the years, we have seen a variety of new and effective polymers which have been designed and synthesized specifically for gene delivery. Moreover, various strategies that aimed at enhancing their physicochemical properties, improving transfection efficiency, reducing cytotoxicity as well as incorporating functional groups that offer better targetability and higher cellular uptake are established. Here, we look at two potential polymeric carriers, chitosan and poly(amidoamine) dendrimers, which have been widely reported for gene delivery. For chitosan, the interest arises from their availability, excellent non-cytotoxicity profile, biodegradability and ease of modification. For poly(amidoamine) dendrimers, the interest arises from their ease of synthesis with controlled structure and size, minimal cytotoxicity, biodegradability and high transfection efficiencies. The latest developments on these polymers for gene delivery will be the main focus of this article. PMID:20618156

  12. Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies.

    PubMed

    Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R

    2014-10-01

    Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA. This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion. Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need.

  13. MO-D-BRB-01: Pediatric Treatment Planning I: Overview of Planning Strategies and Challenges

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Olch, A.

    Most Medical Physicists working in radiotherapy departments see few pediatric patients. This is because, fortunately, children get cancer at a rate nearly 100 times lower than adults. Children have not smoked, abused alcohol, or been exposed to environmental carcinogens for decades, and of course, have not fallen victim to the aging process. Children get very different cancers than adults. Breast or prostate cancers, typical in adults, are rarely seen in children but instead a variety of tumors occur in children that are rarely seen in adults; examples are germinomas, ependymomas and primitive neuroectodermal tumors, which require treatment of the child’smore » brain or neuroblastoma, requiring treatment in the abdomen. The treatment of children with cancer using radiation therapy is one of the most challenging planning and delivery problems facing the physicist. This is because bones, brain, breast tissue, and other organs are more sensitive to radiation in children than in adults. Because most therapy departments treat mostly adults, when the rare 8 year-old patient comes to the department for treatment, the physicist may not understand the clinical issues of his disease which drive the planning and delivery decisions. Additionally, children are more prone than adults to developing secondary cancers after radiation. For bilateral retinoblastoma for example, an irradiated child has a 40% chance of developing a second cancer by age 50. The dosimetric tradeoffs made during the planning process are complex and require careful consideration for children treated with radiotherapy. In the first presentation, an overview of childhood cancers and their corresponding treatment techniques will be given. These can be some of the most complex treatments that are delivered in the radiation therapy department. These cancers include leukemia treated with total body irradiation, medulloblastoma, treated with craniospinal irradiation plus a conformal boost to the posterior

  14. Optimization of Chitosan and Cellulose Acetate Phthalate Controlled Delivery of Methylprednisolone for Treatment of Inflammatory Bowel Disease.

    PubMed

    Jagdale, Swati; Chandekar, Apoorva

    2017-06-01

    Purpose: Inflammatory bowel disease (IBD) is a chronic, relapsing and often life-long disorder. The best way to tackle IBD is to develop a site targeted drug delivery. Methylprednisolone is a potent anti-inflammatory steroid. The relative potency of methylprednisolone to hydrocortisone is at least four is to one. The aim of the present research was to develop a colon targeted drug delivery for treatment of IBD. Methods: Compression coated drug delivery system was designed and optimised. Core tablet contained drug, croscarmellose sodium (CCS-superdisintegrant), avicel (binder) and dicalcium phosphate (diluent). Design of experiment with 3 2 factorial design was applied for optimization of compression coated delivery. Chitosan and cellulose acetate phthalate were chosen as independent variables. Swelling index, hardness and % drug release were dependant variables. Results: Core tablet (C5 batch) containing 2.15% CCS showed disintegration in less than 10sec. FTIR, UV and DSC study had shown absence of any significant physical and chemical interaction between drug and polymers. F8 was found to be optimised formulation. F8 contained 35% chitosan and 17.5% cellulose acetate phthalate. It showed drug release of 86.3% ± 6.1%, hardness 6.5 ± 1.5 and lag time 7 hrs. Simulated media drug release was 97.51 ± 8.6% with 7.5 hrs lag time. The results confirmed that the lag time was highly affected by the coating of the polymers as well as the concentration of the superdisintegrant used in core tablet. Conclusion: In-vitro and in-vivo results confirmed a potential colon targeted drug therapy for treatment of IBD.

  15. Optimization of Chitosan and Cellulose Acetate Phthalate Controlled Delivery of Methylprednisolone for Treatment of Inflammatory Bowel Disease

    PubMed Central

    Jagdale, Swati; Chandekar, Apoorva

    2017-01-01

    Purpose: Inflammatory bowel disease (IBD) is a chronic, relapsing and often life-long disorder. The best way to tackle IBD is to develop a site targeted drug delivery. Methylprednisolone is a potent anti-inflammatory steroid. The relative potency of methylprednisolone to hydrocortisone is at least four is to one. The aim of the present research was to develop a colon targeted drug delivery for treatment of IBD. Methods: Compression coated drug delivery system was designed and optimised. Core tablet contained drug, croscarmellose sodium (CCS-superdisintegrant), avicel (binder) and dicalcium phosphate (diluent). Design of experiment with 32 factorial design was applied for optimization of compression coated delivery. Chitosan and cellulose acetate phthalate were chosen as independent variables. Swelling index, hardness and % drug release were dependant variables. Results: Core tablet (C5 batch) containing 2.15% CCS showed disintegration in less than 10sec. FTIR, UV and DSC study had shown absence of any significant physical and chemical interaction between drug and polymers. F8 was found to be optimised formulation. F8 contained 35% chitosan and 17.5% cellulose acetate phthalate. It showed drug release of 86.3% ± 6.1%, hardness 6.5 ± 1.5 and lag time 7 hrs. Simulated media drug release was 97.51 ± 8.6% with 7.5 hrs lag time. The results confirmed that the lag time was highly affected by the coating of the polymers as well as the concentration of the superdisintegrant used in core tablet. Conclusion: In-vitro and in-vivo results confirmed a potential colon targeted drug therapy for treatment of IBD. PMID:28761822

  16. Short-Term Group Psychotherapy: A Clinical Trial of a New Combination of Pretreatment and Treatment Strategies.

    ERIC Educational Resources Information Center

    Merkel, William T.; Willis, Stephen L.

    1985-01-01

    The paper discusses a clinical trial of pretreatment and treatment strategies to enhance the effectiveness of short-term groups. Pretreatment strategies included preparing patients and increasing the perceived authority of the therapists. Treatment strategies include delineation of a specific treatment focus and a directive approach by the…

  17. Mitochondrial Delivery of Doxorubicin Using MITO-Porter Kills Drug-Resistant Renal Cancer Cells via Mitochondrial Toxicity.

    PubMed

    Yamada, Yuma; Munechika, Reina; Kawamura, Eriko; Sakurai, Yu; Sato, Yusuke; Harashima, Hideyoshi

    2017-09-01

    Most anticancer drugs are intended to function in the nuclei of cancer cells. If an anticancer drug could be delivered to mitochondria, the source of cellular energy, this organelle would be destroyed, resulting in the arrest of the energy supply and the killing of the cancer cells. To achieve such an innovative strategy, a mitochondrial drug delivery system targeted to cancer cells will be required. We recently reported on the development of a MITO-Porter, a liposome for mitochondrial delivery. In this study, we validated the utility of such a cancer therapeutic strategy by delivering anticancer drugs directly to mitochondria. We succeeded in packaging doxorubicin (DOX) as a model cargo in MITO-Porter to produce a DOX-MITO-Porter. We evaluated cellular toxicity of OS-RC-2 cell, a type of DOX-resistant cancer cell, after delivering DOX to mitochondria using the MITO-Porter system. Cell viability was decreased by the DOX-MITO-Porter treatment, while cell viability was not decreased in the case of naked DOX and a conventional DOX liposomal formulation. We also found a relationship between cellular toxicity and mitochondrial toxicity. The use of a MITO-Porter system for mitochondrial delivery of a toxic agent represents a possible therapeutic strategy for treating drug-resistant cancers. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Direct Delivery of Antigens to Dendritic Cells via Antibodies Specific for Endocytic Receptors as a Promising Strategy for Future Therapies

    PubMed Central

    Lehmann, Christian H. K.; Heger, Lukas; Heidkamp, Gordon F.; Baranska, Anna; Lühr, Jennifer J.; Hoffmann, Alana; Dudziak, Diana

    2016-01-01

    Dendritic cells (DCs) are the most potent professional antigen presenting cells and are therefore indispensable for the control of immunity. The technique of antibody mediated antigen targeting to DC subsets has been the basis of intense research for more than a decade. Many murine studies have utilized this approach of antigen delivery to various kinds of endocytic receptors of DCs both in vitro and in vivo. Today, it is widely accepted that different DC subsets are important for the induction of select immune responses. Nevertheless, many questions still remain to be answered, such as the actual influence of the targeted receptor on the initiation of the immune response to the delivered antigen. Further efforts to better understand the induction of antigen-specific immune responses will support the transfer of this knowledge into novel treatment strategies for human diseases. In this review, we will discuss the state-of-the-art aspects of the basic principles of antibody mediated antigen targeting approaches. A table will also provide a broad overview of the latest studies using antigen targeting including addressed DC subset, targeted receptors, outcome, and applied coupling techniques. PMID:27043640

  19. Mucosal delivery of liposome-chitosan nanoparticle complexes.

    PubMed

    Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

  20. Tuberculosis treatment delivery in high burden settings: does patient choice of supervision matter?

    PubMed

    Kironde, S; Meintjies, M

    2002-07-01

    The Northern Cape Province, Republic of South Africa. To determine the effect of patient choice of treatment delivery option on the treatment outcomes of tuberculosis (TB) patients in a high burden setting under actual programme conditions. Cohort study involving 769 new and retreatment TB patients recruited from 45 randomly selected clinics. Patients were interviewed and subsequent follow-up was done through regular visits to the clinics to check progress through formal health records. There was a statistically significant difference (P < 0.001) between the treatment outcome of new patients (70% successful) and re-treatment patients (54% successful). Direct observation of treatment (DOT) was found to have no effect on the treatment outcome of new patients (P = 0.875), but re-treatment patients were found to fare better with than without DOT (OR 14.2, 95% CI 4.18-53.14, P < 0.001). The results obtained for new patients are similar to those of two recent randomised controlled trials on DOT. This study revealed that for new patients, undue emphasis on universal DOT might be unnecessary. It would perhaps be more beneficial to target supervision at those patients who are most likely to benefit from it (i.e., re-treatment patients). This is of particular relevance in high burden, resource-limited settings where universal DOT for all TB patients is generally unfeasible.

  1. Biomimetics: reconstitution of low-density lipoprotein for targeted drug delivery and related theranostic applications.

    PubMed

    Zhu, Chunlei; Xia, Younan

    2017-12-11

    Low-density lipoprotein (LDL), one of the four major groups of lipoproteins for lipid transport in vivo, is emerging as an attractive carrier for the targeted delivery of theranostic agents. In contrast to the synthetic systems, LDL particles are intrinsically biocompatible and biodegradable, together with reduced immunogenicity and natural capabilities to target cancerous cells and to escape from the recognition and elimination by the reticuloendothelial system. Enticed by these attributes, a number of strategies have been developed for reconstituting LDL particles, including conjugation to the apolipoprotein, insertion into the phospholipid layer, and loading into the core. Here we present a tutorial review on the development of reconstituted LDL (rLDL) particles for theranostic applications. We start with a brief introduction to LDL and LDL receptor, as well as the advantages of using rLDL particles as a natural and versatile platform for the targeted delivery of theranostic agents. After a discussion of commonly used strategies for the reconstitution of LDL, we highlight the applications of rLDL particles in the staging of disease progression, treatment of lesioned tissues, and delivery of photosensitizers for photodynamic cancer therapy. We finish this review with a perspective on the remaining challenges and future directions.

  2. Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

    PubMed

    Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Chu, Po-Chun; Pan, Chia-Hsin; Yang, Hung-Wei; Huang, Chiung-Yin; Wang, Jiun-Jie; Yen, Tzu-Chen; Wei, Kuo-Chen

    2010-05-01

    To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015

  3. Optically Based Rapid Screening Method for Proven Optimal Treatment Strategies Before Treatment Begins

    DTIC Science & Technology

    to rapidly test /screen breast cancer therapeutics as a strategy to streamline drug development and provide individualized treatment. The results...system can therefore be used to streamline pre-clinical drug development, by reducing the number of animals , cost, and time required to screen new drugs

  4. Recent advances in light-responsive on-demand drug-delivery systems.

    PubMed

    Linsley, Chase S; Wu, Benjamin M

    2017-02-01

    The convergence of wearable sensors and personalized medicine enhance the ability to sense and control the drug composition and dosage, as well as location and timing of administration. To date, numerous stimuli-triggered smart drug-delivery systems have been developed to detect changes in light, pH, temperature, biomolecules, electric field, magnetic field, ultrasound and mechanical forces. This review examines the major advances within the last 5 years for the three most common light-responsive drug delivery-on-demand strategies: photochemical, photoisomerization and photothermal. Examples are highlighted to illustrate progress of each strategy in drug delivery applications, and key limitations are identified to motivate future research to advance this important field.

  5. Malaria treatment using novel nano-based drug delivery systems.

    PubMed

    Baruah, Uday Krishna; Gowthamarajan, Kuppusamy; Vanka, Ravisankar; Karri, Veera Venkata Satyanarayana Reddy; Selvaraj, Kousalya; Jojo, Gifty M

    2017-08-01

    We reside in an era of technological innovation and advancement despite which infectious diseases like malaria remain to be one of the greatest threats to the humans. Mortality rate caused by malaria disease is a huge concern in the twenty-first century. Multiple drug resistance and nonspecific drug targeting of the most widely used drugs are the main reasons/drawbacks behind the failure in malarial therapy. Dose-related toxicity because of high doses is also a major concern. Therefore, to overcome these problems nano-based drug delivery systems are being developed to facilitate site-specific or target-based drug delivery and hence minimizing the development of resistance progress and dose-dependent toxicity issues. In this review, we discuss about the shortcomings in treating malaria and how nano-based drug delivery systems can help in curtailing the infectious disease malaria.

  6. Optimal resource allocation strategy for two-layer complex networks

    NASA Astrophysics Data System (ADS)

    Ma, Jinlong; Wang, Lixin; Li, Sufeng; Duan, Congwen; Liu, Yu

    2018-02-01

    We study the traffic dynamics on two-layer complex networks, and focus on its delivery capacity allocation strategy to enhance traffic capacity measured by the critical value Rc. With the limited packet-delivering capacity, we propose a delivery capacity allocation strategy which can balance the capacities of non-hub nodes and hub nodes to optimize the data flow. With the optimal value of parameter αc, the maximal network capacity is reached because most of the nodes have shared the appropriate delivery capacity by the proposed delivery capacity allocation strategy. Our work will be beneficial to network service providers to design optimal networked traffic dynamics.

  7. Amplitude gating for a coached breathing approach in respiratory gated 10 MV flattening filter‐free VMAT delivery

    PubMed Central

    Lee, Richard; Gete, Ermias; Duzenli, Cheryl

    2015-01-01

    The purpose of this study was to investigate amplitude gating combined with a coached breathing strategy for 10 MV flattening filter‐free (FFF) volumetric‐modulated arc therapy (VMAT) on the Varian TrueBeam linac. Ten patient plans for VMAT SABR liver were created using the Eclipse treatment planning system (TPS). The verification plans were then transferred to a CT‐scanned Quasar phantom and delivered on a TrueBeam linac using a 10 MV FFF beam and Varian's real‐time position management (RPM) system for respiratory gating based on breathing amplitude. Breathing traces were acquired from ten patients using two kinds of breathing patterns: free breathing and an interrupted (~5 s pause) end of exhale coached breathing pattern. Ion chamber and Gafchromic film measurements were acquired for a gated delivery while the phantom moved under the described breathing patterns, as well as for a nongated stationary phantom delivery. The gate window was set to obtain a range of residual target motion from 2–5 mm. All gated deliveries on a moving phantom have been shown to be dosimetrically equivalent to the nongated deliveries on a static phantom, with differences in point dose measurements under 1% and average gamma 2%/2 mm agreement above 98.7%. Comparison with the treatment planning system also resulted in good agreement, with differences in point‐dose measurements under 2.5% and average gamma 3%/3 mm agreement of 97%. The use of a coached breathing pattern significantly increases the duty cycle, compared with free breathing, and allows for shorter treatment times. Patients' free‐breathing patterns contain considerable variability and, although dosimetric results for gated delivery may be acceptable, it is difficult to achieve efficient treatment delivery. A coached breathing pattern combined with a 5 mm amplitude gate, resulted in both high‐quality dose distributions and overall shortest gated beam delivery times. PACS number: 87.55.Qr PMID:26219000

  8. Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin.

    PubMed

    Wenande, Emily; Tam, Joshua; Bhayana, Brijesh; Schlosser, Steven Kyle; Ishak, Emily; Farinelli, William A; Chlopik, Agata; Hoang, Mai P; Pinkhasov, Omar R; Caravan, Peter; Rox Anderson, R; Haedersdal, Merete

    2018-04-10

    The effectiveness of topical drugs for treatment of non-melanoma skin cancer is greatly reduced by insufficient penetration to deep skin layers. Ablative fractional lasers (AFLs) are known to enhance topical drug uptake by generating narrow microchannels through the skin, but information on AFL-drug delivery in in vivo conditions is limited. In this study, we examined pharmacokinetics, biodistribution and toxicity of two synergistic chemotherapy agents, cisplatin and 5-fluorouracil (5-FU), following AFL-assisted delivery alone or in combination in in vivo porcine skin. Detected at 0-120 h using mass spectrometry techniques, we demonstrated that fractional CO 2 laser pretreatment (196 microchannels/cm 2 , 852 μm ablation depth) leads to rapid drug uptake in 1500 μm deep skin layers, with a sixfold enhancement in peak cisplatin concentrations versus non-laser-treated controls (5 h, P = 0.005). Similarly, maximum 5-FU deposition was measured within an hour of AFL-delivery, and exceeded peak deposition in non-laser-exposed skin that had undergone topical drug exposure for 5 days. Overall, this accelerated and deeper cutaneous drug uptake resulted in significantly increased inflammatory and histopathological effects. Based on clinical scores and transepidermal water loss measurement, AFL intensified local toxic responses to drugs delivered alone and in combination, while systemic drug exposure remained undetectable. Quantitative histopathologic analyses correspondingly revealed significantly reduced epidermal proliferation and greater cellular apoptosis after AFL-drug delivery; particularly after combined cisplatin + 5-FU exposure. In sum, by overcoming the primary limitation of topical drug penetration and providing accelerated, enhanced and deeper delivery, AFL-assisted combination chemotherapy may represent a promising treatment strategy for non-melanoma skin cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Decisional strategy determines whether frame influences treatment preferences for medical decisions.

    PubMed

    Woodhead, Erin L; Lynch, Elizabeth B; Edelstein, Barry A

    2011-06-01

    Decision makers are influenced by the frame of information such that preferences vary depending on whether survival or mortality data are presented. Research is inconsistent as to whether and how age impacts framing effects. This paper presents two studies that used qualitative analyses of think-aloud protocols to understand how the type of information used in the decision making process varies by frame and age. In Study 1, 40 older adults, age 65 to 89, and 40 younger adults, age 18 to 24, responded to a hypothetical lung cancer scenario in a within-subject design. Participants received both a survival and mortality frame. Qualitative analyses revealed that two main decisional strategies were used by all participants: one strategy reflected a data-driven decisional process, whereas the other reflected an experience-driven process. Age predicted decisional strategy, with older adults less likely to use a data-driven strategy. Frame interacted with strategy to predict treatment choice; only those using a data-driven strategy demonstrated framing effects. In Study 2, 61 older adults, age 65 to 98, and 63 younger adults, age 18 to 30, responded to the same scenarios as in Study 1 in a between-subject design. The results of Study 1 were replicated, with age significantly predicting decisional strategy and frame interacting with strategy to predict treatment choice. Findings suggest that framing effects may be more related to decisional strategy than to age. (c) 2011 APA, all rights reserved.

  10. Strategies to improve energy efficiency in sewage treatment plants

    NASA Astrophysics Data System (ADS)

    Au, Mau Teng; Pasupuleti, Jagadeesh; Chua, Kok Hua

    2013-06-01

    This paper discusses on strategies to improve energy efficiency in Sewage Treatment Plant (STP). Four types of STP; conventional activated sludge, extended aeration, oxidation ditch, and sequence batch reactor are presented and strategized to reduce energy consumption based on their influent flow. Strategies to reduce energy consumption include the use of energy saving devices, energy efficient motors, automation/control and modification of processes. It is envisaged that 20-30% of energy could be saved from these initiatives.

  11. In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles

    PubMed Central

    Lopes, Cátia DF; Oliveira, Hugo; Estevão, Inês; Pires, Liliana Raquel; Pêgo, Ana Paula

    2016-01-01

    A major challenge in neuronal gene therapy is to achieve safe, efficient, and minimally invasive transgene delivery to neurons. In this study, we report the use of a nonviral neurotropic poly(ethylene imine)-based nanoparticle that is capable of mediating neuron-specific transfection upon a subcutaneous injection. Nanoparticles were targeted to peripheral neurons by using the nontoxic carboxylic fragment of tetanus toxin (HC), which, besides being neurotropic, is capable of being retrogradely transported from neuron terminals to the cell bodies. Nontargeted particles and naked plasmid DNA were used as control. Five days after treatment by subcutaneous injection in the footpad of Wistar rats, it was observed that 56% and 64% of L4 and L5 dorsal root ganglia neurons, respectively, were expressing the reporter protein. The delivery mediated by HC-functionalized nanoparticles spatially limited the transgene expression, in comparison with the controls. Histological examination revealed no significant adverse effects in the use of the proposed delivery system. These findings demonstrate the feasibility and safety of the developed neurotropic nanoparticles for the minimally invasive delivery of genes to the peripheral nervous system, opening new avenues for the application of gene therapy strategies in the treatment of peripheral neuropathies. PMID:27354797

  12. Light-switchable systems for remotely controlled drug delivery.

    PubMed

    Shim, Gayong; Ko, Seungbeom; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Lee, Jaiwoo; Kwon, Taekhyun; Choi, Han-Gon; Kim, Young Bong; Oh, Yu-Kyoung

    2017-12-10

    Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines. We need a paradigm shift in drug delivery. One strategy that may overcome the limitations of pathophysiology-based drug delivery is the use of remotely controlled delivery technology. Unlike pathophysiology-based active drug targeting strategies, light-switchable systems are not affected by the heterogeneity of cells, tissue types, and/or microenvironments. Instead, they are triggered by remote light (i.e., near-infrared) stimuli, which are absorbed by photoresponsive molecules or three-dimensional nanostructures. The sequential conversion of light to heat or reactive oxygen species can activate drug release and allow it to be spatio-temporally controlled. Light-switchable systems have been used to activate endosomal drug escape, modulate the release of chemical and biological drugs, and alter nanoparticle structures to control the release rates of drugs. This review will address the limitations of pathophysiology-based drug delivery systems, the current status of light-based remote-switch systems, and future directions in the application of light-switchable systems for remotely controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Towards Intravenous Drug Delivery: Augmenting the Stability and Dispersity of Bis-Demethoxy Curcumin Analog by Bottom-Up Strategy.

    PubMed

    Francis, Arul Prakash; Ramaprabhu, Sundara; Devasena, Thiyagarajan

    2016-01-01

    Intravenous route is the best strategy to accomplish fastest and highest delivery of drugs. Hydrophobic drugs like curcumin and its analog exhibit disadvantages like low bioavailability, poor absorption and rapid precipitation on intravenous delivery, all leading to its poor therapeutic value. These can be by-passed by enhancing the dispersity, stability and decreasing the size of the drug by nanotization. Thus, with an intention to deliver bis-demethoxy curcumin analog via intravenous route, we have studied the effect of DMSO, ethanol and acetone on the size, size distribution, stability and yield and identified the best solvent in terms of smallest size, narrow size distribution, more stability and high yield of nano bis-demethoxy curcumin analog (NBDMCA). NBDMCA prepared using DMSO showed the lowest mean particle size cum polydispersity index and highest zeta potential when compared to ethanol and acetone. Hence the DMSO based formulation can provide prolonged action and better efficacy at minimal doses. Thus, the DMSO based NBDMCA can emerge as an ideal therapeutic tool for human use.

  14. AOD treatment agencies: does religious affiliation influence service delivery?

    PubMed

    McIlwraith, Fairlie; Kinner, Stuart A; Najman, Jake M

    2011-11-01

    Religious organisations have been involved in delivering alcohol and other drug (AOD) services since Australian colonial times and are a familiar presence in the AOD sector. However, there is concern in some sectors that AOD services delivered by religious organisations might be influenced by religious ideology, at the expense of evidence-based service provision. A national, cross-sectional survey of non-government AOD agencies was undertaken using a mailed questionnaire. All non-government AOD agencies in Australia, providing at least one face-to-face specialist AOD service, were invited to participate. Agency goals and activities were assessed using the Drug and Alcohol Program Treatment Inventory, which has eight distinct treatment orientations: 12-step, therapeutic community, cognitive behavioural therapy, psychodynamic, family, rehabilitation, dual diagnosis and medical. There was a high degree of uniformity in treatment orientations with religiously affiliated agencies having similar goals and activities to non-religiously affiliated agencies. Cognitive behavioural therapy was most commonly provided and 12-step the least provided. Religiously affiliated agencies were significantly more likely to favour the 12-step orientation in both goals and activities. Concerns that the religious affiliation of non-government organisations might influence AOD service delivery in Australia appear to be overstated. Factors contributing to the observed uniformity of care may include a more strategic, federal approach; and an increasing emphasis on best practice within the sector. The lack of discernable differentiation between religiously affiliated and non-religiously affiliated non-government organisations may also be attributable to changes in the way services are delivered by many religious organisations. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  15. Multifunctional targeted liposomal drug delivery for efficient glioblastoma treatment

    PubMed Central

    Belhadj, Zakia; Zhan, Changyou; Ying, Man; Wei, Xiaoli; Xie, Cao; Yan, Zhiqiang; Lu, Weiyue

    2017-01-01

    Glioblastoma multiforme (GBM) has been considered to be the most malignant brain tumors. Due to the existence of various barriers including the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB) greatly hinder the accumulation and deep penetration of chemotherapeutics, the treatment of glioma remains to be the most challenging task in clinic. In order to circumvent these hurdles, we developed a multifunctional liposomal glioma-targeted drug delivery system (c(RGDyK)/pHA-LS) modified with cyclic RGD (c(RGDyK)) and p-hydroxybenzoic acid (pHA) in which c(RGDyK) could target integrin αvβ3 overexpressed on the BBTB and glioma cells and pHA could target dopamine receptors on the BBB. In vitro, c(RGDyK)/pHA-LS could target glioblastoma cells (U87), brain capillary endothelial cells (bEnd.3) and umbilical vein endothelial cells (HUVECs) through a comprehensive pathway. Besides, c(RGDyK)/pHA-LS could also increase the cytotoxicity of doxorubicin encapsulated in liposomes on glioblastoma cells, and was able to penetrate inside the glioma spheroids after traversing the in vitro BBB and BBTB. In vivo, we demonstrated the targeting ability of c(RGDyK)/pHA-LS to intracranial glioma. As expected, c(RGDyK)/pHA-LS/DOX showed a median survival time of 35 days, which was 2.31-, 1.76- and 1.5-fold higher than that of LS/DOX, c(RGDyK)-LS/DOX, and pHA-LS/DOX, respectively. The findings here suggested that the multifunctional glioma-targeted drug delivery system modified with both c(RGDyK) and pHA displayed strong antiglioma efficiency in vitro and in vivo, representing a promising platform for glioma therapy. PMID:28978003

  16. Emerging Trends On Drug Delivery Strategy of Momordica charantia against Diabetes and its Complications.

    PubMed

    Thent, Zar Chi; Das, Srijit; Zaidun, Nurul Hannim

    2018-01-01

    The incidence of diabetes mellitus has increased drastically over the past few decades. This oxidant-antioxidant imbalance resulting in complication of diabetes mellitus includes macro- and microvascular complications. Resistance to conventional treatment and patient compliance has paved the way to the usage of effective natural products and supplements. Momordica charantia (bitter gourd) is widely consumed in many parts of Malaysia as a vegetable. Momordica charantia (MC) is mainly used in the management of diabetes mellitus. The present review discusses the literature concerning the antidiabetic and antioxidant properties of MC focusing on the complication of diabetes mellitus along with its mode of delivery. We found that among the whole part of MC, its fruit extract has been widely studied, therapeutically. The evidence based analysis of the beneficiary effects of MC on the different organs involved in diabetes complication is also highlighted. This review elucidated an essential understanding of MC based drug delivery system in both clinical and experimental studies and appraised the great potential of the protein based MC extract against diabetes mellitus. The review paper is believed to assist the researchers and medical personnel in treating diabetic associated complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment

    NASA Astrophysics Data System (ADS)

    Hasan, Mahadi; Tarashima, Noriko; Fujikawa, Koki; Ohgita, Takashi; Hama, Susumu; Tanaka, Tamotsu; Saito, Hiroyuki; Minakawa, Noriaki; Kogure, Kentaro

    2016-01-01

    An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we examined fET of cells stably expressing luciferase in the presence of iRed encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not, likely because of the endosomal localization of iRed after delivery. However, fET in the presence of lysosomotropic agent chloroquine significantly improved the RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly decreased following fET with iRed against resistin in the presence of chloroquine. Thus, iRed could be a useful tool to regulate target genes following fET-mediated cytoplasmic delivery with endosomal escape devices.

  18. Nanomedicine strategies for targeting skin inflammation.

    PubMed

    Abdel-Mottaleb, Mona Ma; Try, Celine; Pellequer, Yann; Lamprecht, Alf

    2014-08-01

    Topical treatment of skin diseases is an attractive strategy as it receives high acceptance from patients, resulting in higher compliance and therapeutic outcomes. Recently, the use of variable nanocarriers for dermal application has been widely explored, as they offer several advantages compared with conventional topical preparations, including higher skin penetration, controlled and targeted drug delivery and the achievement of higher therapeutic effects. This article will focus on skin inflammation or dermatitis as it is one of the most common skin problems, describing the different types and causes of dermatitis, as well as the typical treatment regimens. The potential use of nanocarriers for targeting skin inflammation and the achievement of higher therapeutic effects using nanotechnology will be explored.

  19. Lipid-Based Nanoparticles as a Potential Delivery Approach in the Treatment of Rheumatoid Arthritis

    PubMed Central

    Chuang, Shih-Yi; Lin, Chih-Hung; Huang, Tse-Hung

    2018-01-01

    Rheumatoid arthritis (RA), a chronic and joint-related autoimmune disease, results in immune dysfunction and destruction of joints and cartilages. Small molecules and biological therapies have been applied in a wide variety of inflammatory disorders, but their utility as a therapeutic agent is limited by poor absorption, rapid metabolism, and serious side effects. To improve these limitations, nanoparticles, which are capable of encapsulating and protecting drugs from degradation before they reach the target site in vivo, may serve as drug delivery systems. The present research proposes a platform for different lipid nanoparticle approaches for RA therapy, taking advantage of the newly emerging field of lipid nanoparticles to develop a targeted theranostic system for application in the treatment of RA. This review aims to present the recent major application of lipid nanoparticles that provide a biocompatible and biodegradable delivery system to effectively improve RA targeting over free drugs via the presentation of tissue-specific targeting of ligand-controlled drug release by modulating nanoparticle composition. PMID:29342965

  20. Improved Treatment of Pancreatic Cancer With Drug Delivery Nanoparticles Loaded With a Novel AKT/PDK1 Inhibitor.

    PubMed

    Kobes, Joseph E; Daryaei, Iman; Howison, Christine M; Bontrager, Jordan G; Sirianni, Rachael W; Meuillet, Emmanuelle J; Pagel, Mark D

    2016-09-01

    This research study sought to improve the treatment of pancreatic cancer by improving the drug delivery of a promising AKT/PDK1 inhibitor, PHT-427, in poly(lactic-co-glycolic) acid (PLGA) nanoparticles. PHT-427 was encapsulated in single-emulsion and double-emulsion PLGA nanoparticles (SE-PLGA-427 and DE-PLGA-427). The drug release rate was evaluated to assess the effect of the second PLGA layer of DE-PLGA-427. Ex vivo cryo-imaging and drug extraction from ex vivo organs was used to assess the whole-body biodistribution in an orthotopic model of MIA PaCa-2 pancreatic cancer. Anatomical magnetic resonance imaging (MRI) was used to noninvasively assess the effects of 4 weeks of nanoparticle drug treatment on tumor size, and diffusion-weighted MRI longitudinally assessed changes in tumor cellularity. DE-PLGA-427 showed delayed drug release and longer drug retention in the pancreas relative to SE-PLGA-427. Diffusion-weighted MRI indicated a consistent decrease in cellularity during drug treatment with both types of drug-loaded nanoparticles. Both SE- and DE-PLGA-427 showed a 6-fold and 4-fold reduction in tumor volume relative to untreated tumors and an elimination of primary pancreatic tumor in 68% of the mice. These results indicated that the PLGA nanoparticles improved drug delivery of PHT-427 to pancreatic tumors, which improved the treatment of MIA PaCa-2 pancreatic cancer.

  1. Management of patients with placenta accreta in association with fever following vaginal delivery

    PubMed Central

    Zhong, Liuying; Chen, Dunjin; Zhong, Mei; He, Yutian; Su, Chunhong

    2017-01-01

    Abstract This study aims to analyze the clinical characteristics and to manage patients with retained placenta left in situ accompanied by fever following vaginal delivery. Twenty-one patients with retained placenta in association with fever following vaginal delivery were enrolled and managed at the maternity department of our university hospital between 2012 and 2014. All patients had risk factors for development of placenta accreta: previous cesarean sections (4/21), previous curettage (15/21), or uterine malformations (7/21). Placenta accreta was diagnosed following vaginal delivery in all patients, and manual removal of the placenta was attempted in 20 of 21 patients. The placenta left in situ was partial in 19 patients and was complete in 2 patients. All patients were managed with a multidisciplinary approach. Mifepristone was administrated to 16 patients. Fourteen patients received uterine artery embolization. Eleven patients were treated with ultrasound-guided curettage within 24 hours following delivery. Seven patients needed delayed-hysterectomy due to development of complications. Intrauterine operations during labor are not recommended if placenta accreta occurs in the fundus and/or in the cornual region of the uterus. Antibiotic treatment, interventional therapy, and ultrasound-guided curettage within 24 hours following vaginal delivery are the recommended conservative management strategies. PMID:28272244

  2. Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer.

    PubMed

    Tangutoori, Shifalika; Spring, Bryan Q; Mai, Zhiming; Palanisami, Akilan; Mensah, Lawrence B; Hasan, Tayyaba

    2016-01-01

    A lack of intracellular delivery systems has limited the use of biologics such as monoclonal antibodies (mAb) that abrogate molecular signaling pathways activated to promote escape from cancer treatment. We hypothesized that intracellular co-delivery of the photocytotoxic chromophore benzoporphyrin derivative monoacid A (BPD) and the anti-VEGF mAb bevacizumab in a nanophotoactivatable liposome (nanoPAL) might enhance the efficacy of photodynamic therapy (PDT) combined with suppression of VEGF-mediated signaling pathways. As a proof-of-concept we found that nanoPAL-PDT induced enhanced extra- and intracellular bevacizumab delivery and enhanced acute cytotoxicity in vitro. In an in vivo subcutaneous mouse model of pancreatic ductal adenocarcinoma, nanoPAL-PDT achieved significantly enhanced tumor reduction. We attribute this to the optimal incorporation of insoluble BPD into the lipid bilayer, enhancing photocytotoxicity, and the simultaneous spatiotemporal delivery of bevacizumab, ensuring efficient neutralization of the rapid but transient burst of VEGF following PDT. From the Clinical Editor: Most patients with pancreatic ductal adenocarcinoma (PDAC) by the time present the disease it is very advanced, which unavoidably translates to poor survival. For these patients, use of traditional chemotherapy often becomes ineffective due to tumor resistance to drugs. Photodynamic therapy (PDT) can be an effective modality against chemo-resistant cancers. In this article, the authors investigated the co-delivery of a photocytotoxic agent and anti-VEGF mAb using liposomes. This combination was shown to results in enhanced tumor killing. This method should be applicable to other combination of treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. [Cotard's syndrome. Different treatment strategies according to subclassification].

    PubMed

    Madani, Y; Sabbe, B G C

    2007-01-01

    After performing an exploratory factor analysis, Berrios & Luque (1995) identified three subcategories in the Cotard's syndrome: Cotard type I, Cotard type II and Cotard type psychotic depression. The article, which is based on two case studies and an examination of the relevant literature since 1995, explores whether there are different treatment strategies for Cotard type I and the Cotard type psychotic depression. For the Cotard type psychotic depression, electroconvulsive therapy proves to be an effective method of treatment. For Cotard type I, antipsychotic therapy seems to be sufficient.

  4. Whether a novel drug delivery system can overcome the problem of biofilms in respiratory diseases?

    PubMed

    Dua, Kamal; Shukla, Shakti D; Tekade, Rakesh K; Hansbro, Philip M

    2017-02-01

    Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches. There is very limited information about how the deposition of biofilm on the respiratory devices and lung itself affects the drug delivered, the delivery system, and other implications. The present mini review summarizes the basic introduction to the biofilms and its avoidance using various drug delivery systems with special emphasis on the respiratory diseases. Understanding the approaches, principles, and modes of drug delivery involved in preventing biofilm deposition will be of interest to both biological and formulation scientists, thereby opening avenues to explore the new vistas in biofilm research for identifying better treatments for pulmonary infectious diseases.

  5. Novel Strategies on Personalized Medicine for Breast Cancer Treatment: An Update.

    PubMed

    Chan, Carmen W H; Law, Bernard M H; So, Winnie K W; Chow, Ka Ming; Waye, Mary M Y

    2017-11-15

    Breast cancer is the most common cancer type among women worldwide. With breast cancer patients and survivors being reported to experience a repertoire of symptoms that are detrimental to their quality of life, the development of breast cancer treatment strategies that are effective with minimal side effects is therefore required. Personalized medicine, the treatment process that is tailored to the individual needs of each patient, is recently gaining increasing attention for its prospect in the development of effective cancer treatment regimens. Indeed, recent studies have identified a number of genes and molecules that may be used as biomarkers for predicting drug response and severity of common cancer-associated symptoms. These would provide useful clues not only for the determination of the optimal drug choice/dosage to be used in personalized treatment, but also for the identification of gene or molecular targets for the development of novel symptom management strategies, which ultimately would lead to the development of more personalized therapies for effective cancer treatment. In this article, recent studies that would provide potential new options for personalized therapies for breast cancer patients and survivors are reviewed. We suggest novel strategies, including the optimization of drug choice/dosage and the identification of genetic changes that are associated with cancer symptom occurrence and severity, which may help in enhancing the effectiveness and acceptability of the currently available cancer therapies.

  6. Gene delivery for cancer therapy.

    PubMed

    Zhang, Teng

    2014-01-01

    Gene therapy has potential in the treatment of human cancers. However, its clinical implication has only achieved little success due to the lack of an efficient gene delivery system. A major hurdle in the current available approaches is in the ability to transduce target tissues at very high efficiencies that ultimately lead to therapeutic levels of transgene expression. This review outlines the characteristics and utilities of several available gene delivery systems, including their advantages and drawbacks in the context of cancer treatment. A perspective of existing challenges and future directions is also included.

  7. Computerized Educational Delivery Strategies in Nine North American Colleges.

    ERIC Educational Resources Information Center

    Bowles, John C.

    1988-01-01

    Results of survey of high technology educational delivery systems in nine two-year colleges (five in the United States and four in Canada) emphasize the use of computers to provide alternatives to traditional classroom teaching. Topics discussed include open education, self-paced (fleximode) learning, artificial intelligence, software, and…

  8. Design of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription

    NASA Astrophysics Data System (ADS)

    Jang, Mihue; Kim, Jong Hwan; Nam, Hae Yun; Kwon, Ick Chan; Ahn, Hyung Jun

    2015-08-01

    For therapeutic applications of siRNA, there are technical challenges with respect to targeted and systemic delivery. We here report a new siRNA carrier, RNAtr NPs, in a way that multiple tandem copies of RNA hairpins as a result of rolling circle transcription (RCT) can be readily adapted in tumour-targeted and systemic siRNA delivery. RNAtr NPs provide a means of condensing large amounts of multimeric RNA transcripts into the compact nanoparticles, especially without the aid of polycationic agents, and thus reduce the risk of immunogenicity and cytotoxicity by avoiding the use of synthetic polycationic reagents. This strategy allows the design of a platform technology for systemic delivery of siRNA to tumour sites, because RCT reaction, which enzymatically generates RNA polymers in multiple copy numbers at low cost, can lead to directly accessible routes to targeted and systemic delivery. Therefore, RNAtr NPs suggest great potentials as the siRNA therapeutics for cancer treatment.

  9. Results of implementation of a hospital-based strategy to reduce cesarean delivery among low-risk women in Canada.

    PubMed

    Shoemaker, Esther S; Bourgeault, Ivy L; Cameron, Carol; Graham, Ian D; Hutton, Eileen K

    2017-11-01

    To assess the cesarean delivery (CD) rate among low-risk pregnancies before and after implementation of a hospital-based program in Canada. A prospective before-and-after study was conducted to assess the effects of the CARE (CAesarean REduction) strategy, which was developed and implemented at Markham Stouffville Hospital, Toronto, ON, Canada, in 2010 to reduce CD among low-risk women. Hospital records were reviewed to identify changes in the proportions of CD performed during 12 months (April 2009-March 2010) before implementation of the CARE strategy versus 12 months after implementation (April 2012-March 2013) at Markham Stouffville Hospital and 36 hospitals of the same level in the same province. At the intervention hospital, 30.3% (964/3181) of women underwent CD in 2009-2010, compared with 26.4% (803/3045) in 2012-2013 (difference -3.9%, P<0.001). By contrast, no significant difference was recorded in control hospitals (28.1% [23 694/84 361] vs 28.2% [23 683/83 895]; difference 0.1%, P=0.5157). Implementation of the CARE strategy reduced rates of CD among the target population. © 2017 International Federation of Gynecology and Obstetrics.

  10. Polymeric drug delivery systems for intraoral site-specific chemoprevention of oral cancer.

    PubMed

    Desai, Kashappa Goud H

    2018-04-01

    Oral cancer is among the most prevalent cancers in the world. Moreover, it is one of the major health problems and causes of death in many regions of the world. The traditional treatment modalities include surgical removal, radiation therapy, systemic chemotherapy, or a combination of these methods. In recent decades, there has been significant interest in intraoral site-specific chemoprevention via local drug delivery using polymeric systems. Because of its easy accessibility and clear visibility, the oral mucosa is amenable for local drug delivery. A variety of polymeric systems-such as gels, tablets, films, patches, injectable systems (e.g., millicylindrical implants, microparticles, and in situ-forming depots), and nanosized carriers (e.g., polymeric nanoparticles, nanofibers, polymer-drug conjugates, polymeric micelles, nanoliposomes, nanoemulsions, and polymersomes)-have been developed and evaluated for the local delivery of natural and synthetic chemopreventive agents. The findings of in vitro, ex vivo, and in vivo studies and the positive outcome of clinical trials demonstrate that intraoral site-specific drug delivery is an attractive, highly effective and patient-friendly strategy for the management of oral cancer. Intraoral site-specific drug delivery provides unique therapeutic advantages when compared to systemic chemotherapy. Moreover, intraoral drug delivery systems are self-administrable and can be removed when needed, increasing patient compliance. This article covers important aspects and advances related to the design, development, and efficacy of polymeric systems for intraoral site-specific drug delivery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1383-1413, 2018. © 2017 Wiley Periodicals, Inc.

  11. Recent advances in light-responsive on-demand drug-delivery systems

    PubMed Central

    Linsley, Chase S; Wu, Benjamin M

    2017-01-01

    The convergence of wearable sensors and personalized medicine enhance the ability to sense and control the drug composition and dosage, as well as location and timing of administration. To date, numerous stimuli-triggered smart drug-delivery systems have been developed to detect changes in light, pH, temperature, biomolecules, electric field, magnetic field, ultrasound and mechanical forces. This review examines the major advances within the last 5 years for the three most common light-responsive drug delivery-on-demand strategies: photochemical, photoisomerization and photothermal. Examples are highlighted to illustrate progress of each strategy in drug delivery applications, and key limitations are identified to motivate future research to advance this important field. PMID:28088880

  12. Multifunctional aptamer-based nanoparticles for targeted drug delivery to circumvent cancer resistance.

    PubMed

    Liu, Juan; Wei, Tuo; Zhao, Jing; Huang, Yuanyu; Deng, Hua; Kumar, Anil; Wang, Chenxuan; Liang, Zicai; Ma, Xiaowei; Liang, Xing-Jie

    2016-06-01

    By its unique advantages over traditional medicine, nanomedicine has offered new strategies for cancer treatment. In particular, the development of drug delivery strategies has focused on nanoscale particles to improve bioavailability. However, many of these nanoparticles are unable to overcome tumor resistance to chemotherapeutic agents. Recently, new opportunities for drug delivery have been provided by oligonucleotides that can self-assemble into three-dimensional nanostructures. In this work, we have designed and developed functional DNA nanostructures to deliver the chemotherapy drug doxorubicin (Dox) to resistant cancer cells. These nanostructures have two components. The first component is a DNA aptamer, which forms a dimeric G-quadruplex nanostructure to target cancer cells by binding with nucleolin. The second component is double-stranded DNA (dsDNA), which is rich in -GC- base pairs that can be applied for Dox delivery. We demonstrated that Dox was able to efficiently intercalate into dsDNA and this intercalation did not affect the aptamer's three-dimensional structure. In addition, the Aptamer-dsDNA (ApS) nanoparticle showed good stability and protected the dsDNA from degradation in bovine serum. More importantly, the ApS&Dox nanoparticle efficiently reversed the resistance of human breast cancer cells to Dox. The mechanism circumventing doxorubicin resistance by ApS&Dox nanoparticles may be predominantly by cell cycle arrest in S phase, effectively increased cell uptake and decreased cell efflux of doxorubicin. Furthermore, the ApS&Dox nanoparticles could effectively inhibit tumor growth, while less cardiotoxicity was observed. Overall, this functional DNA nanostructure provides new insights into the design of nanocarriers to overcome multidrug resistance through targeted drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. General strategy for the protection of organs at risk in IMRT therapy of a moving body

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abolfath, Ramin M.; Papiez, Lech

    2009-07-15

    We investigated protection strategies of organs at risk (OARs) in intensity modulated radiation therapy (IMRT). These strategies apply to delivery of IMRT to moving body anatomies that show relative displacement of OAR in close proximity to a tumor target. We formulated an efficient genetic algorithm which makes it possible to search for global minima in a complex landscape of multiple irradiation strategies delivering a given, predetermined intensity map to a target. The optimal strategy was investigated with respect to minimizing the dose delivered to the OAR. The optimization procedure developed relies on variability of all parameters available for control ofmore » radiation delivery in modern linear accelerators, including adaptation of leaf trajectories and simultaneous modification of beam dose rate during irradiation. We showed that the optimization algorithms lead to a significant reduction in the dose delivered to OAR in cases where organs at risk move relative to a treatment target.« less

  14. Work-related barriers, facilitators, and strategies of breast cancer survivors working during curative treatment

    PubMed Central

    Sun, Wenjun; Chen, Karen; Terhaar, Abigail; Wiegmann, Douglas A.; Heidrich, Susan M.; Tevaarwerk, Amye J.; Sesto, Mary E.

    2017-01-01

    BACKGROUND Research has identified barriers and facilitators affecting cancer survivors’ return to work (RTW) following the end of active treatment (surgery, chemotherapy and/or radiation therapy). However, few studies have focused on barriers and facilitators that cancer survivors experience while working during active treatment. Strategies used by cancer survivors to solve work-related problems during active treatment are underexplored. OBJECTIVE The aim of this study was to describe factors that impact, either positively or negatively, breast cancer survivors’ work activities during active treatment. METHODS Semi-structured, recorded interviews were conducted with 35 breast cancer survivors who worked during active treatment. Transcripts of interviews were analyzed using inductive content analysis to identify themes regarding work-related barriers, facilitators and strategies. RESULTS Barriers identified included symptoms, emotional distress, appearance change, time constraints, work characteristics, unsupportive supervisors and coworkers, family issues and other illness. Facilitators included positive aspects of work, support outside of work, and coworker and supervisor support. Strategies included activities to improve health-related issues and changes to working conditions and tasks. CONCLUSIONS Breast cancer survivors encounter various barriers during active treatment. Several facilitators and strategies can help survivors maintain productive work activities. PMID:28059814

  15. Lipid nanoparticles as drug/gene delivery systems to the retina.

    PubMed

    del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

    2013-03-01

    This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.

  16. Lactoferrin delivery systems: approaches for its more effective use.

    PubMed

    Onishi, Hiraku

    2011-11-01

    Recently, pharmacotherapy has advanced extensively, but there are still many refractory diseases which cannot be solved fully by existing therapeutic agents. Therefore, alternative medicine and health foods are now attracting much attention, for example, lactoferrin (LF): a multifunctional glycoprotein. As LF is non-toxic and low-cost, its application in healthcare and therapeutics is expected to be widespread. In this review, LF's general basic features are described. The interaction of LF with its receptors activates the immune system, including cytokine production and balance. In particular, the immune activation of orally administered LF is considered as a new strategy for the treatment of refractory diseases, such as inflammatory bowel disease, virus infection and tumor metastasis. Also mentioned are the problems associated with the use of LF. As LF is degraded rapidly in the body due to enzymatic hydrolysis, high amounts or frequent dosing is required; an appropriate delivery system may improve these problems and increase its efficiency. Chemical modifications, such as PEGylation, can enhance the stability of LF in the body, resulting in increased efficacy. Also, liposomes and enteric or microparticulate formulations can promote the function of LF in oral administration due to target site delivery and protection of LF from enzymatic hydrolysis. These delivery systems are expected to improve the utility of LF.

  17. Current Treatment Strategies for Tricuspid Regurgitation.

    PubMed

    Al-Hijji, Mohammed; Fender, Erin A; El Sabbagh, Abdallah; Holmes, David R

    2017-09-14

    Tricuspid regurgitation is common; however, recognition and diagnosis, clinical outcomes, and management strategies are poorly defined. Here, we will describe the etiology and natural history of tricuspid regurgitation (TR), evaluate existing surgical outcomes data, and review the evolving field of percutaneous interventions to treat TR. Previously, the only definitive corrective therapy for TR was surgical valve repair or replacement which is associated with significant operative mortality. Advances in percutaneous valve repair techniques are now being translated to the tricuspid valve. These novel interventions may offer a lower-risk alternative treatment in patients at increased surgical risk. Significant TR adversely impacts survival. Surgery remains the only proven therapy for treatment of TR and may be underutilized due to mixed outcomes data. Early experience with percutaneous interventions is promising, but large clinical experience is lacking. Further study will be required before these therapies are introduced into broader clinical practice.

  18. Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

    PubMed

    Zandstra, Jurjen; van Beuge, Marike M; Zuidema, Johan; Petersen, Arjen H; Staal, Mark; Duque, Luisa F; Rodriguez, Sergio; Lathuile, Audrey A R; Veldhuis, Gert J; Steendam, Rob; Bank, Ruud A; Popa, Eliane R

    2015-10-01

    The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney. We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs. Using a rat model of acute kidney injury, subcapsular injection of placebo and rapamycin monodisperse microspheres (monospheres) was compared to subcutaneous injection, mimicking systemic administration. We did not find any adverse effects related to the delivery method. Irrespective of the injection site, a similar low dose of rapamycin was present in the circulation. However, only local intrarenal delivery of rapamycin from monospheres led to decreased macrophage infiltration and a significantly lower amount of myofibroblasts in the kidney, where systemic administration did not. Local delivery of rapamycin did cause a transient increase in the deposition of collagen I, but not of collagen III. We conclude that therapeutic effects can be increased when rapamycin is delivered subcapsularly by monospheres, which, combined with low systemic concentrations, may lead to an effective intrarenal delivery method.

  19. SCI with Brain Injury: Bedside to Bench Modeling for Developing Treatment and Rehabilitation Strategies

    DTIC Science & Technology

    2013-10-01

    to Bench Modeling For Developing Treatment and Rehabilitation Strategies PRINCIPAL INVESTIGATOR: Geoffrey Manley, MD, PhD RECIPIENT...to Bench Modeling For Developing Treatment and Rehabilitation Strategies 5b. GRANT NUMBER W81XWH-10-1-0912 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR... treatment of this “dual- diagnosis” are lacking. This project proposed using current clinical-practice evidence to guide development of an animal model to

  20. Region-oriented and staged treatment strategy in reconstruction of severe cervical contracture.

    PubMed

    Luo, Xusong; Liu, Fei; Wang, Xi; Yang, Qun; Wang, Shoubao; Zhou, Xianyu; Qian, Yunliang; Yang, Jun; Levin, Lawrence Scott

    2015-01-01

    Severe cervical contracture after burns causes obvious impairment of neck movement and the aesthetic silhouette. Although various surgical techniques for treatment have been described, there is not a definitive strategy to guide treatment. Over the past 6 years, we have been utilizing a region-oriented and staged treatment strategy to guide reconstruction of severe cervical contracture. Satisfactory results have been achieved with this strategy. The first stage of treatment focuses on the anterior cervical region and submental region. Procedures include cicatrix resection, contracture release, division and elevation of the platysma to form two platysma flaps, and skin grafting. Three to six months later, the second stage treatment is performed, which localize to the mental region. This includes scar resection, correction of the lower lip eversion, and reconstruction with free (para)scapular skin flap. Three subtypes of cervicomental angle that we proposed were measured as quantitative tool for evaluation of the reconstruction. 24 patients who completed the treatment were reviewed. By the 3rd postoperative month, their CM angles changed significantly: the soft tissue CM angle was reduced from 135.0° ± 17.3° to 111.1° ± 11.3°, the osseous CM angle increased from 67.1° ± 9.0° to 90.5° ± 11.6° and the dynamic CM angle increased from 21.9° ± 8.7° to 67.4° ± 13.1°. 22 in 24 (91.7%) of these patients gained notable improvement of cervical motion and aesthetic contour. Our results suggest that the region-oriented and staged treatment strategy can achieve satisfactory functional and aesthetic results, combining usage of both skin graft and skin flap while minimizing the donor site morbidity.