Novel drug delivery systems for glaucoma

PubMed Central

Lavik, E; Kuehn, M H; Kwon, Y H

2011-01-01

Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

Radiolabeling of Nanoparticles and Polymers for PET Imaging

PubMed Central

Stockhofe, Katharina; Postema, Johannes M.; Schieferstein, Hanno; Ross, Tobias L.

2014-01-01

Nanomedicine has become an emerging field in imaging and therapy of malignancies. Nanodimensional drug delivery systems have already been used in the clinic, as carriers for sensitive chemotherapeutics or highly toxic substances. In addition, those nanodimensional structures are further able to carry and deliver radionuclides. In the development process, non-invasive imaging by means of positron emission tomography (PET) represents an ideal tool for investigations of pharmacological profiles and to find the optimal nanodimensional architecture of the aimed-at drug delivery system. Furthermore, in a personalized therapy approach, molecular imaging modalities are essential for patient screening/selection and monitoring. Hence, labeling methods for potential drug delivery systems are an indispensable need to provide the radiolabeled analog. In this review, we describe and discuss various approaches and methods for the labeling of potential drug delivery systems using positron emitters. PMID:24699244

Pharmacoinformatic approaches to understand complexation of dendrimeric nanoparticles with drugs

NASA Astrophysics Data System (ADS)

Jain, Vaibhav; Bharatam, Prasad V.

2014-02-01

Nanoparticle based drug delivery systems are gaining popularity due to their wide spectrum advantages over traditional drug delivery systems; among them, dendrimeric nano-vectors are the most widely explored carriers for pharmaceutical and biomedical applications. The precise mechanism of encapsulation of drug molecules inside the dendritic matrix, delivery of drugs into specific cells, interactions of nano-formulation with biological targets and proteins, etc. present a substantial challenge to the scientific understanding of the subject. Computational methods complement experimental techniques in the design and optimization of drug delivery systems, thus minimizing the investment in drug design and development. Significant progress in computer simulations could facilitate an understanding of the precise mechanism of encapsulation of bioactive molecules and their delivery. This review summarizes the pharmacoinformatic studies spanning from quantum chemical calculations to coarse-grained simulations, aimed at providing better insight into dendrimer-drug interactions and the physicochemical parameters influencing the binding and release mechanism of drugs.

Recent advances of controlled drug delivery using microfluidic platforms.

PubMed

Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

2018-03-15

Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Archaeosomes: an excellent carrier for drug and cell delivery.

PubMed

Kaur, Gurmeet; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-09-01

Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.

Nanocomposite thin films for triggerable drug delivery.

PubMed

Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

2018-05-01

Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery

PubMed Central

Mather, Laurence E; Woodhouse, Annie; Ward, M Elizabeth; Farr, Stephen J; Rubsamen, Reid A; Eltherington, Lorne G

1998-01-01

Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist™, Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. Methods Aersolised pulmonary fentanyl base 100–300 μg was administered to healthy volunteers using SmartMist™ and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. Results Plasma concentrations from SmartMist™ were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged 100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. Conclusions Fentanyl delivery using SmartMist™ can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae. PMID:9690947

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.

Novel drug delivery system: an immense hope for diabetics.

PubMed

Rai, Vineet Kumar; Mishra, Nidhi; Agrawal, Ashish Kumar; Jain, Sanyog; Yadav, Narayan Prasad

2016-09-01

Existing medication systems for the treatment of diabetes mellitus (DM) are inconvenient and troublesome for effective and safe delivery of drugs to the specific site. Therefore, investigations are desired to deliver antidiabetics using novel delivery approaches followed by their commercialization. The present review aims to provide a compilation on the latest development in the field of novel drug delivery systems (NDDSs) for antidiabetics with special emphasis on particulate, vesicular and miscellaneous systems. Review of literature (restricted to English language only) was done using electronic databases like Pubmed® and Scirus, i.e. published during 2005-2013. The CIMS/MIMS India Medical Drug Information eBook was used regarding available marketed formulation of antidiabetic drugs. Keywords used were "nanoparticle", "microparticle", "liposomes", "niosomes", "transdermal systems", "insulin", "antidiabetic drugs" and "novel drug delivery systems". Single inclusion was made for one article. If in vivo study was not done then article was seldom included in the manuscript. The curiosity to develop NDDSs of antidiabetic drugs with special attention to the nanoparticulate system followed by microparticulate and lipid-based system is found to emerge gradually to overcome the problems associated with the conventional dosage forms and to win the confidence of end users towards the higher acceptability. In the current scientific panorama when the area of novel drug delivery system has been recognized for its palpable benefits, unique potential of providing physical stability, sustained and site-specific drug delivery for a scheduled period of time can open new vistas for precise, safe and quality treatment of DM.

Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

PubMed

Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

2016-05-01

Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

In situ gelling polymers in ocular drug delivery systems: a review.

PubMed

Mundada, Atish S; Avari, Jasmine G

2009-01-01

The review article aims to highlight the recent developments in various in situ gel-forming polymeric systems that are used to achieve prolonged contact time of drugs with the cornea and increase their ocular bioavailability. These phase-change polymers, which trigger the drug release in response to external stimuli, are the most investigated in controlled drug delivery. The present review summarizes in detail these various polymers, which undergo sol-gel transition due to physical (temperature) or chemical (pH, ions) stimuli when instilled in the eye. As a whole, this article provides valuable insight into current trends in the field of in situ gel-forming ocular drug delivery systems.

A concise review on smart polymers for controlled drug release.

PubMed

Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali

2016-06-01

Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications.

Prefabricated/Precast Bridge Elements and Systems (PBES) for Off-System Bridges

DOT National Transportation Integrated Search

2012-08-01

The : Federal : Highway : Administrations : (FHWA) : Every : Day : Counts : initiative : aims : to : shorten : the : overall : project : delivery : time, : enhance : safety, : and : protect : the : environment : both : on : and : around : co...

Chitosan-functionalised single-walled carbon nanotube-mediated drug delivery of SNX-2112 in cancer cells.

PubMed

Zheng, Lixia; Wu, Shao; Tan, Li; Tan, Huo; Yu, Baodan

2016-09-01

Delivery of amphiphobic drugs (insoluble in both water and oil) has been a great challenge in drug delivery. SNX-2112, a novel inhibitor of Hsp90, is a promising drug candidate for treating various types of cancers; however, the insolubility greatly limits its clinical application. This study aimed to build a new type of drug delivery system using single-walled carbon nanotubes (SWNTs) for controllable release of SNX-2112; chitosan (CHI) was non-covalently added to SWNTs to improve their biocompatibility. SWNTs-CHI demonstrated high drug-loading capability; the release of SNX-2112 was pH triggered and time related. The intracellular reactive oxygen species of SWNTs-CHI increased, compared with that of SWNTs, leading to higher mitogen-activated protein kinase and cell apoptosis. The results of western-blotting, lactate dehydrogenase (LDH) release assay, and cell viability assay analyses indicated that apoptosis-related proteins were abundantly expressed in K562 cells and that the drug delivery system significantly inhibited K562 cells. Thus, SWNT-CHI/SNX-2112 shows great potential as a drug delivery system for cancer therapy. © The Author(s) 2016.

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.

Photonic crystal fibre for industrial laser delivery

NASA Astrophysics Data System (ADS)

O'Driscoll, E. J.; McDonald, J.; Morgan, S.; Simpson, G.; Sidhu, J.; Baggett, J. C.; Hayes, J. R.; Petrovich, M. N.; Finazzi, V.; Polletti, F.; Richardson, D. J.; Horley, R.; Harker, A.; Grunewald, P.; Allott, R.; Judd, E.

2006-12-01

Fiber delivery of intense laser radiation is important for a broad range of application sectors, from medicine through to industrial laser processing of materials, and offers many practical system benefits relative to free space solutions. In recent years, photonic crystal fiber technology has revolutionized the dynamic field of optical fibers, bringing with them a wide range of novel optical properties that make them ideally suited to power delivery with unparalleled control over the beam properties. The DTI funded project: Photonic Fibers for Industrial beam DELivery (PFIDEL), aims to develop novel fiber geometries for use as a delivery system for high power industrial lasers and to assess their potential in a range of "real" industrial applications. In this paper we review, from an industrial laser user perspective, the advantages of each of the fibers studied under PFIDEL. We present results of application demonstrations and discuss how these fibers can positively impact the field of industrial laser systems and processes, in particular for direct write and micromachining applications.

Motherhood: making it safer for Filipino women.

PubMed

Baylon, M C

1996-01-01

In November 1995, in the Philippines, the Department of Health implemented the Women's Health and Safe Motherhood Project. Its target audience is poor women in remote and underserved provinces. It addresses maternal health, reproductive tract infections (RTIs), sexually transmitted diseases (STDs), cervical cancer, domestic violence, and the desire to space births. It aims to improve the quality of women's health services through training of health providers, providing women with information to help them make informed choices, providing regular supplies and drugs, privacy and infection control at service delivery points, providing follow-up care, and improved cost-effective and technically-sound referral systems. The project also aims to ensure accessible service delivery points, well-equipped and maintained facilities, client and community feedback in managing service delivery, and information provision in order to increase acceptability of health services. The major components of the project include service delivery, institutional strengthening (via information, education, and communication; training of health providers; and improvement of the logistics system), community partnership for women's health development, and policy and operations research. The service delivery component will adopt a life-cycle approach to service delivery in Region 8 (urban and rural communities). It will pilot the syndromic approach in the management and detection of RTIs and STDs in 10 provinces. The biggest tasks of the project are upgrading referral networks from provincial and district hospitals to rural health units and barangay health stations and upgrading primary hospitals.

Nanomaterials in cancer-therapy drug delivery system.

PubMed

Zhang, Gen; Zeng, Xin; Li, Ping

2013-05-01

Nanomaterials can enhance the delivery and treatment efficiency of anti-cancer drugs, and the mechanisms of the tumor-reducing activity of nanomaterials with cancer drug have been investigated. The task for drug to reach pathological areas has facilitated rapid advances in nanomedicine. Herein, we summarize promising findings with respect to cancer therapeutics based on nano-drug delivery vectors. Relatively high toxicity of uncoated nanoparticles restricts the use of these materials in humans. In order to reduce toxicity, many approaches have focused on the encapsulation of nanoparticles with biocompatible materials. Efficient delivery systems have been developed that utilized nanoparticles loaded with high dose of cancer drug in the presence of bilayer molecules. Well-established nanotechnologies have been designed for drug delivery with specific bonding. Surface-modified nanoparticles as vehicles for drug delivery system that contains multiple nano-components, each specially designed to achieve aimed task for the emerging application delivery of therapeutics. Drug-coated polymer nanoparticles could efficiently increase the intracellular accumulation of anti-cancer drugs. This review also introduces the nanomaterials with drug on the induction of apoptosis in cancer cells in vitro and in vivo. Direct interactions between the particles and cellular molecules to cause adverse biological responses are also discussed.

Traversing the Skin Barrier with Nano-emulsions.

PubMed

Burger, Cornel; Shahzad, Yasser; Brummer, Alicia; Gerber, Minja; du Plessis, Jeanetta

2017-01-01

In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore aims at summarizing various methods of nano-emulsion formulation and their use as a topical and transdermal delivery vehicle for a number of active pharmaceutical ingredients from different pharmacological classes. This article represents a systematic review of nano-emulsions for topical and transdermal drug delivery. A vast literature was searched and critically analysed. Nano-emulsions are thermokinetically stable dispersion systems, which have been used in topical and transdermal delivery of a number of pharmaceutically active compounds. Nano-emulsions have a narrow droplet size range with tuneable surface properties, which make them an ideal delivery vehicle. Nanoemulsions have a number of advantages over conventional emulsions, including easy preparation using various low and high energy methods, optical transparency, high solubilisation capacity, high stability to droplet aggregation and the ability to penetrate the skin; thus allowing the transdermal delivery of drugs. This review indicated that nano-emulsions are promising vehicle for entrapping various drugs and are suitable for traversing the skin barrier for systemic effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Disease management from the economic point of view].

PubMed

Oberender, Peter; Zerth, Jürgen

2003-06-01

The introduction of disease management programs for chronic diseases aims to achieve a permanent improvement of care. Such an improvement cannot be reached without effective incentives. However, the incentives set in the German Health Care System may cause reactions on the micro level that do not correspond to the aims on the macro level. In the long term, patient empowerment will be needed in order to enable a shared-decision-making of patients and physicians. A market-oriented solution consists of quality competition allowing for various delivery systems and the search for new models that lead to an improvement of care. However, quality competition will have to respect the traditional principle of solidarity underlying the German health care system. Disease management will contribute to an integrated, incentive-oriented delivery system but only if it allows for a variety of care.

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.

Technologies for Controlled, Local Delivery of siRNA

PubMed Central

Sarett, Samantha M.; Nelson, Christopher E.; Duvall, Craig L.

2015-01-01

The discovery of RNAi in the late 1990s unlocked a new realm of therapeutic possibilities by enabling potent and specific silencing of theoretically any desired genetic target. Better elucidation of the mechanism of action, the impact of chemical modifications that stabilize and reduce nonspecific effects of siRNA molecules, and the key design considerations for effective delivery systems has spurred progress toward developing clinically-successful siRNA therapies. A logical aim for initial siRNA translation is local therapies, as delivering siRNA directly to its site of action helps to ensure that a sufficient dose reaches the target tissue, lessens the potential for off-target side effects, and circumvents the substantial systemic delivery barriers. While topical siRNA delivery has progressed into numerous clinical trials, an enormous opportunity also exists to develop sustained-release, local delivery systems that enable both spatial and temporal control of gene silencing. This review focuses on material platforms that establish both localized and controlled gene silencing, with emphasis on the systems that show most promise for clinical translation. PMID:26476177

Colloidal microgels in drug delivery applications

PubMed Central

Vinogradov, Serguei V.

2005-01-01

Colloidal microgels have recently received attention as environmentally responsive systems and now are increasingly used in applications as carriers for therapeutic drugs and diagnostic agents. Synthetic microgels consist of a crosslinked polymer network that provides a depot for loaded drugs, protection against environmental hazards and template for post-synthetic modification or vectorization of the drug carriers. The aim of this manuscript is to review recent attempts to develop new microgel formulations for oral drug delivery, to design metal-containing microgels for diagnostic and therapeutic applications, and to advance approaches including the systemic administration of microgels. Novel nanogel drug delivery systems developed in the authors’ laboratory are discussed in details including aspects of their synthesis, vectorization and recent applications for encapsulation of low molecular weight drugs or formulation of biological macromolecules. The findings reviewed here are encouraging for further development of the nanogels as intelligent drug carriers with such features as targeted delivery and triggered drug release. PMID:17168773

Targeting of herbal bioactives through folate receptors: a novel concept to enhance intracellular drug delivery in cancer therapy.

PubMed

Gupta, Anshita; Kaur, Chanchal Deep; Saraf, Shailendra; Saraf, Swarnlata

2017-06-01

Targeted drug delivery through folate receptor (FR) has emerged as a most biocompatible, target oriented, and non-immunogenic cargoes for the delivery of anticancer drugs. FRs are highly overexpressed in many tumor cells (like ovarian, lung, breast, kidney, brain, endometrial, and colon cancer), and targeting them through conjugates bearing specific ligand with encapsulated nanodrug moiety is undoubtedly, a promising approach toward tumor targeting. Folate, being an endogenous ligand, can be exploited well to affect various cellular events occurring during the progress of tumor, in a more natural and definite way. Thus, the aim of the review lies in summarizing the advancements taken place in the drug delivery system of different therapeutics through FRs and to refine its role as an endogenous ligand, in targeting of synthetic as well as natural bioactives. The review also provides an update on the patents received on the folate-based drug delivery system.

Overcoming the Cutaneous Barrier with Microemulsions

PubMed Central

Lopes, Luciana B.

2014-01-01

Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. PMID:24590260

Recent Advances in the Application of Vitamin E TPGS for Drug Delivery

PubMed Central

Yang, Conglian; Wu, Tingting; Qi, Yan; Zhang, Zhiping

2018-01-01

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future. PMID:29290821

Short and long term improvements in quality of chronic care delivery predict program sustainability.

PubMed

Cramm, Jane Murray; Nieboer, Anna Petra

2014-01-01

Empirical evidence on sustainability of programs that improve the quality of care delivery over time is lacking. Therefore, this study aims to identify the predictive role of short and long term improvements in quality of chronic care delivery on program sustainability. In this longitudinal study, professionals [2010 (T0): n=218, 55% response rate; 2011 (T1): n=300, 68% response rate; 2012 (T2): n=265, 63% response rate] from 22 Dutch disease-management programs completed surveys assessing quality of care and program sustainability. Our study findings indicated that quality of chronic care delivery improved significantly in the first 2 years after implementation of the disease-management programs. At T1, overall quality, self-management support, delivery system design, and integration of chronic care components, as well as health care delivery and clinical information systems and decision support, had improved. At T2, overall quality again improved significantly, as did community linkages, delivery system design, clinical information systems, decision support and integration of chronic care components, and self-management support. Multilevel regression analysis revealed that quality of chronic care delivery at T0 (p<0.001) and quality changes in the first (p<0.001) and second (p<0.01) years predicted program sustainability. In conclusion this study showed that disease-management programs based on the chronic care model improved the quality of chronic care delivery over time and that short and long term changes in the quality of chronic care delivery predicted the sustainability of the projects. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Design and construction of a DNA origami drug delivery system based on MPT64 antibody aptamer for tuberculosis treatment.

PubMed

Ranjbar, Reza; Hafezi-Moghadam, Mohammad Sadegh

2016-02-01

With all of the developments on infectious diseases, tuberculosis (TB) remains a cause of death among people. One of the most promising assembly techniques in nano-technology is "scaffolded DNA origami" to design and construct a nano-scale drug delivery system. Because of the global health problems of tuberculosis, the development of potent new anti-tuberculosis drug delivery system without cross-resistance with known anti-mycobacterial agents is urgently needed. The aim of this study was to design a nano-scale drug delivery system for TB treatment using the DNA origami method. In this study, we presented an experimental research on a DNA drug delivery system for treating Tuberculosis. TEM images were visualized with an FEI Tecnai T12 BioTWIN at 120 kV. The model was designed by caDNAno software and computational prediction of the 3D solution shape and its flexibility was calculated with a CanDo server. Synthesizing the product was imaged using transmission electron microscopy after negative-staining by uranyl formate. We constructed a multilayer 3D DNA nanostructure system by designing square lattice geometry with the scaffolded-DNA-origami method. With changes in the lock and key sequences, we recommend that this system be used for other infectious diseases to target the pathogenic bacteria.

Newer approaches for optimal bioavailability of ocularly delivered drugs: review.

PubMed

Kesavan, K; Balasubramaniam, J; Kant, S; Singh, P N; Pandit, J K

2011-03-01

Eye diseases can cause discomfort and anxiety in patients, with the ultimate fear of loss of vision and facial disfigurement. Many regions of the eye are relatively inaccessible to systemically administered drugs and, as a result, topical drug delivery remains the preferred route in most cases. Drugs may be delivered to treat the precorneal region for conjunctivitis and blepharitis, or to provide intraocular diseases such as glaucoma, uveitis, and cytomegalovirus retinitis. Most of the ophthalmic formulation strategies aim at maximizing ocular drug permeability through prolongation of the drug residence time in the cornea and conjunctival sac, as well as minimizing precorneal drug loss. The conventional topical ocular drug delivery systems show drawbacks such as increased precorneal elimination and high variability in efficacy. Attempts have been made to overcome these problems and enhance ocular bioavailability by the development of newer drug delivery systems. This review is concerned with classification, recent findings and applications and biocompatibility of newer drug delivery systems for the treatment of ocular diseases.

Polyethyleneimine and Chitosan Polymer-Based Mucoadhesive Liquid Crystalline Systems Intended for Buccal Drug Delivery.

PubMed

Calixto, Giovana Maria Fioramonti; Victorelli, Francesca Damiani; Dovigo, Lívia Nordi; Chorilli, Marlus

2018-02-01

The buccal mucosa is accessible, shows rapid repair, has an excellent blood supply, and shows the absence of the first-pass effect, which makes it a very attractive drug delivery route. However, this route has limitations, mainly due to the continuous secretion of saliva (0.5 to 2 L/day), which may lead to dilution, possible ingestion, and unintentional removal of the active drug. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can increase drug permeation through the mucosa and thereby improve drug delivery. This study aimed at developing and characterizing the mechanical, rheological, and mucoadhesive properties of four liquid crystalline precursor systems (LCPSs) composed of four different aqueous phases (i) water (FW), (ii) chitosan (FC), (iii) polyethyleneimine (FP), or (iv) both polymers (FPC); oleic acid was used as the oil phase, and ethoxylated and propoxylated cetyl alcohol was used as the surfactant. Polarized light microscopy and small-angle X-ray scattering indicated that all LCPSs formed liquid crystalline states after incorporation of saliva. Rheological, texture, and mucoadhesive assays showed that FPC had the most suitable characteristics for buccal application. In vitro release study showed that FPC could act as a controlled drug delivery system. Finally, based on in vitro cytotoxicity data, FPC is a safe buccal drug delivery system for the treatment of several buccal diseases.

Research on JD e-commerce's delivery model

NASA Astrophysics Data System (ADS)

Fan, Zhiguo; Ma, Mengkun; Feng, Chaoying

2017-03-01

E-commerce enterprises represented by JD have made a great contribution to the economic growth and economic development of our country. Delivery, as an important part of logistics, has self-evident importance. By establishing efficient and perfect self-built logistics systems and building good cooperation models with third-party logistics enterprises, e-commerce enterprises have created their own logistics advantages. Characterized by multi-batch and small-batch, e-commerce is much more complicated than traditional transaction. It's not easy to decide which delivery model e-commerce enterprises should adopt. Having e-commerce's logistics delivery as the main research object, this essay aims to find a more suitable logistics delivery model for JD's development.

An evolutionary approach to the architecture of effective healthcare delivery systems.

PubMed

Towill, D R; Christopher, M

2005-01-01

Aims to show that material flow concepts developed and successfully applied to commercial products and services can form equally well the architectural infrastructure of effective healthcare delivery systems. The methodology is based on the "power of analogy" which demonstrates that healthcare pipelines may be classified via the Time-Space Matrix. A small number (circa 4) of substantially different healthcare delivery pipelines will cover the vast majority of patient needs and simultaneously create adequate added value from their perspective. The emphasis is firmly placed on total process mapping and analysis via established identification techniques. Healthcare delivery pipelines must be properly engineered and matched to life cycle phase if the service is to be effective. This small family of healthcare delivery pipelines needs to be designed via adherence to very specific-to-purpose principles. These vary from "lean production" through to "agile delivery". The proposition for a strategic approach to healthcare delivery pipeline design is novel and positions much currently isolated research into a comprehensive organisational framework. It therefore provides a synthesis of the needs of global healthcare.

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.

New perspectives in cell delivery systems for tissue regeneration: natural-derived injectable hydrogels.

PubMed

Munarin, Fabiola; Petrini, Paola; Bozzini, Sabrina; Tanzi, Maria Cristina

2012-09-27

Natural polymers, because of their biocompatibility, availability, and physico-chemical properties have been the materials of choice for the fabrication of injectable hydrogels for regenerative medicine. In particular, they are appealing materials for delivery systems and provide sustained and controlled release of drugs, proteins, gene, cells, and other active biomolecules immobilized.In this work, the use of hydrogels obtained from natural source polymers as cell delivery systems is discussed. These materials were investigated for the repair of cartilage, bone, adipose tissue, intervertebral disc, neural, and cardiac tissue. Papers from the last ten years were considered, with a particular focus on the advances of the last five years. A critical discussion is centered on new perspectives and challenges in the regeneration of specific tissues, with the aim of highlighting the limits of current systems and possible future advancements.

Hydrogels for central nervous system therapeutic strategies.

PubMed

Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

2015-12-01

The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described. © IMechE 2015.

Recent Updates on Novel Approaches in Insulin Drug Delivery: A Review of Challenges and Pharmaceutical Implications.

PubMed

Pandey, Manisha; Choudhury, Hira; Yi, Cheah Xiao; Mun, Chen Wei; Ping, Goh Khang; Rou, Guee Xin; Singh, Bhalqish Jeet Kaur A/P Ambar Jeet; Jhee, Angel Ng Ann; Chin, Lee Kai; Kesharwani, Prashant; Gorain, Bapi; Hussain, Zahid

2018-05-22

Diabetes mellitus, a metabolic disorder of glucose metabolism, is mainly associated with insulin resistance to the body cells, or impaired production of insulin by the pancreatic β-cells. Insulin is mainly required to regulate glucose metabolism in type 1 diabetes mellitus patients; however, many patients with type 2 diabetes mellitus also require insulin, especially when their condition cannot be controlled solely by oral hypoglycemic agents. Hence, major researches are ongoing attempting to improve the delivery of insulin in order to make it more convenient to patients who experience side effects from the conventional treatment procedure or non-adherence to insulin regimen due to multiple comorbid conditions. Conventionally, insulin is administered via subcutaneous route which is also one of the sole reasons of patient's non-compliance due to the invasiveness of this method. Several attempts have been done to improve patient compliance, reduce side effects, improve delivery adherence, and to enhance pharmaceutical performance of the insulin therapy. Despite of facing substantial challenges in developing efficient delivery systems for insulin, vast researches have been carried out for the development of smart delivery systems to delivery insulin via ocular, buccal, pulmonary, oral, transdermal, as well as rectal routes. Therefore, the present review was aimed to overview the challenges encountered with the current insulin delivery systems and to summarize recent advancements in technology of various novel insulin delivery systems being discovered and introduced in the current market. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Manufacturing Techniques and Surface Engineering of Polymer Based Nanoparticles for Targeted Drug Delivery to Cancer

PubMed Central

Wang, Yichao; Li, Puwang; Truong-Dinh Tran, Thao; Zhang, Juan; Kong, Lingxue

2016-01-01

The evolution of polymer based nanoparticles as a drug delivery carrier via pharmaceutical nano/microencapsulation has greatly promoted the development of nano- and micro-medicine in the past few decades. Poly(lactide-co-glycolide) (PLGA) and chitosan, which are biodegradable and biocompatible polymers, have been approved by both the Food & Drug Administration (FDA) and European Medicine Agency (EMA), making them ideal biomaterials that can be advanced from laboratory development to clinical oral and parental administrations. PLGA and chitosan encapsulated nanoparticles (NPs) have successfully been developed as new oral drug delivery systems with demonstrated high efficacy. This review aims to provide a comprehensive overview of the fabrication of PLGA and chitosan particulate systems using nano/microencapsulation methods, the current progress and the future outlooks of the nanoparticulate drug delivery systems. Especially, we focus on the formulations and nano/micro-encapsulation techniques using top-down techniques. It also addresses how the different phases including the organic and aqueous ones in the emulsion system interact with each other and subsequently influence the properties of the drug delivery system. Besides, surface modification strategies which can effectively engineer intrinsic physicochemical properties are summarised. Finally, future perspectives and potential directions of PLGA and chitosan nano/microencapsulated drug systems are outlined. PMID:28344283

Association with Amino Acids Does Not Enhance Efficacy of Polymerized Liposomes As a System for Lung Gene Delivery

PubMed Central

Bandeira, Elga; Lopes-Pacheco, Miquéias; Chiaramoni, Nadia; Ferreira, Débora; Fernandez-Ruocco, Maria J.; Prieto, Maria J.; Maron-Gutierrez, Tatiana; Perrotta, Ramiro M.; de Castro-Faria-Neto, Hugo C.; Rocco, Patricia R. M.; Alonso, Silvia del Valle; Morales, Marcelo M.

2016-01-01

Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids [1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine] associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study, lipopolymers were associated with l-arginine, l-tryptophan, or l-cysteine. We hypothesized that the addition of these amino acids would enhance the efficacy of gene delivery to the lungs by the lipopolymers. l-Arginine showed the highest association efficiency due to its positive charge and better surface interactions. None of the formulations caused inflammation or altered lung mechanics, suggesting that these lipopolymers can be safely administered as aerosols. All formulations were able to induce eGFP mRNA expression in lung tissue, but the addition of amino acids reduced delivery efficacy when compared with the simple lipopolymer particle. These results indicate that this system could be further explored for gene or drug delivery targeting lung diseases. PMID:27199766

Potential Use of Alginate-Based Carriers As Antifungal Delivery System

PubMed Central

Spadari, Cristina de Castro; Lopes, Luciana B.; Ishida, Kelly

2017-01-01

Fungal infections have become a major public health problem, growing in number and severity in recent decades due to an increase of immunocompromised patients. The use of therapeutic agents available to treat these fungal infections is limited by their toxicity, low bioavailability, antifungal resistance, and high cost of treatment. Thus, it becomes extremely important to search for new therapeutic options. The use of polymeric systems as drug carriers has emerged as a promising alternative to conventional formulations for antifungals. Alginate is a natural polymer that has been explored in the last decade for development of drug delivery systems due to its non-toxicity, biodegradability, biocompatibility, low cost, mucoadhesive, and non-immunogenic properties. Several antifungal agents have been incorporated in alginate-based delivery systems, including micro and nanoparticles, with great success, displaying promising in vitro and in vivo results for antifungal activities, reduction in the toxicity and the total drug dose used in the treatment, and improved bioavailability. This review aims at discussing the potential use and benefits of alginate-based nanocarriers and other delivery systems containing antifungal agents in the therapy of fungal infections. PMID:28194145

Development of oral food-grade delivery systems: current knowledge and future challenges.

PubMed

Benshitrit, Revital Cohen; Levi, Carmit Shani; Tal, Sharon Levi; Shimoni, Eyal; Lesmes, Uri

2012-01-01

In recent years there has been an increasing interest in the development of new and efficient oral food delivery systems as tools to prevent disease and promote human health and well-being. Such vehicles are sought to protect bioactive ingredients added to food while controlling and targeting their release as they pass through the human gastrointestinal tract (GIT). This review aims to summarize the key concepts of food delivery systems, their characterization and evaluation. Particularly, evaluation of their performance within the human GIT is discussed. To this end an overview of several in vivo and in vitro methods currently applied for the study of such systems is given. Although considered to be still in its infancy, this promising field of research is likely to infiltrate into real products through rational design. In order for such efforts to materialize into real products some challenges still need to be met and are discussed herein. Overall, it seems that adopting a comprehensive pharmacological approach and relevant cutting edge tools are likely to facilitate innovations and help elucidate and perhaps tailor delivery systems' behavior in the human GIT.

Patenting of nanopharmaceuticals in drug delivery: no small issue.

PubMed

du Toit, Lisa Claire; Pillay, Viness; Choonara, Yahya E; Pillay, Samantha; Harilall, Sheri-lee

2007-01-01

Nanotechnology is a rapidly evolving interdisciplinary field based on the manipulation of matter on a submicron scale, encompassing matter between 1 and 100 nanometers (nm). The currently registered nanotechnology patents comprise 35 countries being involved in the global distribution of these patents. Close to 3000 patents were issued in the USA since 1996 with the term 'nano' in the patents, with a considerable number having application in nanomedicine. The large majority of therapeutic patents are focused on drug delivery systems, highlighting an important application globally. Nanopharmaceutical patents are centered mainly on non-communicable diseases, with cancer receiving the greatest focus, followed by hepatitis. Drug delivery systems employing nanotechnology have the ability to allow superior drug absorption, controlled drug release and reduced side-effects, enhancing the effectiveness of existing drug delivery systems. Nanoparticle-based drug delivery systems may be among the first types of products to generate serious nanotechnology patent disputes as the multi-billion dollar pharmaceutical industry begins to adopt them. This review article aimed to locate patented nanopharmaceuticals in drug delivery online, employing pertinent key terms while searching the patent databases. Awarded and pending patents in the past 20 years pertaining to nanopharmaceutical or nano-enabled systems such as micelles, nanoemulsions, nanogels, liposomes, nanofibres, dendrimer technology and polymer therapeutics are presented in the review article, providing an overview of the diversity of the patent applications.

A literature review on integrated perinatal care

PubMed Central

Rodríguez, Charo; des Rivières-Pigeon, Catherine

2007-01-01

Context The perinatal period is one during which health care services are in high demand. Like other health care sub-sectors, perinatal health care delivery has undergone significant changes in recent years, such as the integrative wave that has swept through the health care industry since the early 1990s. Purpose The present study aims at reviewing scholarly work on integrated perinatal care to provide support for policy decision-making. Results Researchers interested in integrated perinatal care have, by assessing the effectiveness of individual clinical practices and intervention programs, mainly addressed issues of continuity of care and clinical and professional integration. Conclusions Improvements in perinatal health care delivery appear related not to structurally integrated health care delivery systems, but to organizing modalities that aim to support woman-centred care and cooperative clinical practice. PMID:17786177

Functionalization of protein-based nanocages for drug delivery applications.

PubMed

Schoonen, Lise; van Hest, Jan C M

2014-07-07

Traditional drug delivery strategies involve drugs which are not targeted towards the desired tissue. This can lead to undesired side effects, as normal cells are affected by the drugs as well. Therefore, new systems are now being developed which combine targeting functionalities with encapsulation of drug cargo. Protein nanocages are highly promising drug delivery platforms due to their perfectly defined structures, biocompatibility, biodegradability and low toxicity. A variety of protein nanocages have been modified and functionalized for these types of applications. In this review, we aim to give an overview of different types of modifications of protein-based nanocontainers for drug delivery applications.

Recent advancements in nanoparticle based drug delivery for gastrointestinal disorders.

PubMed

Mittal, Rahul; Patel, Amit P; Jhaveri, Vasanti M; Kay, Sae-In S; Debs, Luca H; Parrish, James M; Pan, Debbie R; Nguyen, Desiree; Mittal, Jeenu; Jayant, Rahul Dev

2018-03-01

The emergent field of nanoparticles has presented a wealth of opportunities for improving the treatment of human diseases. Recent advances have allowed for promising developments in drug delivery, diagnostics, and therapeutics. Modified delivery systems allow improved drug delivery over traditional pH, microbe, or receptor dependent models, while antibody association allows for more advanced imaging modalities. Nanoparticles have potential clinical application in the field of gastroenterology as they offer several advantages compared to the conventional treatment systems including target drug delivery, enhanced treatment efficacy, and reduced side effects. Areas covered: The aim of this review article is to summarize the recent advancements in developing nanoparticle technologies to treat gastrointestinal diseases. We have covered the application of nanoparticles in various gastrointestinal disorders including inflammatory bowel disease and colorectal cancer. We also have discussed how the gut microbiota affects the nanoparticle based drug delivery in the gastrointestinal tract. Expert opinion: Nanoparticles based drug delivery offers a great platform for targeted drug delivery for gastrointestinal disorders. However, it is influenced by the presence of microbiota, drug interaction with nanoparticles, and cytotoxicity of nanoparticles. With the advancements in nanoparticle technology, it may be possible to overcome these barriers leading to efficient drug delivery for gastrointestinal disorders based on nanoparticle platform.

Delivering Training for Highly Demanding Information Systems

ERIC Educational Resources Information Center

Norton, Andrew Lawrence; Coulson-Thomas, Yvette May; Coulson-Thomas, Colin Joseph; Ashurst, Colin

2012-01-01

Purpose: There is a lack of research covering the training requirements of organisations implementing highly demanding information systems (HDISs). The aim of this paper is to help in the understanding of appropriate training requirements for such systems. Design/methodology/approach: This research investigates the training delivery within a…

Achieving Population Health in Accountable Care Organizations

PubMed Central

Walker, Deborah Klein

2013-01-01

Although “population health” is one of the Institute for Healthcare Improvement’s Triple Aim goals, its relationship to accountable care organizations (ACOs) remains ill-defined and lacks clarity as to how the clinical delivery system intersects with the public health system. Although defining population health as “panel” management seems to be the default definition, we called for a broader “community health” definition that could improve relationships between clinical delivery and public health systems and health outcomes for communities. We discussed this broader definition and offered recommendations for linking ACOs with the public health system toward improving health for patients and their communities. PMID:23678910

Ultra-low profile Ovation device: is it the definitive solution for EVAR?

PubMed

de Donato, G; Setacci, F; Sirignano, P; Galzerano, G; Borrelli, M P; di Marzo, L; Setacci, C

2014-02-01

When Juan Parodi implanted an endograft in a human body for the first time on September 7, 1990 in Buenos Aires, Argentina, the delivery system of the handmade device was primitive, extremely rigid, and had a bulky profile of 27 French (F). Since then, stent-graft technology has evolved rapidly, limitations of earlier-generation devices have been overtaken, and endovascular aneurysm repair (EVAR) eligibility has increased enormously. Nevertheless (still) challenging aortoiliac anatomy such as short and complex proximal aortic neck seal zones and narrow access vessels are responsible for EVAR ineligibility in up to 50% of cases. The Ovation Prime abdominal stent-graft system (TriVascular, Inc., Santa Rosa, CA, USA) is a trimodular device designed with the aortic body delivered via a flexible, hydrophilic-coated, ultra-low profile catheter (14-F outer diameter - OD). The aortic body is provided with a suprarenal nitinol stent with anchors that provide active fixation, while a network of rings and channels that are inflated with a low-viscosity radiopaque polymer during stent-graft deployment, provides effective sealing. The previous EVAR technology aimed to both anchor and seal using stents combined with fabric, with neither optimized for their roles and each forced to compete for the same space within their delivery catheters, which inevitably led to larger profile of the delivery system. The technical revolution of the Ovation endograft includes the idea to truly uncouple the stages of stent-graft fixation and seal during the procedure. In the Ovation endograft platform, stent and fabric are not competing the same space within the delivery system and an ultra-low profile delivery can be achieved without compromise. With such a low-profile delivery catheter, approximately 90% of men and 70% of women with abdominal aortic aneurysm have access vessel diameters considered fit for endovascular repair. The aim of this review paper was to analyze the main properties of Ovation endograft, to emphasize the advantage of the ultra-low profile device, and to sum up current literature.

SU-E-T-755: Timing Characteristics of Proton and Carbon Ion Treatments Using a Synchrotron and Modulated Scanning

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

Zhao, J; Li, Y; Huang, Z

2015-06-15

Purpose: The time required to deliver a treatment impacts not only the number of patients that can be treated each day but also the accuracy of delivery due to potential movements of patient tissues. Both macroscopic and microscopic timing characteristics of a beam delivery system were studied to examine their impacts on patient treatments. Methods: 35 patients were treated during a clinical trial to demonstrate safety and efficacy of a Siemens Iontris system prior to receiving approval from the Chinese Food and Drug Administration. The system has a variable cycle time and can provide proton beams from 48 to 221more » MeV/n and carbon ions from 86 to 430 MeV/n. A modulated scanning beam delivery technique is used where the beam remains stationary at each spot aiming location and is not turned off while the spot quickly moves from one aiming location to the next. The treatment log files for 28 of the trial patients were analyzed to determine several timing characteristics. Results: The average portal time per target dose was 172.5 s/Gy for protons and 150.7 s/Gy for carbon ions. The maximum delivery time for any portal was less than 300 s. The average dwell time per spot was 12 ms for protons and 3.0 ms for carbon ions. The number of aiming positions per energy layer varied from 1 to 258 for protons and 1 to 621 for carbon ions. The average spill time and cycle time per energy layer were 1.20 and 2.68 s for protons and 0.95 and 4.73 s for carbon ions respectively. For 3 of the patients, the beam was gated on and off to reduce the effects of respiration. Conclusion: For a typical target volume of 153 cc as used in this clinical trial, the portal delivery times were acceptable.« less

Pluronic® F-127 and Pluronic Lecithin Organogel (PLO): main features and their applications in topical and transdermal administration of drugs.

PubMed

Almeida, Hugo; Amaral, Maria Helena; Lobão, Paulo; Lobo, José Manuel Sousa

2012-01-01

Topical drug treatment aims at providing high concentrations of drugs at the site of application so as to avoid adverse systemic effects associated with oral administration. Smart polymers, or stimuli-responsive polymers, are able to respond to a stimulus by showing physical or chemical changes in their behaviour as, for example, the delivery of the drug carried by them. The thermo-responsive nature of Pluronic® F-127 (Basf, Ludwigshafen, Germany) makes it an excellent candidate for the delivery of drugs at various application sites. In recent years, PF-127, and later, Pluronic lecithin organogels (PLO), have attracted particular interest in the design of dermal and transdermal delivery systems with a view to promoting, improving or retarding drug permeation through the skin, bearing in mind that for topical delivery systems, accumulation in the skin with minimal permeation is desired, while for systemic delivery, the opposite behaviour is preferred. In this review, we discuss the properties and characteristics of PF-127 and Pluronic lecithin organogels (PLO), and present many examples and advantages of the application of these polymeric systems in topical and transdermal administration of drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods

PubMed Central

Chinna Reddy, P; Chaitanya, K.S.C.; Madhusudan Rao, Y.

2011-01-01

Owing to the ease of the administration, the oral cavity is an attractive site for the delivery of drugs. Through this route it is possible to realize mucosal (local effect) and transmucosal (systemic effect) drug administration. In the first case, the aim is to achieve a site-specific release of the drug on the mucosa, whereas the second case involves drug absorption through the mucosal barrier to reach the systemic circulation. The main obstacles that drugs meet when administered via the buccal route derive from the limited absorption area and the barrier properties of the mucosa. The effective physiological removal mechanisms of the oral cavity that take the formulation away from the absorption site are the other obstacles that have to be considered. The strategies studied to overcome such obstacles include the employment of new materials that, possibly, combine mucoadhesive, enzyme inhibitory and penetration enhancer properties and the design of innovative drug delivery systems which, besides improving patient compliance, favor a more intimate contact of the drug with the absorption mucosa. This presents a brief description of advantages and limitations of buccal drug delivery and the anatomical structure of oral mucosa, mechanisms of drug permeation followed by current formulation design in line with developments in buccal delivery systems and methodology in evaluating buccal formulations. PMID:23008684

Current HPLC Methods for Assay of Nano Drug Delivery Systems.

PubMed

Tekkeli, Serife Evrim Kepekci; Kiziltas, Mustafa Volkan

2017-01-01

In nano drug formulations the mechanism of release is a critical process to recognize controlled and targeted drug delivery systems. In order to gain high bioavailability and specificity from the drug to reach its therapeutic goal, the active substance must be loaded into the nanoparticles efficiently. Therefore, the amount in biological fluids or tissues and the remaining amount in nano carriers are very important parameters to understand the potential of the nano drug delivery systems. For this aim, suitable and validated quantitation methods are required to determine released drug concentrations from nano pharmaceutical formulations. HPLC (High Performance Liquid Chromatography) is one of the most common techniques used for determination of released drug content out of nano drug formulations, in different physical conditions, over different periods of time. Since there are many types of HPLC methods depending on detector and column types, it is a challenge for the researchers to choose a suitable method that is simple, fast and validated HPLC techniques for their nano drug delivery systems. This review's goal is to compare HPLC methods that are currently used in different nano drug delivery systems in order to provide detailed and useful information for researchers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Exploration of the Performance of a Hybrid Closed Loop Insulin Delivery Algorithm That Includes Insulin Delivery Limits Designed to Protect Against Hypoglycemia.

PubMed

de Bock, Martin; Dart, Julie; Roy, Anirban; Davey, Raymond; Soon, Wayne; Berthold, Carolyn; Retterath, Adam; Grosman, Benyamin; Kurtz, Natalie; Davis, Elizabeth; Jones, Timothy

2017-01-01

Hypoglycemia remains a risk for closed loop insulin delivery particularly following exercise or if the glucose sensor is inaccurate. The aim of this study was to test whether an algorithm that includes a limit to insulin delivery is effective at protecting against hypoglycemia under those circumstances. An observational study on 8 participants with type 1 diabetes was conducted, where a hybrid closed loop system (HCL) (Medtronic™ 670G) was challenged with hypoglycemic stimuli: exercise and an overreading glucose sensor. There was no overnight or exercise-induced hypoglycemia during HCL insulin delivery. All daytime hypoglycemia was attributable to postmeal bolused insulin in those participants with a more aggressive carbohydrate factor. HCL systems rely on accurate carbohydrate ratios and carbohydrate counting to avoid hypoglycemia. The algorithm that was tested against moderate exercise and an overreading glucose sensor performed well in terms of hypoglycemia avoidance. Algorithm refinement continues in preparation for long-term outpatient trials.

Model Adoption Exchange Payment System: Executive Summary.

ERIC Educational Resources Information Center

Ambrosino, Robert J.

This executive summary provides a brief description of the Model Adoption Exchange Payment System (MAEPS), a unique payment system aimed at improving the delivery of adoption exchange services throughout the United States. Following a brief introductory overview, MAEPS is described in terms of (1) its six components (registration, listing,…

Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature

PubMed Central

Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Tang, Yisi; Wang, Huiyuan; Xu, Qin; Li, Yaping; Li, Feng; Huang, Yongzhuo

2017-01-01

Poor tumor-targeted and cytoplasmic delivery is a bottleneck for protein toxin-based cancer therapy. Ideally, a protein toxin drug should remain stealthy in circulation for prolonged half-life and reduced side toxicity, but turn activated at tumor. PEGylation is a solution to achieve the first goal, but creates a hurdle for the second because PEG rejects interaction between the drugs and tumor cells therein. Such PEG dilemma is an unsolved problem in protein delivery. Herein proposed is a concept of turning PEG dilemma into prodrug-like feature. A site-selectively PEGylated, gelatinase-triggered cell-penetrating trichosanthin protein delivery system is developed with three specific aims. The first is to develop an intein-based ligation method for achieving site-specific modification of protein toxins. The second is to develop a prodrug feature that renders protein toxins remaining stealthy in blood for reduced side toxicity and improved EPR effect. The third is to develop a gelatinase activatable cell-penetration strategy for enhanced tumor targeting and cytoplasmic delivery. Of note, site-specific modification is a big challenge in protein drug research, especially for such a complicated, multifunctional protein delivery system. We successfully develop a protocol for constructing a macromolecular prodrug system with intein-mediated ligation synthesis. With an on-column process of purification and intein-mediated cleavage, the site-specific PEGylation then can be readily achieved by conjugation with the activated C-terminus, thus constructing a PEG-capped, cell-penetrating trichosanthin system with a gelatinase-cleavable linker that enables tumor-specific activation of cytoplasmic delivery. It provides a promising method to address the PEG dilemma for enhanced protein drug delivery, and importantly, a facile protocol for site-specific modification of such a class of protein drugs for improving their druggability and industrial translation. PMID:27914267

Buccoadhesive drug delivery systems--extensive review on recent patents.

PubMed

Pathan, Shadab A; Iqbal, Zeenat; Sahani, Jasjeet K; Talegaonkar, Sushma; Khar, Roop K; Ahmad, Farhan J

2008-01-01

Peroral administration of drugs, although most preferred by both clinicians and patients has several disadvantages such as hepatic first pass metabolism and enzymatic degradation within the GI tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for administration of these drugs. Among the various transmucosal routes studied the buccal mucosa offers several advantages for controlled drug delivery for extended period of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract is avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form, design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is thus a promising area for continued research with the aim of systemic and local delivery of orally inefficient drugs as well as feasible and attractive alternative for non-invasive delivery of potent protein and peptide drug molecules. Extensive review pertaining specifically to the patents relating to buccal drug delivery is currently available. However, many patents e.g. US patents 6, 585,997; US20030059376A1 etc. have been mentioned in few articles. It is the objective of this article to extensively review buccal drug delivery by discussing the recent patents available. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems.

Investigation of the mediating effects of IT governance-value delivery on service quality and ERP performance

NASA Astrophysics Data System (ADS)

Tsai, Wen-Hsien; Chou, Yu-Wei; Leu, Jun-Der; Chao Chen, Der; Tsaur, Tsen-Shu

2015-02-01

This study aimed to explore the mediating effects of IT governance (ITG)-value delivery in the relationships among the quality of vendor service, the quality of consultant services, ITG-value delivery and enterprise resource planning (ERP) performance. The sampling of this research was acquired from a questionnaire survey concerning ERP implementations in Taiwan. In this survey, 4366 questionnaires were sent to manufacturing and service companies listed in the TOP 5000: The Largest Corporations in Taiwan 2009. The results showed that an ERP system will exhibit a decreased error rate and improved performance if ERP system vendors and consultants provide good service quality. The results also demonstrated that significant relationships exist among the quality of vendor service, the quality of consultant services and value delivery. The contribution of this article is twofold. First, it found that value delivery provides an effective measure of ERP performance under an ITG framework. Second, it provides evidence of the partial mediating effects of value delivery between service quality and ERP performance. In other words, if enterprises want to improve ERP performance, they need to consider factors such as value delivery and the quality of a vendor/consultant's service.

The influences of patient's satisfaction with medical service delivery, assessment of medical service, and trust in health delivery system on patient's life satisfaction in China.

PubMed

Tang, Liyang

2012-09-14

Patient's satisfaction with medical service delivery/assessment of medical service/trust in health delivery system may have significant influence on patient's life satisfaction in China's health delivery system/in various kinds of hospitals.The aim of this study was to test whether and to what extent patient's satisfaction with medical service delivery/patient's assessments of various major aspects of medical service/various major aspects of patient's trust in health delivery system influenced patient's life satisfaction in China's health delivery system/in various kinds of hospitals. This study collaborated with National Bureau of Statistics of China to carry out a 2008 national urban resident household survey in 17 provinces, autonomous regions, and municipalities directly under the central government (N = 3,386), and specified ordered probit models were established to analyze dataset from this household survey. The key considerations in generating patient's life satisfaction involved patient's overall satisfaction with medical service delivery, assessment of doctor-patient communication, assessment of medical cost, assessment of medical treatment process, assessment of medical facility and hospital environment, assessment of waiting time for medical service, trust in prescription, trust in doctor, and trust in recommended medical examination. But the major considerations in generating patient's life satisfaction were different among low level public hospital, high level public hospital, and private hospital. The promotion of patient's overall satisfaction with medical service delivery, the improvement of doctor-patient communication, the reduction of medical cost, the improvement of medical treatment process, the promotion of medical facility and hospital environment, the reduction of waiting time for medical service, the promotion of patient's trust in prescription, the promotion of patient's trust in doctor, and the promotion of patient's trust in recommended medical examination could all help promote patient's life satisfaction. But their promotion effects were different among low level public hospital, high level public hospital, and private hospital.

Levodopa delivery systems: advancements in delivery of the gold standard.

PubMed

Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

2010-02-01

Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the effective management of PD.

Professional Growth & Support Spending Calculator

ERIC Educational Resources Information Center

Education Resource Strategies, 2013

2013-01-01

This "Professional Growth & Support Spending Calculator" helps school systems quantify all current spending aimed at improving teaching effectiveness. Part I provides worksheets to analyze total investment. Part II provides a system for evaluating investments based on purpose, target group, and delivery. In this Spending Calculator…

[Use of a novel polymer, the in-situ gelling mucoadhesive thiolated poly(aspartic acid) in ophthalmic drug delivery].

PubMed

Horvát, Gabriella; Budai-Szűcs, Mária; Berkó, Szilvia; Szabóné-Révész, Piroska; Gyarmati, Benjámin; Szilágyi, Barnabas Áron; Szilágyi, András; Csányi Erzsébet

2015-01-01

The bioavailability of drugs used on mucosal surfaces can be increased by the use of mucoadhesive polymers. A new type of mucoadhesive polymers is the group of thiolated polymers with thiol group containing side chains. These polymers are able to form covalent bonds (disulphide linkages) with the mucin glycoproteins. For the formulation of an ocular drug delivery system (DDS) thiolated poly(aspartic acid) polymer (ThioPASP) was used. Our aim was to determine their biocompatibility, mucoadhesion and drug release property. According to the results it can be established that the thiolated poly(aspartic acid) polymers can be a potential vehicle of an ocular drug delivery system due to their biocompatibility, good mucoadhesive property and drug release profile. Thanks to their properties controlled drug delivery can be achieved and bioavailability of the ophthalmic formulation can be increased, while the usage frequency can be decreased.

Insulin delivery route for the artificial pancreas: subcutaneous, intraperitoneal, or intravenous? Pros and cons.

PubMed

Renard, Eric

2008-07-01

Insulin delivery is a crucial component of a closed-loop system aiming at the development of an artificial pancreas. The intravenous route, which has been used in the bedside artificial pancreas model for 30 years, has clear advantages in terms of pharmacokinetics and pharmacodynamics, but cannot be used in any ambulatory system so far. Subcutaneous (SC) insulin infusion benefits from the broad expansion of insulin pump therapy that promoted the availability of constantly improving technology and fast-acting insulin analog use. However, persistent delays of insulin absorption and action, variability and shortterm stability of insulin infusion from SC-inserted catheters generate effectiveness and safety issues in view of an ambulatory, automated, glucose-controlled, artificial beta cell. Intraperitoneal insulin delivery, although still marginally used in diabetes care, may offer an interesting alternative because of its more-physiological plasma insulin profiles and sustained stability and reliability of insulin delivery.

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

Finasteride topical delivery systems for androgenetic alopecia.

PubMed

Khan, Muhammad Zia Ullah; Khan, Shujaat Ali; Ubaid, Muhammad; Shah, Aamna; Kousar, Rozina; Murtaza, Ghulam

2018-01-23

Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of sexual disorders including decrease in libido, gynecomastia, erectile dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since, hair follicles widely home in 5α-reductase, topical formulations of finasteride in comparison to its oral formulations are expected to potentially reduce its systemic adverse effects. The analysis of literature has revealed some delivery systems developed for the enhanced and localized penetration of finasteride into the skin. These finasteride delivery systems include polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim of this review article is to briefly amass all literature on topical delivery of finasteride to elaborate best dosage form, i.e. formulation having maximum permeation rate. This study will serve as a future perspective regarding topical delivery of finasteride. The literature analysis has exhibited that most of the previous investigators have used propylene glycol in their finasteride-loaded topical formulations, while poloxamer P407, monoolein, transcutol P and choline was used in few formulations. Moreover among all drug delivery systems, finasteride liposomal gel system consisting of 2% methyl cellulose and gel system containing poloxamer P407 exhibited the highest flux with a value of 28.4 ± 1.3 µg/cm2h and 23.1 ± 1.4 µg/cm2h, respectively. Several topical drug delivery techniques such as topical microneedles, aerosol foams, nanoemulsions, microsponges, and emulsifier free formulations, fullerenes, ointments, pastes, creams, gel and lotions are still to be worthy regarding finasteride topical delivery in future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Calcium phosphate nanocoatings and nanocomposites, part 2: thin films for slow drug delivery and osteomyelitis.

PubMed

Ben-Nissan, Besim; Macha, Innocent; Cazalbou, Sophie; Choi, Andy H

2016-01-01

During the last two decades although many calcium phosphate based nanomaterials have been proposed for both drug delivery, and bone regeneration, their coating applications have been somehow slow due to the problems related to their complicated synthesis methods. In order to control the efficiency of local drug delivery of a biomaterial the critical pore sizes as well as good control of the chemical composition is pertinent. A variety of calcium phosphate based nanocoated composite drug delivery systems are currently being investigated. This review aims to give an update into the advancements of calcium phosphate nanocoatings and thin film nanolaminates. In particular recent research on PLA/hydroxyapatite composite thin films and coatings into the slow drug delivery for the possible treatment of osteomyelitis is covered.

Assessing Service Delivery Systems for Assitive Technology in Brazil using HEART Study quality indicators.

PubMed

Maximo, Tulio; Clift, Laurence

2015-01-01

recently in Brazil, there have been investments and improvements in the service delivery system for assistive technology provision. However, there is little documentation of this process, or evidence that users are being involved appropriately. to understand how a ssistive technology service provision currently functions in Belo Horizonte city, Brazil, in order to provide context-specific interventions and recommendations to improve services. Qualitative research design, including visits to key institutions and semi-structured interviews with key stakeholders. Interview questions were divided with two purposes: 1) Exploratory, aiming to understand present service functioning; 2) Evaluative, aiming to assess staff difficulties in applying best existing best practices. Assistive Technology services in Belo Horizonte fall under the 'medical model' definition of service delivery developed by AAATE. It was also found that staff lack training and knowledge support to assess user requirements and involve them during the decision process. Additionally, there is no follow up stage after the device is delivered. The study clearly defines the service provision function and the staff difficulties at Belo Horizonte city, providing information for further studies.

The macrophage as a Trojan horse for antisense oligonucleotide delivery.

PubMed

Novak, James S; Jaiswal, Jyoti K; Partridge, Terence A

2018-06-04

The gateway to the promised land of gene therapy has been obstructed by the problem of accurate and efficient delivery of therapeutic agents to their target sites. This is true both of constructs designed to directly express proteins of interest, and of constructs or agents aimed at modifying the expression of endogenous genes. It is recognized as a major impediment to the effective application of genetic therapies currently or incipiently in clinical trial. Our recent study has examined the mechanism underlying delivery of therapeutic antisense oligonucleotides (ASO) for treating the devastating muscle disease Duchenne muscular dystrophy [1]. Working to understand the mode of ASO delivery in DMD, we discovered that inflammatory cells act as a depot that locally stores the intravenously administered ASO. This local depot of ASO then becomes available to the muscle fibres by way of satellite cells that deliver their cargo by fusion with damaged fibres during muscle repair. This finding points to a potentially novel strategy for systemic ASO delivery, involving the use of the inflammatory cell as a Trojan horse. Such an approach would have the benefit not only of enhancing tissue-specific delivery of ASO, but also of reducing the impact of their rapid clearance from the circulation. Here, we discuss the issues surrounding ASO-mediated exon skipping efficacy for DMD, and outline research aimed at improving targeted ASO delivery.

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

PubMed Central

Richardson, R. Mark; Kells, Adrian P.; Martin, Alastair J.; Larson, Paul S.; Starr, Philip A.; Piferi, Peter G.; Bates, Geoffrey; Tansey, Lisa; Rosenbluth, Kathryn H.; Bringas, John R.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Background/Aims A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion. PMID:21494065

Noninvasive delivery systems for peptides and proteins in osteoporosis therapy: a retroperspective.

PubMed

Hoyer, Herbert; Perera, Glen; Bernkop-Schnürch, Andreas

2010-01-01

The aim of this review is to provide the reader general and inspiring prospects in various attempts to make noninvasive delivery systems of calcitonin and teriparatide feasible and as convenient as possible. Calcitonin and teriparatide play an important role in both calcium homeostasis and bone remodelling. Currently calcitonin is available as a subcutaneous injection and as a nasal spray whereas teriparatide is administered subcutaneously. In the past few years, an increasing number of articles about drug delivery systems for calcitonin and teriparatide have been published. These delivery systems have been developed to overcome the inherent barriers for the uptake across the diverse membranes on the various routes for protein and peptide delivery. Co-administration of permeation enhancers, mucoadhesive agents, viscosity modifying agents, multifunctional polymers, protease inhibitors as well as encapsulation and chemical modification are utilized in order to improve calcitonin and teriparatide absorption after oral, nasal, pulmonal, or buccal administration. The majority of research groups have been working on the development of formulations based on the encapsulation of molecules in biodegradable and biocompatible polymeric nanoparticles. However these observations are based on data obtained under different experimental conditions. Hence, it is difficult to compare the obtained results in order to draw general conclusions about the most promising characteristics required for oral and nasal formulations for these peptides.

Bio-inspired engineering of cell- and virus-like nanoparticles for drug delivery.

PubMed

Parodi, Alessandro; Molinaro, Roberto; Sushnitha, Manuela; Evangelopoulos, Michael; Martinez, Jonathan O; Arrighetti, Noemi; Corbo, Claudia; Tasciotti, Ennio

2017-12-01

The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles' surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles. Copyright © 2017. Published by Elsevier Ltd.

Recapitulation of complex transport and action of drugs at tumor microenvironment using tumor-microenvironment-on-chip

PubMed Central

Han, Bumsoo; Qu, Chunjing; Park, Kinam; Konieczny, Stephen F.; Korc, Murray

2016-01-01

Targeted delivery aims to selectively distribute drugs to targeted tumor tissue but not to healthy tissue. This can address many of clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, complex tumor microenvironment poses various barriers hindering the transport of drugs and drug delivery systems. New tumor models that allow for the systematic study of these complex environments are highly desired to provide reliable test beds to develop drug delivery systems for targeted delivery. Recently, research efforts have yielded new in vitro tumor models, the so called tumor-microenvironment-on-chip, that recapitulate certain characteristics of the tumor microenvironment. These new models show benefits over other conventional tumor models, and have the potential to accelerate drug discovery and enable precision medicines. However, further research is warranted to overcome their limitations and to properly interpret the data obtained from these models. In this article, key features of the in vivo tumor microenvironment that are relevant to drug transport processes for targeted delivery was discussed, and the current status and challenges for developing in vitro transport model systems was reviewed. PMID:26688098

A health systems constraints analysis for neurologic diseases: the example of Timor-Leste.

PubMed

Mateen, Farrah J; Martins, Nelson

2014-04-08

Neurologic care exists within health systems and complex social, political, and economic environments. Identification of obstacles within health systems, defined as "constraints," is crucial to improving the delivery of neurologic care within its macroclimate. Here we use the World Health Organization's 6 building blocks of a health system to examine core services for priority interventions related to neurologic disease: (1) service delivery; (2) health workforce; (3) information; (4) medical products, vaccines, and technologies; (5) financing; and (6) leadership and governance. We demonstrate the use of a constraints analysis for neurologic disorders using the example of Timor-Leste, a newly sovereign and low-income country, which aims to improve neurologic care in the coming years.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

PubMed

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

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.

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

PubMed Central

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel

2016-01-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929

A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems.

PubMed

Bassi da Silva, Jéssica; Ferreira, Sabrina Barbosa de Souza; de Freitas, Osvaldo; Bruschi, Marcos Luciano

2017-07-01

Mucoadhesion is a useful strategy for drug delivery systems, such as tablets, patches, gels, liposomes, micro/nanoparticles, nanosuspensions, microemulsions and colloidal dispersions. Moreover, it has contributed to many benefits like increased residence time at application sites, drug protection, increased drug permeation and improved drug availability. In this context, investigation into the mucoadhesive properties of pharmaceutical dosage forms is fundamental, in order to characterize, understand and simulate the in vivo interaction between the formulation and the biological substrate, contributing to the development of new mucoadhesive systems with effectiveness, safety and quality. There are a lot of in vivo, in vitro and ex vivo methods for the evaluation of the mucoadhesive properties of drug delivery systems. However, there also is a lack of standardization of these techniques, which makes comparison between the results difficult. Therefore, this work aims to show an overview of the most commonly employed methods for mucoadhesion evaluation, relating them to different proposed systems and using artificial or natural mucosa from humans and animals.

[Investigation of Elekta linac characteristics for VMAT].

PubMed

Luo, Guangwen; Zhang, Kunyi

2012-01-01

The aim of this study is to investigate the characteristics of Elekta delivery system for volumetric modulated arc therapy (VMAT). Five VMAT plans were delivered in service mode and dose rates, and speed of gantry and MLC leaves were analyzed by log files. Results showed that dose rates varied between 6 dose rates. Gantry and MLC leaf speed dynamically varied during delivery. The technique of VMAT requires linac to dynamically control more parameters, and these key dynamic variables during VMAT delivery can be checked by log files. Quality assurance procedure should be carried out for VMAT related parameter.

Barriers and enablers to delivery of the Healthy Kids Check: an analysis informed by the Theoretical Domains Framework and COM-B model

PubMed Central

2014-01-01

Background More than a fifth of Australian children arrive at school developmentally vulnerable. To counteract this, the Healthy Kids Check (HKC), a one-off health assessment aimed at preschool children, was introduced in 2008 into Australian general practice. Delivery of services has, however, remained low. The Theoretical Domains Framework, which provides a method to understand behaviours theoretically, can be condensed into three core components: capability, opportunity and motivation, and the COM-B model. Utilising this system, this study aimed to determine the barriers and enablers to delivery of the HKC, to inform the design of an intervention to promote provision of HKC services in Australian general practice. Methods Data from 6 focus group discussions with 40 practitioners from general practices in socio-culturally diverse areas of Melbourne, Victoria, were analysed using thematic analysis. Results Many practitioners expressed uncertainty regarding their capabilities and the practicalities of delivering HKCs, but in some cases HKCs had acted as a catalyst for professional development. Key connections between immunisation services and delivery of HKCs prompted practices to have systems of recall and reminder in place. Standardisation of methods for developmental assessment and streamlined referral pathways affected practitioners’ confidence and motivation to perform HKCs. Conclusion Application of a systematic framework effectively demonstrated how a number of behaviours could be targeted to increase delivery of HKCs. Interventions need to target practice systems, the support of office staff and referral options, as well as practitioners’ training. Many behavioural changes could be applied through a single intervention programme delivered by the primary healthcare organisations charged with local healthcare needs (Medicare Locals) providing vital links between general practice, community and the health of young children. PMID:24886520

Building a polysaccharide hydrogel capsule delivery system for control release of ibuprofen.

PubMed

Chen, Zhi; Wang, Ting; Yan, Qing

2018-02-01

Development of a delivery system which can effectively carry hydrophobic drugs and have pH response is becoming necessary. Here we demonstrate that through preparation of β-cyclodextrin polymer (β-CDP), a hydrophobic drug molecule of ibuprofen (IBU) was incorporated into our prepared β-CDP inner cavities, aiming to improve the poor water solubility of IBU. A core-shell capsule structure has been designed for achieving the drug pH targeted and sustained release. This delivery system was built with polysaccharide polymer of Sodium alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC) by physical cross-linking. The drug pH-response control release is this hydrogel system's chief merit, which has potential value for synthesizing enteric capsule. Besides, due to our simple preparing strategy, optimal conditions can be readily determined and the synthesis process can be accurately controlled, leading to consistent and reproducible hydrogel capsules. In addition, phase-solubility method was used to investigate the solubilization effect of IBU by β-CDP. SEM was used to prove the forming of core and shell structure. FT-IR and 1 H-NMR were also used to perform structural characteristics. By the technique of UV determination, the pH targeted and sustained release study were also performed. The results have proved that our prepared polysaccharide hydrogel capsule delivery system has potential applications as oral drugs delivery in the field of biomedical materials.

Single-step simultaneous side-by-side placement of a self-expandable metallic stent with a 6-Fr delivery system for unresectable malignant hilar biliary obstruction: a feasibility study.

PubMed

Kawakubo, Kazumichi; Kawakami, Hiroshi; Kuwatani, Masaki; Kudo, Taiki; Abe, Yoko; Kawahata, Shuhei; Kubo, Kimitoshi; Kubota, Yoshimasa; Sakamoto, Naoya

2015-02-01

Bilateral self-expandable metallic stent (SEMS) placement for the management of unresectable malignant hilar biliary obstruction (UMHBO) is technically challenging to perform using the existing metallic stents with thick delivery systems. The recently developed 6-Fr delivery systems could facilitate a single-step simultaneous side-by-side placement through the accessory channel of the duodenoscope. The aim of this study was to evaluate the feasibility of this procedure. Between May and September 2013, 13 consecutive patients with UMHBO underwent a single-step simultaneous side-by-side placement of SEMS with the 6-Fr delivery system. The technical success rate, stent patency, and rate of complications were evaluated from the prospectively collected database. Technical success was achieved in 11 (84.6%, 95% confidence interval [CI]: 57.8-95.8) patients. The median procedure time was 25 min. Early and late complications were observed in 23% (one segmental cholangitis and two liver abscesses) and 15% (one segmental cholangitis and one cholecystitis) patients, respectively. Median dysfunction free patency was 263 days (95% CI: 37-263). Five patients (38%) experienced stent occlusion that was successfully managed by endoscopic stent placement. A single-step simultaneous side-by-side placement of SEMS with a 6-Fr delivery system was feasible for the management of UMHBO. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Modified titanium implant as a gateway to the human body: the implant mediated drug delivery system.

PubMed

Park, Young-Seok; Cho, Joo-Youn; Lee, Shin-Jae; Hwang, Chee Il

2014-01-01

The aim of this study was to investigate the efficacy of a proposed new implant mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is applied through a modified titanium implant that is configured to be implanted into bone. The implant is hollow and has multiple microholes that can continuously deliver therapeutic agents into the systematic body. To examine the efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic behavior of dexamethasone in plasma after a single dose was delivered via the modified implant placed in the rabbit tibia. After measuring the plasma concentration, the areas under the curve showed that the IMDDS provided a sustained release for a relatively long period. The result suggests that the IMDDS can deliver a sustained release of certain drug components with a high bioavailability. Accordingly, the IMDDS may provide the basis for a novel approach to treating patients with chronic diseases.

The Adaptive Aerosol Delivery (AAD) technology: Past, present, and future.

PubMed

Denyer, John; Dyche, Tony

2010-04-01

Conventional aerosol delivery systems and the availability of new technologies have led to the development of "intelligent" nebulizers such as the I-neb Adaptive Aerosol Delivery (AAD) System. Based on the AAD technology, the I-neb AAD System has been designed to continuously adapt to changes in the patient's breathing pattern, and to pulse aerosol only during the inspiratory part of the breathing cycle. This eliminates waste of aerosol during exhalation, and creates a foundation for precise aerosol (dose) delivery. To facilitate the delivery of precise metered doses of aerosol to the patient, a unique metering chamber design has been developed. Through the vibrating mesh technology, the metering chamber design, and the AAD Disc function, the aerosol output rate and metered (delivered) dose can be tailored to the demands of the specific drug to be delivered. In the I-neb AAD System, aerosol delivery is guided through two algorithms, one for the Tidal Breathing Mode (TBM), and one for slow and deep inhalations, the Target Inhalation Mode (TIM). The aim of TIM is to reduce the treatment time by increasing the total inhalation time per minute, and to increase lung deposition by reducing impaction in the upper airways through slow and deep inhalations. A key feature of the AAD technology is the patient feedback mechanisms that are provided to guide the patient on delivery performance. These feedback signals, which include visual, audible, and tactile forms, are configured in a feedback cascade that leads to a high level of compliance with the use of the I-neb AAD System. The I-neb Insight and the Patient Logging System facilitate a further degree of sophistication to the feedback mechanisms, by providing information on long term adherence and compliance data. These can be assessed by patients and clinicians via a Web-based delivery of information in the form of customized graphical analyses.

Changes in Local Public Health System Performance Before and After Attainment of National Accreditation Standards.

PubMed

Ingram, Richard C; Mays, Glen P; Kussainov, Nurlan

The aim of this study is to investigate the impact of Public Health Accreditation Board (PHAB) accreditation on the delivery of public health services and on participation from other sectors in the delivery of public health services in local public health systems. This study uses a longitudinal repeated measures design to identify differences between a cohort of public health systems containing PHAB-accredited local health departments and a cohort of public health systems containing unaccredited local health departments. It uses data spanning from 2006 to 2016. This study examines a cohort of local public health systems that serves large populations and contains unaccredited and PHAB-accredited local health departments. Data in this study were collected from the directors of health departments that include local public health systems followed in the National Longitudinal Study of Public Health Systems. The intervention examined is PHAB accreditation. The study focuses on 4 areas: the delivery of core public health services, local health department contribution toward these services, participation in the delivery of these services by other members of the public health system, and public health system makeup. Prior to the advent of accreditation, public health systems containing local health departments that were later accredited by PHAB appear quite similar to their unaccredited peers. Substantial differences between the 2 cohorts appear to manifest themselves after the advent of accreditation. Specifically, the accredited cohort seems to offer a broader array of public health services, involve more partners in the delivery of those services, and enjoy a higher percentage of comprehensive public health systems. The results of this study suggest that accreditation may yield significant benefits and may help public health systems develop the public health system capital necessary to protect and promote the public's health.

Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.

PubMed

Grabovac, Vjera; Föger, Florian; Bernkop-Schnürch, Andreas

2008-02-04

The aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo. The patch system consisted of a mucoadhesive layer, a water insoluble backing layer made of ethylcellulose and an enteric coating made of Eudragit. Drug release studies were performed in media mimicking stomach and intestinal fluids. For in vivo studies patch systems were administered orally to conscious non-diabetic rats. Orally administered insulin in aqueous solution was used as control. After the oral administration of the patch systems a decrease of glucose and increase of insulin blood levels were measured. The mucoadhesive layer, exhibiting a diameter of 2.5mm and a weight of 5mg, comprised polycarbophil-cysteine conjugate (49%), bovine insulin (26%), gluthatione (5%) and mannitol (20%). 74.8+/-4.8% of insulin was released from the delivery system over 6h. Six hours after administration of the patch system mean maximum decrease of blood glucose level of 31.6% of the initial value could be observed. Maximum insulin concentration in blood was 11.3+/-6.2ng/ml and was reached 6h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%. The results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.

Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum

PubMed Central

Zaid Alkilani, Ahlam; McCrudden, Maelíosa T.C.; Donnelly, Ryan F.

2015-01-01

The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies. PMID:26506371

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.

Advances in using chitosan-based nanoparticles for in vitro and in vivo drug and gene delivery.

PubMed

Duceppe, Nicolas; Tabrizian, Maryam

2010-10-01

This review aims to provide an overview of state-of-the-art chitosan-based nanosized carriers for the delivery of therapeutic agents. Chitosan nanocarriers are smart delivery systems owing to the possibility of their property alterations with various approaches, which would confer them with the possibility of spatiotemporal delivery features. The focus of this review is principally on those aspects that have not often been addressed in other reviews. These include the influence of physicochemical properties of chitosan on delivery mechanisms and chitosan modification with a variety of ligand moieties specific for cell surface receptors to increase recognition and uptake of nanocarriers into cells through receptor-mediated endocytosis. Multiple examples that demonstrate the advantages of chitosan-based nanocarriers over other delivery systems of therapeutic agents are highlighted. Particular emphasis is given to the alteration of material properties by functionalization or combination with other polymers for their specific applications. Finally, structural and experimental parameters influencing transfection efficiency of chitosan-based nanocarriers are presented for both in vitro and in vivo gene delivery. The readers will acquire knowledge of parameters influencing the properties of the chitosan-based nanocarriers for delivery of therapeutic agents (genetic material or drugs) in vitro and in vivo. They will get a better idea of the strategies to be adapted to tune the characteristics of chitosan and chitosan derivatives for specific delivery applications. Chitosan is prone to chemical and physical modifications, and is very responsive to environmental stimuli such as temperature and pH. These features make chitosan a smart material with great potential for developing multifunctional nanocarrier systems to deliver large varieties of therapeutic agents administrated in multiple ways with reduced side effects.

Application of mathematical modeling in sustained release delivery systems.

PubMed

Grassi, Mario; Grassi, Gabriele

2014-08-01

This review, presenting as starting point the concept of the mathematical modeling, is aimed at the physical and mathematical description of the most important mechanisms regulating drug delivery from matrix systems. The precise knowledge of the delivery mechanisms allows us to set up powerful mathematical models which, in turn, are essential for the design and optimization of appropriate drug delivery systems. The fundamental mechanisms for drug delivery from matrices are represented by drug diffusion, matrix swelling, matrix erosion, drug dissolution with possible recrystallization (e.g., as in the case of amorphous and nanocrystalline drugs), initial drug distribution inside the matrix, matrix geometry, matrix size distribution (in the case of spherical matrices of different diameter) and osmotic pressure. Depending on matrix characteristics, the above-reported variables may play a different role in drug delivery; thus the mathematical model needs to be built solely on the most relevant mechanisms of the particular matrix considered. Despite the somewhat diffident behavior of the industrial world, in the light of the most recent findings, we believe that mathematical modeling may have a tremendous potential impact in the pharmaceutical field. We do believe that mathematical modeling will be more and more important in the future especially in the light of the rapid advent of personalized medicine, a novel therapeutic approach intended to treat each single patient instead of the 'average' patient.

The influences of patient's satisfaction with medical service delivery, assessment of medical service, and trust in health delivery system on patient's life satisfaction in China

PubMed Central

2012-01-01

Background Patient’s satisfaction with medical service delivery/assessment of medical service/trust in health delivery system may have significant influence on patient’s life satisfaction in China’s health delivery system/in various kinds of hospitals. The aim of this study was to test whether and to what extent patient’s satisfaction with medical service delivery/patient’s assessments of various major aspects of medical service/various major aspects of patient’s trust in health delivery system influenced patient’s life satisfaction in China’s health delivery system/in various kinds of hospitals. Methods This study collaborated with National Bureau of Statistics of China to carry out a 2008 national urban resident household survey in 17 provinces, autonomous regions, and municipalities directly under the central government (N = 3,386), and specified ordered probit models were established to analyze dataset from this household survey. Results The key considerations in generating patient’s life satisfaction involved patient’s overall satisfaction with medical service delivery, assessment of doctor-patient communication, assessment of medical cost, assessment of medical treatment process, assessment of medical facility and hospital environment, assessment of waiting time for medical service, trust in prescription, trust in doctor, and trust in recommended medical examination. But the major considerations in generating patient’s life satisfaction were different among low level public hospital, high level public hospital, and private hospital. Conclusion The promotion of patient’s overall satisfaction with medical service delivery, the improvement of doctor-patient communication, the reduction of medical cost, the improvement of medical treatment process, the promotion of medical facility and hospital environment, the reduction of waiting time for medical service, the promotion of patient’s trust in prescription, the promotion of patient’s trust in doctor, and the promotion of patient’s trust in recommended medical examination could all help promote patient’s life satisfaction. But their promotion effects were different among low level public hospital, high level public hospital, and private hospital. PMID:22978432

Advances in hydrogel delivery systems for tissue regeneration.

PubMed

Toh, Wei Seong; Loh, Xian Jun

2014-12-01

Hydrogels are natural or synthetic polymer networks that have high water-absorbing capacity and closely mimic native extracellular matrices. As hydrogel-based cell delivery systems are being increasingly employed in regenerative medicine, several advances have been made in the hydrogel chemistry and modification for enhanced control of cell fate and functions, and modulation of cell and tissue responses against oxidative stress and inflammation in the tissue environment. This review aims to provide the state-of-the-art overview of the recent advances in field, discusses new perspectives and challenges in the regeneration of specific tissues, and highlights some of the limitations of current systems for possible future advancements. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Recent advances in topical delivery of proteins and peptides mediated by soft matter nanocarriers.

PubMed

Witting, Madeleine; Obst, Katja; Friess, Wolfgang; Hedtrich, Sarah

2015-11-01

Proteins and peptides are increasingly important therapeutics for the treatment of severe and complex diseases like cancer or autoimmune diseases due to their high specificity and potency. Their unique structure and labile physicochemical properties, however, require special attention in the production and formulation process as well as during administration. Aside from conventional systemic injections, the topical application of proteins and peptides is an appealing alternative due to its non-invasive nature and thus high acceptance by patients. For this approach, soft matter nanocarriers are interesting delivery systems which offer beneficial properties such as high biocompatibility, easiness of modifications, as well as targeted drug delivery and release. This review aims to highlight and discuss technological developments in the field of soft matter nanocarriers for the delivery of proteins and peptides via the skin, the eye, the nose, and the lung, and to provide insights in advantages, limitations, and practicability of recent advances. Copyright © 2015 Elsevier Inc. All rights reserved.

MULTI-STAGE DELIVERY NANO-PARTICLE SYSTEMS FOR THERAPEUTIC APPLICATIONS

PubMed Central

Serda, Rita E.; Godin, Biana; Blanco, Elvin; Chiappini, Ciro; Ferrari, Mauro

2010-01-01

Background The daunting task for drug molecules to reach pathological lesions has fueled rapid advances in Nanomedicine. The progressive evolution of nanovectors has led to the development of multi-stage delivery systems aimed at overcoming the numerous obstacles encountered by nanovectors on their journey to the target site. Scope of Review This review summarizes major findings with respect to silicon-based drug delivery vectors for cancer therapeutics and imaging. Based on rational design, well established silicon technologies have been adapted for the fabrication of nanovectors with specific shapes, sizes, and porosities. These vectors are part of a multi-stage delivery system that contains multiple nano-components, each designed to achieve a specific task with the common goal of site-directed delivery of therapeutics. Major Conclusions Quasi-hemispherical and discoidal silicon microparticles are superior to spherical particles with respect to margination in the blood, with particles of different shapes and sizes having unique distributions in vivo. Cellular adhesion and internalization of silicon microparticles is influenced by microparticle shape and surface charge, with the latter dictating binding of serum opsonins. Based on in vitro cell studies, the internalization of porous silicon microparticles by endothelial cells and macrophages is compatible with cellular morphology, intracellular trafficking, mitosis, cell cycle progression, cytokine release, and cell viability. In vivo studies support superior therapeutic efficacy of liposomal encapsulated siRNA when delivered in multi-stage systems compared to free nanoparticles. PMID:20493927

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 found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system's ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.

Implementing injury surveillance systems alongside injury prevention programs: evaluation of an online surveillance system in a community setting.

PubMed

Ekegren, Christina L; Donaldson, Alex; Gabbe, Belinda J; Finch, Caroline F

Previous research aimed at improving injury surveillance standards has focused mainly on issues of data quality rather than upon the implementation of surveillance systems. There are numerous settings where injury surveillance is not mandatory and having a better understanding of the barriers to conducting injury surveillance would lead to improved implementation strategies. One such setting is community sport, where a lack of available epidemiological data has impaired efforts to reduce injury. This study aimed to i) evaluate use of an injury surveillance system following delivery of an implementation strategy; and ii) investigate factors influencing the implementation of the system in community sports clubs. A total of 78 clubs were targeted for implementation of an online injury surveillance system (approximately 4000 athletes) in five community Australian football leagues concurrently enrolled in a pragmatic trial of an injury prevention program called FootyFirst. System implementation was evaluated quantitatively, using the RE-AIM framework, and qualitatively, via semi-structured interviews with targeted-users. Across the 78 clubs, there was 69% reach, 44% adoption, 23% implementation and 9% maintenance. Reach and adoption were highest in those leagues receiving concurrent support for the delivery of FootyFirst. Targeted-users identified several barriers and facilitators to implementation including personal (e.g. belief in the importance of injury surveillance), socio-contextual (e.g. understaffing and athlete underreporting) and systems factors (e.g. the time taken to upload injury data into the online system). The injury surveillance system was implemented and maintained by a small proportion of clubs. Outcomes were best in those leagues receiving concurrent support for the delivery of FootyFirst, suggesting that engagement with personnel at all levels can enhance uptake of surveillance systems. Interview findings suggest that increased uptake could also be achieved by educating club personnel on the importance of recording injuries, developing clearer injury surveillance guidelines, increasing club staffing and better remunerating those who conduct surveillance, as well as offering flexible surveillance systems in a range of accessible formats. By increasing the usage of surveillance systems, data will better represent the target population and increase our understanding of the injury problem, and how to prevent it, in specific settings.

Through-Metal-Wall Power Delivery and Data Transmission for Enclosed Sensors: A Review

PubMed Central

Yang, Ding-Xin; Hu, Zheng; Zhao, Hong; Hu, Hai-Feng; Sun, Yun-Zhe; Hou, Bao-Jian

2015-01-01

The aim of this review was to assess the current viable technologies for wireless power delivery and data transmission through metal barriers. Using such technologies sensors enclosed in hermetical metal containers can be powered and communicate through exterior power sources without penetration of the metal wall for wire feed-throughs. In this review, we first discuss the significant and essential requirements for through-metal-wall power delivery and data transmission and then we: (1) describe three electromagnetic coupling based techniques reported in the literature, which include inductive coupling, capacitive coupling, and magnetic resonance coupling; (2) present a detailed review of wireless ultrasonic through-metal-wall power delivery and/or data transmission methods; (3) compare various ultrasonic through-metal-wall systems in modeling, transducer configuration and communication mode with sensors; (4) summarize the characteristics of electromagnetic-based and ultrasound-based systems, evaluate the challenges and development trends. We conclude that electromagnetic coupling methods are suitable for through thin non-ferromagnetic metal wall power delivery and data transmission at a relatively low data rate; piezoelectric transducer-based ultrasonic systems are particularly advantageous in achieving high power transfer efficiency and high data rates; the combination of more than one single technique may provide a more practical and reliable solution for long term operation. PMID:26694392

Lecithin based lamellar liquid crystals as a physiologically acceptable dermal delivery system for ascorbyl palmitate.

PubMed

Gosenca, Mirjam; Bešter-Rogač, Marija; Gašperlin, Mirjana

2013-09-27

Liquid crystalline systems with a lamellar structure have been extensively studied as dermal delivery systems. Ascorbyl palmitate (AP) is one of the most studied and used ascorbic acid derivatives and is employed as an antioxidant to prevent skin aging. The aim of this study was to develop and characterize skin-compliant dermal delivery systems with a liquid crystalline structure for AP. First, a pseudoternary phase diagram was constructed using Tween 80/lecithin/isopropyl myristate/water at a Tween 80/lecithin mass ratio of 1/1, and the region of lamellar liquid crystals was identified. Second, selected unloaded and AP-loaded lamellar liquid crystal systems were physicochemically characterized with polarizing optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology techniques. The interlayer spacing and rheological parameters differ regarding quantitative composition, whereas the microstructure of the lamellar phase was affected by the AP incorporation, resulting either in additional micellar structures (at 25 and 32 °C) or being completely destroyed at higher temperature (37°C). After this, the study was oriented towards in vitro cytotoxicity evaluation of lamellar liquid crystal systems on a keratinocyte cell line. The results suggest that the lamellar liquid crystals that were developed could be used as a physiologically acceptable dermal delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

PubMed

Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

2005-05-01

Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p < 0.05) better bioavailability than the control system displaying a relative bioavailability of 8.1% The 6 kDa LMWH (300 IU) formulation displayed a relative bioavailability of 10.7% in contrast to the control displaying a relative bioavailability of 2.1%. In conclusion, these results suggest that mucoadhesive thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

Micro- and nanobubbles: a versatile non-viral platform for gene delivery.

PubMed

Cavalli, Roberta; Bisazza, Agnese; Lembo, David

2013-11-18

Micro- and nanobubbles provide a promising non-viral strategy for ultrasound mediated gene delivery. Microbubbles are spherical gas-filled structures with a mean diameter of 1-8 μm, characterised by their core-shell composition and their ability to circulate in the bloodstream following intravenous injection. They undergo volumetric oscillations or acoustic cavitation when insonified by ultrasound and, most importantly, they are able to resonate at diagnostic frequencies. It is due to this behaviour that microbubbles are currently being used as ultrasound contrast agents, but their use in therapeutics is still under investigation. For example, microbubbles could play a role in enhancing gene delivery to cells: when combined with clinical ultrasound exposure, microbubbles are able to favour gene entry into cells by cavitation. Two different delivery strategies have been used to date: DNA can be co-administered with the microbubbles (i.e. the contrast agent) or 'loaded' in purposed-built bubble systems - indeed a number of different technological approaches have been proposed to associate genes within microbubble structures. Nanobubbles, bubbles with sizes in the nanometre order of magnitude, have also been developed with the aim of obtaining more efficient gene delivery systems. Their small sizes allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. In contrast, microbubbles, due to their larger sizes, are unable to extravasate, thus and their targeting capacity is limited to specific antigens present within the vascular lumen. This review provides an overview of the use of microbubbles as gene delivery systems, with a specific focus on recent research into the development of nanosystems. In particular, ultrasound delivery mechanisms, formulation parameters, gene-loading approaches and the advantages of nanometric systems will be described. Copyright © 2013 Elsevier B.V. All rights reserved.

Expression of monellin in a food-grade delivery system in Saccharomyces cerevisiae.

PubMed

Liu, Jun; Yan, Da-zhong; Zhao, Sheng-jun

2015-10-01

Genetically modified (GM) foods have caused much controversy. Construction of a food-grade delivery system is a desirable technique with presumptive impact on industrial applications from the perspective of bio-safety. The aim of this study was to construct a food-grade delivery system for Saccharomyces cerevisiae and to study the expression of monellin from the berries of the West African forest plant Dioscoreophyllum cumminsii in this system. A food-grade system for S. cerevisiae was constructed based on ribosomal DNA (rDNA)-mediated homologous recombination to enable high-copy-number integration of the expression cassette inserted into the rDNA locus. A copper resistance gene (CUP1) was used as the selection marker for yeast transformation. Because variants of transformants containing different copy numbers at the CUP1 locus can be readily selected after growth in the presence of elevated copper levels, we suggest that this system would prove useful in the generation of tandemly iterated gene clusters. Using this food-grade system, a single-chain monellin gene was heterologously expressed. The yield of monellin reached a maximum of 675 mg L(-1) . This system harbors exclusively S. cerevisiae DNA with no antibiotic resistance genes, and it should therefore be appropriate for safe use in the food industry. Monellin was shown to be expressed in this food-grade delivery system. To our knowledge, this is the first report so far on expression of monellin in a food-grade expression system in S. cerevisiae. © 2014 Society of Chemical Industry.

Diatoms: a biotemplating approach to fabricating drug delivery reservoirs.

PubMed

Chao, Joshua T; Biggs, Manus J P; Pandit, Abhay S

2014-11-01

Biotemplating is a rapidly expanding subfield that utilizes nature-inspired systems and structures to create novel functional materials, and it is through these methods that the limitations of current engineering practices may be advanced. The diatom is an exceptional template for drug delivery applications, owing largely to its highly-ordered pores, large surface area, species-specific architecture, and flexibility for surface modifications. Diatoms have been studied in a wide range of biomedical applications and their potential as the next frontier of drug delivery has yet to be fully exploited. In this editorial, the authors aim to review the use of diatoms in the delivery of poorly water-soluble drugs as reported in the literature, discuss the progress and advancements that have been made thus far, identify the shortcomings and limitations in the field, and, lastly, present their expert opinion and convey the future outlook on biotemplating approaches for drug delivery.

A Critical Review of Instructional Design Process of Distance Learning System

ERIC Educational Resources Information Center

Chaudry, Muhammad Ajmal; ur-Rahman, Fazal

2010-01-01

Instructional design refers to planning, development, delivery and evaluation of instructional system. It is an applied field of study aiming at the application of descriptive research outcomes in regular instructional settings. The present study was designed to critically review the process of instructional design at Allama Iqbal Open University…

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

DOE PAGES

Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.; ...

2017-01-13

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

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

Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret.

PubMed

Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs.

Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret

PubMed Central

Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

2016-01-01

We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs. PMID:27822034

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 delivery. Results: Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system’s ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. Conclusions: The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.« less

Chitosan Microspheres in Novel Drug Delivery Systems

PubMed Central

Mitra, Analava; Dey, Baishakhi

2011-01-01

The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

Drug Release Kinetics and Transport Mechanisms of Non-degradable and Degradable Polymeric Delivery Systems

PubMed Central

Fu, Yao; Kao, Weiyuan John

2010-01-01

Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. PMID:20331353

Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz.

PubMed

Vieira, Alexandre Couto Carneiro; Ferreira Fontes, Danilo Augusto; Chaves, Luise Lopes; Alves, Lariza Darlene Santos; de Freitas Neto, José Lourenço; de La Roca Soares, Monica Felts; Soares-Sobrinho, Jose L; Rolim, Larissa Araújo; Rolim-Neto, Pedro José

2015-10-05

Efavirenz (EFZ) is one of the most used drugs in the treatment of AIDS and is the first antiretroviral choice. However, since it has low solubility, it does not exhibit suitable bioavailability, which interferes with its therapeutic action and is classified as a class II drug according Biopharmaceutical Classification System (low solubility and high permeability). Among several drug delivery systems, the multicomponent systems with cyclodextrins and hydrophilic polymers are a promising alternative for increasing the aqueous solubility of the drug. The present study aimed to develop and characterize in a ternary system of EFZ, MβCD and PVP K30. The results showed that the solid ternary system provided a large increase in the dissolution rate which was greater than 80% and was characterized by DSC, TG, XRD, FT-IR and SEM. The use of the ternary system (EFZ, MβCD and PVP K30 1%) proved to be a viable, effective and safe delivery of the drug. The addition of the hydrophilic polymer appeared to be suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and with low concentration of CDs (cyclodextrins). Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanofibers: New Insights for Drug Delivery and Tissue Engineering.

PubMed

Haidar, Mohammad Karim; Eroglu, Hakan

2017-01-01

Nanofibers became one of the major research areas for drug delivery and tissue engineering applications in the last decade. Depending on the simplicity of the preparation method and high drug loading capacity, nanofibers provide many advantages for therapeutic perspectives. In addition, combined systems such as embedding nanoparticles into the nanofiber structures provide a second option for delivery of dual active ingredients in the same formulation. The release rate of the active ingredients can also be modified easily by the formulation parameters depending on the desired release time for treatment. Nanofibers systems are used for the delivery of antibiotics, anticancer drugs, analgesics, hemostatic agents and various proteins for tissue engineering purposes. In addition, various applications such as medical device coating also provide new insights for the clinical use of nanofibers. The most commonly used technique for preparation of nanofibers is the electrospinning, which provides feasibility background for scale up process from laboratory to the industrial applications. The main boundary for nanofibers is the limitations for systemic route. Nanofibers are mainly designed for the delivery of active ingredients for local purposes. Regardless of the therapeutic aim, nanofibers are also perfect 3 dimensional structures that are suitable for tissue regeneration. They provide matrix structure for cell regeneration especially in applications for wound healing. This review is mainly focused on the recent advances on the preparation of nanofibers, applications for drug delivery, tissue engineering and wound healing purposes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Improved oral bioavailability of glyburide by a self-nanoemulsifying drug delivery system.

PubMed

Liu, Hongzhuo; Shang, Kuimao; Liu, Weina; Leng, Donglei; Li, Ran; Kong, Ying; Zhang, Tianhong

2014-01-01

The present study aimed at the development and characterisation of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble glyburide. The solubility of glyburide was determined in various oils, surfactants and co-surfactants which were grouped into two different combinations to construct ternary phase diagrams. The formulations were evaluated for emulsification time, droplet size, zeta-potential, electrical conductivity and stability of nanoemulsions. The optimised SNEDDS loading with 5 mg/g glyburide comprised 55% Cremophor® RH 40, 15% propanediol and 30% Miglyol® 812, which rapidly formed fine oil-in-water nanoemulsions with 46 ± 4 nm particle size. Compared with the commercial micronised tablets (Glynase®PresTab®), enhanced in vitro release profiles of SNEDDS were observed, resulting in the 1.5-fold increase of AUC following oral administration of SNEDDS in fasting beagle dogs. These results indicated that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of glyburide.

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

Expanding Alternative Delivery Systems.

ERIC Educational Resources Information Center

Baltzer, Jan A.

Alternative educational delivery systems that might be useful to community colleges are considered. The following categories of delivery systems are covered: broadcast delivery systems; copy delivery systems, print delivery systems, computer delivery systems, telephone delivery systems, and satellites. Among the applications for broadcast…

Delivery of Type 2 diabetes care in low- and middle-income countries: lessons from Lima, Peru.

PubMed

Cardenas, M K; Miranda, J J; Beran, D

2016-06-01

The health system's response is crucial to addressing the increasing burden of diabetes, particularly that affecting low- and middle-income countries. This study aims to assess the facilitators and barriers that help or hinder access to care for people with diabetes in Peru. We used a survey tool to design and collect qualitative and quantitative data from primary and secondary sources of information at different levels of the health system. We performed 111 interviews in Lima, the capital city of Peru, with patients with diabetes, healthcare providers and healthcare officials. We applied the six building blocks framework proposed by the World Health Organization in our analysis. We found low political commitment, as well as several barriers that directly affect access to medicines, regular laboratory check-ups and follow-up appointments for diabetes, especially at the primary healthcare level. Three major system-level barriers were identified: (1) the availability of information at different healthcare system levels that affects several processes in the healthcare provision; (2) insufficient financial resources; and (3) insufficient human resources trained in diabetes management. Despite an initial political commitment by the Peruvian government to improve the delivery of diabetes care, there exist several key limitations that affect access to adequate diabetes care, especially at the primary healthcare level. In a context in which various low- and middle-income countries are aiming to achieve universal health coverage, this study provides lessons for the implementation of strategies related to diabetes care delivery. © 2016 Diabetes UK.

Mental health care delivery system reform in Belgium: the challenge of achieving deinstitutionalisation whilst addressing fragmentation of care at the same time.

PubMed

Nicaise, Pablo; Dubois, Vincent; Lorant, Vincent

2014-04-01

Most mental health care delivery systems in welfare states currently face two major issues: deinstitutionalisation and fragmentation of care. Belgium is in the process of reforming its mental health care delivery system with the aim of simultaneously strengthening community care and improving integration of care. The new policy model attempts to strike a balance between hospitals and community services, and is based on networks of services. We carried out a content analysis of the policy blueprint for the reform and performed an ex-ante evaluation of its plan of operation, based on the current knowledge of mental health service networks. When we examined the policy's multiple aims, intermediate goals, suggested tools, and their articulation, we found that it was unclear how the new policy could achieve its goals. Indeed, deinstitutionalisation and integration of care require different network structures, and different modes of governance. Furthermore, most of the mechanisms contained within the new policy were not sufficiently detailed. Consequently, three major threats to the effectiveness of the reform were identified. These were: issues concerning the relationship between network structure and purpose, the continued influence of hospitals despite the goal of deinstitutionalisation, and the heterogeneity in the actual implementation of the new policy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases.

PubMed

Schwartz, Jeremy I; Dunkle, Ashley; Akiteng, Ann R; Birabwa-Male, Doreen; Kagimu, Richard; Mondo, Charles K; Mutungi, Gerald; Rabin, Tracy L; Skonieczny, Michael; Sykes, Jamila; Mayanja-Kizza, Harriet

2015-01-01

The burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. Integrated approaches to health service delivery and healthcare worker (HCW) training will be necessary in order to successfully combat the great challenge posed by NCDs. In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD), a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda.

New polymer of lactic-co-glycolic acid-modified polyethylenimine for nucleic acid delivery

PubMed Central

Lü, Jian-Ming; Liang, Zhengdong; Wang, Xiaoxiao; Gu, Jianhua; Yao, Qizhi; Chen, Changyi

2016-01-01

Aim: To develop an improved delivery system for nucleic acids. Materials & methods: We designed, synthesized and characterized a new polymer of lactic-co-glycolic acid-modified polyethylenimine (LGA-PEI). Functions of LGA-PEI polymer were determined. Results: The new LGA-PEI polymer spontaneously formed nanoparticles (NPs) with DNA or RNA, and showed higher DNA or RNA loading efficiency, higher or comparable transfection efficacy, and lower cytotoxicity in several cell types including PANC-1, Jurkat and HEK293 cells, when compared with lipofectamine 2000, branched or linear PEI (25 kDa). In nude mouse models, LGA-PEI showed higher delivery efficiency of plasmid DNA or miRNA mimic into pancreatic and ovarian xenograft tumors. LGA-PEI/DNA NPs showed much lower toxicity than control PEI NPs in mouse models. Conclusion: The new LGA-PEI polymer is a safer and more effective system to deliver DNA or RNA than PEI. PMID:27456396

Mucoadhesive drug delivery systems

PubMed Central

Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

2011-01-01

Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

Health systems and noncommunicable diseases in the Asia-Pacific region: a review of the published literature.

PubMed

Mannava, Priya; Abdullah, Asnawi; James, Chris; Dodd, Rebecca; Annear, Peter Leslie

2015-03-01

Addressing the growing burden of noncommunicable diseases (NCDs) in countries of the Asia-Pacific region requires well-functioning health systems. In low- and middle-income countries (LMICs), however, health systems are generally characterized by inadequate financial and human resources, unsuitable service delivery models, and weak information systems. The aims of this review were to identify (a) health systems interventions being implemented to deliver NCD programs and services and their outcomes and (b) the health systems bottlenecks impeding access to or delivery of these programs and services in LMICs of the Asia-Pacific region. A search of 4 databases for literature published between 1990 and 2010 retrieved 36 relevant studies. For each study, information on basic characteristics, type of health systems bottleneck/intervention, and outcome was extracted, and methodological quality appraised. Health systems interventions and bottlenecks were classified as per the World Health Organization health systems building blocks framework. The review identified interventions and bottlenecks in the building blocks of service delivery, health workforce, financing, health information systems, and medical products, vaccines, and technologies. Studies, however, were heterogeneous in methodologies used, and the overall quality was generally low. There are several gaps in the evidence base around NCDs in the Asia-Pacific region that require further investigation. © 2013 APJPH.

How to achieve optimal organization of primary care service delivery at system level: lessons from Europe.

PubMed

Pelone, Ferruccio; Kringos, Dionne S; Spreeuwenberg, Peter; De Belvis, Antonio G; Groenewegen, Peter P

2013-09-01

To measure the relative efficiency of primary care (PC) in turning their structures into services delivery and turning their services delivery into quality outcomes. Cross-sectional study based on the dataset of the Primary Healthcare Activity Monitor for Europe project. Two Data Envelopment models were run to compare the relative technical efficiency. A sensitivity analysis of the resulting efficiency scores was performed. PC systems in 22 European countries in 2009/2010. Model 1 included data on PC governance, workforce development and economic conditions as inputs and access, coordination, continuity and comprehensiveness of care as outputs. Model 2 included the previous process dimensions as inputs and quality indicators as outputs. There is relatively reasonable efficiency in all countries at delivering as many as possible PC processes at a given level of PC structure. It is particularly important to invest in economic conditions to achieve an efficient structure-process balance. Only five countries have fully efficient PC systems in turning their services delivery into high quality outcomes, using a similar combination of access, continuity and comprehensiveness, although they differ on the adoption of coordination of services. There is a large variation in efficiency levels obtained by countries with inefficient PC in turning their services delivery into quality outcomes. Maximizing the individual functions of PC without taking into account the coherence within the health-care system is not sufficient from a policymaker's point of view when aiming to achieve efficiency.

Quantitative measurement of delivery and gene silencing activities of siRNA polyplexes containing pyridylthiourea-grafted polyethylenimines.

PubMed

Pinel, Sophie; Aman, Emmanuel; Erblang, Felix; Dietrich, Jonathan; Frisch, Benoit; Sirman, Julien; Kichler, Antoine; Sibler, Annie-Paule; Dontenwill, Monique; Schaffner, Florence; Zuber, Guy

2014-05-28

The activity of synthetic interfering nucleic acids (siRNAs) relies on the capacity of delivery systems to efficiently transport nucleic acids into the cytosol of target cells. The pyridylthiourea-grafted 25KDa polyethylenimine (πPEI) is an excellent carrier for siRNA delivery into cells and it was extensively investigated in this report. Quantification of the siRNA-mediated gene silencing efficiency indicated that the πPEI specific delivery activity at the cell level may be measured and appears relatively constant in various cell lines. Delivery experiments assaying inhibitors of various entry pathways or concanamycin A, an inhibitor of the H(+)/ATPase vacuolar pump showed that the πPEI/siRNA polyplexes did not require any specific entry mode but strongly relied on vacuolar acidification for functional siRNA delivery. Next, πPEI polyplexes containing a siRNA targeting the transcription factor HIF-1α, known to be involved in tumor progression, were locally injected into mice xenografted with a human glioblastoma. A 55% reduction of the level of the target mRNA was observed at doses comparable to those used in vitro when the πPEI delivery activity was calculated per cell. Altogether, our study underscores the usefulness of "simple"/rough cationic polymers for siRNA delivery despite their intrinsic limitations. The study underscores as well as that bottom-up strategies make sense. The in vitro experiments can precede in vivo administration and be of high value for selection of the carrier with enhanced specific delivery activity and parallel other research aiming at improving synthetic delivery systems for resilience in the blood and for enhanced tissue-targeting capacity. Copyright © 2014 Elsevier B.V. All rights reserved.

Envisioning a New Health Care System for America.

PubMed

Puffer, James C; Borkan, Jeffrey; DeVoe, Jennifer E; Davis, Ardis; Phillips, Robert L; Green, Larry A; Saultz, John W

2015-09-01

Between August 2013 and April 2014, eight family medicine organizations convened to develop a strategic plan and communication strategy for how our discipline might partner with patients and communities to build a new foundation for American health care. An outline of this initiative, Family Medicine for America's Health (FMAHealth), was formally announced to the public in October 2014. The purpose of this paper and the five papers to follow is to describe the guiding principles of FMAHealth in greater detail. FMAHealth is taking place at a pivotal point in the history of American health care, when the deficiencies of our overly expensive, underperforming health care delivery system are becoming more apparent than ever. By forming strategic partnerships to implement this initiative, family medicine seeks to define a new approach to health system leadership, care delivery, education, and research. This will require substantial reorientation of existing priorities and reimbursement systems, which are focused on delivering services, instead of on improving health. Family medicine is committed to engaging and empowering patients, their families and communities, and other health care professionals to establish a more equitable, effective, and efficient delivery system--a system in which health is the primary design element and the "Triple Aim" is the guiding principle.

The role of methodologies to improve efficiency and effectiveness of care delivery processes for the year 2013.

PubMed

Stefanelli, Mario

2002-11-20

This paper aims at further expanding the vision of future health care delivery systems presented by Haux et al. (2002). Starting from the observation that information and communication technology (ICT) is deeply transforming the shape of organizations as expected, we argue that the coordination of work activities is a fundamental need for any organization. This is even more important for health care organizations since there is an increasing pressure to increase quality of care they deliver without further increasing its costs. However ICT by itself will not cause the desired changes without rethining the way of managing best practice biomedical knowledge and care delivery processes. Thus the paper focuses on the need of developing intense research efforts in the fields of knowledge management and workflow modelling, which have been identified as fundamental to provide suitable solutions to the problems of designing and building innovative health care information systems. Moreover, the paper discusses the role of mobile communication systems. Moreover, the paper discusses the role of mobile communication and speech understanding technologies to support a satisfactory user-system interaction in daily work.

Recent Advances in Anticancer Activities and Drug Delivery Systems of Tannins.

PubMed

Cai, Yuee; Zhang, Jinming; Chen, Nelson G; Shi, Zhi; Qiu, Jiange; He, Chengwei; Chen, Meiwan

2017-07-01

Tannins, polyphenols in medicinal plants, have been divided into two groups of hydrolysable and condensed tannins, including gallotannins, ellagitannins, and (-)-epigallocatechin-3-gallate (EGCG). Potent anticancer activities have been observed in tannins (especially EGCG) with multiple mechanisms, such as apoptosis, cell cycle arrest, and inhibition of invasion and metastases. Furthermore, the combinational effects of tannins and anticancer drugs have been demonstrated in this review, including chemoprotective, chemosensitive, and antagonizing effects accompanying with anticancer effect. However, the applications of tannins have been hindered due to their poor liposolubility, low bioavailability, off-taste, and shorter half-life time in human body, such as EGCG, gallic acid, and ellagic acid. To tackle these obstacles, novel drug delivery systems have been employed to deliver tannins with the aim of improving their applications, such as gelatin nanoparticles, micelles, nanogold, liposomes, and so on. In this review, the chemical characteristics, anticancer properties, and drug delivery systems of tannins were discussed with an attempt to provide a systemic reference to promote the development of tannins as anticancer agents. © 2016 Wiley Periodicals, Inc.

Nutraceutical delivery systems: resveratrol encapsulation in grape seed oil nanoemulsions formed by spontaneous emulsification.

PubMed

Davidov-Pardo, Gabriel; McClements, David Julian

2015-01-15

The aim of this work was to fabricate nanoemulsions-based delivery systems to encapsulate resveratrol. Nanoemulsions were formed using spontaneous emulsification method: 10% oil phase (grape seed oil plus orange oil) and 10% surfactant (Tween 80) were titrated into 80% aqueous phase. An optimum orange oil-to-grape seed oil ratio of 1:1(w/w) formed small droplets (d ≈ 100 nm) with good stability to droplet growth. The maximum amount of resveratrol that could be dissolved in the oil phase was 120 ± 10 μg/ml. The effect of droplet size on the chemical stability of encapsulated resveratrol was examined by preparing systems with different mean droplet diameters of 220 ± 2; 99 ± 3; and 45 ± 0.4 nm. Encapsulation of resveratrol improved its chemical stability after exposure to UV-light: 88% retention in nanoemulsions compared to 50% in dimethylsulphoxide (DMSO). This study showed that resveratrol could be encapsulated within low-energy nanoemulsion-based delivery systems and protected against degradation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polypyrrole Film as a Drug Delivery System for the Controlled Release of Risperidone

NASA Astrophysics Data System (ADS)

Svirskis, Darren; Travas-Sejdic, Jadranka; Rodgers, Anthony; Garg, Sanjay

2009-07-01

Conducting polymers are finding applications in medicine including drug delivery systems, biosensors and templates for the regeneration of nervous pathways. We aim to develop a novel system where the drug release rate can be controlled by electrical stimulation. Polypyrrole (PPY) is being used as a drug delivery system due to its inherent electrical conductivity, ease of preparation and apparent biocompatibility. Risperidone is an atypical antipsychotic drug used in the treatment of psychosis and related disorders, including schizophrenia. PPY was synthesised using p-toluene sulfonic acid as a primary dopant, in the presence of risperidone. A validated high performance liquid chromatography (HPLC) analytical method was used to quantify risperidone release. It has been demonstrated that the release rate of risperidone can be altered through the application, or absence, of electrical stimulation. Technology such as this would find use in drug-delivering implants where the dose could be adjusted through application of external stimulus, optimising benefit to side effect ratio, while simultaneously ensuring patient adherence (which is a particular challenge in mental health conditions).

Roles of dextrans on improving lymphatic drainage for liposomal drug delivery system.

PubMed

Feng, Linglin; Zhang, Lei; Liu, Min; Yan, Zhiqiang; Wang, Chenyu; Gu, Bing; Liu, Yu; Wei, Gang; Zhong, Gaoren; Lu, Weiyue

2010-04-01

Our aim was to develop a novel liposomal drug delivery system containing dextrans to reduce undesirable retention of antineoplastic agents and thus alleviate local tissue damage. At the cell level, diethylaminoethyl-dextran (DEAE-Dx) showed the strongest inhibiting effect on liposome uptake by macrophages among tested dextrans. The distribution of radiolabeled liposomes mixed with dextrans in injection site and draining lymph node was investigated in rats after subcutaneous injection. DEAE-Dx substantially reduced the undesired local retention and promoted the draining of liposome into lymphatics, which was further confirmed by confocal microscopy images revealing the substantial prevention of rhodamine B-labelled liposome sequestration by macrophages in normal lymph node in rats. Pharmacokinetic data indicated the accelerated drainage of liposome through lymphatics back to systemic circulation by mixing with DEAE-Dx. In the toxicological study in rabbits, DEAE-Dx alleviated the local tissue damage caused by liposomal doxorubicin. In conclusion, dextrans, particularly DEAE-Dx, could efficiently enhanced liposomes drainage into lymphatics, which proves themselves as promising adjuvants for lymphatic-targeted liposomal drug delivery system.

Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene

PubMed Central

George, Marina A.; El-Shorbagy, Haidan M.; Bassiony, Heba; Farroh, Khaled Y.; Youssef, Tareq; Salaheldin, Taher A.

2017-01-01

Background Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. Aim of work The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system. Methods and results Gel.NPs were synthesized and characterized (size: 150±2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the recombinant NS2 protein was confirmed by Western blotting to verify the efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin nanoparticles and a successful conjugation was confirmed by labeling and imaging using Confocal Laser Scanning Microscope (CLSM). Interestingly, the transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-α was 50% more efficient than transformation with the gene alone. In addition, conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation efficiency into E. coli DH5-α than the other ratios (1:50 and 2:50). Conclusion Gel.NPs effectively enhanced the gene delivery in bacterial cells without affecting the structure of NS2 gene and could be used as a safe, easy, rapid, cost-effective and non-viral vaccine delivery system for HCV. PMID:28746382

Application of Fused Deposition Modelling (FDM) Method of 3D Printing in Drug Delivery.

PubMed

Long, Jingjunjiao; Gholizadeh, Hamideh; Lu, Jun; Bunt, Craig; Seyfoddin, Ali

2017-01-01

Three-dimensional (3D) printing is an emerging manufacturing technology for biomedical and pharmaceutical applications. Fused deposition modelling (FDM) is a low cost extrusion-based 3D printing technique that can deposit materials layer-by-layer to create solid geometries. This review article aims to provide an overview of FDM based 3D printing application in developing new drug delivery systems. The principle methodology, suitable polymers and important parameters in FDM technology and its applications in fabrication of personalised tablets and drug delivery devices are discussed in this review. FDM based 3D printing is a novel and versatile manufacturing technique for creating customised drug delivery devices that contain accurate dose of medicine( s) and provide controlled drug released profiles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Future of health care delivery in iran, opportunities and threats.

PubMed

Rajabi, F; Esmailzadeh, H; Rostamigooran, N; Majdzadeh, R; Doshmangir, L

2013-01-01

The aim of this study was to determine the impact of important social and technological trends on health care delivery, in the context of developing "Iran's Health System Reform Plan by 2025". A detailed review of the national and international literature was done to identify the main trends affecting health system. To collect the experts' opinions about important trends and their impact on health care delivery, Focus Group Discussions (FGDs) and semi-structured in-depth interviews techniques were used. The study was based on the STEEP model. Final results were approved in an expert's panel session. The important social and technological trends, affecting health system in Iran in the next 15 years are demographic transition, epidemiologic transition, increasing bio-environmental pollution, increasing slums, increasing private sector partnership in health care delivery, moving toward knowledge-based society, development of information and communication technology, increasing use of high technologies in health system, and development of traditional and alternative medicine. The opportunities and threats resulting from the above mentioned trends were also assessed in this study. Increasing healthcare cost due to some trends like demographic and epidemiologic transition and uncontrolled increase in using new technologies in health care is one of the most important threats that the health system will be facing. The opportunities that advancement in technology and moving toward knowledge-based society create are important and should not be ignored.

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 chart review.« less

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 review and physicist weekly chart review. PACS number(s): 87.55.km PMID:27167269

Novel nanocarriers for topical drug delivery: investigating delivery efficiency and distribution in skin using two-photon microscopy

NASA Astrophysics Data System (ADS)

Kirejev, Vladimir; Guldbrand, Stina; Bauer, Brigitte; Smedh, Maria; Ericson, Marica B.

2011-03-01

The complex structure of skin represents an effective barrier against external environmental factors, as for example, different chemical and biochemical compounds, yeast, bacterial and viral infections. However, this impermeability prevents efficient transdermal drug delivery which limits the number of drugs that are able to penetrate the skin efficiently. Current trends in drug application through skin focus on the design and use of nanocarriers for transport of active compounds. The transport systems applied so far have several drawbacks, as they often have low payload, high toxicity, a limited variability of inclusion molecules, or long degradation times. The aim of these current studies is to investigate novel topical drug delivery systems, e.g. nanocarriers based on cyclic oligosaccharides - cyclodextrins (CD) or iron (III)-based metal-organic frameworks (MOF). Earlier studies on cell cultures imply that these drug nanocarriers show promising characteristics compared to other drug delivery systems. In our studies, we use two-photon microscopy to investigate the ability of the nanocarriers to deliver compounds through ex-vivo skin samples. Using near infrared light for excitation in the so called optical window of skin allows deep-tissue visualization of drug distribution and localization. In addition, it is possible to employ two-photon based fluorescence correlation spectroscopy for quantitative analysis of drug distribution and concentrations in different cell layers.

Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.

PubMed

Boonme, Prapaporn; Kaewbanjong, Jarika; Amnuaikit, Thanaporn; Andreani, Tatiana; Silva, Amélia M; Souto, Eliana B

2016-01-01

Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals.

Immunological activation following transcutaneous delivery of HR-gp100 protein

PubMed Central

Frankenburg, Shoshana; Grinberg, Igor; Bazak, Ziva; Fingerut, Lena; Pitcovski, Jacob; Gorodetsky, Raphael; Peretz, Tamar; Spira, Ram M.; Skornik, Yehuda; Goldstein, Ronald S.

2009-01-01

Transcutaneous immunization aims at taking advantage of the skin’s immune system for the purpose of immunoprotection. In the present study we evaluated the potential of topical delivery of a recombinant melanoma protein, HR-gp100, derived from a shorter sequence of the native gp100 gene. The protein was applied on the skin, with and without the addition of two forms of heat labile enterotoxin (nLT and LTB). HR-gp100 fused to Haptide, a cell penetrating 20mer peptide (HR-gp100H) was also tested. Topical HR-gp100 and HR-gp100H application on the ears of mice elicited the production of specific antibodies, and transcutaneous delivery to intact human skin induced dose-dependent LC activation. nLT and LTB also activated LC, but did not further increase the activation induced by HR-gp100. These results show that HR-gp100, an antigenic tumor-derived protein, activates the immune system following transcutaneous delivery, as shown by both Langerhans cell activation and induction of antibody production. PMID:17493711

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved.

PubMed

Inrig, Stephen J; Tiro, Jasmin A; Melhado, Trisha V; Argenbright, Keith E; Craddock Lee, Simon J

2014-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. To better understand how to implement a decentralized regional delivery "hub & spoke" model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow's RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow's RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting.

Evaluating a De-Centralized Regional Delivery System for Breast Cancer Screening and Patient Navigation for the Rural Underserved

PubMed Central

Inrig, Stephen J.; Tiro, Jasmin A.; Melhado, Trisha V.; Argenbright, Keith E.; Craddock Lee, Simon J.

2017-01-01

Providing breast cancer screening services in rural areas is challenging due to the fractured nature of healthcare delivery systems and complex reimbursement mechanisms that create barriers to access for the under- and uninsured. Interventions that reduce structural barriers to mammography, like patient navigation programs, are effective and recommended, especially for minority and underserved women. Although the literature on rural healthcare is significant, the field lacks studies of adaptive service delivery models and rigorous evaluation of evidence-based programs that facilitate routine screening and appropriate follow-up across large geographic areas. Objectives To better understand how to implement a decentralized regional delivery “hub & spoke” model for rural breast cancer screening and patient navigation, we have designed a rigorous, structured, multi-level and mixed-methods evaluation based on Glasgow’s RE-AIM model (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Methods and Design The program is comprised of three core components: 1) Outreach to underserved women by partnering with county organizations; 2) Navigation to guide patients through screening and appropriate follow-up; and 3) Centralized Reimbursement to coordinate funding for screening services through a central contract with Medicaid Breast and Cervical Cancer Services (BCCS). Using Glasgow’s RE-AIM model, we will: 1) assess which counties have the resources and capacity to implement outreach and/or navigation components, 2) train partners in each county on how to implement components, and 3) monitor process and outcome measures in each county at regular intervals, providing booster training when needed. Discussion This evaluation strategy will elucidate how the heterogeneity of rural county infrastructure impacts decentralized service delivery as a navigation program expands. In addition to increasing breast cancer screening access, our model improves and maintains time to diagnostic resolution and facilitates timely referral to local cancer treatment services. We offer this evaluation approach as an exemplar for scientific methods to evaluate the translation of evidence-based federal policy into sustainable health services delivery in a rural setting. PMID:28713882

Nursing Services Delivery Theory: an open system approach

PubMed Central

Meyer, Raquel M; O’Brien-Pallas, Linda L

2010-01-01

meyer r.m. & o’brien-pallas l.l. (2010)Nursing services delivery theory: an open system approach. Journal of Advanced Nursing66(12), 2828–2838. Aim This paper is a discussion of the derivation of the Nursing Services Delivery Theory from the application of open system theory to large-scale organizations. Background The underlying mechanisms by which staffing indicators influence outcomes remain under-theorized and unmeasured, resulting in a ‘black box’ that masks the nature and organization of nursing work. Theory linking nursing work, staffing, work environments, and outcomes in different settings is urgently needed to inform management decisions about the allocation of nurse staffing resources in organizations. Data sources A search of CINAHL and Business Source Premier for the years 1980–2008 was conducted using the following terms: theory, models, organization, organizational structure, management, administration, nursing units, and nursing. Seminal works were included. Discussion The healthcare organization is conceptualized as an open system characterized by energy transformation, a dynamic steady state, negative entropy, event cycles, negative feedback, differentiation, integration and coordination, and equifinality. The Nursing Services Delivery Theory proposes that input, throughput, and output factors interact dynamically to influence the global work demands placed on nursing work groups at the point of care in production subsystems. Implications for nursing The Nursing Services Delivery Theory can be applied to varied settings, cultures, and countries and supports the study of multi-level phenomena and cross-level effects. Conclusion The Nursing Services Delivery Theory gives a relational structure for reconciling disparate streams of research related to nursing work, staffing, and work environments. The theory can guide future research and the management of nursing services in large-scale healthcare organizations. PMID:20831573

Challenges and new strategies for therapeutic peptide delivery to the CNS.

PubMed

McGowan, Jeremy Wd; Bidwell, Gene L; Vig, Parminder Js

2015-07-01

Therapeutic peptides represent a largely untapped resource in medicine today, especially in the central nervous system. Despite their ease of design and remarkably high target specificity, it is difficult to deliver them beyond the blood-brain barrier or into the required intracellular compartments. In addition, the instability of these peptides in vivo precludes their use to combat the symptoms of numerous neurological disorders including Alzheimer's disease and spinocerebellar ataxia. In this review, we aim to characterize recent advances in the delivery of therapeutic peptides to the central nervous system past the blood-brain barrier and discuss the advantages and disadvantages of the examined methods as well as explore new potential directions.

Nanobiotechnology and bone regeneration: a mini-review.

PubMed

Gusić, Nadomir; Ivković, Alan; VaFaye, John; Vukasović, Andreja; Ivković, Jana; Hudetz, Damir; Janković, Saša

2014-09-01

The purpose of this paper is to review current developments in bone tissue engineering, with special focus on the promising role of nanobiotechnology. This unique fusion between nanotechnology and biotechnology offers unprecedented possibilities in studying and modulating biological processes on a molecular and atomic scale. First we discuss the multiscale hierarchical structure of bone and its implication on the design of new scaffolds and delivery systems. Then we briefly present different types of nanostructured scaffolds, and finally we conclude with nanoparticle delivery systems and their potential use in promoting bone regeneration. This review is not meant to be exhaustive and comprehensive, but aims to highlight concepts and key advances in the field of nanobiotechnology and bone regeneration.

Boosting facility deliveries with results-based financing: a mixed-methods evaluation of the government midwifery incentive scheme in Cambodia.

PubMed

Ir, Por; Korachais, Catherine; Chheng, Kannarath; Horemans, Dirk; Van Damme, Wim; Meessen, Bruno

2015-08-15

Increasing the coverage of skilled attendance at births in a health facility (facility delivery) is crucial for saving the lives of mothers and achieving Millennium Development Goal five. Cambodia has significantly increased the coverage of facility deliveries and reduced the maternal mortality ratio in the last decade. The introduction of a nationwide government implemented and funded results-based financing initiative, known as the Government Midwifery Incentive Scheme (GMIS), is considered one of the most important contributors to this. We evaluated GMIS to explore its effects on facility deliveries and the health system. We used a mixed-methods design. An interrupted time series model was applied, using routine longitudinal data on reported deliveries between 2006 and 2011 that were extracted from the health information system. In addition, we interviewed 56 key informants and performed 12 focus group discussions with 124 women who had given birth (once or more) since 2006. Findings from the quantitative data were carefully interpreted and triangulated with those from qualitative data. We found that facility deliveries have tripled from 19% of the estimated number of births in 2006 to 57% in 2011 and this increase was more substantial at health centres as compared to hospitals. Segmented linear regressions showed that the introduction of GMIS in October 2007 made the increase in facility deliveries and deliveries with skilled attendants significantly jump by 18 and 10% respectively. Results from qualitative data also suggest that the introduction of GMIS together with other interventions that aimed to improve access to essential maternal health services led to considerable improvements in public health facilities and a steep increase in facility deliveries. Home deliveries attended by traditional birth attendants decreased concomitantly. We also outline several operational issues and limitations of GMIS. The available evidence strongly suggests that GMIS is an effective mechanism to complement other interventions to improve health system performance and boost facility deliveries as well as skilled birth attendance; thereby contributing to the reduction of maternal mortality. Our findings provide useful lessons for Cambodia to further improve GMIS and for other low-income countries to implement similar results-based financing mechanisms.

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.

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

Poly(NIPAm-AMPS) nanoparticles for targeted delivery of anti-inflammatory cell penetrating peptides

NASA Astrophysics Data System (ADS)

Bartlett, Rush Lloyd, II

Inflammatory diseases such as osteoarthritis and rheumatoid arthritis cause $127.8 billion in US healthcare expenditures each year and are the cause of disability for 27% of disabled persons in the United States. Current treatment options rarely halt disease progression and often result in significant unwanted and debilitating side effects. Our laboratory has previously developed a family of cell penetrating peptides (CPPs) which inhibit the activity of mitogen activated protein kinase activate protein kinase 2 (MK2). MK2 mediates the inflammatory response by activating Tristetraprline (TTP). Once activated, TTP rapidly stabilizes AU rich regions of pro-inflammatory cytokine mRNA which allows translation of pro-inflammatory cytokines to occur. Blocking MK2 with our labs CPPs yields a decrease in inflammatory activity but CPPs by are highly non specific and prone to rapid enzymatic degradation in vivo.. In order to increase the potency of MK2 inhibiting CPPs we have developed a novel nanoparticle drug carrier composed of poly(N-isopropylacrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid). This drug carrier has been shown to have preliminary efficacy in vitro and ex vivo for suppressing pro-inflammatory cytokine production when releasing CPPs. This thesis will present progress made on three aims: Specific Aim 1) Create and validate a NIPAm based drug delivery system that mimics the binding and release previously observed between cell penetrating peptides and glycosaminoglycans. Specific Aim 2) Engineer degradability into poly(NIPAm-AMPS) nanoparticles to enable more drug to be released and qualify that system in vitro. Specific Aim 3) Validate poly(NIPAm-AMPS) nanoparticles for targeted drug delivery in an ex vivo inflammatory model. Overall we have developed a novel anionic nanoparticle system that is biocompatible and efficient at loading and releasing cell penetrating peptides to inflamed tissue. Once loaded with a CPP the nanoparticle drug complex is capable of targeting diseased tissue and preventing the production of pro-inflammatory cytokines in both in vitro and ex vivo models.

A Mechanical Coil Insertion System for Endovascular Coil Embolization of Intracranial Aneurysms

PubMed Central

Haraguchi, K.; Miyachi, S.; Matsubara, N.; Nagano, Y.; Yamada, H.; Marui, N.; Sano, A.; Fujimoto, H.; Izumi, T.; Yamanouchi, T.; Asai, T.; Wakabayashi, T.

2013-01-01

Summary Like other fields of medicine, robotics and mechanization might be introduced into endovascular coil embolization of intracranial aneurysms for effective treatment. We have already reported that coil insertion force could be smaller and more stable when the coil delivery wire is driven mechanically at a constant speed. Another background is the difficulty in synchronizing operators' minds and hands when two operators control the microcatheter and the coil respectively. We have therefore developed a mechanical coil insertion system enabling a single operator to insert coils at a fixed speed while controlling the microcatheter. Using our new system, the operator manipulated the microcatheter with both hands and drove the coil using foot switches simultaneously. A delivery wire force sensor previously reported was used concurrently, allowing the operator to detect excessive stress on the wire. In vitro coil embolization was performed using three methods: simple mechanical advance of the coil; simple mechanical advance of the coil with microcatheter control; and driving (forward and backward) of the coil using foot switches in addition to microcatheter control. The system worked without any problems, and did not interfere with any procedures. In experimental coil embolization, delivery wire control using the foot switches as well as microcatheter manipulation helped to achieve successful insertion of coils. This system could offer the possibility of developing safer and more efficient coil embolization. Although we aim at total mechanization and automation of procedures in the future, microcatheter manipulation and synchronized delivery wire control are still indispensable using this system. PMID:23693038

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 to be tested in this aim is that mild hyperthermia produced with HIFU will have the same effect as that produced by PPTT in improving the delivery of macromolecular systems to solid tumors. Finally, in the third aim, the enhanced delivery of targeted polymer therapeutics to prostate tumors in mice models will be investigated using mild hyperthermia produced with HIFU. In the long term, it is anticipated that HIFU can be used in conjunction with delivery of polymer-drug conjugates for enhanced efficacy and reduced toxicity of chemotherapy to produce a clinically relevant treatment of advanced prostate cancer.

A Secular Trend in Birth Weight and Delivery Practices in Periurban Vietnam During 2005-2012.

PubMed

Duong, Duc Minh; Nguyen, Anh Duy; Nguyen, Chuong Canh; Le, Vui Thi; Hoang, Son Ngoc; Bui, Ha Thi Thu

2017-07-01

The remarkable increase in Vietnamese economic conditions can increase the birth weight in neonates and better delivery practices among women. The Chi Linh Health and Demographic Surveillance System started in 2004. An open cohort of data consisting of about 57 561 people from 17 993 households has been followed primarily with respect to demography, economy, and education. The aim of this research is to study secular trends in delivery practice and birth weight in the past decade (2005-2012) in Chi Linh. We found a significant change in delivery rates at hospitals and cesarean section rates, but the birth weights over a decade of drastic economic development were stable. Furthermore, the findings show significant associations of birth weight and delivery practices with the child's sex, mother's age, and household income. Our results might be considered as representative for other similar periurban settings in Vietnam. We suggest that appropriate policies should be developed given the reduction in the use of delivery services in commune health centers in urban areas.

TIDE: an intelligent home-based healthcare information & diagnostic environment.

PubMed

Abidi, S S

1999-01-01

The 21st century promises to usher in an era of Internet based healthcare services--Tele-Healthcare. Such services augur well with the on-going paradigm shift in healthcare delivery patterns, i.e. patient centred services as opposed to provider centred services and wellness maintenance as opposed to illness management. This paper presents a Tele-Healthcare info-structure TIDE--an 'intelligent' wellness-oriented healthcare delivery environment. TIDE incorporates two WWW-based healthcare systems: (1) AIMS (Automated Health Monitoring System) for wellness maintenance and (2) IDEAS (Illness Diagnostic & Advisory System) for illness management. Our proposal comes from an attempt to rethink the sources of possible leverage in improving healthcare; vis-à-vis the provision of a continuum of personalised home-based healthcare services that emphasise the role of the individual in self health maintenance.

Nanoparticles used in medical applications for the lung: hopes for nanomedicine and fears for nanotoxicity

NASA Astrophysics Data System (ADS)

Boland, S.; Guadagnini, R.; Baeza-Squiban, A.; Hussain, S.; Marano, F.

2011-07-01

Nanotechnology is a promising tool for the development of innovative treatment strategies allowing to overcome obstacles encountered by classical drug delivery. This has led to the development of nanomedicine. Indeed, nano-delivery systems (NDS) may allow the controlled release of therapeutics, protection of drugs against degradation, targeted drug delivery and facilitated transport across barriers. All these advantages of NDS are particularly interesting for treatments of the lung which is a challenging organ in respect to drug delivery. However, for the development of nanomaterials aimed to transport therapeutics, there is also a need to assess the potential health hazards of these new materials, especially as a variety of nanoparticles have been shown to induce toxicity related to their nanometer size leading to the new field of nanotoxicology. We will address both aspects of NDS, specifically in respect to lung treatments: their potential benefits and the possible adverse health effects of these materials.

Contaminated water delivery as a simple and effective method of experimental Salmonella infection

PubMed Central

O’Donnell, Hope; Pham, Oanh H.; Benoun, Joseph M.; Ravesloot-Chávez, Marietta M.; McSorley, Stephen J.

2016-01-01

Aims In most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the gastrointestinal tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response. Materials and Methods C57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water. Results We demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 hours allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry. Conclusions Together, these data question the need for gavage delivery for infection with oral pathogens. PMID:26439708

Towards magnetic-enhanced cellular uptake, MRI and chemotherapeutics delivery by magnetic mesoporous silica nanoparticles.

PubMed

Liu, Qian; Zhang, Jixi; Xia, Weiliang; Gu, Hongchen

2012-10-01

A type of nanoparticle with three functional modalities was prepared with the aim of providing a multifunctional drug delivery system. The nanoparticle was 50 nm in size, with 2.7 nm mesopores and a magnetic nanocrystal core, which was further doped with FITC to enable the tracking of cellular uptake. We demonstrated that the internalization of the nanoparticles in tumor cells could be enhanced by applying an external magnetic field and furthermore, this kind of nanoparticle could be used in magnetic targeted drug delivery. With high transverse relaxivity, the magnetic nanoparticles shortened proton relaxation time and induced high magnetic resonance imaging contrast in tumor cells. Studies on anticancer drug loading and delivery capacity of anticancer drugs also showed that this type of nanoparticles could load water-soluble doxorubicin, and produce a prominent inhibitive effect against tumor cells. Taken together, the presented nanoparticles could become a promising agent in cancer theranostics.

Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration.

PubMed Central

Van Os, E C; Zins, B J; Sandborn, W J; Mays, D C; Tremaine, W J; Mahoney, D W; Zinsmeister, A R; Lipsky, J J

1996-01-01

BACKGROUND: 6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity. AIM: To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via three colonic delivery formulations. METHODS: Twenty four healthy human subjects each received 50 mg of azathioprine by one of four delivery formulations (each n = 6): oral; delayed release oral; hydrophobic rectal foam; and hydrophilic rectal foam. All subjects also received a 50 mg dose of intravenous azathioprine during a separate study period. Plasma concentrations of 6-mercaptopurine were determined by high pressure liquid chromatography. RESULTS: The bioavailabilities of 6-mercaptopurine after colonic azathioprine administration via delayed release oral, hydrophobic rectal foam, and hydrophilic rectal foam (7%, 5%, 1%; respectively) were significantly lower than the bioavailability of 6-mercaptopurine after oral azathioprine administration (47%) by Wilcoxon rank sum pairwise comparison. CONCLUSIONS: Azathioprine delivered to the colon by delayed release oral and rectal foam formulations considerably reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of these colonic delivery methods, which can potentially limit toxicity by local delivery of high doses of azathioprine, should be investigated in patients with inflammatory bowel disease. PMID:8881811

Local application of an ibandronate/collagen sponge improves femoral fracture healing in ovariectomized rats

PubMed Central

Liu, Yansong; Hou, Zhiyong; Chen, Wei; Jin, Lin; Tian, Ye; Ju, Linlin; Liu, Bo; Dong, Tianhua; Zhang, Fei

2017-01-01

Non-union is a major clinical problem in the healing of fractures, especially in patients with osteoporosis. The systemic administration of drugs is time consuming and large doses are demanding and act slowly, whereas local release acts rapidly, increases the quality and quantity of the bone tissue. We hypothesize that local delivery demonstrates better therapeutic effects on an osteoporotic fracture. The aim of this paper is to investigate the effect of the local application of ibandronate loaded with a collagen sponge on regulating bone formation and remodeling in an osteoporotic rat model of fracture healing. We found that the local delivery of ibandronate exhibited excellent effects on improving the bone microarchitecture and suppressed effects on bone remodeling. At 4 weeks, more callus formation and improvement of mechanical character and microstructure were observed in a local delivery via μCT, mechanical test, histological research and serum analysis. The suppression of bone remodeling was compared with a systemic treatment at 12 weeks, and the structural mechanical properties and microarchitecture were also improved with local delivery. This research identifies an earlier, safer and integrated approach for local delivery of ibandronate with collagen and provides a better strategy for the treatment of osteoporotic fracture in rats. PMID:29108027

Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

PubMed

Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

2017-05-19

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

Nanotechnology inspired advanced engineering fundamentals for optimizing drug delivery.

PubMed

Kassem, Ahmed Alaa

2018-02-06

Drug toxicity and inefficacy are commonly experienced problems with drug therapy failure. To face these problems, extensive research work took place aiming to design new dosage forms for drug delivery especially nanoparticulate systems. These systems are designed to increase the quantity of the therapeutic molecule delivered to the desired site concurrently with reduced side effects. In order to achieve this objective, nanocarriers must principally display suitable drug vehiculization abilities and a controlled biological destiny of drug molecules. Only the intelligent design of the nanomedicine will accomplish these fundamentals. The present review article is dedicated to the discussion of the important fundamentals to be considered in the fabrication of nanomedicines. These include the therapeutic agent, the nanocarrier and the functionalization moieties. Special consideration is devoted to the explanation and compilation of highly potential fabrication approaches assisting how to control the in vivo destiny of the nanomedicine. Finally, some nanotechnology-based drug delivery systems, for the development of nanomedicine, are also discussed. The nanotechnology-based drug delivery systems showed remarkable outcomes based on passive and active targeting as well as improvement of the drug pharmacodynamic and pharmacokinetic profiles. Multifunctional nanocarrier concept affords a revolutionary drug delivery approach for maximizing the efficacy, safety and monitoring the biological fate of the therapeutic molecule. Nanomedicines may enhance the efficacy of therapeutic molecules and reduce their toxic effects. Meanwhile, further research works are required to rightly optimize (and define) the effectiveness, nanotoxicity, in vivo destiny and feasibility of these nanomedicines which, from a preclinical standpoint, are actually promising. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Controlled release of chlorhexidine digluconate using β-cyclodextrin and microfibrillated cellulose.

PubMed

Lavoine, Nathalie; Tabary, Nicolas; Desloges, Isabelle; Martel, Bernard; Bras, Julien

2014-09-01

This study aims to develop a high-performance delivery system using microfibrillated cellulose (MFC)-coated papers as a controlled release system combined with the well-known drug delivery agent, β-cyclodextrin (βCD). Chlorhexidine digluconate (CHX), an antibacterial molecule, was mixed with a suspension of MFC or a βCD solution or mixed with both the substances, before coating onto a cellulosic substrate. The intermittent diffusion of CHX (i.e., diffusion interrupted by the renewal of the release medium periodically) was conducted in an aqueous medium, and the release mechanism of CHX was elucidated by field emission gun-scanning electron microscopy, SEM, NMR, and Fourier transform infrared analyses. According to the literature, both βCD and MFC are efficient controlled delivery systems. This study indicated that βCD releases CHX more gradually and over a longer period of time compared to MFC, which is mainly due to the ability of βCD to form an inclusion complex with CHX. Furthermore from the release study, a complementary action when the two compounds were combined was deduced. MFC mainly affected the burst effect, while βCD primarily controlled the amount of CHX released over time. In this paper, two different types of controlled release systems are proposed and compared. Depending on the final application, the use of βCD alone would release low amounts of active molecules over time (slow delivery), whereas the combination of β-cyclodextrin and MFC would be more suitable for the release of higher amounts of active molecules over time (rapid delivery). Copyright © 2014 Elsevier B.V. All rights reserved.

A preliminary assessment of two hospital food service systems using parameters of food safety and consumer opinion.

PubMed

Hartwell, H; Edwards, J S

2001-12-01

The goal of any hospital caterer should be to provide food that meets nutritional requirements, satisfies the patient, improves morale and is microbiologically safe. Food distribution to hospital wards plays a critical role. The aim of this study was to compare two hospital food service systems using parameters of food safety and consumer opinion. An NHS hospital was selected where food delivery was due to change from a plated system to a cafeteria trolley system. Samples (50 g) of dishes (n = 27) considered to be high-risk were collected for three consecutive days from breakfast, lunch and supper meals. The samples were taken from a pre-ordered tray (similar to that of a patient) in the plated system and from the trolley on the ward in the cafeteria system of meal delivery (approximately six months after its introduction). Consumer opinions cards (n = 180) were distributed and interviews also conducted. Microbiologically, the quality of food items delivered by both systems was satisfactory. However, concern was raised with the plated system, not for hot foods cooling down but for chilled foods warming up and being sustained in ambient conditions. Overall consumer satisfaction and experience was enhanced with the trolley system. Food was hotter and generally perceived to be of a better quality. Satisfaction with cold desserts was not dependent on the delivery system.

A microfluidic reciprocating intracochlear drug delivery system with reservoir and active dose control

PubMed Central

Kim, Ernest S.; Gustenhoven, Erich; Mescher, Mark J.; Pararas, Erin E. Leary; Smith, Kim A.; Spencer, Abigail J.; Tandon, Vishal; Borenstein, Jeffrey T.; Fiering, Jason

2014-01-01

Reciprocating microfluidic drug delivery, as compared to steady or pulsed infusion, has unique features which may be advantageous in many therapeutic applications. We have previously described a device, designed for wearable use in small animal models, which periodically infuses then withdraws a sub-microliter volume of drug solution to and from the endogenous fluid of the inner ear. This delivery approach results in zero net volume of liquid transfer while enabling mass transport of compounds to the cochlea by means of diffusion and mixing. We report here on an advanced wearable delivery system aimed at further miniaturization and complex dose protocols. Enhancements to the system include the incorporation of a planar micropump to generate reciprocating flow and a novel drug reservoir which maintains zero net volume delivery and permits programmable modulation of the drug concentration in the infused bolus. The reciprocating pump is fabricated from laminated polymer films and employs a miniature electromagnetic actuator to meet the size and weight requirements of a head-mounted in vivo guinea pig testing system. The reservoir comprises a long microchannel in series with a micropump, connected in parallel with the reciprocating flow network. We characterized in vitro the response and repeatability of the planar pump and compared the results with a lumped element simulation. We also characterized the performance of the reservoir, including repeatability of dosing and range of dose modulation. Acute in vivo experiments were performed in which the reciprocating pump was used to deliver a test compound to the cochlea of anesthetized guinea pigs to evaluate short-term safety and efficacy of the system. These advances are key steps toward realization of an implantable device for long-term therapeutic applications in humans. PMID:24302432

Introduction: health of the health care system in Korea.

PubMed

Kim, Dong Soo

2010-03-01

This study is a mega evaluation of Korea's health care system as developed thus far. It aims to review the historical context in which this system was developed and the political stage and motivation for such development. It will highlight unique features of the system and some comparative analysis with other developed nations. Then it will introduce selective, specific areas and aspects of the health care system, service delivery, and practices. It will suggest its implications for future direction.

Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

PubMed

Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

2009-01-01

We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system.

The LIFEspan model of transitional rehabilitative care for youth with disabilities: healthcare professionals' perspectives on service delivery.

PubMed

Hamdani, Yani; Proulx, Meghann; Kingsnorth, Shauna; Lindsay, Sally; Maxwell, Joanne; Colantonio, Angela; Macarthur, Colin; Bayley, Mark

2014-01-01

LIFEspan is a service delivery model of continuous coordinated care developed and implemented by a cross-organization partnership between a pediatric and an adult rehabilitation hospital. Previous work explored enablers and barriers to establishing the partnership service. This paper examines healthcare professionals' (HCPs') experiences of 'real world' service delivery aimed at supporting transitional rehabilitative care for youth with disabilities. This qualitative study - part of an ongoing mixed method longitudinal study - elicited HCPs' perspectives on their experiences of LIFEspan service delivery through in-depth interviews. Data were categorized into themes of service delivery activities, then interpreted from the lens of a service integration/coordination framework. Five main service delivery themes were identified: 1) addressing youth's transition readiness and capacities; 2) shifting responsibility for healthcare management from parents to youth; 3) determining services based on organizational resources; 4) linking between pediatric and adult rehabilitation services; and, 5) linking with multi-sector services. LIFEspan contributed to service delivery activities that coordinated care for youth and families and integrated inter-hospital services. However, gaps in service integration with primary care, education, social, and community services limited coordinated care to the rehabilitation sector. Recommendations are made to enhance service delivery using a systems/sector-based approach.

Institutional delivery in public and private sectors in South Asia: a comparative analysis of prospective data from four demographic surveillance sites.

PubMed

Das, Sushmita; Alcock, Glyn; Azad, Kishwar; Kuddus, Abdul; Manandhar, Dharma S; Shrestha, Bhim Prasad; Nair, Nirmala; Rath, Shibanand; More, Neena Shah; Saville, Naomi; Houweling, Tanja A J; Osrin, David

2016-09-20

Maternity care in South Asia is available in both public and private sectors. Using data from demographic surveillance sites in Bangladesh, Nepal and rural and urban India, we aimed to compare institutional delivery rates and public-private share. We used records of maternity care collected in socio-economically disadvantaged communities between 2005 and 2011. Institutional delivery was summarized by four potential determinants: household asset index, maternal schooling, maternal age, and parity. We developed logistic regression models for private sector institutional delivery with these as independent covariates. The data described 52 750 deliveries. Institutional delivery proportion varied and there were differences in public-private split. In Bangladesh and urban India, the proportion of deliveries in the private sector increased with wealth, maternal education, and age. The opposite was observed in rural India and Nepal. The proportion of institutional delivery increased with economic status and education. The choice of sector is more complex and provision and perceived quality of public sector services is likely to play a role. Choices for safe maternity are influenced by accessibility, quantity and perceived quality of care. Along with data linkage between private and public sectors, increased regulation should be part of the development of the pluralistic healthcare systems that characterize south Asia.

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment.

PubMed

Chávez-Fumagalli, Miguel Angel; Ribeiro, Tatiana Gomes; Castilho, Rachel Oliveira; Fernandes, Simone Odília Antunes; Cardoso, Valbert Nascimento; Coelho, Cecília Steinberg Perilo; Mendonça, Débora Vasconcelos Costa; Soto, Manuel; Tavares, Carlos Alberto Pereira; Faraco, André Augusto Gomes; Coelho, Eduardo Antonio Ferraz

2015-01-01

Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.

Analysis of structure and dynamics of superfine polyhydroxybutyrate fibers for targeted drug delivery

NASA Astrophysics Data System (ADS)

Olkhov, A.; Kucherenko, E.; Pantyukhov, P.; Zykova, A.; Karpova, S.; Iordanskii, A.

2017-02-01

Creation of polymer matrix systems for targeted drug delivery into a living organism is a challenging problem of modern treatment of various diseases and injuries. Poly-3-hydroxybutyrate (PHB) is commonly used for development of therapeutic systems. The aim of this article is to examine the changes in structure and morphology of fibers in presence of dipyridamole (DPD) as model drug for controlled release. It was found that addition of dipyridamole led to disappearance of spindle-shaped nodules on fibers of PHB in comparison with pure PHB. The research of thermophysical parameters showed that specific melting enthalpy (and the degree of crystallinity) of PHB fibers increased with the addition of DPD. With the increasing of DPD content in PHB fibers, more perfect and equilibrium crystal structure was formed. According to analysis of intercrystalline regions of PHB fibers, it was found that as the crystallinity of PHB in intergranular regions rose, the corresponding decrease of radical rotation speed was observed. It was concluded that fibers of PHB can be used for creating therapeutic systems for targeted and prolonged drug delivery.

Current applications of big data in obstetric anesthesiology.

PubMed

Klumpner, Thomas T; Bauer, Melissa E; Kheterpal, Sachin

2017-06-01

The narrative review aims to highlight several recently published 'big data' studies pertinent to the field of obstetric anesthesiology. Big data has been used to study rare outcomes, to identify trends within the healthcare system, to identify variations in practice patterns, and to highlight potential inequalities in obstetric anesthesia care. Big data studies have helped define the risk of rare complications of obstetric anesthesia, such as the risk of neuraxial hematoma in thrombocytopenic parturients. Also, large national databases have been used to better understand trends in anesthesia-related adverse events during cesarean delivery as well as outline potential racial/ethnic disparities in obstetric anesthesia care. Finally, real-time analysis of patient data across a number of disparate health information systems through the use of sophisticated clinical decision support and surveillance systems is one promising application of big data technology on the labor and delivery unit. 'Big data' research has important implications for obstetric anesthesia care and warrants continued study. Real-time electronic surveillance is a potentially useful application of big data technology on the labor and delivery unit.

PLGA based drug delivery systems: Promising carriers for wound healing activity.

PubMed

Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

2016-03-01

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.

Silk Electrogel Based Gastroretentive Drug Delivery System

NASA Astrophysics Data System (ADS)

Wang, Qianrui

Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.

Delivery of drugs, growth factors, genes and stem cells via intrapericardial, epicardial and intramyocardial routes for sustained local targeted therapy of myocardial disease.

PubMed

Maslov, Mikhail; Foianini, Stephan; Lovich, Mark

2017-10-01

Local myocardial delivery (LMD) of therapeutic agents is a promising strategy that aims to treat various myocardial pathologies. It is designed to deliver agents directly to the myocardium and minimize their extracardiac concentrations and side effects. LMD aims to enhance outcomes of existing therapies by broadening their therapeutic window and to utilize new agents that could not be otherwise be implemented systemically. Areas covered: This article provides a historical overview of six decades LMD evolution in terms of the approaches, including intrapericardial, epicardial, and intramyocardial delivery, and the wide array of classes of agents used to treat myocardial pathologies. We examines delivery of pharmaceutical compounds, targeted gene transfection and cell implantation techniques to produce therapeutic effects locally. We outline therapeutic indications, successes and failures as well as technical approaches for LMD. Expert opinion: While LMD is more complicated than conventional oral or intravenous administration, given recent advances in interventional cardiology, it is safe and may provide better therapeutic outcomes. LMD is complex as many factors impact pharmacokinetics and biologic result. The choice between routes of LMD is largely driven not only by the myocardial pathology but also by the nature and physicochemical properties of the therapeutic agents.

Pain Experience and Behavior Management in Pediatric Dentistry: A Comparison between Traditional Local Anesthesia and the Wand Computerized Delivery System.

PubMed

Garret-Bernardin, Annelyse; Cantile, Tiziana; D'Antò, Vincenzo; Galanakis, Alexandros; Fauxpoint, Gabriel; Ferrazzano, Gianmaria Fabrizio; De Rosa, Sara; Vallogini, Giulia; Romeo, Umberto; Galeotti, Angela

2017-01-01

Aim. To evaluate the pain experience and behavior during dental injection, using the Wand computerized delivery system versus conventional local anesthesia in children and adolescents. Methods. An observational crossover split mouth study was performed on 67 patients (aged 7 to 15 years), requiring local anesthesia for dental treatments in both sides of the dental arch. Patients received both types of injections in two separate appointments, one with the use of a Computer Delivery System (the Wand STA system) and one with the traditional syringe. The following data were recorded: pain rating; changes in heart rate; level of collaboration; patient satisfaction. The data were analyzed using ANOVA for quantitative outcomes and nonparametric analysis (Kruskal-Wallis) for qualitative parameters. Results. The use of the Wand system determined significantly lower pain ratings and lower increase of heart rate than the traditional syringe. During injection, the number of patients showing a relaxed behavior was higher with the Wand than with the traditional local anesthesia. The patient level of satisfaction was higher with the Wand compared to the conventional local anesthesia. Conclusions. The Wand system may provide a less painful injection when compared to the conventional local anesthesia and it seemed to be better tolerated with respect to a traditional syringe.

Pain Experience and Behavior Management in Pediatric Dentistry: A Comparison between Traditional Local Anesthesia and the Wand Computerized Delivery System

PubMed Central

D'Antò, Vincenzo; Fauxpoint, Gabriel; De Rosa, Sara; Vallogini, Giulia

2017-01-01

Aim. To evaluate the pain experience and behavior during dental injection, using the Wand computerized delivery system versus conventional local anesthesia in children and adolescents. Methods. An observational crossover split mouth study was performed on 67 patients (aged 7 to 15 years), requiring local anesthesia for dental treatments in both sides of the dental arch. Patients received both types of injections in two separate appointments, one with the use of a Computer Delivery System (the Wand STA system) and one with the traditional syringe. The following data were recorded: pain rating; changes in heart rate; level of collaboration; patient satisfaction. The data were analyzed using ANOVA for quantitative outcomes and nonparametric analysis (Kruskal–Wallis) for qualitative parameters. Results. The use of the Wand system determined significantly lower pain ratings and lower increase of heart rate than the traditional syringe. During injection, the number of patients showing a relaxed behavior was higher with the Wand than with the traditional local anesthesia. The patient level of satisfaction was higher with the Wand compared to the conventional local anesthesia. Conclusions. The Wand system may provide a less painful injection when compared to the conventional local anesthesia and it seemed to be better tolerated with respect to a traditional syringe. PMID:28293129

Nanotechnology applied to treatment of mucopolysaccharidoses.

PubMed

Schuh, Roselena S; Baldo, Guilherme; Teixeira, Helder F

2016-12-01

Mucopolysaccharidoses (MPS) are genetic disorders caused by the accumulation of glycosaminoglycans due to deficiencies in the lysosomal enzymes responsible for their catabolism. Current treatments are not fully effective and are not available for all MPS types. Accordingly, researchers have tested novel therapies for MPS, including nanotechnology-based enzyme delivery systems and gene therapy. In this review, we aim to analyze some of the approaches involving nanotechnology as alternative treatments for MPS. Areas covered: We analyze nanotechnology-based systems, focusing on the biomaterials, such as polymers and lipids, that comprise these nanostructures, and we have highlighted studies that describe their use as enzyme and gene delivery systems for the treatment of MPS diseases. Expert opinion: Some protocols, such as the use of polymer-based systems or nanostructured carriers associated with enzymes and nanotechnology-based carriers for gene therapy, along with combined approaches, seem to be the future of MPS therapy.

Lost in translation? Theory, policy and practice in systems-based environmental approaches to obesity prevention in the Healthy Towns programme in England.

PubMed

Sautkina, Elena; Goodwin, Denise; Jones, Andy; Ogilvie, David; Petticrew, Mark; White, Martin; Cummins, Steven

2014-09-01

This paper explores how system-wide approaches to obesity prevention were 'theorised' and translated into practice in the 'Healthy Towns' programme implemented in nine areas in England. Semi-structured interviews with 20 informants, purposively selected to represent national and local programme development, management and delivery were undertaken. Results suggest that informants articulated a theoretical understanding of a system-wide approach to obesity prevention, but simplifying this complex task in the context of uncertainty over programme aims and objectives, and absence of a clear direction from the central government, resulted in local programmes relying on traditional multi-component approaches to programme delivery. The development of clear, practical guidance on implementation should form a central part of future system-wide approaches to obesity prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

Feedback (F) Fueling Adaptation (A) Network Growth (N) and Self-Organization (S): A Complex Systems Design and Evaluation Approach to Professional Development

ERIC Educational Resources Information Center

Yoon, Susan A.; Klopfer, Eric

2006-01-01

This paper reports on the efficacy of a professional development framework premised on four complex systems design principles: Feedback, Adaptation, Network Growth and Self-organization (FANS). The framework is applied to the design and delivery of the first 2 years of a 3-year study aimed at improving teacher and student understanding of…

Unmanned Ground Vehicles for Integrated Force Protection

DTIC Science & Technology

2004-04-01

employed. 2 Force Protection 18 MAR 02 Security Posts Squad Laptop Fire Tm Ldr Wearable Computers OP/LP Def Fight Psn SRT Sensors USA, USMC, Allied...visual systems. Attaching sensors and response devices on a monorail proved to be much more technically challenging than expected. Film producers and...facilitate experimentation with weapon aiming and firing techniques from the MRHA. grated Marsupial Delivery System was developed to transport smaller

Mucoadhesive Chitosan-Pectinate Nanoparticles for the Delivery of Curcumin to the Colon.

PubMed

Alkhader, Enas; Billa, Nashiru; Roberts, Clive J

2017-05-01

In the present study, we report the properties of a mucoadhesive chitosan-pectinate nanoparticulate formulation able to retain its integrity in the milieu of the upper gastrointestinal tract and subsequently, mucoadhere and release curcumin in colon conditions. Using this system, we aimed to deliver curcumin to the colon for the possible management of colorectal cancer. The delivery system comprised of a chitosan-pectinate composite nanopolymeric with a z-average of 206.0 nm (±6.6 nm) and zeta potential of +32.8 mV (±0.5 mV) and encapsulation efficiency of 64%. The nanoparticles mucoadhesiveness was higher at alkaline pH compared to acidic pH. Furthermore, more than 80% release of curcumin was achieved in pectinase-enriched medium (pH 6.4) as opposed to negligible release in acidic and enzyme-restricted media at pH 6.8. SEM images of the nanoparticles after exposure to the various media indicate a retained matrix in acid media as opposed to a distorted/fragmented matrix in pectinase-enriched medium. The data strongly indicates that the system has the potential to be applied as a colon-targeted mucoadhesive curcumin delivery system for the possible treatment of colon cancer.

Managerial process improvement: a lean approach to eliminating medication delivery.

PubMed

Hussain, Aftab; Stewart, LaShonda M; Rivers, Patrick A; Munchus, George

2015-01-01

Statistical evidence shows that medication errors are a major cause of injuries that concerns all health care oganizations. Despite all the efforts to improve the quality of care, the lack of understanding and inability of management to design a robust system that will strategically target those factors is a major cause of distress. The paper aims to discuss these issues. Achieving optimum organizational performance requires two key variables; work process factors and human performance factors. The approach is that healthcare administrators must take in account both variables in designing a strategy to reduce medication errors. However, strategies that will combat such phenomena require that managers and administrators understand the key factors that are causing medication delivery errors. The authors recommend that healthcare organizations implement the Toyota Production System (TPS) combined with human performance improvement (HPI) methodologies to eliminate medication delivery errors in hospitals. Despite all the efforts to improve the quality of care, there continues to be a lack of understanding and the ability of management to design a robust system that will strategically target those factors associated with medication errors. This paper proposes a solution to an ambiguous workflow process using the TPS combined with the HPI system.

New Avenues for Nanoparticle-Related Therapies

NASA Astrophysics Data System (ADS)

Zhao, Michael; Liu, Mingyao

2018-05-01

Development of nanoparticle-based drug delivery systems has been attempted for the treatment of cancer over the past decade. The enhanced permeability and retention (EPR) effect is the major mechanism to passively deliver nanodrugs to tumor tissue. However, a recent systematic review demonstrated limited success of these studies, with the clearance of nanoparticles by the mononuclear phagocytic system (MPS) being a major hurdle. Herein, we propose that nanotechnologists should reconsider their research focuses, aiming for therapeutic targets other than cancer. Treatments for diseases that do not (or less) rely on EPR should be considered, such as active targeting or MPS evasion systems. For example, systemic delivery of drugs through intravenous injection can be used to treat sepsis, multi-organ failure, metabolic disorders, blood diseases, immune and autoimmune diseases, etc. Local delivery of nanodrugs to organs such as the lung, rectum, or bladder may enhance the local drug concentration with less clearance via MPS. In transplant settings, ex vivo organ perfusion provides a new route to repair injury of isolated organs in the absence of MPS. Based on a similar concept, chemotherapy with in vivo lung perfusion techniques and other isolated organ perfusion provides opportunities for cancer therapy.

Assembled modules technology for site-specific prolonged delivery of norfloxacin.

PubMed

Oliveira, Paulo Renato; Bernardi, Larissa Sakis; Strusi, Orazio Luca; Mercuri, Salvatore; Segatto Silva, Marcos A; Colombo, Paolo; Sonvico, Fabio

2011-02-28

The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for individual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability. Copyright © 2010. Published by Elsevier B.V.

Design of a potential colonic drug delivery system of mesalamine.

PubMed

Gohel, Mukesh C; Parikh, Rajesh K; Nagori, Stavan A; Dabhi, Mahesh R

2008-01-01

The aim of the present investigation was to develop a site-specific colonic drug delivery system, built on the principles of the combination of pH and time sensitivity. Press-coated mesalamine tablets with a coat of HPMC E-15 were over-coated with Eudragit S100. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2, 6.0, 7.2 and 6.4 mimicking different regions of gastrointestinal tract. The optimized batch (F2) showed less than 6% of drug release before reaching colonic pH 6.4 and complete drug release was obtained thereafter within 2 hr. A short-term dissolution stability study demonstrated statistical insignificant difference in drug release.

Society of Behavioral Medicine's (SBM) position on emerging policy issues regarding electronic nicotine delivery systems (ENDS): A need for regulation.

PubMed

Rojewski, Alana M; Coleman, Nortorious; Toll, Benjamin A

2016-09-01

Electronic nicotine delivery systems (ENDS), commonly known as electronic cigarettes (or e-cigarettes), are widely available in the USA, yet almost entirely unregulated on a national level. Researchers are currently gathering data to understand the individual and public health effects of ENDS, as well as the role that ENDS may play in tobacco treatment. Given these uncertainties, regulatory efforts should be aimed at understanding and minimizing any potential harms of ENDS. The Society of Behavioral Medicine (SBM) supports stronger regulation of ENDS, incorporation of ENDS into clean air policies, and special consideration of safety standards to protect vulnerable populations. SBM also supports research on ENDS to guide policy decisions.

Effects of feed delivery frequency in different environmental conditions on time budget of lactating dairy cows.

PubMed

Mattachini, Gabriele; Bava, Luciana; Sandrucci, Anna; Tamburini, Alberto; Riva, Elisabetta; Provolo, Giorgio

2017-08-01

This study aimed to examine the influence of feed delivery frequency and environmental conditions on daily time budget of lactating dairy cows. The study was carried out in two commercial dairy farms with Holstein herds. Fifty lactating dairy cows milked in automatic milking units (AMS farm) and 96 primiparous lactating dairy cows milked in a conventional milking parlour (conventional farm) were exposed to different frequencies of feed delivery replicated in different periods of the year (warm and mild) that were characterized by different temperature-humidity indices (THI). On each farm, feeding treatments consisted of two different feed delivery frequencies (1× and 2× on the AMS farm; 2× and 3× on the conventional farm). All behaviours of the cows were monitored for the last 8 d of each treatment period using continuous video recording. The two data sets from different farm systems were considered separately for analysis. On both farms, environmental conditions expressed as THI affected time budgets and the pattern of the behavioural indices throughout the day. The variation in the frequency of feed delivery seems to affect the cow's time budget only in a limited way. Standing time of cows on the conventional farm and the time spent by cows in the milking waiting area on the AMS farm both increased in response to increased feeding frequency. Although feed delivery frequency showed limited influence on cow's time budget, the effect on standing time could be carefully considered, especially on farms equipped with AMS where the type of cow traffic system (e.g., milking first) might amplify the negative consequences of more frequent feed delivery. Further investigations are required to evaluate the effect of THI and feed delivery frequency on other aspects of behavioural activity.

Gene delivery for periodontal tissue engineering: current knowledge - future possibilities.

PubMed

Chen, Fa-Ming; Ma, Zhi-Wei; Wang, Qin-Tao; Wu, Zhi-Fen

2009-08-01

The cellular and molecular events of periodontal healing are coordinated and regulated by an elaborate system of signaling molecules, pointing to a primary strategy for functional periodontal compartment regeneration to replicate components of the natural cellular microenvironment by providing an artificial extracellular matrix (ECM) and by delivering growth factors. However, even with optimal carriers, the localized delivery of growth factors often requires a large amount of protein to stimulate significant effects in vivo, which increases the risk and unwanted side effects. A simple and relatively new approach to bypassing this dilemma involves converting cells into protein producing factories. This is done by a so-called gene delivery method, where therapeutic agents to be delivered are DNA plasmids that include the gene encoding desired growth factors instead of recombinant proteins. As localized depots of genes, novel gene delivery systems have the potential to release their cargo in a sustained and controlled manner and finally provide time- and space- dependent levels of encoded proteins during all stages of tissue regrowth, offering great versatility in their application and prompting new tissue engineering strategy in periodontal regenerative medicine. However, gene therapy in Periodontology is clearly in its infancy. Significant efforts still need to be made in developing safe and effective delivery platforms and clarifying how gene delivery, in combination with tissue engineering, may mimic the critical aspects of natural biological processes occurring in periodontal development and repair. The aim of this review is to trace an outline of the state-of-the-art in the application of gene delivery and tissue engineering strategies for periodontal healing and regeneration.

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

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

PubMed

Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

2015-01-01

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases

PubMed Central

Schwartz, Jeremy I.; Dunkle, Ashley; Akiteng, Ann R.; Birabwa-Male, Doreen; Kagimu, Richard; Mondo, Charles K.; Mutungi, Gerald; Rabin, Tracy L.; Skonieczny, Michael; Sykes, Jamila; Mayanja-Kizza, Harriet

2015-01-01

Background The burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. Methods Integrated approaches to health service delivery and healthcare worker (HCW) training will be necessary in order to successfully combat the great challenge posed by NCDs. Results In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD), a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. Discussion Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda. PMID:25563451

Rapid interferometric imaging of printed drug laden multilayer structures

NASA Astrophysics Data System (ADS)

Sandler, Niklas; Kassamakov, Ivan; Ehlers, Henrik; Genina, Natalja; Ylitalo, Tuomo; Haeggstrom, Edward

2014-02-01

The developments in printing technologies allow fabrication of micron-size nano-layered delivery systems to personal specifications. In this study we fabricated layered polymer structures for drug-delivery into a microfluidic channel and aimed to interferometrically assure their topography and adherence to each other. We present a scanning white light interferometer (SWLI) method for quantitative assurance of the topography of the embedded structure. We determined rapidly in non-destructive manner the thickness and roughness of the structures and whether the printed layers containing polymers or/and active pharmaceutical ingredients (API) adhere to each other. This is crucial in order to have predetermined drug release profiles. We also demonstrate non-invasive measurement of a polymer structure in a microfluidic channel. It shown that traceable interferometric 3D microscopy is a viable technique for detailed structural quality assurance of layered drug-delivery systems. The approach can have impact and find use in a much broader setting within and outside life sciences.

The magnetic graphene-based nanocomposite: An efficient anticancer delivery system

NASA Astrophysics Data System (ADS)

Jafarizad, Abbas; Jaymand, Mehdi; Taghizadehghalehjougi, Ali; Mohammadi-Nasr, Saeed; Jabbari, Amir Mohammad

2018-01-01

The aim of this study is the development of an efficient anticancer drug delivery nanosystem using PEGylated graphene oxide/magnetite nanoparticles (PEG-GO/Fe3O4). The nanosystem was loaded with mitoxantrone (MTX) as a universal anticancer drug. The cytotoxicity effect of the MTX-loaded GO-PEG/Fe3O4 nanocomposite was studied against U87 MG cell line using MTT cell viablity assay. The mechanism of action, the genes contributed in apoptosis (Casp 9, and Casp 3) and survival (BcL-2, BAX) have been investigated using quantitative real time-PCR. As the results of biological assays, controlled drug release behavior of the developed nanosystem as well as the inherent physicochemical and biological characteristics of both magnetit nanoparticles and graphene nanomaterials, we envision that the GO-PEG/Fe3O4 nanocomposite may be applied as enhanced drug delivery system for various cancer therapies (e.g., brain cancer) using both chemo- and photothermal therapy methods.

Developing and integrating a practice model for health finance reform into wound healing programs: an examination of the triple aim approach.

PubMed

Flattau, Anna; Thompson, Maureen; Meara, Anne

2013-10-01

Throughout the United States, government and private payers are exploring new payment models such as accountable care organizations and shared savings agreements. These models are widely based on the construct of the Triple Aim, a set of three principles for health services reform: improving population-based outcomes, improving patient care experiences, and reducing costs through better delivery systems. Wound programs may adapt to the new health financing environment by incorporating initiatives known to promote the Triple Aim, such as diabetes amputation reduction and pressure ulcer prevention programs, and by rethinking how health services can best be delivered to meet these new criteria. The existing literature supports that programmatic approaches can improve care, quality, and cost, especially in the field of diabetic foot ulcers. Wound healing programs have opportunities to develop new business plan models that provide quality, cost-efficient care to their patient population and to be leaders in the development of new types of partnerships with payers and health delivery organizations.

Nanovehicular Intracellular Delivery Systems

PubMed Central

PROKOP, ALES; DAVIDSON, JEFFREY M.

2013-01-01

This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. PMID:18200527

Micromachined devices: the impact of controlled geometry from cell-targeting to bioavailability.

PubMed

Tao, Sarah L; Desai, Tejal A

2005-12-05

Advances in microelectomechanical systems (MEMS) have allowed the microfabrication of polymeric substrates and the development of a novel class of controlled delivery devices. These vehicles have specifically tailored three-dimensional physical and chemical features which, together, provide the capacity to target cells, promote unidirectional controlled release, and enhance permeation across the intestinal epithelial barrier. Examining the biological response at the microdevice biointerface may provide insight into the benefits of customized surface chemistry and structure in terms of complex drug delivery vehicle design. Therefore, the aim of this work was to determine the interfacial effects of selective surface chemistry and architecture of tomato lectin (TL)-modified poly(methyl methacrylate) (PMMA) drug delivery microdevices on the Caco-2 cell line, a model of the gastrointestinal tract.

Therapy Stratifications and Novel Approach in Pursuit of AIDS Related Kaposi's Sarcoma Management- A paradigm for Non Invasiveness.

PubMed

Sharma, Meenu; Sharma, Vijay; Pathak, Kamla

2015-01-01

Cancer in individuals suffering with HIV and AIDS has become a common source of morbidity and mortality, especially in the underdeveloped world in which Kaposi's sarcoma is the most occurring tumor of vascular endothelium frequently seen in patients suffering from AIDS. Suffering individuals are invariably co-infected with HIV and HHV-8 virus. The conventional modes for chemotherapies may be clinically useful in patients with Kaposi's sarcoma. Though advancements in treatment modalities of AIDS related Kaposi's sarcoma have been successfully achieved, till date an exclusive therapy of golden standard has not been principally defined that can deliver the drug via non-invasive route. Novel concepts of treatment primarily address the factors that are associated with the pathogenesis of critical disease. On the other hand local therapies are aimed at eradicating primary lesions; and systemic chemotherapies are aimed to treat widespread visceral involvement. Increased understanding of the mechanisms underlying viral tumorigenesis will hopefully portray new therapeutic strategies. This review discusses novel drug delivery strategies that have been investigated for the effective and safe management of AIDS related kaposi's sarcoma. The review also highlights, the lipid based ultradeformable vesicular system that offers attractive drug delivery platform capable of delivering its payload without using invasive technique. These systems offer advance models for efficacious treatment of the future therapy aiming Kaposi's sarcoma.

Controlled extended octenidine release from a bacterial nanocellulose/Poloxamer hybrid system.

PubMed

Alkhatib, Y; Dewaldt, M; Moritz, S; Nitzsche, R; Kralisch, D; Fischer, D

2017-03-01

Although bacterial nanocellulose (BNC) has been widely investigated in the last 10years as drug delivery system, up to now no long-term controlled release of drugs could be realized. Therefore, the aim of the present work was the development of a BNC-based drug delivery system that provides prolonged retention time for the antiseptic octenidine up to one week with improved mechanical and antimicrobial properties as well as a high biocompatibility. BNC was modified by incorporation of differently concentrated Poloxamers 338 and 407 as micelles and gels that were extensively investigated regarding size, surface charge, and dynamic viscosity. Depending on type and concentration of the Poloxamer, a retarded octenidine release up to one week could be accomplished. Additionally, superior material properties such as high compression stability and water binding could be achieved. The antimicrobial activity of octenidine against Staphylococcus aureus and Pseudomonas aeruginosa was not changed by the use of Poloxamers. Excellent biocompatibility of the Poloxamer loaded BNC could be demonstrated after local administration in a shell-less hen's egg model. In conclusion, a long-term delivery system consisting of BNC and Poloxamer could be developed for octenidine as a ready-to-use system e.g. for long-term dermal wound treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

COLLABORATIVE RESEARCH AND DEVELOPMENT (CR&D) Delivery Order 0067: Molecular Simulations for Hydrated Polymer Fuel Membranes

DTIC Science & Technology

2007-11-01

proton transfer. 1. INTRODUCTION While polymer electrolyte membrane fuel cells ( PEMFCs ) hold out the possibility for providing several important...Among the broader aims of the research is to develop PEMFC systems which can operate at higher temperatures than presently achievable while still...efforts have provided insight into the mechanisms which enable proton conduction in PEMFCs . Hydrated membranes are two-phase systems, an

Development of self-nanoemulsifying drug delivery system for oral bioavailability enhancement of valsartan in beagle dogs.

PubMed

Li, Zhenbao; Zhang, Wenjuan; Gao, Yan; Xiang, Rongwu; Liu, Yan; Hu, Mingming; Zhou, Mei; Liu, Xiaohong; Wang, Yongjun; He, Zhonggui; Sun, Yinghua; Sun, Jin

2017-02-01

Valsartan, an angiotensin II receptor antagonist, is widely used to treat high blood pressure in the clinical setting. However, its poor water solubility results in the low oral bioavailability. The aim of this study was to improve dissolution rate and oral bioavailability by developing a self-nanoemulsifying drug delivery system. Saturation solubility of valsartan in various oils, surfactants, and cosurfactants was investigated, and the optimized formulation was determined by central composite design-response surface methodology. The shape of resultant VAL-SNEDDS was spherical with an average diameter of about 27 nm. And the drug loading efficiency is approximately 14 wt%. Differential scanning calorimetry and XRD studies disclosed the molecular or amorphous state of valsartan in VAL-SNEDDS. The dissolution study indicated that the self-nanoemulsifying drug delivery systems (SNEDDS) exhibited significantly enhanced dissolution compared with market capsules (Diovan®) in various media. Furthermore, the stability of formulation revealed that valsartan SNEDDS was stable under low temperature and accelerated test condition. Furthermore, the pharmacokinetics demonstrated that C max and AUC (0-∞) of SNEDDS capsules were about three- and twofold higher than Diovan® in beagle dogs, respectively. Meanwhile, the safety evaluation implied that VAL-SNEDDS was innocuous to beagle dogs during 15 days of continuous administration. Our results suggested that VAL-SNEDDS was a potential and safe delivery system with enhanced dissolution rate and oral bioavailability, as well as offered a strategy for the engineering of poorly water-soluble drugs in the clinical setting.

Star-shaped poly(oligoethylene glycol) copolymer-based gels: Thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery.

PubMed

Soliman, Mahmoud E; Elmowafy, Enas; Casettari, Luca; Alexander, Cameron

2018-05-30

The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Patient and provider perspectives on the design and implementation of an electronic consultation system for kidney care delivery in Canada: a focus group study.

PubMed

Bello, Aminu K; Molzahn, Anita E; Girard, Louis P; Osman, Mohamed A; Okpechi, Ikechi G; Glassford, Jodi; Thompson, Stephanie; Keely, Erin; Liddy, Clare; Manns, Braden; Jinda, Kailash; Klarenbach, Scott; Hemmelgarn, Brenda; Tonelli, Marcello

2017-03-02

We assessed stakeholder perceptions on the use of an electronic consultation system (e-Consult) to improve the delivery of kidney care in Alberta. We aim to identify acceptability, barriers and facilitators to the use of an e-Consult system for ambulatory kidney care delivery. This was a qualitative focus group study using a thematic analysis design. Eight focus groups were held in four locations in the province of Alberta, Canada. In total, there were 72 participants in two broad stakeholder categories: patients (including patients' relatives) and providers (including primary care physicians, nephrologists, other care providers and policymakers). The e-Consult system was generally acceptable across all stakeholder groups. The key barriers identified were length of time required for referring physicians to complete the e-Consult due to lack of integration with current electronic medical records, and concerns that increased numbers of requests might overwhelm nephrologists and lead to a delayed response or an unsustainable system. The key facilitators identified were potential improvement of care coordination, dissemination of best practice through an educational platform, comprehensive data to make decisions without the need for face-to-face consultation, timely feedback to primary care providers, timeliness/reduced delays for patients' rapid triage and identification of cases needing urgent care and improved access to information to facilitate decision-making in patient care. Stakeholder perceptions regarding the e-Consult system were favourable, and the key barriers and facilitators identified will be considered in design and implementation of an acceptable and sustainable electronic consultation system for kidney care delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Enhanced efficacy of TD53, a novel algicidal agent, against the harmful algae via the liposomal delivery system.

PubMed

Han, Hyo-Kyung; Kim, Yeon-Mi; Lim, Soo-Jeong; Hong, Soon-Seok; Jung, Seul-Gi; Cho, Hoon; Lee, Wonjae; Jin, Eonseon

2011-02-28

The present study aimed to design the liposomal delivery system for TD53, a novel algicial drug in order to improve the delivery properties of TD53 and evaluate its algicidal effects as well as selectivity against harmful and non-harmful algae. Liposomes of TD53 were prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) by a lyophilization, resulting in relatively small size vesicles (234±38nm) and narrow size distribution (PI=0.130±0.027). The drug leakage from the liposome was negligible in the F/2 media (<2% during 96h incubation). Subsequently algicidal activity of liposomal TD53 against harmful and nonharmful algae was evaluated at various concentrations. The IC(50) values of TD53 in liposome against harmful algae such as Chattonella marina, Heterosigma akashiwo and Cocholodinium polykrikoides were 2.675, 2.029, and 0.480μM, respectively, and were reduced by approximately 50% compared to those obtained from non-liposomal TD53. In contrast, the algicidal effect of liposomal TD53 was insignificant against non-harmful algae including Navicula pelliculosa, Nannochloropsis oculata and Phaeodactylum EPV. Those results suggested that liposomal delivery systems might be effective to enhance the efficacy of TD53 while maintaining the selectivity to harmful algal species. Copyright © 2010 Elsevier B.V. All rights reserved.

The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept.

PubMed

Bernkop-Schnürch, Andreas; Pinter, Yvonne; Guggi, Davide; Kahlbacher, Hermann; Schöffmann, Gudrun; Schuh, Maximilian; Schmerold, Ivo; Del Curto, Maria Dorly; D'Antonio, Mauro; Esposito, Pierandrea; Huck, Christian

2005-08-18

It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

Buparvaquone Nanostructured Lipid Carrier: Development of an Affordable Delivery System for the Treatment of Leishmaniases.

PubMed

Monteiro, Lis Marie; Löbenberg, Raimar; Cotrim, Paulo Cesar; Barros de Araujo, Gabriel Lima; Bou-Chacra, Nádia

2017-01-01

Buparvaquone (BPQ), a veterinary drug, was formulated as nanostructured lipid carriers (NLC) for leishmaniases treatment. The formulation design addressed poor water solubility of BPQ and lack of human drug delivery system. The DSC/TG and microscopy methods were used for solid lipids screening. Softisan® 154 showed highest BPQ solubility in both methods. The BPQ solubility in liquid lipids using HPLC revealed Miglyol® 812 as the best option. Response surface methodology (RSM) was used to identify the optimal Softisan154 : Miglyol 812 ratios (7 : 10 to 2 : 1) and Kolliphor® P188 and Tween® 80 concentration (>3.0% w/w) aiming for z -average in the range of 100-300 nm for macrophage delivery. The NLC obtained by high-pressure homogenization showed low z -averages (<350 nm), polydispersity (<0.3), and encapsulation efficiency close to 100%. DSC/TG and microscopy in combination proved to be a powerful tool to select the solid lipid. The relationship among the variables, demonstrated by a linear mathematical model using RSM, allowed generating a design space. This design space showed the limits in which changes in the variables influenced the z -average. Therefore, these drug delivery systems have the potential to improve the availability of affordable medicines due to the low cost of raw materials, using well established, reliable, and feasible scale-up technology.

Accuracy of Blood Loss Measurement during Cesarean Delivery.

PubMed

Doctorvaladan, Sahar V; Jelks, Andrea T; Hsieh, Eric W; Thurer, Robert L; Zakowski, Mark I; Lagrew, David C

2017-04-01

Objective  This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design  In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland-Altman method. Results  Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R 2  = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R 2  = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R 2  = 0.304). Conclusion  During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes.

Accuracy of Blood Loss Measurement during Cesarean Delivery

PubMed Central

Doctorvaladan, Sahar V.; Jelks, Andrea T.; Hsieh, Eric W.; Thurer, Robert L.; Zakowski, Mark I.; Lagrew, David C.

2017-01-01

Objective This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland–Altman method. Results Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R2 = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R2 = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R2 = 0.304). Conclusion During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes. PMID:28497007

Wood to energy: using southern interface fuels for bioenergy

Treesearch

C. Staudhammer; L.A. Hermansen; D. Carter; Ed Macie

2011-01-01

This publications aims to increase awareness of potential uses for woody biomass in the southern wildland-urban interface (WUI) and to disseminate knowledge about putting bioenergy production systems in place, while addressing issues unique to WUI areas. Chapter topics include woody biomass sources in the wildland-urban interface; harvesting, preprocessing and delivery...

Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

PubMed

Morille, Marie; Passirani, Catherine; Vonarbourg, Arnaud; Clavreul, Anne; Benoit, Jean-Pierre

2008-01-01

Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection and for multi-located tumor sites, i.e. metastases. Non-viral vectors based on the use of cationic lipids or polymers appear to have promising potential, given the problems of safety encountered with viral vectors. Using these non-viral vectors, the current challenge is to obtain a similarly effective transfection to viral ones. Based on the advantages and disadvantages of existing vectors and on the hurdles encountered with these carriers, the aim of this review is to describe the "perfect vector" for systemic gene therapy against cancer.

The significance of transferrin receptors in oncology: the development of functional nano-based drug delivery systems.

PubMed

Tortorella, Stephanie; Karagiannis, Tom C

2014-01-01

Anticancer therapeutic research aims to improve clinical management of the disease through the development of strategies that involve currently-relevant treatment options and targeted delivery. Tumour-specific and -targeted delivery of compounds to the site of malignancy allows for enhanced cellular uptake, increased therapeutic benefit with high intratumoural drug concentrations, and decreased systemic exposure. Due to the upregulation of transferrin receptor expression in a wide variety of cancers, its function and its highly efficient recycling pathway, strategies involving the selective targeting of the receptor are well documented. Direct conjugation and immunotoxin studies using the transferrin peptide or anti-transferrin receptor antibodies as the targeting moiety have established the capacity to enhance cellular uptake, cross the blood brain barrier, limit systemic toxicity and reverse multi-drug resistance. Limitations in direct conjugation, including the difficulty in linking an adequate amount of therapeutic compound to the ligand or antibody have identified the requirement to develop novel delivery methods. The application of nanoparticulate theory in the development of functional drug delivery systems has proven to be most promising, with the ability to selectively modify size-dependent properties and surface chemistry. The transferrin modification on a range of nanoparticle formulations enhances selective cellular uptake through transferrin-mediated processes, and increases therapeutic benefit through the ability to encapsulate high concentrations of relevant drug to the tumour site. Although ineffective in crossing the blood brain barrier in its free form, chemotherapeutic compounds including doxorubicin, may be loaded into transferrin-conjugated nanocarriers and impart cytotoxic effects in glioma cells in vitro and in vivo. Additionally, transferrin-targeted nanoparticles may be used in selective diagnostic applications with enhanced selectivity and sensitivity. Four transferrin-modified nano-based drug delivery systems are currently in early phases of human clinical trials. Despite the collective promise, inconsistencies in some studies have exposed some limitations in current formulations and the difficulty in translating preliminary studies into clinically-relevant therapeutic options. The main objective of this review is to investigate the development of transferrin targeted nano-based drug delivery systems in order to establish the use of transferrin as a cancer-targeted moiety, and to ultimately evaluate the progression of cancer therapeutic strategies for future research.

Self-Assembled Cubic Liquid Crystalline Nanoparticles for Transdermal Delivery of Paeonol

PubMed Central

Li, Jian-Chun; Zhu, Na; Zhu, Jin-Xiu; Zhang, Wen-Jing; Zhang, Hong-Min; Wang, Qing-Qing; Wu, Xiao-Xiang; Wang, Xiu; Zhang, Jin; Hao, Ji-Fu

2015-01-01

Background The aim of this study was to optimize the preparation method for self-assembled glyceryl monoolein-based cubosomes containing paeonol and to characterize the properties of this transdermal delivery system to improve the drug penetration ability in the skin. Material/Methods In this study, the cubic liquid crystalline nanoparticles loaded with paeonol were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel by high-pressure homogenization. We evaluated the Zeta potential of these promising skin-targeting drug-delivery systems using the Malvern Zeta sizer examination, and various microscopies and differential scanning calorimetry were also used for property investigation. Stimulating studies were evaluated based on the skin irritation reaction score standard and the skin stimulus intensity evaluation standard for paeonol cubosomes when compared with commercial paeonol ointment. In vitro tests were performed on excised rat skins in an improved Franz diffusion apparatus. The amount of paeonol over time in the in vitro penetration and retention experiments both was determined quantitatively by HPLC. Results Stimulating studies were compared with the commercial ointment which indicated that the paeonol cubic liquid crystalline nanoparticles could reduce the irritation in the skin stimulating test. Thus, based on the attractive characteristics of the cubic crystal system of paeonol, we will further exploit the cosmetic features in the future studies. Conclusions The transdermal delivery system of paeonol with low-irritation based on the self-assembled cubic liquid crystalline nanoparticles prepared in this study might be a promising system of good tropical preparation for skin application. PMID:26517086

Lipid Nanocarriers for Oral Delivery of Serenoa repens CO2 Extract: A Study of Microemulsion and Self-Microemulsifying Drug Delivery Systems.

PubMed

Guccione, Clizia; Bergonzi, Maria Camilla; Awada, Khaled M; Piazzini, Vieri; Bilia, Anna Rita

2018-07-01

The aim of this study was the development and characterization of lipid nanocarriers using food grade components for oral delivery of Serenoa repens CO 2 extract, namely microemulsions (MEs) and self-microemulsifying drug delivery systems (SMEDDSs) to improve the oral absorption. A commercial blend (CB) containing 320 of S. repens CO 2 extract plus the aqueous soluble extracts of nettle root and pineapple stem was formulated in two MEs and two SMEDDSs. The optimized ME loaded with the CB (CBM2) had a very low content of water (only 17.3%). The drug delivery systems were characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography (HPLC) with a diode-array detector analyses in order to evaluate the size, the homogeneity, the morphology, and the encapsulation efficiency. β -carotene was selected as marker for the quantitative HPLC analysis. Additionally, physical and chemical stabilities were acceptable during 3 wk at 4 °C. Stability of these nanocarriers in simulated stomach and intestinal conditions was proved. Finally, the improvement of oral absorption of S. repens was studied in vitro using parallel artificial membrane permeability assay. An enhancement of oral permeation was found in both CBM2 and CBS2 nanoformulations comparing with the CB and S. repens CO 2 extract. The best performance was obtained by the CBM2 nanoformulation (~ 17%) predicting a 30 - 70% passive oral human absorption in vivo . Georg Thieme Verlag KG Stuttgart · New York.

Supercritical fluid technologies: an innovative approach for manipulating the solid-state of pharmaceuticals.

PubMed

Pasquali, Irene; Bettini, Ruggero; Giordano, Ferdinando

2008-02-14

Solid-state, crystallographic purity and careful monitoring of the polymorphism of drugs and excipients are currently an integral part of the development of modern drug delivery systems. The reproducible preparation of organic crystals in a specific form and size is a major issue that must be addressed. A recent approach for obtaining pharmaceutical materials in pure physical form is represented by the technologies based on supercritical fluids. The present work aims to provide a critical review of the recent advances in the use of supercritical fluids for the preparation and control of the specific physical form of pharmaceutical substances with particular attention to those fluids used for drug delivery systems. These innovative technologies are highly promising for future application in particle design and engineering.

Needle-free and microneedle drug delivery in children: a case for disease-modifying antirheumatic drugs (DMARDs).

PubMed

Shah, Utpal U; Roberts, Matthew; Orlu Gul, Mine; Tuleu, Catherine; Beresford, Michael W

2011-09-15

Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied. Copyright © 2011 Elsevier B.V. All rights reserved.

Microneedles: A New Frontier in Nanomedicine Delivery.

PubMed

Larrañeta, Eneko; McCrudden, Maelíosa T C; Courtenay, Aaron J; Donnelly, Ryan F

2016-05-01

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN.

Self-nanoemulsifying drug-delivery system for improved oral bioavailability of rosuvastatin using natural oil antihyperlipdemic.

PubMed

Abo Enin, Hadel A

2015-01-01

The aim is improving the antihyperlipidemic activity of Rosuvastatin Calcium (Rs) through improving its solubility using self-nanoemulsifying drug delivery system (SNEDDS) containing natural oil full of unsaturated fatty acid and omega 3. A 7 × 3(2) full factorial design was adopted for optimization of oil ratio, Surfactant: Co-surfactant (S:CoS) ratio and oil:S/CoS ratio. Ternary phase diagrams were constructed for optimizing the system with drug loading (10 and 20%). The optimized SNEDD systems were evaluated according to their physical evaluation and drug release. Furthermore, the anti-hyperlipidemia efficacy was compared with commercially marketed product on rates followed by clinical study. The system containing Tween 80:PEG 400 (3:1) and olive oil:garlic oil (1:1) as an oily phase has droplet size less than 100 nm, ZP (+23.43 ± 2.58 mV), PDI (<0.02) and cloud point (>90 °C). In vitro drug release studies showed remarkable enhancement of the Rs release from Rs-SNEDDS. The antihyperlipidemic effect of Rs-SNEDDS is greater than that of the commercial tablets and the pure drug on rates and in hyperlipidemic patients. Rs-SNEDDS is a promising drug delivery system for improving the drug solubility and antihyperlipidemic effect using natural oils as (olive oil and garlic oil).

Systems and Components Fuel Delivery System, Water Delivery System, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

Induction of a robust immune response against avian influenza virus following transdermal inoculation with H5-DNA vaccine formulated in modified dendrimer-based delivery system in mouse model.

PubMed

Bahadoran, Azadeh; Ebrahimi, Mehdi; Yeap, Swee Keong; Safi, Nikoo; Moeini, Hassan; Hair-Bejo, Mohd; Hussein, Mohd Zobir; Omar, Abdul Rahman

2017-01-01

This study was aimed to evaluate the immunogenicity of recombinant plasmid deoxyribonucleic acid (DNA), pBud-H5-green fluorescent protein (GFP)-interferon-regulatory factor (IRF)3 following delivery using polyamidoamine (PAMAM) dendrimer and transactivator of transcription (TAT)-conjugated PAMAM dendrimer as well as the effect of IRF3 as the genetic adjuvant. BALB/c mice were vaccinated transdermally with pBud-H5-GFP, PAMAM/pBud-H5-GFP, TAT-PAMAM/pBud-H5-GFP, and TAT-PAMAM/pBud-H5-GFP-IRF3. The expression analysis of H5 gene from the blood by using quantitative real-time reverse transcriptase polymerase chain reaction confirmed the ability of PAMAM dendrimer as a carrier for gene delivery, as well as the ability of TAT peptide to enhance the delivery efficiency of PAMAM dendrimer. Mice immunized with modified PAMAM by TAT peptide showed higher hemagglutination inhibition titer, and larger CD3 + /CD4 + T cells and CD3 + /CD8 + T cells population, as well as the production of cytokines, namely, interferon (IFN)-γ, interleukin (IL)-2, IL-15, IL-12, IL-6, and tumor necrosis factor-α compared with those immunized with native PAMAM. These results suggest that the function of TAT peptide as a cell-penetrating peptide is able to enhance the gene delivery, which results in rapid distribution of H5 in the tissues of the immunized mice. Furthermore, pBud-H5-GFP co-expressing IRF3 as a genetic adjuvant demonstrated the highest hemagglutination inhibition titer besides larger CD3 + /CD4 + and CD3 + /CD8 + T cells population, and strong Th1-like cytokine responses among all the systems tested. In conclusion, TAT-PAMAM dendrimer-based delivery system with IRF3 as a genetic adjuvant is an attractive transdermal DNA vaccine delivery system utilized to evaluate the efficacy of the developed DNA vaccine in inducing protection during challenge with virulent H5N1 virus.

Applications of Light-Responsive Systems for Cancer Theranostics.

PubMed

Chen, Hongzhong; Zhao, Yanli

2018-06-27

Achieving controlled and targeted delivery of chemotherapeutic drugs and other therapeutic agents to tumor sites is challenging. Among many stimulus strategies, light as a mode of action shows various advantages such as high spatiotemporal selectivity, minimal invasiveness and easy operation. Thus, drug delivery systems (DDSs) have been designed with the incorporation of various functionalities responsive to light as an exogenous stimulus. Early development has focused on guiding chemotherapeutic drugs to designated location, followed by the utilization of UV irradiation for controlled drug release. Because of the disadvantages of UV light such as phototoxicity and limited tissue penetration depth, scientists have moved the research focus onto developing nanoparticle systems responsive to light in the visible region (400-700 nm), aiming to reduce the phototoxicity. In order to enhance the tissue penetration depth, near-infrared light triggered DDSs become increasingly important. In addition, light-based advanced systems for fluorescent and photoacoustic imaging, as well as photodynamic and photothermal therapy have also been reported. Herein, we highlight some of recent developments by applying light-responsive systems in cancer theranostics, including light activated drug release, photodynamic and photothermal therapy, and bioimaging techniques such as fluorescent and photoacoustic imaging. Future prospect of light-mediated cancer treatment is discussed at the end of the review. This Spotlights on Applications article aims to provide up-to-date information about the rapidly developing field of light-based cancer theranostics.

Natural product-based nanomedicine: recent advances and issues

PubMed Central

Watkins, Rebekah; Wu, Ling; Zhang, Chenming; Davis, Richey M; Xu, Bin

2015-01-01

Natural products have been used in medicine for many years. Many top-selling pharmaceuticals are natural compounds or their derivatives. These plant- or microorganism-derived compounds have shown potential as therapeutic agents against cancer, microbial infection, inflammation, and other disease conditions. However, their success in clinical trials has been less impressive, partly due to the compounds’ low bioavailability. The incorporation of nanoparticles into a delivery system for natural products would be a major advance in the efforts to increase their therapeutic effects. Recently, advances have been made showing that nanoparticles can significantly increase the bioavailability of natural products both in vitro and in vivo. Nanotechnology has demonstrated its capability to manipulate particles in order to target specific areas of the body and control the release of drugs. Although there are many benefits to applying nanotechnology for better delivery of natural products, it is not without issues. Drug targeting remains a challenge and potential nanoparticle toxicity needs to be further investigated, especially if these systems are to be used to treat chronic human diseases. This review aims to summarize recent progress in several key areas relevant to natural products in nanoparticle delivery systems for biomedical applications. PMID:26451111

New Insight in Improving Therapeutic Efficacy of Antipsychotic Agents: An Overview of Improved In Vitro and In Vivo Performance, Efficacy Upgradation and Future Prospects.

PubMed

Ei Thu, Hnin; Hussain, Zahid; Shuid, Ahmad Nazrun

2018-01-01

Psychotic disorders are recognized as severe mental disorders that rigorously affect patient's personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are the major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents. In recent decades, nanotechnology-based delivery systems have gained remarkable attention of the researchers to mitigate the pharmaceutical issues related to the antipsychotic therapies and to optimize their oral drug delivery, therapeutic outcomes, and patient compliance. Therefore, the present review was aimed to summarize the available in vitro and in vivo evidences signifying the pharmaceutical importance of the advanced delivery systems in improving the aqueous solubility, transmembrane permeability, oral bioavailability and therapeutic outcome of the antipsychotic agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The application of polysaccharide-based nanogels in peptides/proteins and anticancer drugs delivery.

PubMed

Zhang, Lin; Pan, Jifei; Dong, Shibo; Li, Zhaoming

2017-09-01

Finding adequate carriers for proteins/peptides and anticancer drugs delivery has become an urgent need, owing to the growing number of therapeutic macromolecules and the increasing amount of cancer incidence. Polysaccharide-based nanogels have attracted interest as carriers for proteins/peptides and anticancer drugs because of their characteristic properties like biodegradability, biocompatibility, stimuli-responsive behaviour, softness and swelling to help achieve a controlled, triggered response at the target site. In addition, the groups of the polysaccharide backbone are able to be modified to develop functional nanogels. Some polysaccharides have the intrinsic ability to recognise specific cell types, allowing the design of targeted drug delivery systems through receptor-mediated endocytosis. This review is aimed at describing and exploring the potential of polysaccharides that are used in nanogels which can help to deliver proteins/peptides and anticancer drugs.

Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics

PubMed Central

Fatouh, Ahmed M; Elshafeey, Ahmed H; Abdelbary, Ahmed

2017-01-01

Purpose Agomelatine is a novel antidepressant drug suffering from an extensive first-pass metabolism leading to a diminished absolute bioavailability. The aim of the study is: first to enhance its absolute bioavailability, and second to increase its brain delivery. Methods To achieve these aims, the nasal route was adopted to exploit first its avoidance of the hepatic first-pass metabolism to increase the absolute bioavailability, and second the direct nose-to-brain pathway to enhance the brain drug delivery. Solid lipid nanoparticles were selected as a drug delivery system to enhance agomelatine permeability across the blood–brain barrier and therefore its brain delivery. Results The optimum solid lipid nanoparticles have a particle size of 167.70 nm ±0.42, zeta potential of −17.90 mV ±2.70, polydispersity index of 0.12±0.10, entrapment efficiency % of 91.25%±1.70%, the percentage released after 1 h of 35.40%±1.13% and the percentage released after 8 h of 80.87%±5.16%. The pharmacokinetic study of the optimized solid lipid nanoparticles revealed a significant increase in each of the plasma peak concentration, the AUC(0–360 min) and the absolute bioavailability compared to that of the oral suspension of Valdoxan® with the values of 759.00 ng/mL, 7,805.69 ng⋅min/mL and 44.44%, respectively. The optimized solid lipid nanoparticles gave a drug-targeting efficiency of 190.02, which revealed more successful brain targeting by the intranasal route compared with the intravenous route. The optimized solid lipid nanoparticles had a direct transport percentage of 47.37, which indicates a significant contribution of the direct nose-to-brain pathway in the brain drug delivery. Conclusion The intranasal administration of agomelatine solid lipid nanoparticles has effectively enhanced both the absolute bioavailability and the brain delivery of agomelatine. PMID:28684900

Delivering democracy? An analysis of New Zealand's District Health Board elections, 2001 and 2004.

PubMed

Gauld, Robin

2005-08-01

The district health board (DHB) system is New Zealand's present structure for the governance and delivery of publicly-funded health care. An aim of the DHB system is to democratise health care governance, and a key element of DHBs is elected membership of their governing boards. This article focuses on the electoral component of DHBs. It reports on the first DHB elections of 2001 and recent 2004 elections. The article presents and discusses data regarding candidates, the electoral process, voter behaviour and election results. It suggests that the extent to which the DHB elections are contributing to aims of democratisation is questionable.

From volume to value? Can a value-based approach help deliver the ambitious aims of the NHS cardiovascular disease outcomes strategy?

PubMed

Dunbar-Rees, Rupert; Panch, Trishan; Dancy, Mark

2014-06-01

The last year has seen the publication of two papers which will radically shape the future organisation of healthcare in general, and cardiovascular disease in particular: Cardiovascular Outcomes Strategy (Department of Health) and The Strategy That Will Fix Healthcare (Harvard Business Review). Both publications set out a health delivery mechanism based around improvement of outcomes for groups of patients with similar needs. Instead of organising care around disease categories, it is proposed that the cardiovascular diseases are treated as a single family of diseases. We are reaching the limits of what an activity-based system organised around existing provider structures can sustainably deliver. Unless we find delivery systems which reduce costs while at the same time improving outcomes that are meaningful to patients, then we will be faced with a future of healthcare rationing. The increasing burden of chronic disease and ongoing quality concerns in delivery systems has created a 'burning platform', which must be addressed if we are to maintain a system which offers high-quality care free at the point of delivery. This paper explores what an outcomes and value-based system could look like when applied to cardiovascular disease. It explores what it means for providers and patients if we start to think about outcomes by patients with similar needs, rather than by intervention, or by clinical specialty. As a specific example, the paper explores the features of an Integrated Circulation Service, what the challenges and implications might be, and whether there is any evidence that this would deliver improved outcomes, at a lower cost to the system.

Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors.

PubMed

Ge, Zhishen; Chen, Qixian; Osada, Kensuke; Liu, Xueying; Tockary, Theofilus A; Uchida, Satoshi; Dirisala, Anjaneyulu; Ishii, Takehiko; Nomoto, Takahiro; Toh, Kazuko; Matsumoto, Yu; Oba, Makoto; Kano, Mitsunobu R; Itaka, Keiji; Kataoka, Kazunori

2014-03-01

Adequate retention in systemic circulation is the preliminary requirement for systemic gene delivery to afford high bioavailability into the targeted site. Polyplex micelle formulated through self-assembly of oppositely-charged poly(ethylene glycol) (PEG)-polycation block copolymer and plasmid DNA has gained tempting perspective upon its advantageous core-shell architecture, where outer hydrophilic PEG shell offers superior stealth behaviors. Aiming to promote these potential characters toward systemic applications, we strategically introduced hydrophobic cholesteryl moiety at the ω-terminus of block copolymer, anticipating to promote not only the stability of polyplex structure but also the tethered PEG crowdedness. Moreover, Mw of PEG in the PEGylated polyplex micelle was elongated up to 20 kDa for expecting further enhancement in PEG crowdedness. Furthermore, cyclic RGD peptide as ligand molecule to integrin receptors was installed at the distal end of PEG in order for facilitating targeted delivery to the tumor site as well as promoting cellular uptake and intracellular trafficking behaviors. Thus constructed cRGD conjugated polyplex micelle with the elevated PEG shielding was challenged to a modeled intractable pancreatic cancer in mice, achieving potent tumor growth suppression by efficient gene expression of antiangiogenic protein (sFlt-1) at the tumor site. Copyright © 2013 Elsevier Ltd. All rights reserved.

Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles.

PubMed

Yuan, Xue; Xie, Qian; Su, Keyu; Li, Zhijie; Dong, Dong; Wu, Baojian

2017-01-01

Arenobufagin (ABG) is a major active component of toad venom, a traditional Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its pharmacological studies in vivo due to administration difficulties. In this study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene glycol)-block-poly (d,l-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique. The obtained ABG-PNs were 105 nm in size with a small polydispersity index of 0.08. The entrapment efficiency and drug loading were 71.9% and 4.58%, respectively. Cellular uptake of ABG-PNs was controlled by specific clathrin-mediated endocytosis. In addition, ABG-PNs showed improved drug pharmacokinetics with an increased area under the curve value (a 1.73-fold increase) and a decreased elimination clearance (37.8% decrease). The nanomicelles showed increased drug concentrations in the liver and lung. In contrast, drug concentrations in both heart and brain were decreased. Moreover, the nanomicelles enhanced the anticancer effect of the pure drug probably via increased cellular uptake of drug molecules. In conclusion, the mPEG-PLGA-based nanomicelle system is a satisfactory carrier for the systemic delivery of ABG.

Innovative pharmaceutical approaches for the management of inner ear disorders.

PubMed

Musazzi, Umberto M; Franzé, Silvia; Cilurzo, Francesco

2018-04-01

The sense of hearing is essential for permitting human beings to interact with the environment, and its dysfunctions can strongly impact on the quality of life. In this context, the cochlea plays a fundamental role in the transformation of the airborne sound waves into electrical signals, which can be processed by the brain. However, several diseases and external stimuli (e.g., noise, drugs) can damage the sensorineural structures of cochlea, inducing progressive hearing dysfunctions until deafness. In clinical practice, the current pharmacological approaches to treat cochlear diseases are based on the almost exclusive use of systemic steroids. In the last decades, the efficacy of novel therapeutic molecules has been proven, taking advantage from a better comprehension of the pathological mechanisms underlying many cochlear diseases. In addition, the feasibility of intratympanic administration of drugs also permitted to overcome the pharmacokinetic limitations of the systemic drug administration, opening new frontiers in drug delivery to cochlea. Several innovative drug delivery systems, such as in situ gelling systems or nanocarriers, were designed, and their efficacy has been proven in vitro and in vivo in cochlear models. The current review aims to describe the art of state in the cochlear drug delivery, highlighting lights and shadows and discussing the most critical aspects still pending in the field.

Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle.

PubMed

Helbling, Ignacio M; Busatto, Carlos A; Fioramonti, Silvana A; Pesoa, Juan I; Santiago, Liliana; Estenoz, Diana A; Luna, Julio A

2018-02-20

Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5-8 days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system. Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data. Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69-75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained. The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.

Hurricane Charley Exposure and Hazard of Preterm Delivery, Florida 2004.

PubMed

Grabich, Shannon C; Robinson, Whitney R; Engel, Stephanie M; Konrad, Charles E; Richardson, David B; Horney, Jennifer A

2016-12-01

Objective Hurricanes are powerful tropical storm systems with high winds which influence many health effects. Few studies have examined whether hurricane exposure is associated with preterm delivery. We aimed to estimate associations between maternal hurricane exposure and hazard of preterm delivery. Methods We used data on 342,942 singleton births from Florida Vital Statistics Records 2004-2005 to capture pregnancies at risk of delivery during the 2004 hurricane season. Maternal exposure to Hurricane Charley was assigned based on maximum wind speed in maternal county of residence. We estimated hazards of overall preterm delivery (<37 gestational weeks) and extremely preterm delivery (<32 gestational weeks) in Cox regression models, adjusting for maternal/pregnancy characteristics. To evaluate heterogeneity among racial/ethnic subgroups, we performed analyses stratified by race/ethnicity. Additional models investigated whether exposure to multiples hurricanes increased hazard relative to exposure to one hurricane. Results Exposure to wind speeds ≥39 mph from Hurricane Charley was associated with a 9 % (95 % CI 3, 16 %) increase in hazard of extremely preterm delivery, while exposure to wind speed ≥74 mph was associated with a 21 % (95 % CI 6, 38 %) increase. Associations appeared greater for Hispanic mothers compared to non-Hispanic white mothers. Hurricane exposure did not appear to be associated with hazard of overall preterm delivery. Exposure to multiple hurricanes did not appear more harmful than exposure to a single hurricane. Conclusions Hurricane exposure may increase hazard of extremely preterm delivery. As US coastal populations and hurricane severity increase, the associations between hurricane and preterm delivery should be further studied.

Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery

PubMed Central

Lin, Hongwei; Xie, Qingchun; Huang, Xin; Ban, Junfeng; Wang, Bo; Wei, Xing

2018-01-01

Aim The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. Methods In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. Results The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. Conclusion The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP. PMID:29467573

Barriers in the Delivery of Emergency Obstetric and Neonatal Care in Post-Conflict Africa: Qualitative Case Studies of Burundi and Northern Uganda

PubMed Central

Chi, Primus Che; Bulage, Patience; Urdal, Henrik; Sundby, Johanne

2015-01-01

Objectives Maternal and neonatal mortality and morbidity rates are particularly grim in conflict, post-conflict and other crisis settings, a situation partly blamed on non-availability and/or poor quality of emergency obstetric and neonatal care (EmONC) services. The aim of this study was to explore the barriers to effective delivery of EmONC services in post-conflict Burundi and Northern Uganda, in order to provide policy makers and other relevant stakeholders context-relevant data on improving the delivery of these lifesaving services. Methods This was a qualitative comparative case study that used 42 face-to-face semi-structured in-depth interviews and 4 focus group discussions for data collection. Participants were 32 local health providers and 37 staff of NGOs working in the area of maternal health. Data was analysed using the framework approach. Results The availability, quality and distribution of EmONC services were major challenges across the sites. The barriers in the delivery of quality EmONC services were categorised into two major themes; human resources-related challenges, and systemic and institutional failures. While some of the barriers were similar, others were unique to specific sites. The common barriers included shortage of qualified staff; lack of essential installations, supplies and medications; increasing workload, burn-out and turnover; and poor data collection and monitoring systems. Barriers unique to Northern Uganda were demoralised personnel and lack of recognition; poor referral system; inefficient drug supply system; staff absenteeism in rural areas; and poor coordination among key personnel. In Burundi, weak curriculum; poor harmonisation and coordination of training; and inefficient allocation of resources were the unique challenges. To improve the situation across the sites, efforts are ongoing to improve the training and recruitment of more staff; harmonise and strengthen the curriculum and training; increase the number of EmONC facilities; and improve staff supervision, monitoring and support. Conclusions Post-conflict health systems face different challenges in the delivery of EmONC services and as such require context-specific interventions to improve the delivery of these services. PMID:26405800

Barriers in the Delivery of Emergency Obstetric and Neonatal Care in Post-Conflict Africa: Qualitative Case Studies of Burundi and Northern Uganda.

PubMed

Chi, Primus Che; Bulage, Patience; Urdal, Henrik; Sundby, Johanne

2015-01-01

Maternal and neonatal mortality and morbidity rates are particularly grim in conflict, post-conflict and other crisis settings, a situation partly blamed on non-availability and/or poor quality of emergency obstetric and neonatal care (EmONC) services. The aim of this study was to explore the barriers to effective delivery of EmONC services in post-conflict Burundi and Northern Uganda, in order to provide policy makers and other relevant stakeholders context-relevant data on improving the delivery of these lifesaving services. This was a qualitative comparative case study that used 42 face-to-face semi-structured in-depth interviews and 4 focus group discussions for data collection. Participants were 32 local health providers and 37 staff of NGOs working in the area of maternal health. Data was analysed using the framework approach. The availability, quality and distribution of EmONC services were major challenges across the sites. The barriers in the delivery of quality EmONC services were categorised into two major themes; human resources-related challenges, and systemic and institutional failures. While some of the barriers were similar, others were unique to specific sites. The common barriers included shortage of qualified staff; lack of essential installations, supplies and medications; increasing workload, burn-out and turnover; and poor data collection and monitoring systems. Barriers unique to Northern Uganda were demoralised personnel and lack of recognition; poor referral system; inefficient drug supply system; staff absenteeism in rural areas; and poor coordination among key personnel. In Burundi, weak curriculum; poor harmonisation and coordination of training; and inefficient allocation of resources were the unique challenges. To improve the situation across the sites, efforts are ongoing to improve the training and recruitment of more staff; harmonise and strengthen the curriculum and training; increase the number of EmONC facilities; and improve staff supervision, monitoring and support. Post-conflict health systems face different challenges in the delivery of EmONC services and as such require context-specific interventions to improve the delivery of these services.

Hydrogel-thickened nanoemulsions based on essential oils for topical delivery of psoralen: Permeation and stability studies.

PubMed

Barradas, Thaís Nogueira; Senna, Juliana Perdiz; Cardoso, Stephani Araujo; Nicoli, Sara; Padula, Cristina; Santi, Patrizia; Rossi, Francesca; de Holanda E Silva, K Gyselle; Mansur, Claudia R Elias

2017-07-01

Nanoemulsions (NE) have attracted much attention due to their as dermal delivery systems for lipophilic drugs such as psoralens. However, NE feature low viscosity which might be unsuitable for topical application. In this work, we produced hydrogel-thickened nanoemulsions (HTN) using chitosan as thickening polymer to overcome the low viscosity attributed to NE. The aim of this study is to develop and characterize oil-in-water (o/w) HTN based on sweet fennel and clove essential oil to transdermal delivery of 8-methoxsalen (8-MOP). NE components (oil, surfactant) were selected on the basis of solubility and droplet size and processed in a high-pressure homogenizer (HPH). Drug loaded NE and HTN were characterized for particle size, stability under storage and centrifugation, rheological behavior, transdermal permeation and skin accumulation. Transdermal permeation of 8-MOP from HTN was determined by using Franz diffusion cell. Transdermal permeation from HTN using clove essential oil showed strong dependency chitosan molecular weight. On the other hand, HTN using sweet fennel oil showed an unexpected pH-dependent behavior not fully understood at the moment. These results need further investigation, nevertheless HTN revealed to be interesting and complex dermal delivery systems for poorly soluble drugs. Copyright © 2016. Published by Elsevier B.V.

Design of a transdermal delivery system for aspirin as an antithrombotic drug.

PubMed

Ammar, H O; Ghorab, M; El-Nahhas, S A; Kamel, R

2006-12-11

Aspirin has become the gold standard to which newer antiplatelet drugs are compared for reducing risks of cardiovascular diseases, while keeping low cost. Oral aspirin has a repertoire of gastrointestinal side effects even at low doses and requires high frequent dosing because it undergoes extensive presystemic metabolism. Transdermal delivery offers an alternative route that bypasses the gut and may be more convenient and safer for aspirin delivery especially during long-term use. This study comprised formulation of aspirin in different topical bases. Release studies revealed that hydrocarbon gel allowed highest drug release. In vitro permeation studies revealed high drug permeation from hydrocarbon gel. Several chemical penetration enhancers were monitored for augmenting the permeation from this base. Combination of propylene glycol and alcohol showed maximum enhancing effect and, hence, was selected for biological investigation. The biological performance of the selected formulation was assessed by measuring the inhibition of platelet aggregation relevant to different dosage regimens aiming to minimize both drug dose and frequency of application. The results demonstrated the feasibility of successfully influencing platelet function and revealed that the drug therapeutic efficacy in transdermal delivery system is dose independent. Biological performance was re-assessed after storage and the results revealed stability and persistent therapeutic efficacy.

Human fetal bone cells in delivery systems for bone engineering.

PubMed

Tenorio, Diene M H; Scaletta, Corinne; Jaccoud, Sandra; Hirt-Burri, Nathalie; Pioletti, Dominique P; Jaques, Bertrand; Applegate, Lee Ann

2011-11-01

The aim of this study was to culture human fetal bone cells (dedicated cell banks of fetal bone derived from 14 week gestation femurs) within both hyaluronic acid gel and collagen foam, to compare the biocompatibility of both matrices as potential delivery systems for bone engineering and particularly for oral application. Fetal bone cell banks were prepared from one organ donation and cells were cultured for up to 4 weeks within hyaluronic acid (Mesolis®) and collagen foams (TissueFleece®). Cell survival and differentiation were assessed by cell proliferation assays and histology of frozen sections stained with Giemsa, von Kossa and ALP at 1, 2 and 4 weeks of culture. Within both materials, fetal bone cells could proliferate in three-dimensional structure at ∼70% capacity compared to monolayer culture. In addition, these cells were positive for ALP and von Kossa staining, indicating cellular differentiation and matrix production. Collagen foam provides a better structure for fetal bone cell delivery if cavity filling is necessary and hydrogels would permit an injectable technique for difficult to treat areas. In all, there was high biocompatibility, cellular differentiation and matrix deposition seen in both matrices by fetal bone cells, allowing for easy cell delivery for bone stimulation in vivo. Copyright © 2011 John Wiley & Sons, Ltd.

Systemic Injection of Neural Stem/Progenitor Cells in Mice with Chronic EAE

PubMed Central

Donegà, Matteo; Giusto, Elena; Cossetti, Chiara; Schaeffer, Julia; Pluchino, Stefano

2014-01-01

Neural stem/precursor cells (NPCs) are a promising stem cell source for transplantation approaches aiming at brain repair or restoration in regenerative neurology. This directive has arisen from the extensive evidence that brain repair is achieved after focal or systemic NPC transplantation in several preclinical models of neurological diseases. These experimental data have identified the cell delivery route as one of the main hurdles of restorative stem cell therapies for brain diseases that requires urgent assessment. Intraparenchymal stem cell grafting represents a logical approach to those pathologies characterized by isolated and accessible brain lesions such as spinal cord injuries and Parkinson's disease. Unfortunately, this principle is poorly applicable to conditions characterized by a multifocal, inflammatory and disseminated (both in time and space) nature, including multiple sclerosis (MS). As such, brain targeting by systemic NPC delivery has become a low invasive and therapeutically efficacious protocol to deliver cells to the brain and spinal cord of rodents and nonhuman primates affected by experimental chronic inflammatory damage of the central nervous system (CNS). This alternative method of cell delivery relies on the NPC pathotropism, specifically their innate capacity to (i) sense the environment via functional cell adhesion molecules and inflammatory cytokine and chemokine receptors; (ii) cross the leaking anatomical barriers after intravenous (i.v.) or intracerebroventricular (i.c.v.) injection; (iii) accumulate at the level of multiple perivascular site(s) of inflammatory brain and spinal cord damage; and (i.v.) exert remarkable tissue trophic and immune regulatory effects onto different host target cells in vivo. Here we describe the methods that we have developed for the i.v. and i.c.v. delivery of syngeneic NPCs in mice with experimental autoimmune encephalomyelitis (EAE), as model of chronic CNS inflammatory demyelination, and envisage the systemic stem cell delivery as a valuable technique for the selective targeting of the inflamed brain in regenerative neurology. PMID:24798882

Antioxidant delivery pathways in the anterior eye.

PubMed

Umapathy, Ankita; Donaldson, Paul; Lim, Julie

2013-01-01

Tissues in the anterior segment of the eye are particular vulnerable to oxidative stress. To minimise oxidative stress, ocular tissues utilise a range of antioxidant defence systems which include nonenzymatic and enzymatic antioxidants in combination with repair and chaperone systems. However, as we age our antioxidant defence systems are overwhelmed resulting in increased oxidative stress and damage to tissues of the eye and the onset of various ocular pathologies such as corneal opacities, lens cataracts, and glaucoma. While it is well established that nonenzymatic antioxidants such as ascorbic acid and glutathione are important in protecting ocular tissues from oxidative stress, less is known about the delivery mechanisms used to accumulate these endogenous antioxidants in the different tissues of the eye. This review aims to summarise what is currently known about the antioxidant transport pathways in the anterior eye and how a deeper understanding of these transport systems with respect to ocular physiology could be used to increase antioxidant levels and delay the onset of eye diseases.

Organizational Culture, Values, and Routines in Iranian Medical Schools

ERIC Educational Resources Information Center

Bikmoradi, Ali; Brommels, Mats; Shoghli, Alireza; Zavareh, Davoud Khorasani; Masiello, Italo

2009-01-01

In Iran, restructuring of medical education and the health care delivery system in 1985 resulted in a rapid shift from elite to mass education, ultimately leading to an increase in the number of medical schools, faculties, and programs and as well as some complications. This study aimed to investigate views on academic culture, values, and…

Prospective EFL Teachers' Perceptions of ICT Integration: A Study of Distance Higher Education in Turkey

ERIC Educational Resources Information Center

Hismanoglu, Murat

2012-01-01

This paper aims to investigate the perceptions of prospective EFL teachers in the distance higher education system toward ICT implementation in teaching English as a foreign language. The majority of respondents who expressed negative attitudes to ICT integration found the nature, level and delivery of the training inadequate and accordingly…

Structure of block copolymer micelles in the presence of co-solvents

NASA Astrophysics Data System (ADS)

Robertson, Megan; Wang, Shu; Le, Kim Mai; Piemonte, Rachele; Madsen, Louis

2015-03-01

Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using scattering experiments and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.

Influencing the structure of block copolymer micelles with small molecule additives

NASA Astrophysics Data System (ADS)

Robertson, Megan; Singh, Avantika; Cooksey, Tyler; Kidd, Bryce; Piemonte, Rachele; Wang, Shu; Mai Le, Kim; Madsen, Louis

Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using small-angle scattering and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.

Electrostatic Self-Assembled Chitosan-Pectin Nano- and Microparticles for Insulin Delivery.

PubMed

Maciel, Vinicius B V; Yoshida, Cristiana M P; Pereira, Susana M S S; Goycoolea, Francisco M; Franco, Telma T

2017-10-12

A polyelectrolyte complex system of chitosan-pectin nano- and microparticles was developed to encapsulate the hormone insulin. The aim of this work was to obtain small particles for oral insulin delivery without chemical crosslinkers based on natural and biodegradable polysaccharides. The nano- and microparticles were developed using chitosans (with different degrees of acetylation: 15.0% and 28.8%) and pectin solutions at various charge ratios (n⁺/n - given by the chitosan/pectin mass ratio) and total charge. Nano- and microparticles were characterized regarding particle size, zeta potential, production yield, encapsulation efficiency, stability in different media, transmission electron microscopy and cytotoxicity assays using Caco-2 cells. The insulin release was evaluated in vitro in simulated gastric and intestinal media. Small-sized particles (~240-~1900 nm) with a maximum production yield of ~34.0% were obtained. The highest encapsulation efficiency (~62.0%) of the system was observed at a charge ratio (n⁺/n - ) 5.00. The system was stable in various media, particularly in simulated gastric fluid (pH 1.2). Transmission electron microscopy (TEM) analysis showed spherical shape particles when insulin was added to the system. In simulated intestinal fluid (pH 6.8), controlled insulin release occurred over 2 h. In vitro tests indicated that the proposed system presents potential as a drug delivery for oral administration of bioactive peptides.

Anti-Inflammatory Activity of Babassu Oil and Development of a Microemulsion System for Topical Delivery

PubMed Central

Reis, Mysrayn Y. F. A.; dos Santos, Simone M.; Silva, Danielle R.; Navarro, Daniela M. A. Ferraz; Santos, Geanne K. N.; Hallwass, Fernando; Bianchi, Otávio; Silva, Alexandre G.; Melo, Janaína V.; Machado, Giovanna; Saraiva, Karina L. A.

2017-01-01

Babassu oil extraction is the main income source in nut breakers communities in northeast of Brazil. Among these communities, babassu oil is used for cooking but also medically to treat skin wounds and inflammation, and vulvovaginitis. This study aimed to evaluate the anti-inflammatory activity of babassu oil and develop a microemulsion system with babassu oil for topical delivery. Topical anti-inflammatory activity was evaluated in mice ear edema using PMA, arachidonic acid, ethyl phenylpropiolate, phenol, and capsaicin as phlogistic agents. A microemulsion system was successfully developed using a Span® 80/Kolliphor® EL ratio of 6 : 4 as the surfactant system (S), propylene glycol and water (3 : 1) as the aqueous phase (A), and babassu oil as the oil phase (O), and analyzed through conductivity, SAXS, DSC, TEM, and rheological assays. Babassu oil and lauric acid showed anti-inflammatory activity in mice ear edema, through inhibition of eicosanoid pathway and bioactive amines. The developed formulation (39% A, 12.2% O, and 48.8% S) was classified as a bicontinuous to o/w transition microemulsion that showed a Newtonian profile. The topical anti-inflammatory activity of microemulsified babassu oil was markedly increased. A new delivery system of babassu microemulsion droplet clusters was designed to enhance the therapeutic efficacy of vegetable oil. PMID:29430254

Formulation and characterization of liquid crystal systems containing azelaic acid for topical delivery.

PubMed

Aytekin, Merve; Gursoy, R Neslihan; Ide, Semra; Soylu, Elif H; Hekimoglu, Sueda

2013-02-01

The aim of this study is to prepare and characterize azelaic acid (AzA) containing liquid crystal (LC) drug delivery systems for topical use. Two ternary phase diagrams, containing liquid paraffin as the oil component and a mixture of two nonionic surfactants (Brij 721P and Brij 72), were constructed. Formulations chosen from the phase diagrams were characterized by polarized light microscopy, rheological analyses, differential scanning calorimetry (DSC), and small angle x-ray scattering spectroscopy. Polarized light microscopy proved that except the oil/water emulsion (O/W E), other formulations showed lamellar LC structure. In vitro release studies indicated that the fastest release was achieved by the Lamellar LC (LLC) and O/W E systems, whereas slower release was obtained from the emulsion containing lamellar LC (E-LLC) and distorted lamellar LC (D-LLC) systems. Results of rheological measurements both supported the results of in vitro release studies and showed that the emulsion containing the LC (E-LLC) system had the most stable structure. The formulations and their effect on stratum corneum (SC) were evaluated by DSC studies. The lamellar LC (LLC), emulsion containing lamellar liquid crystal (E-LLC), and O/W E formulations had an effect on both lipid and protein components of SC, whereas distorted lamellar liquid crystal (D-LLC) system had an effect on only the lipid components of SC. LLC systems could be considered promising for the topical delivery of AzA.

Assessing the contribution of the dental care delivery system to oral health care disparities.

PubMed

Pourat, Nadereh; Andersen, Ronald M; Marcus, Marvin

2015-01-01

Existing studies of disparities in access to oral health care for underserved populations often focus on supply measures such as number of dentists. This approach overlooks the importance of other aspects of the dental care delivery system, such as personal and practice characteristics of dentists, that determine the capacity to provide care. This study aims to assess the role of such characteristics in access to care of underserved populations. We merged data from the 2003 California Health Interview Survey and a 2003 survey of California dentists in their Medical Study Service Areas (MSSAs). We examined the role of overall supply and other characteristics of dentists in income and racial/ethnic disparities in access, which was measured by annual dental visits and unmet need for dental care due to costs. We found that some characteristics of MSSAs, including higher proportions of dentists who were older, white, busy or overworked, and did not accept public insurance or discounted fees, inhibited access for low-income and minority populations. These findings highlight the importance of monitoring characteristics of dentists in addition to traditional measures of supply such as licensed-dentist-to-population ratios. The findings identify specific aspects of the delivery system such as dentists' participation in Medicaid, provision of discounted care, busyness, age, race/ethnicity, and gender that should be regularly monitored. These data will provide a better understanding of how the dental care delivery system is organized and how this knowledge can be used to develop more narrowly targeted policies to alleviate disparities. © 2014 American Association of Public Health Dentistry.

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

PubMed

Ye, Bai-Liang; Zheng, Ru; Ruan, Xiao-Jiao; Zheng, Zhi-Hai; Cai, Hua-Jie

2018-01-01

Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load.

PubMed

Iredahl, Fredrik; Högstedt, Alexandra; Henricson, Joakim; Sjöberg, Folke; Tesselaar, Erik; Farnebo, Simon

2016-10-01

Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load. Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI). Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load. Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load. © 2016 John Wiley & Sons Ltd.

Nanoencapsulation, an efficient and promising approach to maximize wound healing efficacy of curcumin: A review of new trends and state-of-the-art.

PubMed

Hussain, Zahid; Thu, Hnin Ei; Ng, Shiow-Fern; Khan, Shahzeb; Katas, Haliza

2017-02-01

Wound healing is a multifarious and vibrant process of replacing devitalized and damaged cellular structures, leading to restoration of the skin's barrier function, re-establishment of tissue integrity, and maintenance of the internal homeostasis. Curcumin (CUR) and its analogs have gained widespread recognition due to their remarkable anti-inflammatory, anti-infective, anticancer, immunomodulatory, antioxidant, and wound healing activities. However, their pharmaceutical significance is limited due to inherent hydrophobic nature, poor water solubility, low bioavailability, chemical instability, rapid metabolism and short half-life. Owing to their pharmaceutical limitations, newer strategies have been attempted in recent years aiming to mitigate problems related to the effective delivery of curcumanoids and to improve their wound healing potential. These advanced strategies include nanovesicles, polymeric micelles, conventional liposomes and hyalurosomes, nanocomposite hydrogels, electrospun nanofibers, nanohybrid scaffolds, nanoconjugates, nanostructured lipid carriers (NLCs), nanoemulsion, nanodispersion, and polymeric nanoparticles (NPs). The superior wound healing activities achieved after nanoencapsulation of the CUR are attributed to its target-specific delivery, longer retention at the target site, avoiding premature degradation of the encapsulated cargo and the therapeutic superiority of the advanced delivery systems over the conventional delivery. We have critically reviewed the literature and summarize the convincing evidence which explore the pharmaceutical significance and therapeutic feasibility of the advanced delivery systems in improving wound healing activities of the CUR and its analogs. Copyright © 2016 Elsevier B.V. All rights reserved.

Bioactive Molecule-loaded Drug Delivery Systems to Optimize Bone Tissue Repair.

PubMed

Oshiro, Joao Augusto; Sato, Mariana Rillo; Scardueli, Cassio Rocha; Lopes de Oliveira, Guilherme Jose Pimentel; Abucafy, Marina Paiva; Chorilli, Marlus

2017-01-01

Bioactive molecules such as peptides and proteins can optimize the repair of bone tissue; however, the results are often unpredictable when administered alone, owing to their short biological half-life and instability. Thus, the development of bioactive molecule-loaded drug delivery systems (DDS) to repair bone tissue has been the subject of intense research. DDS can optimize the repair of bone tissue owing to their physicochemical properties, which improve cellular interactions and enable the incorporation and prolonged release of bioactive molecules. These characteristics are fundamental to favor bone tissue homeostasis, since the biological activity of these factors depends on how accessible they are to the cell. Considering the importance of these DDS, this review aims to present relevant information on DDS when loaded with osteogenic growth peptide and bone morphogenetic protein. These are bioactive molecules that are capable of modulating the differentiation and proliferation of mesenchymal cells in bone tissue cells. Moreover, we will present different approaches using these peptide and protein-loaded DDS, such as synthetic membranes and scaffolds for bone regeneration, synthetic grafts, bone cements, liposomes, and micelles, which aim at improving the therapeutic effectiveness, and we will compare their advantages with commercial systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Novel technologies: A weapon against tuberculosis.

PubMed

Hari, B N Vedha; Chitra, Karuna Priya; Bhimavarapu, Ramadevi; Karunakaran, Prabhu; Muthukrishnan, N; Rani, B Samyuktha

2010-12-01

Tuberculosis (TB) is a leading chronic bacterial infection. Despite potentially curative pharmacotherapies being available for over 50 years, the length of the treatment and the pill burden can hamper patient lifestyle. Low compliance and adherence to administration schedules remain the main reasons for therapeutic failure and contribute to the development of multidrug-resistant strains. The design of novel antibiotics attempts to overcome drug resistance, to shorten the treatment course, and to reduce drug interactions. In this framework, nanotechnology appears as one of the promising approaches for the development of more effective medicines. The present review thoroughly overviews the development of novel microparticulate, encapsulation, and various other carrier-based drug delivery systems for incorporating the principal anti-TB agents. Drug delivery systems have been designed that either target the site of TB or reduce the dosing frequency with the aim of improving patient healthcare.

Potential drug delivery approaches for XFS-associated and XFS-associated glaucoma.

PubMed

Kulkarni, Shreya S; Kompella, Uday B

2014-01-01

Key tissue targets in treating exfoliation syndrome (XFS) and the associated glaucoma include lens, iris, and ciliary body, which produce the exfoliative material, and the trabecular meshwork, which may be impaired by the exfoliative material. In addition to antiglaucoma drug therapy, strategies for treating the disease include approaches for preventing formation of exfoliative material as well as those aimed at digesting exfoliative material. A variety of drug molecules including small molecules, protein drugs, and nucleic acids are potential candidates for treating XFS. Potential drug classes include antioxidants, lysyl oxidase-like 1 enhancers, antifibrotics, anti-inflammatory agents, proteases, and chaperones. However, the delivery of these agents to the target tissues in the anterior segment is hindered by protective static and dynamic barriers of the eye. Thus, unique drug delivery approaches are needed for each drug type (small molecules, proteins, and nucleic acids). In addition, there is a need for sustaining drug therapy for treating XFS, which can potentially be addressed by using nanoparticles, microparticles, implants, and contact lens delivery systems. This article provides an overview of drug delivery challenges and opportunities in treating XFS with the focus being on nanomedicines.

Development of semisolid self-microemulsifying drug delivery systems (SMEDDSs) filled in hard capsules for oral delivery of aciclovir.

PubMed

Djekic, Ljiljana; Jankovic, Jovana; Čalija, Bojan; Primorac, Marija

2017-08-07

The study aimed to develop semisolid self-microemulsifying drug delivery systems (SMEDDSs) as carriers for oral delivery of aciclovir in hard hydroxypropylmethyl cellulose (HPMC) capsules. Six self-dispersing systems (SD1-SD6) were prepared by loading aciclovir into the semisolid formulations consisting of medium chain length triglycerides (lipid), macrogolglycerol hydroxystearate (surfactant), polyglyceryl-3-dioleate (cosurfactant), glycerol (hydrophilic cosolvent), and macrogol 8000 (viscosity modifier). Their characterization was performed in order to identify the semisolid system with rheological behaviour suitable for filling in hard HPMC capsules and fast dispersibility in acidic and alkaline aqueous media with formation of oil-in-water microemulsions. The optimal SMEDDS was loaded with aciclovir at two levels (2% and 33.33%) and morphology and aqueous dispersibility of the obtained systems were examined by applying light microscopy and photon correlation spectroscopy (PCS), respectively. The assessment of diffusivity of aciclovir from the SMEDDSs by using an enhancer cell model, showed that it was increased at a higher drug loading. Differential scanning calorimetry (DSC) analysis indicated that the SMEDDSs were semisolids at temperatures up to 50°C and physically stable and compatible with HPMC capsules for 3 months storage at 25°C and 4°C. The results of in vitro release study revealed that the designed solid dosage form based on the semisolid SMEDDS loaded with the therapeutic dose of 200mg, may control partitioning of the solubilized drug from in situ formed oil-in-water microemulsion carrier into the sorrounding aqueous media, and hence decrease the risk for precipitation of the drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Beyond the rhetoric: what do we mean by a 'model of care'?

PubMed

Davidson, Patricia; Halcomb, Elizabeth; Hickman, L; Phillips, J; Graham, B

2006-01-01

Contemporary health care systems are constantly challenged to revise traditional methods of health care delivery. These challenges are multifaceted and stem from: (1) novel pharmacological and non-pharmacological treatments; (2) changes in consumer demands and expectations; (3) fiscal and resource constraints; (4) changes in societal demographics in particular the ageing of society; (5) an increasing burden of chronic disease; (6) documentation of limitations in traditional health care delivery; (7) increased emphasis on transparency, accountability, evidence-based practice (EBP) and clinical governance structures; and (8) the increasing cultural diversity of the community. These challenges provoke discussion of potential alternative models of care, with scant reference to defining what constitutes a model of care. This paper aims to define what is meant by the term 'model of care' and document the pragmatic systems and processes necessary to develop, plan, implement and evaluate novel models of care delivery. Searches of electronic databases, the reference lists of published materials, policy documents and the Internet were conducted using key words including 'model*', 'framework*', 'models, theoretical' and 'nursing models, theoretical'. The collated material was then analysed and synthesised into this review. This review determined that in addition to key conceptual and theoretical perspectives, quality improvement theory (eg. collaborative methodology), project management methods and change management theory inform both pragmatic and conceptual elements of a model of care. Crucial elements in changing health care delivery through the development of innovative models of care include the planning, development, implementation, evaluation and assessment of the sustainability of the new model. Regardless of whether change in health care delivery is attempted on a micro basis (eg. ward level) or macro basis (eg. national or state system) in order to achieve sustainable, effective and efficient changes a well-planned, systematic process is essential.

Novel drug delivery systems in pain therapy.

PubMed

Al Malyan, M; Becchi, C; Boncinelli, S; Ashammakhi, N

2007-03-01

Pain is an unpleasant sensory experience resulting from damage to bodily tissues. It is considered a significant public health problem because it affects 1/5 of the world population and causes loss of great amounts of money. Pain reflects a mixture of pathological, psychological and genetic conditions that need deep understanding to be efficiently treated. If under-treated, pain results in serious immune and metabolic problems. Pain management faces many problems that limit its control. For instance, efficiency of pain killers is limited, pain killers give rise to serious side effects and inability of drug administration methods to help in pain control. Technology can overcome some of these problems and the introduction of implantable controlled drug delivery systems (CDDS), manufactured from biodegradable materials, offers a solution. Implantable CDDS provide good level of pain control, as they continuously provide drug, reduce side effects and improve patients' compliance. Biodegradable type of implantable CDDS are polymer based devices that are fabricated to locally deliver drugs in a pre-designed manner. They are currently a focus of research in the field of pain therapy in order to explore their chance to offer an alternative to the conventional methods for drug delivery. This paper aims to highlight the dimensions of pain issue and to overview the basics of drug release from polymers used for CDDS in pain management. In addition, it discusses the recent advances in the technologically designed drug delivery systems in the field of pain medicine and their clinical applications. Future perspectives are also presented.

Buparvaquone Nanostructured Lipid Carrier: Development of an Affordable Delivery System for the Treatment of Leishmaniases

PubMed Central

Löbenberg, Raimar; Cotrim, Paulo Cesar

2017-01-01

Buparvaquone (BPQ), a veterinary drug, was formulated as nanostructured lipid carriers (NLC) for leishmaniases treatment. The formulation design addressed poor water solubility of BPQ and lack of human drug delivery system. The DSC/TG and microscopy methods were used for solid lipids screening. Softisan® 154 showed highest BPQ solubility in both methods. The BPQ solubility in liquid lipids using HPLC revealed Miglyol® 812 as the best option. Response surface methodology (RSM) was used to identify the optimal Softisan154 : Miglyol 812 ratios (7 : 10 to 2 : 1) and Kolliphor® P188 and Tween® 80 concentration (>3.0% w/w) aiming for z-average in the range of 100–300 nm for macrophage delivery. The NLC obtained by high-pressure homogenization showed low z-averages (<350 nm), polydispersity (<0.3), and encapsulation efficiency close to 100%. DSC/TG and microscopy in combination proved to be a powerful tool to select the solid lipid. The relationship among the variables, demonstrated by a linear mathematical model using RSM, allowed generating a design space. This design space showed the limits in which changes in the variables influenced the z-average. Therefore, these drug delivery systems have the potential to improve the availability of affordable medicines due to the low cost of raw materials, using well established, reliable, and feasible scale-up technology. PMID:28255558

EGFR targeted PLGA nanoparticles using gemcitabine for treatment of pancreatic cancer.

PubMed

Aggarwal, Sahil; Yadav, Sachin; Gupta, Swati

2011-02-01

The present study aimed to prepare and characterize anti EGFR monoclonal antibody (mab) conjugated Gemcitabine loaded PLGA nanoparticles for their selective delivery to pancreatic cells and evaluation of the systems in vitro. It was observed that direct covalent coupling of antibodies to glutaraldehyde activated nanoparticles is an appropriate method to achieve cell-type specific drug carrier systems based on polymeric nanoparticles that have potential to be applied for targeted chemotherapy in EGFR positive cancer.

Inkjet Printing of Proteins: an Experimental Approach.

PubMed

Montenegro-Nicolini, Miguel; Miranda, Víctor; Morales, Javier O

2017-01-01

Peptides and proteins represent a promissory group of molecules used by the pharmaceutical industry for drug therapy with great potential for development. However, the administration of these molecules presents a series of difficulties, making necessary the exploration of new alternatives like the buccal route of administration to improve drug therapy compliance. Although drop-on demand printers have been explored for small molecule drugs with promising results, the development of delivery systems for peptides and proteins through inkjet printing has seen little development. Therefore, the aim of this study was to assess the feasibility of using a thermal inkjet printing system for dispensing lysozyme and ribonuclease-A as model proteins. To address the absorption limitations of a potential buccal use, a permeation enhancer (sodium deoxycholate) was also studied in formulations. We found that a conventional printer successfully printed both proteins, exhibiting very high printing efficiency. Furthermore, the protein structure was not affected and minor effects were observed in the enzymatic activity after the printing process. In conclusion, we provide evidence for the usage of an inexpensive, easy to use, reliable, and reproducible thermal inkjet printing system to dispense proteins solutions for potential buccal application. Our research significantly contributes to present an alternative for manufacturing biologics delivery systems, with emphasis in buccal applications. Next steps of developments will be aimed at the use of new materials for printing, controlled release, and protection strategies for proteins and peptides.

Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

PubMed

Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

2017-12-01

Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer: an in vitro study.

PubMed

Song, Weixiang; Luo, Yindeng; Zhao, Yajing; Liu, Xinjie; Zhao, Jiannong; Luo, Jie; Zhang, Qunxia; Ran, Haitao; Wang, Zhigang; Guo, Dajing

2017-05-01

The aim of this study was to improve tumor-targeted therapy for breast cancer by designing magnetic nanobubbles with the potential for targeted drug delivery and multimodal imaging. Herceptin-decorated and ultrasmall superparamagnetic iron oxide (USPIO)/paclitaxel (PTX)-embedded nanobubbles (PTX-USPIO-HER-NBs) were manufactured by combining a modified double-emulsion evaporation process with carbodiimide technique. PTX-USPIO-HER-NBs were examined for characterization, specific cell-targeting ability and multimodal imaging. PTX-USPIO-HER-NBs exhibited excellent entrapment efficiency of Herceptin/PTX/USPIO and showed greater cytotoxic effects than other delivery platforms. Low-frequency ultrasound triggered accelerated PTX release. Moreover, the magnetic nanobubbles were able to enhance ultrasound, magnetic resonance and photoacoustics trimodal imaging. These results suggest that PTX-USPIO-HER-NBs have potential as a multimodal contrast agent and as a system for ultrasound-triggered drug release in breast cancer.

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.

MRI-Guided Focused Ultrasound as a New Method of Drug Delivery

PubMed Central

Thanou, M.; Gedroyc, W.

2013-01-01

Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery. PMID:23738076

Critical interactions between the Global Fund-supported HIV programs and the health system in Ghana.

PubMed

Atun, Rifat; Pothapregada, Sai Kumar; Kwansah, Janet; Degbotse, D; Lazarus, Jeffrey V

2011-08-01

The support of global health initiatives in recipient countries has been vigorously debated. Critics are concerned that disease-specific programs may be creating vertical and parallel service delivery structures that to some extent undermine health systems. This case study of Ghana aimed to explore how the Global Fund-supported HIV program interacts with the health system there and to map the extent and nature of integration of the national disease program across 6 key health systems functions. Qualitative interviews of national stakeholders were conducted to understand the perceptions of the strengths and weaknesses of the relationship between Global Fund-supported activities and the health system and to identify positive synergies and unintended consequences of integration. Ghana has a well-functioning sector-wide approach to financing its health system, with a strong emphasis on integrated care delivery. Ghana has benefited from US $175 million of approved Global Fund support to address the HIV epidemic, accounting for almost 85% of the National AIDS Control Program budget. Investments in infrastructure, human resources, and commodities have enabled HIV interventions to increase exponentially. Global Fund-supported activities have been well integrated into key health system functions to strengthen them, especially financing, planning, service delivery, and demand generation. Yet, with governance and monitoring and evaluation functions, parallel structures to national systems have emerged, leading to inefficiencies. This case study demonstrates that interactions and integration are highly varied across different health system functions, and strong government leadership has facilitated the integration of Global Fund-supported activities within national programs.

Nanoparticle-mediated siRNA delivery assessed in a 3D co-culture model simulating prostate cancer bone metastasis.

PubMed

Fitzgerald, Kathleen A; Guo, Jianfeng; Raftery, Rosanne M; Castaño, Irene Mencía; Curtin, Caroline M; Gooding, Matt; Darcy, Raphael; O' Brien, Fergal J; O' Driscoll, Caitriona M

2016-09-25

siRNA has emerged as a potential therapeutic for the treatment of prostate cancer but effective delivery remains a major barrier to its clinical application. This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-mediated siRNA delivery and gene knockdown. PC3 or LNCaP prostate cancer cells were co-cultured with hFOB 1.19 osteoblast cells in 2D on plastic tissue culture plates and in 3D on collagen scaffolds mimicking the bone microenvironment. To characterise the co-culture model, cell proliferation, enzyme secretion and the utility of two different gene delivery vectors to mediate siRNA uptake and gene knockdown were assessed. Cell proliferation was reduced by∼50% by day 7 in the co-culture system relative to monoculture (PC3 and LNCaP co-cultures, in 2D and 3D) and an enhanced level of MMP9 (a marker of bone metastasis) was secreted into the media (1.2-4-fold increase depending on the co-culture system). A cationic cyclodextrin gene delivery vector proved significantly less toxic in the co-culture system relative to the commercially available vector Lipofectamine 2000(®). In addition, knockdown of both the GAPDH gene (minimum 15%) and RelA subunit of the NF-κB transcription factor (minimum 20%) was achieved in 2D and 3D cell co-cultures. Results indicate that the prostate cancer-osteoblast in vitro co-culture model was more physiologically relevant vs the monoculture. This model has the potential to help improve the design and efficacy of gene delivery formulations, to more accurately predict in vivo performance and, therefore, to reduce the risk of product failure in late-stage clinical development. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy

PubMed Central

Suñé-Pou, Marc; Prieto-Sánchez, Silvia; El Yousfi, Younes; Boyero-Corral, Sofía; Nardi-Ricart, Anna; Nofrerias-Roig, Isaac; Pérez-Lozano, Pilar; García-Montoya, Encarna; Miñarro-Carmona, Montserrat; Ticó, Josep Ramón; Suñé-Negre, Josep Mª; Hernández-Munain, Cristina; Suñé, Carlos

2018-01-01

Background Cationic solid lipid nanoparticles (SLNs) have been given considerable attention for therapeutic nucleic acid delivery owing to their advantages over viral and other nanoparticle delivery systems. However, poor delivery efficiency and complex formulations hinder the clinical translation of SLNs. Aim The aim of this study was to formulate and characterize SLNs incorporating the cholesterol derivative cholesteryl oleate to produce SLN–nucleic acid complexes with reduced cytotoxicity and more efficient cellular uptake. Methods Five cholesteryl oleate-containing formulations were prepared. Laser diffraction and laser Doppler microelectrophoresis were used to evaluate particle size and zeta potential, respectively. Nanoparticle morphology was analyzed using electron microscopy. Cytotoxicity and cellular uptake of lipoplexes were evaluated using flow cytometry and fluorescence microscopy. The gene inhibition capacity of the lipoplexes was assessed using siRNAs to block constitutive luciferase expression. Results We obtained nanoparticles with a mean diameter of approximately 150–200 nm in size and zeta potential values of 25–40 mV. SLN formulations with intermediate concentrations of cholesteryl oleate exhibited good stability and spherical structures with no aggregation. No cell toxicity of any reference SLN was observed. Finally, cellular uptake experiments with DNA-and RNA-SLNs were performed to select one reference with superior transient transfection efficiency that significantly decreased gene activity upon siRNA complexation. Conclusion The results indicate that cholesteryl oleate-loaded SLNs are a safe and effective platform for nonviral nucleic acid delivery. PMID:29881274

Advanced Materials and Processing for Drug Delivery: The Past and the Future

PubMed Central

Zhang, Ying; Chan, Hon Fai; Leong, Kam W.

2012-01-01

Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. PMID:23088863

Interventions to Improve the Response of Professionals to Children Exposed to Domestic Violence and Abuse: A Systematic Review.

PubMed

Turner, William; Hester, Marianne; Broad, Jonathan; Szilassy, Eszter; Feder, Gene; Drinkwater, Jessica; Firth, Adam; Stanley, Nicky

2017-01-01

Exposure of children to domestic violence and abuse (DVA) is a form of child maltreatment with short- and long-term behavioural and mental health impact. Health care professionals are generally uncertain about how to respond to domestic violence and are particularly unclear about best practice with regards to children's exposure and their role in a multiagency response. In this systematic review, we report educational and structural or whole-system interventions that aim to improve professionals' understanding of, and response to, DVA survivors and their children. We searched 22 bibliographic databases and contacted topic experts for studies reporting quantitative outcomes for any type of intervention aiming to improve professional responses to disclosure of DVA with child involvement. We included interventions for physicians, nurses, social workers and teachers. Twenty-one studies met the inclusion criteria: three randomised controlled trials (RCTs), 18 pre-post intervention surveys. There were 18 training and three system-level interventions. Training interventions generally had positive effects on participants' knowledge, attitudes towards DVA and clinical competence. The results from the RCTs were consistent with the before-after surveys. Results from system-level interventions aimed to change organisational practice and inter-organisational collaboration demonstrates the benefit of coordinating system change in child welfare agencies with primary health care and other organisations. Implications for policy and research are discussed. © 2015 The Authors. Child Abuse Review published by John Wiley & Sons Ltd. 'We searched 22 bibliographic databases and contacted topic experts'. We reviewed published evidence on interventions aimed at improving professionals' practice with domestic violence survivors and their children.Training programmes were found to improve participants' knowledge, attitudes and clinical competence up to a year after delivery.Key elements of successful training include interactive discussion, booster sessions and involving specialist domestic violence practitioners.Whole-system approaches aiming to promote coordination and collaboration across agencies appear promising but require funding and high levels of commitment from partners. 'Training programmes were found to improve participants' knowledge, attitudes and clinical competence up to a year after delivery'.

[Characterization of access to normal childbirth care in Bahia State, Brazil, based on graph theory].

PubMed

Sousa, Ludmilla Monfort Oliveira; Araújo, Edna Maria de; Miranda, José Garcia Vivas

2017-12-18

Origin-destination flow is a phenomenon that can be modeled as a network. Graph theory is a mathematical tool to characterize a network and thus allows studying the topological properties and temporal and spatial development of a set of related elements. The article aims to estimate the topological evolution of an inter-municipal network of normal deliveries. We selected the admissions for normal deliveries in the Hospital Information System of the Brazilian Unified National Health System, from 2008 to 2014, for women residing in Bahia State, Brazil. The following indices were applied: entry degree (from how many municipalities the women came for childbirth), exit degree (to how many municipalities they left), entry flow (how many women came), exit flow (how many women left), and the mean size of the exit edge (distance traveled). Analyses between macro-regions used the following indicators: proportion of normal deliveries performed outside the municipality of residence and mean size of the exit edge. The results indicate an increase in deliveries performed outside the municipality of residence, in addition to the persistence of concentration of deliveries in the hub municipalities in the Health Regions, and an increase in the distance between the municipality of residence and the municipality where the delivery took place. The organization of networks for normal childbirth poses an on-going challenge. It is important to analyze the flow of women for childbirth care in order to support the establishment of inter-municipal references to guarantee safe labor and childbirth. In conclusion, it is necessary to develop a regionalized network to meet the demand by pregnant women in the territory with universal and equitable coverage.

Combination lung cancer chemotherapy: Design of a pH-sensitive transferrin-PEG-Hz-lipid conjugate for the co-delivery of docetaxel and baicalin.

PubMed

Li, Shuang; Wang, Lin; Li, Na; Liu, Yucai; Su, Hui

2017-11-01

The aim of the present study is to design a novel dual-ligand lipid based nanoparticle system. It is conducted by a specific ligand and pH sensitive lipid conjugate. Docetaxel (DTX) and baicalein (BA) are co-delivered by this system for combination lung cancer chemotherapy. Firstly, transferrin (Tf)-polyethylene glycol (PEG)-hydrazone (hz)-glyceryl monostearate (GMS), Tf-PEG-hz-GMS, was synthesized. Tf decorated DTX and BA loaded solid lipid nanoparticles (Tf-D/B-SLNs) were prepared by emulsification method. The capability of Tf-D/B-SLNs in suppressing lung cancer cells in vitro and in vivo was investigated. The results revealed the better antitumor efficiency of Tf-D/B-SLNs than the non-decorated SLNs and single drug loaded SLNs. Significant synergistic effects were observed in the dual drugs loaded systems. The best tumor inhibition ability and the lowest systemic toxicity also proved the pH-sensitive co-delivery nano-system could be a promising strategy for treatment of lung cancer. Copyright © 2017. Published by Elsevier Masson SAS.

Nanotechnology based approaches for anti-diabetic drugs delivery.

PubMed

Kesharwani, Prashant; Gorain, Bapi; Low, Siew Yeng; Tan, Siew Ann; Ling, Emily Chai Siaw; Lim, Yin Khai; Chin, Chuan Ming; Lee, Pei Yee; Lee, Chun Mey; Ooi, Chun Haw; Choudhury, Hira; Pandey, Manisha

2018-02-01

Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management. Copyright © 2017 Elsevier B.V. All rights reserved.

School-based service delivery for homeless students: relevant laws and overcoming access barriers.

PubMed

Sulkowski, Michael L; Joyce-Beaulieu, Diana K

2014-11-01

Schools in the United States are facing a record number of homeless students. These students are highly at-risk for experiencing negative life outcomes, and they face considerable academic and social-emotional functional impairments. To help address the complex needs of homeless students, this article reviews the intersection of laws and practices that impact homeless students, as well as contemporary school-based service delivery efforts to support the academic and social-emotional needs of these students. In addition, this article also reviews several barriers to school-based service delivery for homeless students and ways to overcome these barriers. These barriers include confusion regarding consent and record-sharing procedures, ineffectively utilizing homeless liaisons, and misapplying tenants of Multitiered Systems of Support (MTSS), which is a school-based service-delivery framework that has been adopted by and implemented in many U.S. schools. Ultimately, this article aims to provide members of school communities with practical information that they can use to support the homeless youth they encounter and serve. (c) 2014 APA, all rights reserved.

Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery

NASA Astrophysics Data System (ADS)

Mody, Karishma T.; Popat, Amirali; Mahony, Donna; Cavallaro, Antonino S.; Yu, Chengzhong; Mitter, Neena

2013-05-01

Vaccines have been at the forefront of improving human health for over two centuries. The challenges faced in developing effective vaccines flow from complexities associated with the immune system and requirement of an efficient and safe adjuvant to induce a strong adaptive immune response. Development of an efficient vaccine formulation requires careful selection of a potent antigen, efficient adjuvant and route of delivery. Adjuvants are immunological agents that activate the antigen presenting cells (APCs) and elicit a strong immune response. In the past decade, the use of mesoporous silica nanoparticles (MSNs) has gained significant attention as potential delivery vehicles for various biomolecules. In this review, we aim to highlight the potential of MSNs as vaccine delivery vehicles and their ability to act as adjuvants. We have provided an overview on the latest progress on synthesis, adsorption and release kinetics and biocompatibility of MSNs as next generation antigen carriers and adjuvants. A comprehensive summary on the ability of MSNs to deliver antigens and elicit both humoral and cellular immune responses is provided. Finally, we give insight on fundamental challenges and some future prospects of these nanoparticles as adjuvants.

SU-F-T-471: Simulated External Beam Delivery Errors Detection with a Large Area Ion Chamber Transmission Detector

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

Hoffman, D; Dyer, B; Kumaran Nair, C

Purpose: The Integral Quality Monitor (IQM), developed by iRT Systems GmbH (Koblenz, Germany) is a large-area, linac-mounted ion chamber used to monitor photon fluence during patient treatment. Our previous work evaluated the change of the ion chamber’s response to deviations from static 1×1 cm2 and 10×10 cm2 photon beams and other characteristics integral to use in external beam detection. The aim of this work is to simulate two external beam radiation delivery errors, quantify the detection of simulated errors and evaluate the reduction in patient harm resulting from detection. Methods: Two well documented radiation oncology delivery errors were selected formore » simulation. The first error was recreated by modifying a wedged whole breast treatment, removing the physical wedge and calculating the planned dose with Pinnacle TPS (Philips Radiation Oncology Systems, Fitchburg, WI). The second error was recreated by modifying a static-gantry IMRT pharyngeal tonsil plan to be delivered in 3 unmodulated fractions. A radiation oncologist evaluated the dose for simulated errors and predicted morbidity and mortality commiserate with the original reported toxicity, indicating that reported errors were approximately simulated. The ion chamber signal of unmodified treatments was compared to the simulated error signal and evaluated in Pinnacle TPS again with radiation oncologist prediction of simulated patient harm. Results: Previous work established that transmission detector system measurements are stable within 0.5% standard deviation (SD). Errors causing signal change greater than 20 SD (10%) were considered detected. The whole breast and pharyngeal tonsil IMRT simulated error increased signal by 215% and 969%, respectively, indicating error detection after the first fraction and IMRT segment, respectively. Conclusion: The transmission detector system demonstrated utility in detecting clinically significant errors and reducing patient toxicity/harm in simulated external beam delivery. Future work will evaluate detection of other smaller magnitude delivery errors.« less

Studies on self-nanoemulsifying drug delivery system of flurbiprofen employing long, medium and short chain triglycerides.

PubMed

Daar, Junaid; Khan, Ahmad; Khan, Jallat; Khan, Amjad; Khan, Gul Majid

2017-03-01

The aim of the study was to successfully design, formulate and evaluate self-nanoemulsifying drug delivery system (SNEDDS) of poorly aqueous soluble drug viz. flurbiprofen using long (LCT), medium (MCT) and short chain triglycerides (SCT). The SNEDDS are thermodynamically stable lipid based drug delivery systems which consist of mixture of oil, surfactant and co-surfactant. Upon aqueous dilution, this mixture produces nano-emulsion spontaneously on slight agitation. The excipients intended to be used were screened for their potential to dissolve the drug and to form clear dispersion upon aqueous dilution. Labrafil M 1944 CS, capryol-90 and triacetin were selected as long, medium and short chain triglycerides, respectively, as lipids while tween-80 and polyethylene glycol-400 (PEG-400)/ethanol (3:1 ratio) were selected as surfactant and co-surfactant, respectively. The excipients were studied at every possible combination ratios using pseudo-ternary diagram. The LCT, MCT and SCT-SNEDDS were optimized using thermodynamic studies, percentage transmittance value, viscosity, refractive index (RI), electrical conductivity, globule size analysis and in-vitro drug release studies. The drug release profiles of optimized SNEDDS were then compared with market product at different pH mediums. The LCT-SNEDDS was considered to be superior for enhancement of the drug bioavailability when compared with other SNEDDS formulations and market product.

Design and evaluation of self-nanoemulsifying pellets of repaglinide.

PubMed

Desai, N S; Nagarsenker, M S

2013-09-01

The aim of study was to develop self-nanoemulsifying pellets (SNEP) for oral delivery of poorly water soluble drug, repaglinide (RPG). Solubility of RPG in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). The surfactants and cosurfactants were screened for their ability to emulsify oily phase. Ternary phase diagrams were constructed to identify nanoemulsification area for the selected systems. SNEDDS formulations with globule size less than 100 nm were evaluated for in vivo anti-hyperglycemic activity in neonatal streptozotocin rat model. A significant reduction in glucose levels was produced by optimized SNEDDS formulation in comparison to the control group. The optimized SNEDDS formulations were pelletized via extrusion/spheronization technique using microcrystalline cellulose and lactose. SNEP were characterized by X-ray powder diffraction and scanning electron microscopy. X-ray diffraction study indicated loss of crystallinity of RPG in SNEP. The SNEP exhibited good flow properties, mechanical strength and formed nanoemulsion with globule size less than 200 nm. SNEP showed in vitro release of more than 80% RPG in 10 min which was significantly higher than RPG containing reference pellets. In conclusion, our studies illustrated that RPG, a poorly water soluble drug can be successfully formulated into SNEP which can serve as a promising system for the delivery of poorly water soluble drugs.

Near-Infrared Imaging Method for the In Vivo Assessment of the Biodistribution of Nanoporous Silicon Particles

PubMed Central

Tasciotti, Ennio; Godin, Biana; Martinez, Jonathan O.; Chiappini, Ciro; Bhavane, Rohan; Liu, Xuewu; Ferrari, Mauro

2011-01-01

In the development of new nanoparticle-based technologies for therapeutic and diagnostic purposes, understanding the fate of nanoparticles in the body is crucial. We recently developed a multistage vector delivery system comprising biodegradable and biocompatible nanoporous silicon particles (first-stage microparticles [S1MPs]) able to host, protect, and deliver second-stage therapeutic and diagnostic nanoparticles (S2NPs) on intravenous injection. This delivery system aims at sequentially overcoming the biologic barriers en route to the target delivery site by separating and assigning tasks to the coordinated logic-embedded vectors constituting it. In this work, by conjugating a near-infrared dye on the surface of the S1MP without compromising the porous structure and potential loading of S2NPs, we were able to monitor the in vivo distribution of S1MPs in healthy mice using an optical imaging system. It was observed that particles predominantly accumulated in the liver and spleen at the end of 24 hours. Further quantification of S1MPs in the major organs of the animals by elemental analysis of silicon using inductively coupled plasma-atomic electron spectroscopy verified the accuracy of in vivo near-infrared imaging as a tool for evaluation of nanovector biodistribution. PMID:21303615

Acute and Subchronic Toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from Chloroform Bay Leaf Extract (Eugenia Polyantha W.) with Palm Kernel Oil as A Carrier

NASA Astrophysics Data System (ADS)

Prihapsara, F.; Mufidah; Artanti, A. N.; Harini, M.

2018-03-01

The present study was aimed to study the acute and subchronic toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with Palm Kernel Oil as carrier. In acute toxicity test, five groups of rat (n=5/groups) were orally treated with Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with doses at 48, 240, 1200 and 6000 mg/kg/day respectively, then the median lethal dose LD50, advers effect and mortality were recorded up to 14 days. Meanwhile, in subchronic toxicity study, 4 groups of rats (n=6/group) received by orally treatment of SNEDDS from chloroform bay leaf extract with doses at 91.75; 183.5; 367 mg/kg/day respectively for 28 days, and biochemical, hematological and histopatological change in tissue such as liver, kidney, and pancreatic were determined. The result show that LD50 is 1045.44 mg/kg. Although histopathological examination of most of the organs exhibited no structural changes, some moderate damage was observed in high‑ dose group animals (367 mg/kg/day). The high dose of SNEDDS extract has shown mild signs of toxicity on organ function test.

Effect of ultra-high pressure homogenization on the interaction between bovine casein micelles and ritonavir.

PubMed

Corzo-Martínez, M; Mohan, M; Dunlap, J; Harte, F

2015-03-01

The aim of this work was to develop a milk-based powder formulation appropriate for pediatric delivery of ritonavir (RIT). Ultra-high pressure homogenization (UHPH) at 0.1, 300 and 500 MPa was used to process a dispersion of pasteurized skim milk (SM) and ritonavir. Loading efficiency was determined by RP-HPLC-UV; characterization of RIT:SM systems was carried out by apparent average hydrodynamic diameter and rheological measurements as well as different analytical techniques including Trp fluorescence, UV spectroscopy, DSC, FTIR and SEM; and delivery capacity of casein micelles was determined by in vitro experiments promoting ritonavir release. Ritonavir interacted efficiently with milk proteins, especially, casein micelles, regardless of the processing pressure; however, results suggest that, at 0.1 MPa, ritonavir interacts with caseins at the micellar surface, whilst, at 300 and 500 MPa, ritonavir is integrated to the protein matrix during UHPH treatment. Likewise, in vitro experiments showed that ritonavir release from micellar casein systems is pH dependent; with a high retention of ritonavir during simulated gastric digestion and a rapid delivery under conditions simulating the small intestine environment. Skim milk powder, especially, casein micelles are potentially suitable and efficient carrier systems to develop novel milk-based and low-ethanol powder formulations of ritonavir appropriate for pediatric applications.

Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.

PubMed

Del Río-Sancho, S; Serna-Jiménez, C E; Sebastián-Morelló, M; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; Kalia, Y N; Merino, V; López-Castellano, A

2017-01-30

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81μgcm -2 h -1 whereas the highest iontophoretic transport was 46.4±3.6μgcm -2 h -1 . These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Continuing Professional Education Delivery Systems.

ERIC Educational Resources Information Center

Weeks, James P.

This investigation of delivery systems for continuing professional education provides an overview of current operational delivery systems in continuing professional education, drawing on experience as found in the literature. Learning theories and conclusions are woven into the descriptive text. Delivery systems profiled in the paper include the…

Nanoparticles for bone tissue engineering.

PubMed

Vieira, Sílvia; Vial, Stephanie; Reis, Rui L; Oliveira, J Miguel

2017-05-01

Tissue engineering (TE) envisions the creation of functional substitutes for damaged tissues through integrated solutions, where medical, biological, and engineering principles are combined. Bone regeneration is one of the areas in which designing a model that mimics all tissue properties is still a challenge. The hierarchical structure and high vascularization of bone hampers a TE approach, especially in large bone defects. Nanotechnology can open up a new era for TE, allowing the creation of nanostructures that are comparable in size to those appearing in natural bone. Therefore, nanoengineered systems are now able to more closely mimic the structures observed in naturally occurring systems, and it is also possible to combine several approaches - such as drug delivery and cell labeling - within a single system. This review aims to cover the most recent developments on the use of different nanoparticles for bone TE, with emphasis on their application for scaffolds improvement; drug and gene delivery carriers, and labeling techniques. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:590-611, 2017. © 2017 American Institute of Chemical Engineers.

Comparative health systems research among Kaiser Permanente and other integrated delivery systems: a systematic literature review.

PubMed

Maeda, Jared Lane K; Lee, Karen M; Horberg, Michael

2014-01-01

Because of rising health care costs, wide variations in quality, and increased patient complexity, the US health care system is undergoing rapid changes that include payment reform and movement toward integrated delivery systems. Well-established integrated delivery systems, such as Kaiser Permanente (KP), should work to identify the specific system-level factors that result in superior patient outcomes in response to policymakers' concerns. Comparative health systems research can provide insights into which particular aspects of the integrated delivery system result in improved care delivery. To provide a baseline understanding of comparative health systems research related to integrated delivery systems and KP. Systematic literature review. We conducted a literature search on PubMed and the KP Publications Library. Studies that compared KP as a system or organization with other health care systems or across KP facilities internally were included. The literature search identified 1605 articles, of which 65 met the study inclusion criteria and were examined by 3 reviewers. Most comparative health systems studies focused on intra-KP comparisons (n = 42). Fewer studies compared KP with other US (n = 15) or international (n = 12) health care systems. Several themes emerged from the literature as possible factors that may contribute to improved care delivery in integrated delivery systems. Of all studies published by or about KP, only a small proportion of articles (4%) was identified as being comparative health systems research. Additional empirical studies that compare the specific factors of the integrated delivery system model with other systems of care are needed to better understand the "system-level" factors that result in improved and/or diminished care delivery.

Communications data delivery system analysis task 2 report : high-level options for secure communications data delivery systems.

DOT National Transportation Integrated Search

2012-05-16

This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...

Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation

PubMed Central

Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Wu, Wei

2011-01-01

Background: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery. Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH. Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and α-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate. Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally. PMID:21822379

Design and evaluation of an intravesical delivery system for superficial bladder cancer: preparation of gemcitabine HCl-loaded chitosan–thioglycolic acid nanoparticles and comparison of chitosan/poloxamer gels as carriers

PubMed Central

Ay Şenyiğit, Zeynep; Karavana, Sinem Yaprak; İlem-Özdemir, Derya; Çalışkan, Çağrı; Waldner, Claudia; Şen, Sait; Bernkop-Schnürch, Andreas; Baloğlu, Esra

2015-01-01

This study aimed to develop an intravesical delivery system of gemcitabine HCl for superficial bladder cancer in order to provide a controlled release profile, to prolong the residence time, and to avoid drug elimination via urination. For this aim, bioadhesive nanoparticles were prepared with thiolated chitosan (chitosan–thioglycolic acid conjugate) and were dispersed in bioadhesive chitosan gel or in an in situ gelling poloxamer formulation in order to improve intravesical residence time. In addition, nanoparticle-loaded gels were diluted with artificial urine to mimic in vivo conditions in the bladder and were characterized regarding changes in gel structure. The obtained results showed that chitosanthioglycolic acid nanoparticles with a mean diameter of 174.5±3.762 nm and zeta potential of 32.100±0.575 mV were successfully developed via ionotropic gelation and that the encapsulation efficiency of gemcitabine HCl was nearly 20%. In vitro/ex vivo characterization studies demonstrated that both nanoparticles and nanoparticle-loaded chitosan and poloxamer gels might be alternative carriers for intravesical administration of gemcitabine HCl, prolonging its residence time in the bladder and hence improving treatment efficacy. However, when the gel formulations were diluted with artificial urine, poloxamer gels lost their in situ gelling properties at body temperature, which is in conflict with the aimed formulation property. Therefore, 2% chitosan gel formulation was found to be a more promising carrier system for intravesical administration of nanoparticles. PMID:26508855

Drug delivery systems with modified release for systemic and biophase bioavailability.

PubMed

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

The state of medical informatics in India: a roadmap for optimal organization.

PubMed

Sarbadhikari, Suptendra Nath

2005-04-01

In India, the healthcare delivery systems are based on manual record keeping despite a good telecommunication infrastructure. Unfortunately, Indian policy makers are yet to realize the importance of medical informatics (including tele-health, which comprises e-Health and Telemedicine) in delivering healthcare. In the medical curriculum also, nowhere is this treated as a subject or even as a tool for learning. The final aim of most of the medical and paramedical students should be to become good users, and if possible, also experts for advancing medical knowledge base through medical informatics. In view of the fast changing world of medical informatics, it is essential to formulate a flexible syllabus rather than a rigid one for incorporating into the regular curriculum of medical and paramedical education. Only after that one may expect all members of the healthcare delivery systems to adopt and apply medical informatics optimally as a routine tool for their services.

Telemedicine in the Malaysian Multimedia Super Corridor: towards personalized lifetime health plans.

PubMed

Abidi, S S; Yusoff, Z

1999-01-01

The Malaysian Telemedicine initiative advocates a paradigm shift in healthcare delivery patterns by way of implementing a person-centred and wellness-focused healthcare system. This paper introduces the Malaysian Telemedicine vision, its functionality and associated operational conditions. In particular, we focus on the conceptualisation of one key Telemedicine component i.e. the Lifetime Health Plan (LHP) system--a distributed multimodule application for the periodic monitoring and generation of health-care advisories for all Malaysians. In line with the LHP project, we present an innovative healthcare delivery info-structure--LifePlan--that aims to provide life-long, pro-active, personalised, wellness-oriented healthcare services to assist individuals to manage and interpret their health needs. Functionally, LifePlan based healthcare services are delivered over the WWW, packaged as Personalised Lifetime Health Plans that allow individuals to both monitor their health status and to guide them in healthcare planning.

Development of bupivacaine decorated reduced graphene oxide and its local anesthetic effect-In vivo study.

PubMed

Zhang, Zhi; Zhang, Xin; Li, Aixiang; Ma, Chuangen

2018-03-01

The present works aims to develop bupivacaine modified reduced graphene oxide (BPV/RGO), and comparative evaluation of their anesthetic effect with free bupivacaine (BPV). The prepared BPV/RGO was studied by using various spectroscopic and microscopic characterization studies. In vitro drug release from BPV/RGO was studied using HPLC analysis. The cytotoxicity of BPV/RGO was studied against fibroblast (3T3) cells. In vivo evaluation of anesthetic effects was performed on animal models. BPV/RGO showed a prolonged in vitro release and lower cytotoxicity when compared to free BPV. Also, BPV/RGO showed a significantly prolonged analgesic effect when compared to free BPV. Further, the prepared BPV/RGO drug delivery system demonstrated to function as gifted to overcome the drawbacks of free BPV and other available drug delivery systems by prolonging the anesthetic effect with poor cytotoxicity. Copyright © 2018. Published by Elsevier B.V.

Sucrose esters as natural surfactants in drug delivery systems--a mini-review.

PubMed

Szűts, Angéla; Szabó-Révész, Piroska

2012-08-20

Sucrose esters (SEs) are widely used in the food and cosmetic industries and there has recently been great interest in their applicability in different pharmaceutical fields. They are natural and biodegradable excipients with well-known emulsifying and solubilizing behavior. Currently the most common pharmaceutical applications of SEs are for the enhancement of drug dissolution and drug absorption/permeation, and in controlled-release systems. Although the number of articles on SEs is continuously increasing, they have not yet been widely used in the pharmaceutical industry. The aim of this review is to discuss and summarize some of the findings and applications of SEs in different areas of drug delivery. The article highlights the main properties of SEs and focuses on their use in pharmaceutical technology and on their regulatory and toxicological status. Copyright © 2012 Elsevier B.V. All rights reserved.

Perinatal outcomes of singleton term breech deliveries in Basra.

PubMed

Alshaheen, H; Abd Al-Karim, A

2010-01-01

This study aimed to assess the perinatal morbidity and mortality in breech deliveries, to study the correlation of parity and birth weight with perinatal mortality by mode of delivery. Of 210 women in labour in Basra maternity and child hospital, 97 underwent vaginal breech deliveries and 113 delivered by caesarean section. Birth trauma was restricted to vaginal deliveries. The perinatal mortality was significantly higher in vaginal deliveries (8.2%) compared with caesarean deliveries (0.9%). A higher perinatal mortality was recorded among infants > 3500-4000 g birth weight in vaginal deliveries. Caesarean section reduced the perinatal mortality in both nulliparous and parous women in term breech infants.

Nanostructured porous silicon-mediated drug delivery.

PubMed

Martín-Palma, Raúl J; Hernández-Montelongo, Jacobo; Torres-Costa, Vicente; Manso-Silván, Miguel; Muñoz-Noval, Álvaro

2014-08-01

The particular properties of nanostructured porous silicon (nanoPS) make it an attractive material for controlled and localized release of therapeutics within the body, aiming at increased efficacy and reduced risks of potential side effects. Since this is a rapidly evolving field as a consequence of the number of research groups involved, a critical review of the state of the art is necessary. In this work, the most promising and successful applications of nanoPS in the field of drug delivery are reviewed and discussed. Two key issues such as drug loading and release are also analyzed in detail. The development of multifunctional (hybrid) systems, aiming at imparting additional functionalities to the nanoPS particles such as luminescence, magnetic response and/or plasmonic effects (allowing simultaneous tracking and guiding), is also examined. Nanostructured materials based on silicon are promising platforms for pharmaceutical applications given their ability to degrade and low toxicity. However, a very limited number of clinical applications have been demonstrated so far.

Challenges in immunisation service delivery for refugees in Australia: A health system perspective.

PubMed

Mahimbo, A; Seale, H; Smith, M; Heywood, A

2017-09-12

Refugees are at risk of being under-immunised in their countries of origin, in transit and post-resettlement in Australia. Whilst studies have focused on identifying barriers to accessibility of health services among refugees, few focus on providers' perspectives on immunisation service delivery to this group. Health service providers are well placed to provide insights into the pragmatic challenges associated with refugee health service delivery, which can be useful in identifying strategies aimed at improving immunisation coverage among this group. A qualitative study involving 30 semi-structured interviews was undertaken with key stakeholders in immunisation service delivery across all States and Territories in Australia between December 2014 and December 2015. Thematic analysis was undertaken. Variability in accessing program funding and vaccines, lack of a national policy for catch-up vaccination, unclear roles and responsibilities for catch-up, a lack of a central immunisation register and insufficient training among general practitioners were seen as the main challenges impacting on immunisation service delivery for refugees. This study provides insight into the challenges that impact on effective immunisation service delivery for refugees. Deliberate strategies such as national funding for relevant vaccines, improved data collection nationally and increased guidance for general practitioners on catch-up immunisation for refugees would help to ensure equitable access across all age groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Thiolated chitosans: design and in vivo evaluation of a mucoadhesive buccal peptide drug delivery system.

PubMed

Langoth, Nina; Kahlbacher, Hermann; Schöffmann, Gudrun; Schmerold, Ivo; Schuh, Maximilian; Franz, Sonja; Kurka, Peter; Bernkop-Schnürch, Andreas

2006-03-01

Intravenous application of pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified as a promising strategy for the treatment of type 2 diabetes. To generate a more applicable formulation, it was the aim of this study to develop a sustained buccal delivery system for this promising therapeutic peptide. 2-Iminothiolane was covalently bound to chitosan to improve the mucoadhesive and permeation-enhancing properties of chitosan used as drug carrier matrix. The resulting chitosan-4-thiobutylamidine conjugate was homogenized with the enzyme inhibitor and permeation mediator glutathione (gamma-Glu-Cys-Gly), Brij 35, and PACAP (formulation A). The mixture was lyophilized and compressed into flat-faced discs (18 mm in diameter). One formulation was additionally coated on one side with palm wax (formulation B). Tablets consisting of unmodified chitosan and PACAP (formulation C) or of unmodified chitosan, Brij 35, and PACAP (formulation D) served as controls. Bioavailability studies were performed in pigs by buccal administration of these test formulations. Blood samples were analyzed via an ELISA method. Formulations A and B led to an absolute bioavailability of 1%, whereas PACAP did not reach the systemic circulation when administered via formulations C and D. Moreover, in the case of formulations A and B, a continuously raised plasma level of the peptide drug being in the therapeutic range could be maintained over the whole period of application (6 h). Formulations A and B were removed by moderate force from the buccal mucosa after 6 h, whereas formulations C and D detached from the mucosa 4 h after application. The study reveals this novel mucoadhesive delivery system to be a promising approach for buccal delivery of PACAP.

Silica encapsulated lipid-based drug delivery systems for reducing the fed/fasted variations of ziprasidone in vitro.

PubMed

Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

2016-04-01

Ziprasidone is a poorly water-soluble antipsychotic drug that demonstrates low fasted state oral bioavailability and a clinically significant two-fold increase in absorption when dosed postprandially. Owing to significant compliance challenges faced by schizophrenic patients, a novel oral formulation of ziprasidone that demonstrates improved fasted state absorption and a reduced food effect is of major interest, and is therefore the aim of this research. Three lipid-based drug delivery systems (LBDDS) were developed and investigated: (a) a self-nanoemulsifying drug delivery system (SNEDDS), (b) a solid SNEDDS formulation, and (c) silica-lipid hybrid (SLH) microparticles. SNEDDS was developed using Capmul MCM® and Tween 80®, and solid SNEDDS was fabricated by spray-drying SNEDDS with Aerosil 380® silica nanoparticles as the solid carrier. SLH microparticles were prepared in a similar manner to solid SNEDDS using a precursor lipid emulsion composed of Capmul MCM® and soybean lecithin. The performance of the developed formulations was evaluated under simulated digesting conditions using an in vitro lipolysis model, and pure (unformulated) ziprasidone was used as a control. While pure ziprasidone exhibited the lowest rate and extent of drug solubilization under fasting conditions and a significant 2.4-fold increase in drug solubilization under fed conditions, all three LBDDS significantly enhanced the extent of drug solubilization under fasting conditions between 18- and 43-folds in comparison to pure drug. No significant difference in drug solubilization for the fed and fasted states was observed for the three LBDDS systems. To highlight the potential of LBDDS, mechanism(s) of action and various performance characteristics are discussed. Importantly, LBDDS are identified as an appropriate formulation strategy to explore further for the improved oral delivery of ziprasidone. Copyright © 2016 Elsevier B.V. All rights reserved.

Oxygen delivery during cardiopulmonary bypass (and renal outcome) using two systems of extracorporeal circulation: a retrospective review.

PubMed

Bennett, Mark J; Rajakaruna, Cha; Bazerbashi, Samer; Webb, Gerry; Gomez-Cano, Mayam; Lloyd, Clinton

2013-06-01

To investigate the combined influence of blood flow and haemodilution with either a miniaturized (Mini-CPB) or a conventional cardiopulmonary bypass (C-CPB) circuit on average oxygen delivery during bypass. The influence of this on clinical outcome, particularly renal dysfunction after routine coronary artery bypass surgery (CABG), was measured. Retrospective analysis in two groups of 160 patients based on the surgeon's preference for bypass circuit. We compared consecutive patients undergoing isolated CABG surgery by two surgeons using Mini-CPB with a matched cohort of patients, from the same period, undergoing isolated CABG surgery by four other surgeons using a C-CPB. No trial-related intervention occurred. Data on bypass circuit parameters and clinical outcomes were acquired from routinely collected data sources. Average cardiopulmonary bypass pump flow was significantly lower with Mini-CPB compared with C-CPB. Mini-CPB resulted in significantly less haemodilution. The resultant calculated average oxygen delivery provided by the two systems was the same. Percentage change in plasma creatinine was significantly and inversely related to the oxygen delivery during CPB. There was no difference in percentage change in plasma creatinine between groups. The risk of having Acute Kidney Injury Network (AKIN) score ≥ 1 increased 1% for every 1 ml min(-1) m(-2) decrease in oxygen delivery (P = 0.0001, OR 0.990, 95% CI 0.984-0.995). Despite aiming for the same target pump flow, periodic limitations of venous return to the pump resulted in a significant reduction in average flow delivered to the patient by Mini-CPB. Less haemodilution compensated for this reduction, so that the average oxygen delivery was the same. The association between oxygen delivery and postoperative change in plasma creatinine was evident in both groups. Further work to understand whether there is a particular cohort of patients who benefit (or are put at risk) by one method of CPB vs the other is warranted.

Statistical quality control for volumetric modulated arc therapy (VMAT) delivery by using the machine's log data

NASA Astrophysics Data System (ADS)

Cheong, Kwang-Ho; Lee, Me-Yeon; Kang, Sei-Kwon; Yoon, Jai-Woong; Park, Soah; Hwang, Taejin; Kim, Haeyoung; Kim, Kyoung Ju; Han, Tae Jin; Bae, Hoonsik

2015-07-01

The aim of this study is to set up statistical quality control for monitoring the volumetric modulated arc therapy (VMAT) delivery error by using the machine's log data. Eclipse and a Clinac iX linac with the RapidArc system (Varian Medical Systems, Palo Alto, USA) are used for delivery of the VMAT plan. During the delivery of the RapidArc fields, the machine determines the delivered monitor units (MUs) and the gantry angle's position accuracy and the standard deviations of the MU ( σMU: dosimetric error) and the gantry angle ( σGA: geometric error) are displayed on the console monitor after completion of the RapidArc delivery. In the present study, first, the log data were analyzed to confirm its validity and usability; then, statistical process control (SPC) was applied to monitor the σMU and the σGA in a timely manner for all RapidArc fields: a total of 195 arc fields for 99 patients. The MU and the GA were determined twice for all fields, that is, first during the patient-specific plan QA and then again during the first treatment. The sMU and the σGA time series were quite stable irrespective of the treatment site; however, the sGA strongly depended on the gantry's rotation speed. The σGA of the RapidArc delivery for stereotactic body radiation therapy (SBRT) was smaller than that for the typical VMAT. Therefore, SPC was applied for SBRT cases and general cases respectively. Moreover, the accuracy of the potential meter of the gantry rotation is important because the σGA can change dramatically due to its condition. By applying SPC to the σMU and σGA, we could monitor the delivery error efficiently. However, the upper and the lower limits of SPC need to be determined carefully with full knowledge of the machine and log data.

Extending and implementing the Persistent ID pillars

NASA Astrophysics Data System (ADS)

Car, Nicholas; Golodoniuc, Pavel; Klump, Jens

2017-04-01

The recent double decade anniversary of scholarly persistent identifier use has triggered journal special editions such as "20 Years of Persistent Identifiers". For such a publication, it is apt to consider the longevity of some persistent identifier (PID) mechanisms (Digital Object Identifiers) and the partial disappearance of others (Life Sciences IDs). We have previously postulated a set of "PID Pillars" [1] which are design principles aimed at ensuring PIDs can survive technology and social change and thus persist for the long term that we have drawn from our observations of PIDs at work over many years. The principles: describe how to ensure identifiers' system and organisation independence; codify the delivery of essential PID system functions; mandate a separation of PID functions from data delivery mechanisms; and require generation of policies detailing how change is handled. In this presentation, first we extend on our previous work of introducing the pillars by refining their descriptions, giving specific suggestions for each and presenting some work that addresses them. Second, we propose a baseline data model for persistent identifiers that, if used, would assist the separation of PID metadata and PID system functioning. This would allow PID system function specifics to change over time (e.g. resolver services or even resolution protocols) and yet preserve the PIDs themselves. Third, we detail our existing PID system — the PID Service [2] — that partially implements the pillars and describe both its successes and shortcomings. Finally, we describe our planned next-generation system that will aim to use the baseline data model and fully implement the pillars.

[Governance in a project addressing care of disabled elderly persons within the regional healthcare system of Tuscany, Italy].

PubMed

Pedace, Claudio; Rosa, Antonella; Francesconi, Paolo; Acampora, Anna; Ricciardi, Walter; Damiani, Gianfranco

2017-01-01

Population aging and the concurrent increase of age-related chronic degenerative diseases and disability are associated with an increased proportion of elderly persons who are dependent in activities of daily living (ADL). ADL-dependent persons need continuous and long-term health and social care according to the "taking charge" rationale, in order to warrant access and continuity of care. A healthcare system needs to respond to the long-term and complex needs, such as those of disabled elderly people, by providing appropriate health and social care services in Primary Care. A Primary Health Care system is organized according to two governance levels have distinct aims but are closely inter-dependent in their operational mechanisms. The system governance is accountable for the community and individual health protection while the delivery governance is accountable for the provision of services in accordance with appropriateness, safety and economic criteria. Delivery governance can be considered "integrated governance" as a synergy exists between two decision-making systems guiding provider choices, which are corporate governance and clinical governance. The aim of this study was to analyse the abovementioned governance levels within the healthcare system in Tuscany (Italy) referring to long-term residential care for disabled elderly people. The case of excessive accesses to emergency departments from different types of Nursing Homes (NH) is used as an example to analyse different levels of responsibility involved in the management of a critical phenomenon. Suggestions for improvement in the different levels of governance for disabled elderly people are provided, in order to support institutional programming activities.

A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media.

PubMed

Kotla, Niranjan G; Singh, Sima; Maddiboyina, Balaji; Sunnapu, Omprakash; Webster, Thomas J

2016-01-01

The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and 5% w/v grade "A" honey. Approximately 10(10)-10(11) colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials' community by elucidating an easier assay for colonic drug delivery.

Perinatal services and outcomes in Quang Ninh province, Vietnam.

PubMed

Nga, Nguyen T; Målqvist, Mats; Eriksson, Leif; Hoa, Dinh P; Johansson, Annika; Wallin, Lars; Persson, Lars-Åke; Ewald, Uwe

2010-10-01

We report baseline results of a community-based randomized trial for improved neonatal survival in Quang Ninh province, Vietnam (NeoKIP; ISRCTN44599712). The NeoKIP trial seeks to evaluate a method of knowledge implementation called facilitation through group meetings at local health centres with health staff and community key persons. Facilitation is a participatory enabling approach that, if successful, is well suited for scaling up within health systems. The aim of this baseline report is to describe perinatal services provided and neonatal outcomes. Survey of all health facility registers of service utilization, maternal deaths, stillbirths and neonatal deaths during 2005 in the province. Systematic group interviews of village health workers from all communes. A Geographic Information System database was also established. Three quarters of pregnant women had ≥3 visits to antenatal care. Two hundred and five health facilities, including 18 hospitals, provided delivery care, ranging from 1 to 3258 deliveries/year. Totally there were 17 519 births and 284 neonatal deaths in the province. Neonatal mortality rate was 16/1000 live births, ranging from 10 to 44/1000 in the different districts, with highest rates in the mountainous parts of the province. Only 8% had home deliveries without skilled attendance, but those deliveries resulted in one-fifth of the neonatal deaths. A relatively good coverage of perinatal care was found in a Vietnamese province, but neonatal mortality varied markedly with geography and level of care. A remaining small proportion of home deliveries generated a substantial part of mortality. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.

How Mode of Delivery Affects Comprehension of an Operations Management Simulation: Online vs Face-to-Face Classrooms

ERIC Educational Resources Information Center

Riley, Jason M.; Ellegood, William A.; Solomon, Stanislaus; Baker, Jerrine

2017-01-01

Purpose: This study aims to understand how mode of delivery, online versus face-to-face, affects comprehension when teaching operations management concepts via a simulation. Conceptually, the aim is to identify factors that influence the students' ability to learn and retain new concepts. Design/methodology/approach: Leveraging Littlefield…

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

PubMed Central

Ko, Young Tag; Choi, Dong-Kug

2018-01-01

Solid lipid nanoparticle (SLN) delivery systems have a wide applicability in the delivery of phyto-bioactive compounds to treat various chronic diseases, including diabetes, cancer, obesity and neurodegenerative diseases. The multiple benefits of SLN delivery include improved stability, smaller particle size, leaching prevention and enhanced lymphatic uptake of the bioactive compounds through oral delivery. However, the burst release makes the SLN delivery systems inadequate for the oral delivery of various phyto-bioactive compounds that can treat such chronic diseases. Recently, the surface-modified SLN (SMSLN) was observed to overcome this limitation for oral delivery of phyto-bioactive compounds, and there is growing evidence of an enhanced uptake of curcumin delivered orally via SMSLNs in the brain. This review focuses on different SLN and SMSLN systems that are useful for oral delivery of phyto-bioactive compounds to treat various chronic diseases. PMID:29588585

Integrated delivery systems focus on service delivery after capitation efforts stall.

PubMed

2005-03-01

Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver.

Biomaterials for drug delivery systems.

PubMed

Buckles, R G

1983-01-01

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

The utilization rate of the regional health information exchange: how it impacts on health care delivery outcomes.

PubMed

Mäenpää, Tiina; Asikainen, Paula; Gissler, Mika; Siponen, Kimmo; Maass, Marianne; Saranto, Kaija; Suominen, Tarja

2012-01-01

Interest in improving quality and effectiveness is the primary driver for health information exchange efforts across a health care system to improve the provision of public health care services. The aim here was to describe and identify the impact of a regional health information exchange (HIE) using quantitative statistics for 2004-2008 in one hospital district in Finland. We conducted a comparative, longitudinal 5-year follow-up study to evaluate the utilization rates of HIE, and the impact on health care delivery outcomes. The selected outcomes were total laboratory tests, radiology examinations, appointments, emergency visits, and referrals. The HIE utilization rates increased annually in all 10 federations of municipalities, and the viewing of reference information increased steadily in each professional group over the 5-year study period. In these federations, a significant connection was found to the number of laboratory tests and radiology examinations, with a statistically significant increase in the number of viewed references and use of HIE. The higher the numbers of emergency visits and appointments, the higher the numbers of emergency referrals to specialized care, viewed references, and HIE usage among the groups of different health care professionals. There is increasing interest in HIE usage through regional health information system among health professionals to improve health care delivery regionally and bring information on the patient directly to care delivery. It will be important to study which changes in working methods in the service system are explained by RHIS. Also, the experiences of the change that has taken place should be studied among the different stakeholders, administrative representatives, and patients.

A precision-guided MWNT mediated reawakening the sunk synergy in RAS for anti-angiogenesis lung cancer therapy.

PubMed

Su, Yujie; Hu, Yahui; Wang, Yu; Xu, Xiangting; Yuan, Yang; Li, Yunman; Wang, Zeyuan; Chen, Kerong; Zhang, Fangrong; Ding, Xuefang; Li, Min; Zhou, Jianping; Liu, Yuan; Wang, Wei

2017-09-01

Multi-walled carbon nanotube (MWNT) with its versatility has exhibited tremendous superiority in drug delivery. Despite plenty of researches on MWNT based delivery systems, precision-guided assistances to maximize their profitable properties are still lacking in substantive progress. We developed here a dual-targeting and co-delivery system based on MWNT for antiangiogenesis therapy in lung cancer which aimed at renin-angiotensin system (RAS) dysregulation by synergistically conducting angiotensin II type 1 receptor (AT 1 R) and type 2 receptor (AT 2 R) pathway. In this work, iRGD peptide connected to polyethyleneimine (PEI) was linked to MWNT skeleton, accompanying with candesartan (CD) conjugated to MWNT mediated by cystamine (SS). The functionalized MWNT is assembled with plasmid AT 2 (pAT 2 ) to form iRGD-PEI-MWNT-SS-CD/pAT 2 complexes. iRGD and CD act as pilots for complexes to dually target symbolic ανβ3-integrin and AT 1 R both overexpressed on tumor angiogenic endothelium and lung cancer cell. CD as chemotherapy showed synergistic downregulation of VEGF when combining of pAT 2 and efficiently inhibited angiogenesis. iRGD-PEI-MWNT-SS-CD/pAT 2 complexes greatly appreciated drug activities by changing drug distribution and exhibited remarkable tumor growth suppression in A549 xenograft nude mice. Our work presents that such dual-targeting strategy highly improves the delivery performance of MWNT and open a new avenue for RAS related lung cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

A method to assess obstetric outcomes using the 10-Group Classification System: a quantitative descriptive study

PubMed Central

Rossen, Janne; Lucovnik, Miha; Eggebø, Torbjørn Moe; Tul, Natasa; Murphy, Martina; Vistad, Ingvild; Robson, Michael

2017-01-01

Objectives Internationally, the 10-Group Classification System (TGCS) has been used to report caesarean section rates, but analysis of other outcomes is also recommended. We now aim to present the TGCS as a method to assess outcomes of labour and delivery using routine collection of perinatal information. Design This research is a methodological study to describe the use of the TGCS. Setting Stavanger University Hospital (SUH), Norway, National Maternity Hospital Dublin, Ireland and Slovenian National Perinatal Database (SLO), Slovenia. Participants 9848 women from SUH, Norway, 9250 women from National Maternity Hospital Dublin, Ireland and 106 167 women, from SLO, Slovenia. Main outcome measures All women were classified according to the TGCS within which caesarean section, oxytocin augmentation, epidural analgesia, operative vaginal deliveries, episiotomy, sphincter rupture, postpartum haemorrhage, blood transfusion, maternal age >35 years, body mass index >30, Apgar score, umbilical cord pH, hypoxic–ischaemic encephalopathy, antepartum and perinatal deaths were incorporated. Results There were significant differences in the sizes of the groups of women and the incidences of events and outcomes within the TGCS between the three perinatal databases. Conclusions The TGCS is a standardised objective classification system where events and outcomes of labour and delivery can be incorporated. Obstetric core events and outcomes should be agreed and defined to set standards of care. This method provides continuous and available observations from delivery wards, possibly used for further interpretation, questions and international comparisons. The definition of quality may vary in different units and can only be ascertained when all the necessary information is available and considered together. PMID:28706102

Multifunctional, chitosan-based nano therapeutics: design and application for two- and three-dimensional cell culture systems

NASA Astrophysics Data System (ADS)

Suarato, Giulia

There is a constant demand for sensitive and effective anti-cancer drug delivery systems, capable of detecting early-stage pathological conditions and increasing patient survival. Recently, chitosan-based drug delivery nanocomplexes have shown to smartly respond to the distinctive features of the tumor microenvironment, a complex network of extracellular molecules, stromal and endothelial cells, which supports the tumor formation and its metastatic invasion. Due to biocompatibility, easy chemical tailorability, and pH-responsiveness, chitosan has emerged as a promising candidate for the formulation of supramolecular multifunctional materials. The present study focuses on the design, fabrication and characterization of fluorescently labelled, hydrophobically modified glycol chitosan nano-micelles (HGC NPs), suitably tailored for the delivery of anti-neoplastic compounds to various tumor models. Doxorubicin-loaded HGC NPs have been delivered to a bone cancer model, both in monolayer and in 3D spheroid configuration, to assess for differences in the delivery profiles and in the therapeutic efficacy. Compared to the free drug, nanocomplexes showed rapid uptake and a more homogeneous distribution in 3D spheroids, a powerful cellular tool which recapitulates some of the in vivo tumor microenvironment features. In a second part of this thesis work, with the purpose of designing an active targeting tumor-homing nano-therapeutic system, HGC NPs have been linked, via avidin-biotin interaction, with a IVS4 peptide, a small molecule with inhibitory activity on MMP-14-mediated functions. An extensive study conducted on triple negative breast cancer cells in monolayer revealed the MMP-14-IVS4-HGC association at the cancer cell membrane, the preferential uptake, and the consequent impairment of protease-associated migratory ability. As an additional application of our engineered construct, HGC micelles have been decorated with a liver kinase B1 (LKB1), a critical kinase involved in neuronal cell polarization, with the aim of regulating axon development. Our preliminary data indicated that, when treated with HGC-LKB1 NPs, primary ray embryo hippocampal neurons in vitro presented a multiple axon phenotype, validating the potential use of our multifunctional system as local protein delivery agent. In addition, we successfully performed for the first time in utero electroporation delivery of the chitosan nano-micelles, demonstrating the in vivo uptake potential of our system.

Experiments and synthesis of bone-targeting epirubicin with the water-soluble macromolecular drug delivery systems of oxidized-dextran.

PubMed

Yu, Li; Cai, Lin; Hu, Hao; Zhang, Yi

2014-05-01

Epirubicin (EPI) is a broad spectrum antineoplastic drug, commonly used as a chemotherapy method to treat osteosarcoma. However, its application has been limited by many side-effects. Therefore, targeted drug delivery to bone has been the aim of current anti-bone-tumor drug studies. Due to the exceptional affinity of Bisphosphonates (BP) to bone, 1-amino-ethylene-1, 1-dephosphate acid (AEDP) was chosen as the bone targeting moiety for water-soluble macromolecular drug delivery systems of oxidized-dextran (OXD) to transport EPI to bone in this article. The bone targeting drug of AEDP-OXD-EPI was designed for the treatment of malignant bone tumors. The successful conjugation of AEDP-OXD-EPI was confirmed by analysis of FTIR and (1)H-NMR spectra. To study the bone-seeking potential of AEDP-OXD-EPI, an in vitro hydroxyapatite (HAp) binding assay and an in vivo experiment of bone-targeting capacity were established. The effectiveness of AEDP-OXD-EPI was demonstrated by inducing apoptosis and necrosis of MG-63 tumor cell line. The obtained experimental data indicated that AEDP-OXD-EPI is an ideal bone-targeting anti-tumor drug.

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.

Design, modeling and simulation of MEMS-based silicon Microneedles

NASA Astrophysics Data System (ADS)

Amin, F.; Ahmed, S.

2013-06-01

The advancement in semiconductor process engineering and nano-scale fabrication technology has made it convenient to transport specific biological fluid into or out of human skin with minimum discomfort. Fluid transdermal delivery systems such as Microneedle arrays are one such emerging and exciting Micro-Electro Mechanical System (MEMS) application which could lead to a total painless fluid delivery into skin with controllability and desirable yield. In this study, we aimed to revisit the problem with modeling, design and simulations carried out for MEMS based silicon hollow out of plane microneedle arrays for biomedical applications particularly for transdermal drug delivery. An approximate 200 μm length of microneedle with 40 μm diameter of lumen has been successfully shown formed by isotropic and anisotropic etching techniques using MEMS Pro design tool. These microneedles are arranged in size of 2 × 4 matrix array with center to center spacing of 750 μm. Furthermore, comparisons for fluid flow characteristics through these microneedle channels have been modeled with and without the contribution of the gravitational forces using mathematical models derived from Bernoulli Equation. Physical Process simulations have also been performed on TCAD SILVACO to optimize the design of these microneedles aligned with the standard Si-Fabrication lines.

Physical Factors Affecting Plasmid DNA Compaction in Stearylamine-Containing Nanoemulsions Intended for Gene Delivery

PubMed Central

Silva, André Leandro; Júnior, Francisco Alexandrino; Verissimo, Lourena Mafra; Agnez-Lima, Lucymara Fassarella; Egito, Lucila Carmem Monte; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Socrates Tabosa

2012-01-01

Cationic lipids have been used in the development of non-viral gene delivery systems as lipoplexes. Stearylamine, a cationic lipid that presents a primary amine group when in solution, is able to compact genetic material by electrostatic interactions. In dispersed systems such as nanoemulsions this lipid anchors on the oil/water interface confering a positive charge to them. The aim of this work was to evaluate factors that influence DNA compaction in cationic nanoemulsions containing stearylamine. The influence of the stearylamine incorporation phase (water or oil), time of complexation, and different incubation temperatures were studied. The complexation rate was assessed by electrophoresis migration on agarose gel 0.7%, and nanoemulsion and lipoplex characterization was done by Dynamic Light Scattering (DLS). The results demonstrate that the best DNA compaction process occurs after 120 min of complexation, at low temperature (4 ± 1 °C), and after incorporation of the cationic lipid into the aqueous phase. Although the zeta potential of lipoplexes was lower than the results found for basic nanoemulsions, the granulometry did not change. Moreover, it was demonstrated that lipoplexes are suitable vehicles for gene delivery. PMID:24281666

Novel Pentablock Copolymers as Thermosensitive Self-Assembling Micelles for Ocular Drug Delivery

PubMed Central

Alami-Milani, Mitra; Zakeri-Milani, Parvin; Valizadeh, Hadi; Salehi, Roya; Salatin, Sara; Naderinia, Ali; Jelvehgari, Mitra

2017-01-01

Many studies have focused on how drugs are formulated in the sol state at room temperature leading to the formation of in situ gel at eye temperature to provide a controlled drug release. Stimuli-responsive block copolymer hydrogels possess several advantages including uncomplicated drug formulation and ease of application, no organic solvent, protective environment for drugs, site-specificity, prolonged and localized drug delivery, lower systemic toxicity, and capability to deliver both hydrophobic and hydrophilic drugs. Self-assembling block copolymers (such as diblock, triblock, and pentablock copolymers) with large solubility variation between hydrophilic and hydrophobic segments are capable of making temperature-dependent micellar assembles, and with further increase in the temperature, of jellifying due to micellar aggregation. In general, molecular weight, hydrophobicity, and block arrangement have a significant effect on polymer crystallinity, micelle size, and in vitro drug release profile. The limitations of creature triblock copolymers as initial burst release can be largely avoided using micelles made of pentablock copolymers. Moreover, formulations based on pentablock copolymers can sustain drug release for a longer time. The present study aims to provide a concise overview of the initial and recent progresses in the design of hydrogel-based ocular drug delivery systems. PMID:28507933

Transdermal delivery of paeonol using cubic gel and microemulsion gel

PubMed Central

Luo, Maofu; Shen, Qi; Chen, Jinjin

2011-01-01

Background The aim of this study was to develop new systems for transdermal delivery of paeonol, in particular microemulsion gel and cubic gel formulations. Methods Various microemulsion vehicles were prepared using isopropyl myristate as an oil phase, polyoxyethylated castor oil (Cremophor® EL) as a surfactant, and polyethylene glycol 400 as a cosurfactant. In the optimum microemulsion gel formulation, carbomer 940 was selected as the gel matrix, and consisted of 1% paeonol, 4% isopropyl myristate, 28% Cremophor EL/polyethylene glycol 400 (1:1), and 67% water. The cubic gel was prepared containing 3% paeonol, 30% water, and 67% glyceryl monooleate. Results A skin permeability test using excised rat skins indicated that both the cubic gel and microemulsion gel formulations had higher permeability than did the paeonol solution. An in vivo pharmacokinetic study done in rats showed that the relative bioavailability of the cubic gel and microemulsion gel was enhanced by about 1.51-fold and 1.28-fold, respectively, compared with orally administered paeonol suspension. Conclusion Both the cubic gel and microemulsion gel formulations are promising delivery systems to enhance the skin permeability of paeonol, in particular the cubic gel. PMID:21904450

The role of Primary Healthcare in the coordination of Health Care Networks in Rio de Janeiro, Brazil, and Lisbon region, Portugal.

PubMed

Lapão, Luís Velez; Arcêncio, Ricardo Alexandre; Popolin, Marcela Paschoal; Rodrigues, Ludmila Barbosa Bandeira

2017-03-01

Considering the trajectory of Rio de Janeiro e Lisboa region regarding strengths of the their health local systems to achieve health for all and equity, the study aimed to compare the organization of the Primary Healthcare from both regions, searching to identify the advancement which in terms of the Delivery Health Networks' coordination. It is a case study with qualitative approach and assessment dimensions. It was used material available online such as scientific manuscripts and gray literature. The results showed the different grades regarding Delivery Health Networks. Lisboa region present more advancement, because of its historic issues, it has implemented Primary Healthcare expanded and nowadays it achieved enough maturity related to coordination of its health local system and Rio de Janeiro suffers still influence from historic past regarding Primary Healthcare selective. The both regions has done strong bids in terms of electronic health records and telemedicine. After of the study, it is clearer the historic, cultural and politics and legal issue that determined the differences of the Primary Healthcare coordinator of the Delivery Health Network in Rio de Janeiro and Lisboa region.

Application of shRNA-containing herpes simplex virus type 1 (HSV-1)-based gene therapy for HSV-2-induced genital herpes.

PubMed

Liu, Zhihong; Xiang, Yang; Wei, Zhun; Yu, Bo; Shao, Yong; Zhang, Jie; Yang, Hong; Li, Manmei; Guan, Ming; Wan, Jun; Zhang, Wei

2013-11-01

HSV-1-based vectors have been widely used to achieve targeted delivery of genes into the nervous system. In the current study, we aim to use shRNA-containing HSV-1-based gene delivery system for the therapy of HSV-2 infection. Guinea pigs were infected intravaginally with HSV-2 and scored daily for 100 days for the severity of vaginal disease. HSV-2 shRNA-containing HSV-1 was applied intravaginally daily between 8 and 14 days after HSV-2 challenge. Delivery of HSV-2 shRNA-containing HSV-1 had no effect on the onset of disease and acute virus shedding in animals, but resulted in a significant reduction in both the cumulative recurrent lesion days and the number of days with recurrent disease. Around half of the animals in the HSV-2 shRNA group did not develop recurrent disease 100 days post HSV-2 infection. In conclusion, HSV-2 shRNA-containing HSV-1 particles are effective in reducing the recurrence of genital herpes caused by HSV-2. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhancement of oral bioavailability of atorvastatin calcium by self-emulsifying drug delivery systems (SEDDS).

PubMed

Kadu, Pawan J; Kushare, Sachin S; Thacker, Dhaval D; Gattani, Surendra G

2011-02-01

The aim of the present study was to formulate a self-emulsifying drug delivery system of atorvastatin calcium and its characterization including in vitro and in vivo potential. The solubility of atorvastatin calcium was determined in various vehicles such as Captex 355, Captex 355 EP/NF, Ethyl oleate, Capmul MCM, Capmul PG-8, Gelucire 44/14, Tween 80, Tween 20, and PEG 400. Pseudoternary phase diagrams were plotted on the basis of solubility data of drug in various components to evaluate the microemulsification region. Formulation development and screening was carried out based on results obtained from phase diagrams and characteristics of resultant microemulsion. Prepared formulations were tested for microemulsifying properties and evaluated for clarity, precipitation, viscosity determination, drug content and in vitro dissolution. The optimized formulation further evaluated for particle size distribution, zeta potential, stability studies and in vivo potential. In vivo performance of the optimized formulation was evaluated using a Triton-induced hypercholesterolemia model in male Albino Wistar rats. The formulation significantly reduced serum lipid levels as compared with atorvastatin calcium. Thus studies illustrated the potential use for the delivery of hydrophobic drug such as atorvastatin calcium by oral route.

Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study.

PubMed

Leroux, M; Desveaux, C; Parcevaux, M; Julliac, B; Gouyon, J B; Dallay, D; Pellegrin, J L; Boukerrou, M; Blanco, P; Lazaro, E

2015-11-01

The aim of this study was to evaluate the effect of hydroxychloroquine (HCQ) on fetal preterm delivery and intrauterine growth restriction (IUGR) in a cohort of pregnant women with systemic lupus erythematosus (SLE). Over an 11-year period (January 1, 2001 to December 31, 2011), all women with SLE and admitted to deliver after 22 weeks of gestation to Bordeaux University Hospital (France), were retrospectively enrolled in the present study. The population was then split into two groups based on the treatment they received: HCQ exposed (HCQ+) versus HCQ non-exposed (HCQ-) group. 118 pregnancies were included, 41 in the HCQ+ group and 77 in the HCQ- group. The rate of adverse fetal outcome was significantly lower in the HCQ+ group (p = 0.001), particularly in terms of preterm delivery, 15.8% versus 44.2% (p = 0.006), and IUGR, 10.5% versus 28.6% (p = 0.03). No adverse outcomes were reported in the HCQ+ group. HCQ reduces neonatal morbidity in women with SLE by significantly decreasing the rate of prematurity and intrauterine growth restriction. © The Author(s) 2015.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Cationic nanoemulsions as nucleic acids delivery systems.

PubMed

Teixeira, Helder Ferreira; Bruxel, Fernanda; Fraga, Michelle; Schuh, Roselena Silvestri; Zorzi, Giovanni Konat; Matte, Ursula; Fattal, Elias

2017-12-20

Since the first clinical studies, knowledge in the field of gene therapy has advanced significantly, and these advances led to the development and subsequent approval of the first gene medicines. Although viral vectors-based products offer efficient gene expression, problems related to their safety and immune response have limited their clinical use. Thus, design and optimization of nonviral vectors is presented as a promising strategy in this scenario. Nonviral systems are nanotechnology-based products composed of polymers or lipids, which are usually biodegradable and biocompatible. Cationic liposomes are the most studied nonviral carriers and knowledge about these systems has greatly evolved, especially in understanding the role of phospholipids and cationic lipids. However, the search for efficient delivery systems aiming at gene therapy remains a challenge. In this context, cationic nanoemulsions have proved to be an interesting approach, as their ability to protect and efficiently deliver nucleic acids for diverse therapeutic applications has been demonstrated. This review focused on cationic nanoemulsions designed for gene therapy, providing an overview on their composition, physicochemical properties, and their efficacy on biological response in vitro and in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of a thiolated chitosan scaffold for local delivery of BMP-2 for osteogenic differentiation and ectopic bone formation.

PubMed

Bae, In-Ho; Jeong, Byung-Chul; Kook, Min-Suk; Kim, Sun-Hun; Koh, Jeong-Tae

2013-01-01

Thiolated chitosan (Thio-CS) is a well-established pharmaceutical excipient for drug delivery. However, its use as a scaffold for bone formation has not been investigated. The aim of this study was to evaluate the potential of Thio-CS in bone morphogenetic protein-2 (BMP-2) delivery and bone formation. In vitro study showed that BMP-2 interacted with the Thio-CS and did not affect the swelling behavior. The release kinetics of BMP-2 from the Thio-CS was slightly delayed (70%) within 7 days compared with that from collagen gel (Col-gel, 85%), which is widely used in BMP-2 delivery. The BMP-2 released from Thio-CS increased osteoblastic cell differentiation but did not show any cytotoxicity until 21 days. Analysis of the in vivo ectopic bone formation at 4 weeks of posttransplantation showed that use of Thio-CS for BMP-2 delivery induced more bone formation to a greater extent (1.8 fold) than that of Col-gel. However, bone mineral density in both bones was equivalent, regardless of Thio-CS or Col-gel carrier. Taken together, Thio-CS system might be useful for delivering osteogenic protein BMP-2 and present a promising bone regeneration strategy.

Strength of primary care service delivery: a comparative study of European countries, Australia, New Zealand, and Canada.

PubMed

Pavlič, Danica R; Sever, Maja; Klemenc-Ketiš, Zalika; Švab, Igor; Vainieri, Milena; Seghieri, Chiara; Maksuti, Alem

2018-05-01

AimWe sought to examine strength of primary care service delivery as measured by selected process indicators by general practitioners from 31 European countries plus Australia, Canada, and New Zealand. We explored the relation between strength of service delivery and healthcare expenditures. The strength of a country's primary care is determined by the degree of development of a combination of core primary care dimensions in the context of its healthcare system. This study analyses the strength of service delivery in primary care as measured through process indicators in 31 European countries plus Australia, New Zealand, and Canada. A comparative cross-sectional study design was applied using the QUALICOPC GP database. Data on the strength of primary healthcare were collected using a standardized GP questionnaire, which included 60 questions divided into 10 dimensions related to process, structure, and outcomes. A total of 6734 general practitioners participated. Data on healthcare expenditure were obtained from World Bank statistics. We conducted a correlation analysis to analyse the relationship between strength and healthcare expenditures.FindingsOur findings show that the strength of service delivery parameters is less than optimal in some countries, and there are substantial variations among countries. Continuity and comprehensiveness of care are significantly positively related to national healthcare expenditures; however, coordination of care is not.

Rumen-stable delivery systems.

PubMed

Papas; Wu

1997-12-08

Ruminants have a distinct digestive system which serves a unique symbiotic relationship between the host animal and predominantly anaerobic rumen bacteria and protozoa. Rumen fermentation can be both beneficial by enabling utilization of cellulose and non-protein nitrogen and detrimental by reducing the nutritive value of some carbohydrates, high biological value proteins and by hydrogenating unsaturated lipids. In addition it can also result in the modification and inactivation of many pharmacologically active ingredients administered to the host animal via the oral route. The advances in ruminant nutrition and health demand a rumen-stable delivery system which can deliver the active ingredient post-ruminally while simultaneously meet efficacy, safety and cost criteria. In contrast to drug delivery systems for humans, the demand for low-cost has hindered the development of effective rumen-stable delivery systems. Historically, heat and chemical treatment of feed components, low solubility analogues or lipid-based formulations have been used to achieve some degree of rumen-stability, and products have been developed accordingly. Recently, a polymeric pH-dependent rumen-stable delivery system has been developed and commercialized. The rationale of this delivery system is based on the pH difference between ruminal and abomasal fluids. The delivery system is composed of a basic polymer, a hydrophobic substance and a pigment material. It can be applied as a coating to solid particles via a common encapsulation method such as air-suspension coating. In the future, the delivery system could be used to deliver micronutrients and pharmaceuticals post-ruminally to ruminant animals. A further possible application of the delivery system is that it could also be combined with other controlled delivery devices/systems in order to enhance slow release or to achieve targeted delivery needs for ruminants. This paper discusses the rumen protection and the abomasal release mechanism of the polymeric coating. It also reviews other rumen stable delivery systems and methods for evaluating their in vitro and in vivo performance.

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.

Project Delivery System Mode Decision Based on Uncertain AHP and Fuzzy Sets

NASA Astrophysics Data System (ADS)

Kaishan, Liu; Huimin, Li

2017-12-01

The project delivery system mode determines the contract pricing type, project management mode and the risk allocation among all participants. Different project delivery system modes have different characteristics and applicable scope. For the owners, the selection of the delivery mode is the key point to decide whether the project can achieve the expected benefits, it relates to the success or failure of project construction. Under the precondition of comprehensively considering the influence factors of the delivery mode, the model of project delivery system mode decision was set up on the basis of uncertain AHP and fuzzy sets, which can well consider the uncertainty and fuzziness when conducting the index evaluation and weight confirmation, so as to rapidly and effectively identify the most suitable delivery mode according to project characteristics. The effectiveness of the model has been verified via the actual case analysis in order to provide reference for the construction project delivery system mode.

Approaches to Neural Tissue Engineering Using Scaffolds for Drug Delivery

PubMed Central

Willerth, Stephanie M.; Sakiyama-Elbert, Shelly E.

2007-01-01

This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented. PMID:17482308

Modeling the Delivery Physiology of Distributed Learning Systems.

ERIC Educational Resources Information Center

Paquette, Gilbert; Rosca, Ioan

2003-01-01

Discusses instructional delivery models and their physiology in distributed learning systems. Highlights include building delivery models; types of delivery models, including distributed classroom, self-training on the Web, online training, communities of practice, and performance support systems; and actors (users) involved, including experts,…

Improving health care, Part 1: The clinical value compass.

PubMed

Nelson, E C; Mohr, J J; Batalden, P B; Plume, S K

1996-04-01

CLINICAL VALUE COMPASS APPROACH: The clinical Value Compass, named to reflect its similarity in layout to a directional compass, has at its four cardinal points (1) functional status, risk status, and well-being; (2) costs; (3) satisfaction with health care and perceived benefit; and (4) clinical outcomes. To manage and improve the value of health care services, providers will need to measure the value of care for similar patient populations, analyze the internal delivery processes, run tests of changed delivery processes, and determine if these changes lead to better outcomes and lower costs. GETTING STARTED--OUTCOMES AND AIM: In the case example, the team's aim is "to find ways to continually improve the quality and value of care for AMI (acute myocardial infection) patients." VALUE MEASURES--SELECT A SET OF OUTCOME AND COST MEASURES: Four to 12 outcome and cost measures are sufficient to get started. In the case example, the team chose 1 or more measures for each quadrant of the value compass. An operational definition is a clearly specified method explaining how to measure a variable. Measures in the case example were based on information from the medical record, administrative and financial records, and patient reports and ratings at eight weeks postdischarge. Measurement systems that quantify the quality of processes and results of care are often add-ons to routine care delivery. However, the process of measurement should be intertwined with the process of care delivery so that front-line providers are involved in both managing the patient and measuring the process and related outcomes and costs.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

2012-01-01

This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

Micro injector sample delivery system for charged molecules

DOEpatents

Davidson, James C.; Balch, Joseph W.

1999-11-09

A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (>96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2011 CFR

2011-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2010 CFR

2010-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2013 CFR

2013-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2014 CFR

2014-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

Code of Federal Regulations, 2012 CFR

2012-10-01

... systems for the delivery of video programming. 63.02 Section 63.02 Telecommunication FEDERAL... systems for the delivery of video programming. (a) Any common carrier is exempt from the requirements of... with respect to the establishment or operation of a system for the delivery of video programming. [64...

Preventing Continuous Positive Airway Pressure Failure: Evidence-Based and Physiologically Sound Practices from Delivery Room to the Neonatal Intensive Care Unit.

PubMed

Wright, Clyde J; Sherlock, Laurie G; Sahni, Rakesh; Polin, Richard A

2018-06-01

Routine use of continuous positive airway pressure (CPAP) to support preterm infants with respiratory distress is an evidenced-based strategy to decrease incidence of bronchopulmonary dysplasia. However, rates of CPAP failure remain unacceptably high in very premature neonates, who are at high risk for developing bronchopulmonary dysplasia. Using the GRADE framework to assess the quality of available evidence, this article reviews strategies aimed at decreasing CPAP failure, starting with delivery room interventions and followed through to system-based efforts in the neonatal intensive care unit. Despite best efforts, some very premature neonates fail CPAP. Also reviewed are predictors of CPAP failure in this vulnerable population. Copyright © 2018 Elsevier Inc. All rights reserved.

Final Technical Report to proposal DE-FG02-95ER20187

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

Dangl, Jeff

Our long term aim over our many years of generous DOE-BES funding was to understand mechanisms by which the pathogen virulence factors (called ‘type III effectors’) AvrRpm1 and AvrB activate the plant NLR immune receptor RPM1. In general effectors are delivered from the infecting bacteria into host cells by the type III pilus, where they manipulate host machinery to help pathogens overcome host defense. Delivery of effectors to increase virulence is a general feature of all classes of plant pathogens, from fungi to insects to oomcyetes and bacteria. Hence, understanding the overall diversity of effectors, their myriad delivery systems andmore » their effectors on host cell biology, is of central importance in plant immunology.« less

The educative practice of professional caregivers at shelters: coping with violence lived by female adolescents.

PubMed

Penna, Lucia Helena Garcia; Carinhanha, Joana Iabrudi; Leite, Ligia Costa

2009-01-01

This study aimed to identify strategies caregiving professionals at shelters discuss and use in care delivery to violence situations lived by female adolescents; and to discuss educative practice as a care technology for coping with violence. Based on qualitative research, the data were produced through interviews with caregivers at a municipal adolescent shelter and were interpreted according to content analysis. The results evidenced individual and institutional strategies for care delivery to the adolescents. In conclusion, educative actions are care technologies in the reframing process of life's value by female adolescents living on the streets or in shelters, considering the cultural diversity - a dialogical action systemized and institutionalized for coping with the violence they experience.

Emerging potential of stimulus-responsive nanosized anticancer drug delivery systems for systemic applications.

PubMed

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Madeshwaran, Thiagarajan; Hiep, Tran Tuan; Kandasamy, Umadevi; Oh, Kyung Taek; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2018-02-01

The development of novel drug delivery systems based on well-defined polymer therapeutics has led to significant improvements in the treatment of multiple disorders. Advances in material chemistry, nanotechnology, and nanomedicine have revolutionized the practices of drug delivery. Stimulus-responsive material-based nanosized drug delivery systems have remarkable properties that allow them to circumvent biological barriers and achieve targeted intracellular drug delivery. Specifically, the development of novel nanocarrier-based therapeutics is the need of the hour in managing complex diseases. In this review, we have briefly described the fundamentals of drug targeting to diseased tissues, physiological barriers in the human body, and the mechanisms/modes of drug-loaded carrier systems. To that end, this review serves as a comprehensive overview of the recent developments in stimulus-responsive drug delivery systems, with focus on their potential applications and impact on the future of drug delivery.

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.

Sterile Product Packaging and Delivery Systems.

PubMed

Akers, Michael J

2015-01-01

Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

Performance Analysis of Cyber Security Awareness Delivery Methods

NASA Astrophysics Data System (ADS)

Abawajy, Jemal; Kim, Tai-Hoon

In order to decrease information security threats caused by human-related vulnerabilities, an increased concentration on information security awareness and training is necessary. There are numerous information security awareness training delivery methods. The purpose of this study was to determine what delivery method is most successful in providing security awareness training. We conducted security awareness training using various delivery methods such as text based, game based and a short video presentation with the aim of determining user preference delivery methods. Our study suggests that a combined delvery methods are better than individual secrity awareness delivery method.

A global health delivery framework approach to epilepsy care in resource-limited settings.

PubMed

Cochran, Maggie F; Berkowitz, Aaron L

2015-11-15

The Global Health Delivery (GHD) framework (Farmer, Kim, and Porter, Lancet 2013;382:1060-69) allows for the analysis of health care delivery systems along four axes: a care delivery value chain that incorporates prevention, diagnosis, and treatment of a medical condition; shared delivery infrastructure that integrates care within existing healthcare delivery systems; alignment of care delivery with local context; and generation of economic growth and social development through the health care delivery system. Here, we apply the GHD framework to epilepsy care in rural regions of low- and middle-income countries (LMIC) where there are few or no neurologists. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation and evaluation of press coated tablets for pulsatile drug delivery using hydrophilic and hydrophobic polymers.

PubMed

Rane, Ashish Babulal; Gattani, Surendra Ganeshlal; Kadam, Vinayak Dinkar; Tekade, Avinash Ramrao

2009-11-01

The aim of present investigation was to develop press coated tablet for pulsatile drug delivery of ketoprofen using hydrophilic and hydrophobic polymers. The drug delivery system was designed to deliver the drug at such a time when it could be most needful to patient of rheumatoid arthritis. The press coated tablets containing ketoprofen in the inner core was formulated with an outer shell by different weight ratio of hydrophobic polymer (micronized ethyl cellulose powder) and hydrophilic polymers (glycinemax husk or sodium alginate). The release profile of press coated tablet exhibited a lag time followed by burst release, in which outer shell ruptured into two halves. Authors also investigated factors influencing on lag time such as particle size and viscosity of ethyl cellulose, outer coating weight and paddle rpm. The surface morphology of the tablet was examined by a scanning electron microscopy. Differential scanning calorimeter and Fourier transformed infrared spectroscopy study showed compatibility between ketoprofen and coating material.

Discrete-choice modelling of patient preferences for modes of drug administration.

PubMed

Tetteh, Ebenezer Kwabena; Morris, Steve; Titcheneker-Hooker, Nigel

2017-12-01

The administration of (biologically-derived) drugs for various disease conditions involves consumption of resources that constitutes a direct monetary cost to healthcare payers and providers. An often ignored cost relates to a mismatch between patients' preferences and the mode of drug administration. The "intangible" benefits of giving patients what they want in terms of the mode of drug delivery is seldom considered. This study aims to evaluate, in monetary terms, end-user preferences for the non-monetary attributes of different modes of drug administration using a discrete-choice experiment. It provides empirical support to the notion that there are significant benefits from developing patient-friendly approaches to drug delivery. The gross benefits per patient per unit administration is in the same order of magnitude as the savings in resource costs of administering drugs. The study argues that, as long as the underlying manufacturing science is capable, a patient-centred approach to producing drug delivery systems should be encouraged and pursued.

RFID technology for hazardous waste management and tracking.

PubMed

Namen, Anderson Amendoeira; Brasil, Felipe da Costa; Abrunhosa, Jorge José Gouveia; Abrunhosa, Glaucia Gomes Silva; Tarré, Ricardo Martinez; Marques, Flávio José Garcia

2014-09-01

The illegal dumping of hazardous waste is one of the most concerning occurrences related to illegal waste activities. The waste management process is quite vulnerable, especially when it comes to assuring the right destination for the delivery of the hazardous waste. The purpose of this paper is to present a new system design and prototype for applying the RFID technology so as to guarantee the correct destination for the hazardous waste delivery. The aim of this innovative approach, compared with other studies that employ the same technology to the waste disposal process, is to focus on the certification that the hazardous waste will be delivered to the right destination site and that no inappropriate disposal will occur in the transportation stage. These studies were carried out based on data collected during visits to two hazardous waste producer companies in Brazil, where the material transportation and delivery to a company in charge of the waste disposal were closely monitored. © The Author(s) 2014.

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.

Sensitivity Analysis of Algan/GAN High Electron Mobility Transistors to Process Variation

DTIC Science & Technology

2008-02-01

delivery system gas panel including both hydride and alkyl delivery modules and the vent/valve configurations [14...Reactor Gas Delivery Systems A basic schematic diagram of an MOCVD reactor delivery gas panel is shown in Figure 13. The reactor gas delivery...system, or gas panel , consists of a network of stainless steel tubing, automatic valves and electronic mass flow controllers (MFC). There are separate

An Application of Queues to Offensive Support Indirect Fire Weapons Systems

DTIC Science & Technology

2005-01-01

weapons systems capability is founded on delivery systems, operational procedures, ammunition and technologies from the 1960s. The changing nature of...fire away from busy delivery systems to less busy delivery systems by calculating the comparative estimation of busyness as given in equation (17... changes in the battlefield. Ideally, the delivery systems could be provided with 9 DSTO-TR-1662 Track of gun movements (100 cals-for-lire) 100 90 so 70 60

Transitioning From Volume to Value: One Academic Medical Center's Approach to Improving Population Health.

PubMed

Halvorson, Stephanie A C; Tanski, Mary E; Yackel, Thomas R

2017-05-01

The U.S. health care system is undergoing a major transformation. Clinical delivery systems are now being paid according to the value of the care they provide, in accordance with the Triple Aim, which incorporates improving the quality and cost of care and the patient experience. Increasingly, financial risk is being transferred from insurers to clinical delivery systems that become responsible for both episode-based clinical care and the longitudinal care of patients. Thus, these delivery systems need to develop strategies to manage the health of populations. Academic medical centers (AMCs) serve a unique role in many markets yet may be ill prepared for this transformation. In 2013, Oregon Health & Science University (OHSU) partnered with a large health insurer and six other hospitals across the state to form Propel Health, a collaborative partnership designed to deliver the tools, methods, and support necessary for population health management. OHSU also developed new internal structures and transformed its business model to embrace this value-based care model. Each Propel Health partner included the employees and dependents enrolled in its employee medical plan, for approximately 55,000 covered individuals initially. By 2017, Propel Health is expected to cover 110,000 individuals. Other outcomes to measure in the future include the quality and cost of care provided under this partnership. Anticipated challenges to overcome include insufficient primary care networks, conflicting incentives, local competition, and the magnitude of the transformation. Still, the time is right for AMCs to commit to improving the health of populations.

The Dynamics of Community Health Care Consolidation: Acquisition of Physician Practices

PubMed Central

Christianson, Jon B; Carlin, Caroline S; Warrick, Louise H

2014-01-01

Context Health care delivery systems are becoming increasingly consolidated in urban areas of the United States. While this consolidation could increase efficiency and improve quality, it also could raise the cost of health care for payers. This article traces the consolidation trajectory in a single community, focusing on factors influencing recent acquisitions of physician practices by integrated delivery systems. Methods We used key informant interviews, supplemented by document analysis. Findings The acquisition of physician practices is a process that will be difficult to reverse in the current health care environment. Provider revenue uncertainty is a key factor driving consolidation, with public and private attempts to control health care costs contributing to that uncertainty. As these efforts will likely continue, and possibly intensify, community health care systems now are less consolidated than they will be in the future. Acquisitions of multispecialty and primary care practices by integrated delivery systems follow a common process, with relatively predictable issues relating to purchase agreements, employment contracts, and compensation. Acquisitions of single-specialty practices are less common, with motivations for acquisitions likely to vary by specialty type, group size, and market structure. Total cost of care contracting could be an important catalyst for practice acquisitions in the future. Conclusions In the past, market and regulatory forces aimed at controlling costs have both encouraged and rewarded the consolidation of providers, with important new developments likely to create momentum for further consolidation, including acquisitions of physician practices. PMID:25199899

The dynamics of community health care consolidation: acquisition of physician practices.

PubMed

Christianson, Jon B; Carlin, Caroline S; Warrick, Louise H

2014-09-01

Health care delivery systems are becoming increasingly consolidated in urban areas of the United States. While this consolidation could increase efficiency and improve quality, it also could raise the cost of health care for payers. This article traces the consolidation trajectory in a single community, focusing on factors influencing recent acquisitions of physician practices by integrated delivery systems. We used key informant interviews, supplemented by document analysis. The acquisition of physician practices is a process that will be difficult to reverse in the current health care environment. Provider revenue uncertainty is a key factor driving consolidation, with public and private attempts to control health care costs contributing to that uncertainty. As these efforts will likely continue, and possibly intensify, community health care systems now are less consolidated than they will be in the future. Acquisitions of multispecialty and primary care practices by integrated delivery systems follow a common process, with relatively predictable issues relating to purchase agreements, employment contracts, and compensation. Acquisitions of single-specialty practices are less common, with motivations for acquisitions likely to vary by specialty type, group size, and market structure. Total cost of care contracting could be an important catalyst for practice acquisitions in the future. In the past, market and regulatory forces aimed at controlling costs have both encouraged and rewarded the consolidation of providers, with important new developments likely to create momentum for further consolidation, including acquisitions of physician practices. © 2014 Milbank Memorial Fund.

In vivo evaluation of an oral delivery system for P-gp substrates based on thiolated chitosan.

PubMed

Föger, Florian; Schmitz, Thierry; Bernkop-Schnürch, Andreas

2006-08-01

Recently, thiolated polymers, so called thiomers, have been reported to modulate drug absorption by inhibition of intestinal P-glycoprotein (P-gp). The aim of the present study was to provide a proof-of-principle for a delivery system based on thiolated chitosan in vivo in rats, using rhodamine-123 (Rho-123) as representative P-gp substrate. In vitro, the permeation enhancing effect of unmodified chitosan, chitosan-4 thiobutylamidine (Ch-TBA) and the combination of Ch-TBA with reduced glutathione (GSH) was evaluated by using freshly excised rat intestinal mucosa mounted in Ussing-type chambers. In comparison to buffer only, Rho-123 transport in presence of 0.5% (w/v) chitosan, 0.5% (w/v) Ch-TBA and the combination of 0.5% (w/v) Ch-TBA/0.5% (w/v) GSH, was 1.8-fold, 2.6-fold, 3.8-fold improved, respectively. Furthermore, enteric-coated tablets based on unmodified chitosan or Ch-TBA/GSH, were investigated in vivo. In rats, the Ch-TBA/GSH tablets increased the area under the plasma concentration time curve (AUC0-12) of Rho-123 by 217% in comparison to buffer control and by 58% in comparison to unmodified chitosan. This in vivo study showed that a delivery system based on thiolated chitosan significantly increased the oral bioavailability of P-gp substrate Rho-123.

Determination of in vivo behavior of mitomycin C-loaded o/w soybean oil microemulsion and mitomycin C solution via gamma camera imaging.

PubMed

Kotmakçı, Mustafa; Kantarcı, Gülten; Aşıkoğlu, Makbule; Ozkılıç, Hayal; Ertan, Gökhan

2013-09-01

In this study, a microemulsion system was evaluated for delivery of mitomycin C (MMC). To track the distribution of the formulated drug after intravenous administration, radiochemical labeling and gamma scintigraphy imaging were used. The aim was to evaluate a microemulsion system for intravenous delivery of MMC and to compare its in vivo behavior with that of the MMC solution. For microemulsion formulation, soybean oil was used as the oil phase. Lecithin and Tween 80 were surfactants and ethanol was the cosurfactant. To understand the whole body localization of MMC-loaded microemulsion, MMC was labeled with radioactive technetium and gamma scintigraphy was applied for visualization of drug distribution. Radioactivity in the bladder 30 minutes after injection of the MMC solution was observed, according to static gamma camera images. This shows that urinary excretion of the latter starts very soon. On the other hand, no radioactivity appeared in the urinary bladder during the 90 minutes following the administration of MMC-loaded microemulsion. The unabated radioactivity in the liver during the experiment shows that the localization of microemulsion formulation in the liver is stable. In the light of the foregoing, it is suggested that this microemulsion formulation may be an appropriate carrier system for anticancer agents by intravenous delivery in hepatic cancer chemotherapy.

EFFECT OF ULTRA-HIGH PRESSURE HOMOGENIZATION ON THE INTERACTION BETWEEN BOVINE CASEIN MICELLES AND RITONAVIR

PubMed Central

Corzo-Martínez, M.; Mohan, M.; Dunlap, J.; Harte, F.

2014-01-01

Purpose The aim of this work was to develop a milk-based powder formulation appropriate for pediatric delivery of ritonavir (RIT). Methods Ultra-high pressure homogenization (UHPH) at 0.1, 300 and 500 MPa was used to process a dispersion of pasteurized skim milk (SM) and ritonavir. Loading efficiency was determined by RP-HPLC-UV; characterization of RIT:SM systems was carried out by apparent average hydrodynamic diameter and rheological measurements as well as different analytical techniques including Trp fluorescence, UV spectroscopy, DSC, FTIR and SEM; and delivery capacity of casein micelles was determined by in vitro experiments promoting ritonavir release. Results Ritonavir interacted efficiently with milk proteins, especially, casein micelles, regardless of the processing pressure; however, results suggest that, at 0.1 MPa, ritonavir interacts with caseins at the micellar surface, whilst, at 300 and 500 MPa, ritonavir is integrated to the protein matrix during UHPH treatment. Likewise, in vitro experiments showed that ritonavir release from micellar casein systems is pH dependent; with a high retention of ritonavir during simulated gastric digestion and a rapid delivery under conditions simulating the small intestine environment. Conclusions Skim milk powder, especially, casein micelles are potentially suitable and efficient carrier systems to develop novel milk-based and low-ethanol powder formulations of ritonavir appropriate for pediatric applications. PMID:25270571

Use of computer-assisted drug therapy outside the operating room.

PubMed

Singh, Preet Mohinder; Borle, Anuradha; Goudra, Basavana G

2016-08-01

The number of procedures performed in the out-of-operating room setting under sedation has increased many fold in recent years. Sedation techniques aim to achieve rapid patient turnover through the use of short-acting drugs with minimal residual side-effects (mainly propofol and opioids). Even for common procedures, the practice of sedation delivery varies widely among providers. Computer-based sedation models have the potential to assist sedation providers and offer a more consistent and safer sedation experience for patients. Target-controlled infusions using propofol and other short-acting opioids for sedation have shown promising results in terms of increasing patient safety and allowing for more rapid wake-up times. Target-controlled infusion systems with real-time patient monitoring can titrate drug doses automatically to maintain optimal depth of sedation. The best recent example of this is the propofol-based Sedasys sedation system. Sedasys redefined individualized sedation by the addition of an automated clinical parameter that monitors depth of sedation. However, because of poor adoption and cost issues, it has been recently withdrawn by the manufacturer. Present automated drug delivery systems can assist in the provision of sedation for out-of-operating room procedures but cannot substitute for anesthesia providers. Use of the available technology has the potential to improve patient outcomes, decrease provider workload, and have a long-term economic impact on anesthesia care delivery outside of the operating room.

Targeted nanomedicine for cancer therapeutics: Towards precision medicine overcoming drug resistance.

PubMed

Bar-Zeev, Maya; Livney, Yoav D; Assaraf, Yehuda G

2017-03-01

Intrinsic anticancer drug resistance appearing prior to chemotherapy as well as acquired resistance due to drug treatment, remain the dominant impediments towards curative cancer therapy. Hence, novel targeted strategies to overcome cancer drug resistance constitute a key aim of cancer research. In this respect, targeted nanomedicine offers innovative therapeutic strategies to overcome the various limitations of conventional chemotherapy, enabling enhanced selectivity, early and more precise cancer diagnosis, individualized treatment as well as overcoming of drug resistance, including multidrug resistance (MDR). Delivery systems based on nanoparticles (NPs) include diverse platforms enabling a plethora of rationally designed therapeutic nanomedicines. Here we review NPs designed to enhance antitumor drug uptake and selective intracellular accumulation using strategies including passive and active targeting, stimuli-responsive drug activation or target-activated release, triggered solely in the cancer cell or in specific organelles, cutting edge theranostic multifunctional NPs delivering drug combinations for synergistic therapy, while facilitating diagnostics, and personalization of therapeutic regimens. In the current paper we review the recent findings of the past four years and discuss the advantages and limitations of the various novel NPs-based drug delivery systems. Special emphasis is put on in vivo study-based evidences supporting significant therapeutic impact in chemoresistant cancers. A future perspective is proposed for further research and development of complex targeted, multi-stage responsive nanomedical drug delivery systems for personalized cancer diagnosis and efficacious therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of the interaction forces in a drug carrier complex of doxorubicin with a drug-binding peptide.

PubMed

Gocheva, Gergana; Ilieva, Nina; Peneva, Kalina; Ivanova, Anela

2018-04-01

Polypeptide-based materials are used as building blocks for drug delivery systems aimed at toxicity decrease in chemotherapeutics. A molecular-level approach is adopted for investigating the non-covalent interactions between doxorubicin and a recently synthesized drug-binging peptide as a key part of a system for delivery to neoplastic cells. Molecular dynamics simulations in aqueous solution at room and body temperature are applied to investigate the structure and the binding modes within the drug-peptide complex. The tryptophans are outlined as the main chemotherapeutic adsorption sites, and the importance of their placement in the peptide sequence is highlighted. The drug-peptide binging energy is evaluated by density functional theory calculations. Principal component analysis reveals comparable importance of several types of interaction for the binding strength. π-Stacking is dominant, but other factors are also significant: intercalation, peptide backbone stacking, electrostatics, dispersion, and solvation. Intra- and intermolecular H-bonding also stabilizes the complexes. The influence of solvent molecules on the binding energy is mild. The obtained data characterize the drug-to-peptide attachment as a mainly attractive collective process with interactions spanning a broad range of values. These results explain with atomistic detail the experimentally registered doxorubicin-binging ability of the peptide and outline the complex as a prospective carrying unit that can be employed in design of drug delivery systems. © 2017 John Wiley & Sons A/S.

Combination of injectable ethinyl estradiol and drospirenone drug-delivery systems and characterization of their in vitro release.

PubMed

Nippe, Stefanie; General, Sascha

2012-11-20

Our aim was to investigate the in vitro release and combination of ethinyl estradiol (EE) and drospirenone (DRSP) drug-delivery systems. DRSP poly(lactic-co-glycolic acid) (PLGA) microparticles and organogels containing DRSP microcrystals were prepared and characterized with regard to properties influencing drug release. The morphology and release kinetics of DRSP PLGA microparticles indicated that DRSP is dispersed in the polymer. The in vitro release profiles correlated well with in vivo data. Although DRSP degradation is known to be acid-catalyzed, DRSP was relatively stable in the PLGA matrix. Aqueous DRSP PLGA microparticle suspensions were combinable with EE PLGA microparticles and EE poly(butylcyanoacrylate) (PBCA) microcapsules without interacting. EE release from PLGA microparticles was faster than DRSP release; EE release is assumed to be primarily controlled by drug diffusion. Liquid-filled EE PBCA microcapsules were shown to be more robust than air-filled EE PBCA microcapsules; the bursting of microcapsules accelerating the drug delivery was therefore delayed. The drug release profile for DRSP organogels was fairly linear with the square root of time. The system was not combinable with EE PBCA microcapsules. In contrast, incorporation of EE PLGA microparticles in organogels resulted in prolonged EE release. The drug release of EE and DRSP was thus approximated. Copyright © 2012 Elsevier B.V. All rights reserved.

Bis-quaternary gemini surfactants as components of nonviral gene delivery systems: a comprehensive study from physicochemical properties to membrane interactions.

PubMed

Cardoso, Ana M; Morais, Catarina M; Silva, Sandra G; Marques, Eduardo F; de Lima, Maria C Pedroso; Jurado, Maria Amália S

2014-10-20

Gemini surfactants have been successfully used as components of gene delivery systems. In the present work, a family of gemini surfactants, represented by the general structure [CmH2m+1(CH3)2N(+)(CH2)sN(+)(CH3)2CmH2m+1]2Br(-), or simply m-s-m, was used to prepare cationic gene carriers, aiming at their application in transfection studies. An extensive characterization of the gemini surfactant-based complexes, produced with and without the helper lipids cholesterol and DOPE, was carried out in order to correlate their physico-chemical properties with transfection efficiency. The most efficient complexes were those containing helper lipids, which, combining amphiphiles with propensity to form structures with different intrinsic curvatures, displayed a morphologically labile architecture, putatively implicated in the efficient DNA release upon complex interaction with membranes. While complexes lacking helper lipids were translocated directly across the lipid bilayer, complexes containing helper lipids were taken up by cells also by macropinocytosis. This study contributes to shed light on the relationship between important physico-chemical properties of surfactant-based DNA vectors and their efficiency to promote gene transfer, which may represent a step forward to the rational design of gene delivery systems. Copyright © 2014 Elsevier B.V. All rights reserved.

The effectiveness of introducing Group Prenatal Care (GPC) in selected health facilities in a district of Bangladesh: study protocol.

PubMed

Sultana, Marufa; Mahumud, Rashidul Alam; Ali, Nausad; Ahmed, Sayem; Islam, Ziaul; Khan, Jahangir A M; Sarker, Abdur Razzaque

2017-01-31

Despite high rates of antenatal care and relatively good access to health facilities, maternal and neonatal mortality remain high in Bangladesh. There is an immediate need for implementation of evidence-based, cost-effective interventions to improve maternal and neonatal health outcomes. The aim of the study is to assess the effect of the intervention namely Group Prenatal Care (GPC) on utilization of standard number of antenatal care, post natal care including skilled birth attendance and institutional deliveries instead of usual care. The study is quasi-experimental in design. We aim to recruit 576 pregnant women (288 interventions and 288 comparisons) less than 20 weeks of gestational age. The intervention will be delivered over around 6 months. The outcome measure is the difference in maternal service coverage including ANC and PNC coverage, skilled birth attendance and institutional deliveries between the intervention and comparison group. Findings from the research will contribute to improve maternal and newborn outcome in our existing health system. Findings of the research can be used for planning a new strategy and improving the health outcome for Bangladeshi women. Finally addressing the maternal health goal, this study is able to contribute to strengthening health system.

Promoting tissue regeneration by modulating the immune system.

PubMed

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support existing regenerative strategies or could be an alternative to using stem cells and growth factors. The first part of this review we highlight key immune mechanisms involved in the tissue healing process and marks them as potential target for designing regenerative strategies. In the second part, we discuss various approaches using biomaterials and drug delivery systems that aim at modulating the components of the immune system to promote tissue regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and Transdermal Application.

PubMed

Jain, Shashank; Patel, Niketkumar; Shah, Mansi K; Khatri, Pinak; Vora, Namrata

2017-02-01

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid-based delivery systems (vesicular carriers and lipid particulate systems) have been the most successful. Vesicular carriers consist of liposomes, ultradeformable liposomes, and ethosomes, while lipid particulate systems consist of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers. These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Ultradeformable Liposomes: a Novel Vesicular Carrier For Enhanced Transdermal Delivery of Procyanidins: Effect of Surfactants on the Formation, Stability, and Transdermal Delivery.

PubMed

Chen, Rencai; Li, Rongli; Liu, Qian; Bai, Chao; Qin, Benlin; Ma, Yue; Han, Jing

2017-07-01

The aims of this work were to develop a novel vesicular carrier, procyanidins, ultradeformable liposomes (PUDLs), to expand the applications for procyanidins, and increase their stability and transdermal delivery. In this study, we prepared procyanidins ultradeformable liposomes using thin film hydration method and evaluated their encapsulation efficiency, vesicle deformability, storage stability, and skin permeation in vitro. The influence of different surfactants on the properties of PUDLs was also investigated. The results obtained showed that the PUDLs containing Tween 80 had a high entrapment efficiency (80.27 ± 0.99%), a small particle size (140.6 ± 19 nm), high elasticity, and prolonged drug release. Compared with procyanidins solution, the stability of procyanidins in PUDLs improved significantly when stored at 4, 25, and 30°C. The penetration rate of PUDLs was 6.25-fold greater than that of procyanidins solution. Finally, the results of our study suggested that PUDLs could increase the transdermal flux, prolong the release and improve the stability of procyanidins, and could serve as an effective dermal delivery system for procyanidins.

Intra Articular Therapeutic Delivery for Post Traumatic Osteoarthritis

DTIC Science & Technology

2016-10-01

method. Our central hypotheses are that joint retention time and therapeutic efficacy will be influenced by amniotic membrane particle size ...three Specific Aims: Aim 1: Evaluate the effects of human amniotic membrane (AM) particle size distribution on particle retention and progression of OA...following trauma. Factors we hypothesized would impact therapeutic efficacy of dHACM included particle size , timing of treatment, and frequency of delivery

Creating learning environments.

PubMed

Ollier, D

1995-01-01

The Healthcare Forum Journal has compiled this compendium to serve as a resource in building learning organizations. Our aim is to help healthcare organizations, policymakers, and others (payers, providers, patients, physicians, and citizens) rethink the system of healthcare delivery by opening up a dialogue--the ideas presented in Sandra Seagal's interview, ¿The Pillars of Learning¿, provide the groundwork for understanding how human dynamics impact learning, and the further resources section offers readers an annotated bibliography on the subject, as well as a listing of organizations that focus on systems thinking and how to create organizations that continually learn.

Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems.

PubMed

Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I

2018-05-17

Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing. Copyright © 2018 Elsevier B.V. All rights reserved.

Current and emerging lipid-based systems for transdermal drug delivery.

PubMed

Singla, Sumeet K; Sachdeva, Vishal

2015-01-01

Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

Delivery of Forecasted Atmospheric Ozone and Dust for the New Mexico Environmental Public Health Tracking System - An Open Source Geospatial Solution

NASA Astrophysics Data System (ADS)

Hudspeth, W. B.; Sanchez-Silva, R.; Cavner, J. A.

2010-12-01

New Mexico's Environmental Public Health Tracking System (EPHTS), funded by the Centers for Disease Control (CDC) Environmental Public Health Tracking Network (EPHTN), aims to improve health awareness and services by linking health effects data with levels and frequency of environmental exposure. As a public health decision-support system, EPHTS systems include: state-of-the-art statistical analysis tools; geospatial visualization tools; data discovery, extraction, and delivery tools; and environmental/public health linkage information. As part of its mandate, EPHTS issues public health advisories and forecasts of environmental conditions that have consequences for human health. Through a NASA-funded partnership between the University of New Mexico and the University of Arizona, NASA Earth Science results are fused into two existing models (the Dust Regional Atmospheric Model (DREAM) and the Community Multiscale Air Quality (CMAQ) model) in order to improve forecasts of atmospheric dust, ozone, and aerosols. The results and products derived from the outputs of these models are made available to an Open Source mapping component of the New Mexico EPHTS. In particular, these products are integrated into a Django content management system using GeoDjango, GeoAlchemy, and other OGC-compliant geospatial libraries written in the Python and C++ programming languages. Capabilities of the resultant mapping system include indicator-based thematic mapping, data delivery, and analytical capabilities. DREAM and CMAQ outputs can be inspected, via REST calls, through temporal and spatial subsetting of the atmospheric concentration data across analytical units employed by the public health community. This paper describes details of the architecture and integration of NASA Earth Science into the EPHTS decision-support system.

Fighting cancer with nanomedicine---drug-polyester nanoconjugates for targeted cancer therapy

NASA Astrophysics Data System (ADS)

Yin, Qian

The aim of my Ph. D. research is to develop drug-polyester nanoconjugates (NCs) as a novel translational polymeric drug delivery system that can successfully evade non-specific uptake by reticuloendothelial system (RES) and facilitate targeted cancer diagnosis and therapy. By uniquely integrating well-established chemical reaction-controlled ring opening polymerization (ROP) with nanoprecipitation technique, I successfully developed a polymeric NC system based on poly(lactic acid) and poly(O-carboxyanhydrides) (OCA) that allows for the quantitative loading and controlled release of a variety of anticancer drugs. The developed NC system could be easily modified with parmidronate, one of bisphosphonates commonly used as the treatment for disease characterized by osteolysis, to selectively deliver doxorubicin (Doxo) to the bone tissues and substantially to improve their therapeutic efficiency in inhibiting the growth of osteosarcoma in both murine and canine models. More importantly, the developed NCs could avidly bind to human serum albumin, a ubiquitous protein in the blood, to bypass the endothelium barrier and penetrate into tumor tissues more deeply and efficiently. When compared with PEGylated NCs, these albumin-bound NCs showed significantly reduced accumulation in RES and enhanced tumor accumulation, which consequently contributed to higher their tumor inhibition capabilities. In addition, the developed NC system allows easy incorporation of X-ray computed tomography (CT) contrast agents to largely facilitate personalized therapy by improving diagnosis accuracy and monitoring therapeutic efficacy. Through the synthetic and formulation strategy I developed, a large quantity (grams or larger-scale) of drug-polyester NCs can be easily obtained, which can be used as a model drug delivery system for fundamental studies as well as a real drug delivery system for disease treatment in clinical settings.

Using systems thinking to identify workforce enablers for a whole systems approach to urgent and emergency care delivery: a multiple case study.

PubMed

Manley, Kim; Martin, Anne; Jackson, Carolyn; Wright, Toni

2016-08-09

Overcrowding in emergency departments is a global issue, which places pressure on the shrinking workforce and threatens the future of high quality, safe and effective care. Healthcare reforms aimed at tackling this crisis have focused primarily on structural changes, which alone do not deliver anticipated improvements in quality and performance. The purpose of this study was to identify workforce enablers for achieving whole systems urgent and emergency care delivery. A multiple case study design framed around systems thinking was conducted in South East England across one Trust consisting of five hospitals, one community healthcare trust and one ambulance trust. Data sources included 14 clinical settings where upstream or downstream pinch points are likely to occur including discharge planning and rapid response teams; ten regional stakeholder events (n = 102); a qualitative survey (n = 48); and a review of literature and analysis of policy documents including care pathways and protocols. The key workforce enablers for whole systems urgent and emergency care delivery identified were: clinical systems leadership, a single integrated career and competence framework and skilled facilitation of work based learning. In this study, participants agreed that whole systems urgent and emergency care allows for the design and implementation of care delivery models that meet complexity of population healthcare needs, reduce duplication and waste and improve healthcare outcomes and patients' experiences. For this to be achieved emphasis needs to be placed on holistic changes in structures, processes and patterns of the urgent and emergency care system. Often overlooked, patterns that drive the thinking and behavior in the workplace directly impact on staff recruitment and retention and the overall effectiveness of the organization. These also need to be attended to for transformational change to be achieved and sustained. Research to refine and validate a single integrated career and competence framework and to develop standards for an integrated approach to workplace facilitation to grow the capacity of facilitators that can use the workplace as a resource for learning is needed.

Superparamagnetic Iron Oxide Nanoparticle-Based Delivery Systems for Biotherapeutics

PubMed Central

Mok, Hyejung; Zhang, Miqin

2014-01-01

Introduction Superparamagnetic iron oxide nanoparticle (SPION)-based carrier systems have many advantages over other nanoparticle-based systems. They are biocompatible, biodegradable, facilely tunable, and superparamagnetic and thus controllable by an external magnetic field. These attributes enable their broad biomedical applications. In particular, magnetically-driven carriers are drawing considerable interest as an emerging therapeutic delivery system because of their superior delivery efficiency. Area covered This article reviews the recent advances in use of SPION-based carrier systems to improve the delivery efficiency and target specificity of biotherapeutics. We examine various formulations of SPION-based delivery systems, including SPION micelles, clusters, hydrogels, liposomes, and micro/nanospheres, as well as their specific applications in delivery of biotherapeutics. Expert opinion Recently, biotherapeutics including therapeutic cells, proteins and genes have been studied as alternative treatments to various diseases. Despite the advantages of high target specificity and low adverse effects, clinical translation of biotherapeutics has been hindered by the poor stability and low delivery efficiency compared to chemical drugs. Accordingly, biotherapeutic delivery systems that can overcome these limitations are actively pursued. SPION-based materials can be ideal candidates for developing such delivery systems because of their excellent biocompatibility and superparamagnetism that enables long-term accumulation/retention at target sites by utilization of a suitable magnet. In addition, synthesis technologies for production of finely-tuned, homogeneous SPIONs have been well developed, which may promise their rapid clinical translation. PMID:23199200

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.

Magnetic responsive of paclitaxel delivery system based on SPION and palmitoyl chitosan

NASA Astrophysics Data System (ADS)

Mansouri, Mona; Nazarpak, Masoumeh Haghbin; Solouk, Atefeh; Akbari, Somaye; Hasani-Sadrabadi, Mohammad Mahdi

2017-01-01

Concerns over cancer treatment have largely focused on chemotherapy and its consequent side effects. Utilizing nanocarriers is thought to be a panacea for mitigating the limitations of chemotherapy, and increasing its safety and efficacy. Magnetically driven Paclitaxel delivery systems are among the commonly investigated types of nanocarriers over the last two decades. In this context, we tried to highlight the application of an AC magnetic field and validate its consequential effects on drug delivery pattern and cell death in such nanodevices. So the aim of this study is to develop an appropriate matrix (Palmitoyl chitosan) co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) and anticancer drug, Paclitaxel (PTX) via the nanoprecipitation process. Synthesized nanoparticles were characterized by Dynamic Light Scattering (DLS) and their magnetic properties were investigated by Vibrating Sample Magnetometer (VSM). At initial loading of 10 wt% Paclitaxel, the maximum loading efficiency of nanoparticles with and without SPIONs was in the range of 69% and 72.3%, respectively. In addition, in vitro release data revealed that by the application of a magnetic field, release kinetic changed to the magnetic responsive pattern. Encapsulating anticancer drug in a synthesized nanosystem not only increased the amount of drug in cancer cells but also enhanced cell death (MCF-7) due to hyperthermic effects of SPIONs in the presence of an external magnetic field. In summary, these findings indicate that the resultant nanoparticles may serve as a biocompatible and biodegradable carrier for the precise delivery of powerful cytotoxic anticancer agents such as PTX.

Comparing mandated health care reforms: the Affordable Care Act, accountable care organizations, and the Medicare ESRD program.

PubMed

Watnick, Suzanne; Weiner, Daniel E; Shaffer, Rachel; Inrig, Jula; Moe, Sharon; Mehrotra, Rajnish

2012-09-01

In addition to extending health insurance coverage, the Affordable Care Act of 2010 aims to improve quality of care and contain costs. To this end, the act allowed introduction of bundled payments for a range of services, proposed the creation of accountable care organizations (ACOs), and established the Centers for Medicare and Medicaid Innovation to test new care delivery and payment models. The ACO program began April 1, 2012, along with demonstration projects for bundled payments for episodes of care in Medicaid. Yet even before many components of the Affordable Care Act are fully in place, the Medicare ESRD Program has instituted legislatively mandated changes for dialysis services that resemble many of these care delivery reform proposals. The ESRD program now operates under a fully bundled, case-mix adjusted prospective payment system and has implemented Medicare's first-ever mandatory pay-for-performance program: the ESRD Quality Incentive Program. As ACOs are developed, they may benefit from the nephrology community's experience with these relatively novel models of health care payment and delivery reform. Nephrologists are in a position to assure that the ACO development will benefit from the ESRD experience. This article reviews the new ESRD payment system and the Quality Incentive Program, comparing and contrasting them with ACOs. Better understanding of similarities and differences between the ESRD program and the ACO program will allow the nephrology community to have a more influential voice in shaping the future of health care delivery in the United States.

Hyaluronic acid modified pH-sensitive liposomes for targeted intracellular delivery of doxorubicin.

PubMed

Paliwal, Shivani Rai; Paliwal, Rishi; Agrawal, Govind Prasad; Vyas, Suresh Prasad

2016-12-01

Surface-modified pH-sensitive liposomal system may be useful for intracellular delivery of chemotherapeutics. Achieving site-specific targeting with over-expressed hyaluronic acid (HA) receptors along with using pH sensitive liposome carrier for intracellular drug delivery was the aim of this study. Stealth HA-targeted pH-sensitive liposomes (SL-pH-HA) were developed and evaluated to achieve effective intracellular delivery of doxorubicin (DOX) vis-a-vis enhanced antitumor activity. The in vitro release studies demonstrated that the release of DOX from SL-pH-HA was pH-dependent, i.e. faster at mildly acidic pH ∼5, compared to physiological pH ∼7.4. SLpH-HA was evaluated for their cytotoxicity potential on CD44 receptor expressing MCF-7 cells. The half maximal inhibitory concentration (IC50) of SL-pH-HA and SL-HA were about 1.9 and 2.5 μM, respectively, after 48 h of incubation. The quantitative uptake study revealed higher localization of targeted liposomes in the receptor positive cells, which was further confirmed by fluorescent microscopy. The antitumor efficacy of the DOX-loaded HA-targeted pH-sensitive liposomes was also verified in a tumor xenograft mouse model. DOX was efficiently delivered to the tumor site by active targeting via HA and CD44 receptor interaction. The major side-effect of conventional DOX formulation, i.e. cardiotoxicity was also estimated by measuring serum enzyme levels of LDH and CPK and found to be minimized with developed formulation. Overall, HA targeted pH-sensitive liposomes were significantly more potent than the non-targeted liposomes in cells expressing high levels of CD44. Results strongly implies the promise of such liposomal system as an intracellular drug delivery carrier developed for potential anticancer treatment.

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.

In vitro and in vivo evaluation of a water-in-oil microemulsion system for enhanced peptide intestinal delivery.

PubMed

Liu, Dongyun; Kobayashi, Taku; Russo, Steven; Li, Fengling; Plevy, Scott E; Gambling, Todd M; Carson, Johnny L; Mumper, Russell J

2013-01-01

Peptide and protein drugs have become the new generation of therapeutics, yet most of them are only available as injections, and reports on oral local intestinal delivery of peptides and proteins are quite limited. The aim of this work was to develop and evaluate a water-in-oil (w/o) microemulsion system in vitro and in vivo for local intestinal delivery of water-soluble peptides after oral administration. A fluorescent labeled peptide, 5-(and-6)-carboxytetramethylrhodamine labeled HIV transactivator protein TAT (TAMRA-TAT), was used as a model peptide. Water-in-oil microemulsions consisting of Miglyol 812, Capmul MCM, Tween 80, and water were developed and characterized in terms of appearance, viscosity, conductivity, morphology, and particle size analysis. TAMRA-TAT was loaded and its enzymatic stability was assessed in modified simulated intestinal fluid (MSIF) in vitro. In in vivo studies, TAMRA-TAT intestinal distribution was evaluated using fluorescence microscopy after TAMRA-TAT microemulsion, TAMRA-TAT solution, and placebo microemulsion were orally gavaged to mice. The half-life of TAMRA-TAT in microemulsion was enhanced nearly three-fold compared to that in the water solution when challenged by MSIF. The treatment with TAMRA-TAT microemulsion after oral administration resulted in greater fluorescence intensity in all intestine sections (duodenum, jejunum, ileum, and colon) compared to TAMRA-TAT solution or placebo microemulsion. The in vitro and in vivo studies together suggested TAMRA-TAT was better protected in the w/o microemulsion in an enzyme-containing environment, suggesting that the w/o microemulsions developed in this study may serve as a potential delivery vehicle for local intestinal delivery of peptides or proteins after oral administration.

Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems--enhancement of oral bioavailability.

PubMed

Hashem, Fahima M; Al-Sawahli, Majid M; Nasr, Mohamed; Ahmed, Osama A A

2015-01-01

Poor water solubility of a drug is a major challenge in drug delivery research and a main cause for limited bioavailability and pharmacokinetic parameters. This work aims to utilize custom fractional factorial design to assess the development of self-nanoemulsifying drug delivery systems (SNEDDS) and solid nanosuspensions (NS) in order to enhance the oral delivery of atorvastatin (ATR). According to the design, 14 experimental runs of ATR SNEDDS were formulated utilizing the highly ATR solubilizing SNEDDS components: oleic acid, Tween 80, and propylene glycol. In addition, 12 runs of NS were formulated by the antisolvent precipitation-ultrasonication method. Optimized formulations of SNEDDS and solid NS, deduced from the design, were characterized. Optimized SNEDDS formula exhibited mean globule size of 73.5 nm, zeta potential magnitude of -24.1 mV, and 13.5 μs/cm of electrical conductivity. Optimized solid NS formula exhibited mean particle size of 260.3 nm, 7.4 mV of zeta potential, and 93.2% of yield percentage. Transmission electron microscopy showed SNEDDS droplets formula as discrete spheres. The solid NS morphology showed flaky nanoparticles with irregular shapes using scanning electron microscopy. The release behavior of the optimized SNEDDS formula showed 56.78% of cumulative ATR release after 10 minutes. Solid NS formula showed lower rate of release in the first 30 minutes. Bioavailability estimation in Wistar albino rats revealed an augmentation in ATR bioavailability, relative to ATR suspension and the commercial tablets, from optimized ATR SNEDDS and NS formulations by 193.81% and 155.31%, respectively. The findings of this work showed that the optimized nanocarriers enhance the oral delivery and pharmacokinetic profile of ATR.

p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

NASA Astrophysics Data System (ADS)

Swami, Rajan; Singh, Indu; Kulhari, Hitesh; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

2015-06-01

Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by 1HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere®). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases.

PubMed

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H F; Karla, Pradeep K; Boddu, Sai H S

2018-02-27

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.

Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

PubMed Central

Bachu, Rinda Devi; Chowdhury, Pallabitha; Al-Saedi, Zahraa H. F.; Karla, Pradeep K.; Boddu, Sai H. S.

2018-01-01

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed. PMID:29495528

Comparison of double intravenous vasopressor automated system using nexfin versus manual vasopressor bolus administration for maintenance of haemodynamic stability during spinal anaesthesia for caesarean delivery: A randomised double-blind controlled trial.

PubMed

Sng, Ban Leong; Du, Wei; Lee, Man Xin; Ithnin, Farida; Mathur, Deepak; Leong, Wan Ling; Sultana, Rehena; Han, Nian-Lin R; Sia, Alex Tiong Heng

2018-05-01

Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. A randomised, double-blind controlled trial. Single-centre, KK Women's and Children's Hospital, Singapore. Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; P < 0.0001). There was no difference in the incidence of reactive hypertension or the total vasopressor requirement. The DIVA group had less wobble in system performance. Maternal and neonatal outcomes were similar. The DIVA system achieved better control of maternal blood pressure after spinal anaesthesia than manual vasopressor bolus administration. Clinicaltrials.gov identifier: NCT02277730.

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

An update on applications of nanostructured drug delivery systems in cancer therapy: a review.

PubMed

Aberoumandi, Seyed Mohsen; Mohammadhosseini, Majid; Abasi, Elham; Saghati, Sepideh; Nikzamir, Nasrin; Akbarzadeh, Abolfazl; Panahi, Yunes; Davaran, Soodabeh

2017-09-01

Cancer is a main public health problem that is known as a malignant tumor and out-of-control cell growth, with the potential to assault or spread to other parts of the body. Recently, remarkable efforts have been devoted to develop nanotechnology to improve the delivery of anticancer drug to tumor tissue as minimizing its distribution and toxicity in healthy tissue. Nanotechnology has been extensively used in the advance of new strategies for drug delivery and cancer therapy. Compared to customary drug delivery systems, nano-based drug delivery method has greater potential in different areas, like multiple targeting functionalization, in vivo imaging, extended circulation time, systemic control release, and combined drug delivery. Nanofibers are used for different medical applications such as drug delivery systems.

The influence of distance and level of care on delivery place in rural Zambia: a study of linked national data in a geographic information system.

PubMed

Gabrysch, Sabine; Cousens, Simon; Cox, Jonathan; Campbell, Oona M R

2011-01-25

Maternal and perinatal mortality could be reduced if all women delivered in settings where skilled attendants could provide emergency obstetric care (EmOC) if complications arise. Research on determinants of skilled attendance at delivery has focussed on household and individual factors, neglecting the influence of the health service environment, in part due to a lack of suitable data. The aim of this study was to quantify the effects of distance to care and level of care on women's use of health facilities for delivery in rural Zambia, and to compare their population impact to that of other important determinants. Using a geographic information system (GIS), we linked national household data from the Zambian Demographic and Health Survey 2007 with national facility data from the Zambian Health Facility Census 2005 and calculated straight-line distances. Health facilities were classified by whether they provided comprehensive EmOC (CEmOC), basic EmOC (BEmOC), or limited or substandard services. Multivariable multilevel logistic regression analyses were performed to investigate the influence of distance to care and level of care on place of delivery (facility or home) for 3,682 rural births, controlling for a wide range of confounders. Only a third of rural Zambian births occurred at a health facility, and half of all births were to mothers living more than 25 km from a facility of BEmOC standard or better. As distance to the closest health facility doubled, the odds of facility delivery decreased by 29% (95% CI, 14%-40%). Independently, each step increase in level of care led to 26% higher odds of facility delivery (95% CI, 7%-48%). The population impact of poor geographic access to EmOC was at least of similar magnitude as that of low maternal education, household poverty, or lack of female autonomy. Lack of geographic access to emergency obstetric care is a key factor explaining why most rural deliveries in Zambia still occur at home without skilled care. Addressing geographic and quality barriers is crucial to increase service use and to lower maternal and perinatal mortality. Linking datasets using GIS has great potential for future research and can help overcome the neglect of health system factors in research and policy. Please see later in the article for the Editors' Summary.

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.

A Novel Nonviral Gene Delivery System: Multifunctional Envelope-Type Nano Device

NASA Astrophysics Data System (ADS)

Hatakeyama, Hiroto; Akita, Hidetaka; Kogure, Kentaro; Harashima, Hideyoshi

In this review we introduce a new concept for developing a nonviral gene delivery system which we call "Programmed Packaging." Based on this concept, we succeeded in developing a multifunctional envelope-type nano device (MEND), which exerts high transfection activities equivalent to those of an adenovirus in a dividing cell. The use of MEND has been extended to in vivo applications. PEG/peptide/DOPE ternary conjugate (PPD)-MEND, a new in vivo gene delivery system for the targeting of tumor cells that dissociates surface-modified PEG in tumor tissue by matrix metalloproteinase (MMP) and exerts significant transfection activities, was developed. In parallel with the development of MEND, a quantitative gene delivery system, Confocal Image-assisted 3-dimensionally integrated quantification (CIDIQ), also was developed. This method identified the rate-limiting step of the nonviral gene delivery system by comparing it with adenoviral-mediated gene delivery. The results of this analysis provide a new direction for the development of rational nonviral gene delivery systems.

Sonographic large fetal head circumference and risk of cesarean delivery.

PubMed

Lipschuetz, Michal; Cohen, Sarah M; Israel, Ariel; Baron, Joel; Porat, Shay; Valsky, Dan V; Yagel, Oren; Amsalem, Hagai; Kabiri, Doron; Gilboa, Yinon; Sivan, Eyal; Unger, Ron; Schiff, Eyal; Hershkovitz, Reli; Yagel, Simcha

2018-03-01

Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4-2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5-minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo.

PubMed

Obata, Yosuke; Tajima, Shoji; Takeoka, Shinji

2010-03-03

We developed pH-responsive liposomes containing synthetic glutamic acid-based zwitterionic lipids and evaluated their properties both in vitro and in vivo with the aim of constructing an efficient liposome-based systemic drug delivery system. The glutamic acid-based lipids; 1,5-dihexadecyl N-glutamyl-L-glutamate (L1) and 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (L2) were synthesized as a pH-responsive component of liposomes that respond to endosomal pH. The zeta potential of liposomes containing L1 or L2 was positive when the solution pH was below 4.6 or 5.6, respectively, but negative at higher pH values. The pH-responsive liposomes showed improved fusogenic potential to an endosome-mimicking anionic membrane at acidic pH, where the zeta potential of the liposomes was positive. We then prepared doxorubicin (DOX)-encapsulating liposomes containing L1 or L2, and clarified by confocal microscopic studies that the contents were rapidly transferred into both the cytoplasm and nucleus. Release of DOX from the endosomes mediated by the pH-responsive liposomes dramatically inhibited cancer cell growth. The L2-liposomes were slightly more effective than L1-liposomes as a drug delivery system. Intravenously injected L2-liposomes displayed blood persistence comparable to that of conventional phospholipid (PC)-based liposomes. Indeed, the antitumor efficacy of L2-liposomes was higher than that of PC-based liposomes against a xenograft breast cancer tumor in vivo. Thus, the high performance of L2-liposomes results from both efficient intracellular drug delivery and comparable blood persistence in comparison with the conventional PC-based liposomes in vitro and in vivo. Copyright 2009 Elsevier B.V. All rights reserved.

A method to assess obstetric outcomes using the 10-Group Classification System: a quantitative descriptive study.

PubMed

Rossen, Janne; Lucovnik, Miha; Eggebø, Torbjørn Moe; Tul, Natasa; Murphy, Martina; Vistad, Ingvild; Robson, Michael

2017-07-12

Internationally, the 10-Group Classification System (TGCS) has been used to report caesarean section rates, but analysis of other outcomes is also recommended. We now aim to present the TGCS as a method to assess outcomes of labour and delivery using routine collection of perinatal information. This research is a methodological study to describe the use of the TGCS. Stavanger University Hospital (SUH), Norway, National Maternity Hospital Dublin, Ireland and Slovenian National Perinatal Database (SLO), Slovenia. 9848 women from SUH, Norway, 9250 women from National Maternity Hospital Dublin, Ireland and 106 167 women, from SLO, Slovenia. All women were classified according to the TGCS within which caesarean section, oxytocin augmentation, epidural analgesia, operative vaginal deliveries, episiotomy, sphincter rupture, postpartum haemorrhage, blood transfusion, maternal age >35 years, body mass index >30, Apgar score, umbilical cord pH, hypoxic-ischaemic encephalopathy, antepartum and perinatal deaths were incorporated. There were significant differences in the sizes of the groups of women and the incidences of events and outcomes within the TGCS between the three perinatal databases. The TGCS is a standardised objective classification system where events and outcomes of labour and delivery can be incorporated. Obstetric core events and outcomes should be agreed and defined to set standards of care. This method provides continuous and available observations from delivery wards, possibly used for further interpretation, questions and international comparisons. The definition of quality may vary in different units and can only be ascertained when all the necessary information is available and considered together. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Tailoring magnetic PLGA nanoparticles suitable for doxorubicin delivery

NASA Astrophysics Data System (ADS)

Tansık, Gülistan; Yakar, Arzu; Gündüz, Ufuk

2014-01-01

One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells, which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale-based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an external magnetic field. Thus, the drug can be carried to the targeted site safely. The aim of this study is to prepare poly( dl-lactic- co-glycolic acid) (PLGA)-coated magnetic nanoparticles and load anti-cancer drug, doxorubicin to them. For this purpose, magnetite (Fe3O4) iron oxide nanoparticles were synthesized as a magnetic core material (MNP) and then coated with oleic acid. Oleic acid-coated MNP (OA-MNP) was encapsulated into PLGA. Effects of different OA-MNP/PLGA ratios on magnetite entrapment efficiency were investigated. Doxorubicin-loaded magnetic polymeric nanoparticles (DOX-PLGA-MNP) were prepared. After the characterization of prepared nanoparticles, their cytotoxic effects on MCF-7 cell line were studied. PLGA-coated magnetic nanoparticles (PLGA-MNP) had a proper size and superparamagnetic character. The highest magnetite entrapment efficiency of PLGA-MNP was estimated as 63 % at 1:8 ratio. Cytotoxicity studies of PLGA-MNP did not indicate any notable cell death between the concentration ranges of 2 and 125 μg/ml. Drug loading efficiency was estimated as 32 %, and it was observed that DOX-PLGA-MNP showed significant cytotoxicity on MCF-7 cells compared to PLGA-MNP. The results showed that prepared nanoparticles have desired size and superparamagnetic characteristics without serious toxic effects on cells. These nanoparticles may be suitable for targeted drug delivery applications.

Combination of SEDDS and Preactivated Thiomer Technology: Incorporation of a Preactivated Thiolated Amphiphilic Polymer into Self-Emulsifying Delivery Systems.

PubMed

Hetényi, Gergely; Griesser, Janine; Nardin, Isabelle; Bernkop-Schnürch, Andreas

2017-06-01

The aim of the study was to create novel mucoadhesive drug delivery systems by incorporating amphiphilic hydrophobically modified, thiolated and preactivated polymers (preactivated thiomers) into self-emulsifying drug delivery systems (SEDDS). L-Cysteine methyl ester was covalently attached to the polymeric backbone of Pemulen TR-2 and preactivated using 2-mercaptonicotinic acid (2-MNA). These thiomers were incorporated in a concentration of 0.3% (w/v) into SEDDS. The size distribution and the zeta potential of the emulsions were evaluated by dynamic light scattering. Mucoadhesive properties of thiomers-SEDDS spiked with FDA (fluorescein diacetate) were examined utilizing rheological measurement, permeation studies and in vitro residence time study on porcine mucosa. Cell viability tests were additionally performed. 734 ± 58 μmol L-Cysteine methyl ester and 562 ± 71 μmol 2-MNA could be attached per gram polymer of Pemulen TR-2. Emulsions exhibited a droplet size range between 180 and 270 nm. Blank SEDDS possessed a zeta potential value between -5.7 and -8.6 mV, whereas thiomers-SEDDS between -14.6 and -17.2 mV. Viscous modulus of thiomer and preactivated thiomer containing SEDDS-mucus mixture was 8-fold and 11-fold increased in comparison to reference. The amount of FDA permeated the mucus layer was 2-fold lower in case of thiomers-SEDDS compared to blank SEDDS. A prolonged residence time was observed for thiomers-SEDDS over 45 min. During cell viability studies no severe toxic effects were detected. The novel developed SEDDS with incorporated thiomers might be a promising tool for mucoadhesive oral drug delivery.

Transdermal delivery of AT1 receptor antagonists reduce blood pressure and reveals a vasodilatory effect in kidney blood vessels.

PubMed

Michalatou, Michaila; Androutsou, Maria Eleni; Antonopoulos, Markos; Vlahakos, Demetrios V; Agelis, George; Zulli, Anthony; Qaradakhi, Tawar; Mikkelsen, Kathleen; Apostolopoulos, Vasso; Matsoukas, John

2018-04-19

The Renin Angiotensin System (RAS) is pharmacologically targeted to reduce blood pressure, and patient compliance to oral medications is a clinical issue. The mechanisms of action of angiotensin receptor blockers (ARBs) in reducing blood pressure are not well understood, and is purported to be via a reduction of angiotensin II signaling. We aimed to develop a transdermal delivery method for ARBs (losartan potassium and valsartan) and to determine if ARBs reveal a vasodilatory effect of the novel RAS peptide, alamandine. In addition we determined the anti-hypertensive effects of the transdermal delivery patch. In vitro and in vivo experiments were performed to develop an appropriate therapeutic system, promising an alternative and more effective therapy in the treatment of hypertension. A variety of penetration enhancers were selected such as isopropyl myristate, propylene glycol, transcutol and dimenthyl sulfoxide to obtain a constant release of drugs through human skin. Small resistance vessels (kidney interlobar arteries) were mounted in organ baths and incubated with an ARB. Vasodilatory curves to alamandine were constructed Results: The in vivo studies demonstrates that systemic absorption of valsartan and losartan potassium using the appropriate formulations provides a steady state release and anti-hypertensive effect even after 24 hours of transdermal administration. No apparent skin irritations (erythema, edema) were observed with the tested formulations. We also show that blocking the AT1 receptor of rabbit interlobar arteries in vitro reveals a vasodilatory effect of alamandine. This study reveals potential mechanism of AT1 receptor blockade via alamandine, and is an important contribution in developing a favorable, convenient and painless antihypertensive therapy of prolonged duration through transdermal delivery of AT1 blockers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multi-channel gas-delivery system

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

Rozenzon, Yan; Trujillo, Robert T.; Beese, Steven C.

One embodiment of the present invention provides a gas-delivery system for delivering reaction gas to a reactor chamber. The gas-delivery system includes a main gas-inlet port for receiving reaction gases and a gas-delivery plate that includes a plurality of gas channels. A gas channel includes a plurality of gas holes for allowing the reaction gases to enter the reactor chamber from the gas channel. The gas-delivery system further includes a plurality of sub-gas lines coupling together the main gas-inlet port and the gas-delivery plate, and a respective sub-gas line is configured to deliver a portion of the received reaction gasesmore » to a corresponding gas channel.« less

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.

PubMed

Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Badshah, Shaikh Atik; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

2015-10-09

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

Impact of Introduction of Blended Learning in Gross Anatomy on Student Outcomes

ERIC Educational Resources Information Center

Green, Rodney A.; Whitburn, Laura Y.

2016-01-01

Blended learning has become increasingly common, in a variety of disciplines, to take advantage of new technology and potentially increase the efficiency and flexibility of delivery. This study aimed to describe blended delivery of a gross anatomy course and to evaluate the effectiveness of the delivery in terms of student outcomes. A gross…

Handheld Delivery System for Modified Boron-Type Fire Extinguishment Agent

DTIC Science & Technology

1993-11-01

was to develop and test a handheld portable delivery system for use with the modified boron-type fire extinguishing agent for metal fires . B...BACKGROUND A need exists for an extinguishing agent and accompanying delivery system that are effective against complex geometry metal fires . A modified...agent and its delivery system have proven effective against complex geometry metal fires containing up to 200 pounds of magnesium metal. Further

Status of Statewide Career Information Delivery Systems.

ERIC Educational Resources Information Center

Dunn, Wynonia L.

Intended as a resource document as well as a status report on all the statewide career information delivery systems (CIDS) in operation, this report examines the status of 39 statewide information systems. (Career information delivery systems are computer-based systems that provide national, state, and local information to individuals who are in…

A Systems Approach to Nitrogen Delivery

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

Goins, Bobby

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should bemore » less frustration associated with the delivery process.« less

Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses.

PubMed

Ribeiro, Andreza Maria; Figueiras, Ana; Veiga, Francisco

2015-01-01

Conventional ophthalmic systems present very low corneal systemic bioavailability due to the nasolacrimal drainage and the difficulty to deliver the drug in the posterior segment of ocular tissue. For these reasons, recent advances have focused on the development of new ophthalmic drug delivery systems. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings in soft contact lenses (SCL) and the applications of novel pharmaceutical systems for ocular drug delivery. Among the new therapeutic approaches in ophthalmology, SCL are novel continuous-delivery systems, providing high and sustained levels of drugs to the cornea. The tendency of research in ophthalmic drug delivery systems development are directed towards a combination of several technologies (bio-inspired and molecular imprinting techniques) and materials (cyclodextrins, surfactants, specific monomers). There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but also at the same time slow down the clearance of the drug. Different materials can be applied during the development of contact lenses and can be combined with natural inspired strategies of drug immobilization and release, providing successful tools for ocular drug delivery systems.

Recent developments in leishmaniasis vaccine delivery systems.

PubMed

Bhowmick, Sudipta; Ali, Nahid

2008-07-01

The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

PubMed

Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

2017-08-12

Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-value<0.001). 66% of mothers reported receiving enough information during pregnancy on childhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Building clinical and organizational resilience to reconcile safety threats, tensions and trade-offs: insights from theory and evidence.

PubMed

Jeffs, Lianne; Tregunno, Deborah; MacMillan, Kathleen; Espin, Sherry

2009-01-01

Healthcare delivery settings are complex adaptive and tightly coupled, interrelated systems. Within the larger healthcare system, a key subsystem is the "clinical microsystem" level. It is at this level that clinicians are faced with high levels of uncertainty in their daily work - uncertainty that impacts the quality and safety of care that patients receive. The first aim of this paper is to enhance healthcare leaders' understanding of what is currently known about safety threats and strategies to manage the inherent tensions and trade-offs that occur in everyday practice. The second aim is to inform strategies that build clinical and organizational resilience through a multi-level framework derived from the collective theoretical and empirical work. Together, this information can strengthen safety practices throughout healthcare organizations.

Target isolation system, high power laser and laser peening method and system using same

DOEpatents

Dane, C. Brent; Hackel, Lloyd A.; Harris, Fritz

2007-11-06

A system for applying a laser beam to work pieces, includes a laser system producing a high power output beam. Target delivery optics are arranged to deliver the output beam to a target work piece. A relay telescope having a telescope focal point is placed in the beam path between the laser system and the target delivery optics. The relay telescope relays an image between an image location near the output of the laser system and an image location near the target delivery optics. A baffle is placed at the telescope focal point between the target delivery optics and the laser system to block reflections from the target in the target delivery optics from returning to the laser system and causing damage.

Biodegradable polymers for targeted delivery of anti-cancer drugs.

PubMed

Doppalapudi, Sindhu; Jain, Anjali; Domb, Abraham J; Khan, Wahid

2016-06-01

Biodegradable polymers have been used for more than three decades in cancer treatment and have received increased interest in recent years. A range of biodegradable polymeric drug delivery systems designed for localized and systemic administration of therapeutic agents as well as tumor-targeting macromolecules has entered into the clinical phase of development, indicating the significance of biodegradable polymers in cancer therapy. This review elaborates upon applications of biodegradable polymers in the delivery and targeting of anti-cancer agents. Design of various drug delivery systems based on biodegradable polymers has been described. Moreover, the indication of polymers in the targeted delivery of chemotherapeutic drugs via passive, active targeting, and localized drug delivery are also covered. Biodegradable polymer-based drug delivery systems have the potential to deliver the payload to the target and can enhance drug availability at desired sites. Systemic toxicity and serious side effects observed with conventional cancer therapeutics can be significantly reduced with targeted polymeric systems. Still, there are many challenges that need to be met with respect to the degradation kinetics of the system, diffusion of drug payload within solid tumors, targeting tumoral tissue and tumor heterogeneity.

Role of Components in the Formation of Self-microemulsifying Drug Delivery Systems.

PubMed

Gurram, A K; Deshpande, P B; Kar, S S; Nayak, Usha Y; Udupa, N; Reddy, M S

2015-01-01

Pharmaceutical research is focused in designing novel drug delivery systems to improve the bioavailability of poorly water soluble drugs. Self-microemulsifying drug delivery systems, one among the lipid-based dosage forms were proven to be promising in improving the oral bioavailability of such drugs by enhancing solubility, permeability and avoiding first-pass metabolism via enhanced lymphatic transport. Further, they have been successful in avoiding both inter and intra individual variations as well as the dose disproportionality. Aqueous insoluble drugs, in general, show greater solubility in lipid based excipients, and hence they are formulated as lipid based drug delivery systems. The extent of solubility of a hydrophobic drug in lipid excipients i.e. oil, surfactant and co-surfactant (components of self-microemulsifying drug delivery systems) greatly affects the drug loading and in producing stable self-microemulsifying drug delivery systems. The present review highlighted the influence of physicochemical factors and structural features of the hydrophobic drug on its solubility in lipid excipients and an attempt was made to explore the role of each component of self-microemulsifying drug delivery systems in the formation of stable microemulsion upon dilution.

Microemulsions for Colorectal Cancer Treatments. General Considerations and Formulation of Methotrexate.

PubMed

Flores, Sergio E; Rial-Hermida, M Isabel; Ramirez, Jorge C; Pazos, Alejandro; Concheiro, Angel; Alvarez-Lorenzo, Carmen; Peralta, René D

2016-01-01

Microemulsions combine the advantages of emulsions with those of nanocarriers, overcoming the stability problems of the former and providing facile scalable systems with compartments adequate for high drug loadings. Recently, microemulsions are gaining attention in the formulation of anticancer drugs not only for topical treatment, but also for systemic delivery as well as for the development of theranostic systems. The aim of this paper is two-fold. First, an updated review about general features, preparation, characterization and pharmaceutical applications, with a special focus on colorectal cancer, is provided. Second, a case study of formulation of methotrexate in microemulsions is presented. Various essential oils (menthol, trans-anethole, α-tocopherol) and surfactants (TPGS-1000, Maxemul 6112, Noigen RN-20) were investigated for the preparation of o/w microemulsions for the delivery of methotrexate, and the ability of methotrexate-loaded microemulsions to inhibit cancer cell growth was then evaluated. Disregarding the surfactants used, menthol and trans-anethole led to cytotoxic microemulsions, whereas α-tocopherol based-formulations induced cell proliferation. These findings highlight the role that the oily component may play in the efficacy and safety of the microemulsions.

Acoustic manipulation: Bessel beams and active carriers

NASA Astrophysics Data System (ADS)

Rajabi, Majid; Mojahed, Alireza

2017-10-01

In this paper, we address the interaction of zero-order acoustic Bessel beams as an acoustic manipulation tool, with an active spherical shell, as a carrier in drug, agent, or material delivery systems, in order to investigate the controllability of exerted acoustic radiation force as the driver. The active body is comprised of a spherical elastic shell stimulated in its monopole mode of vibrations with the same frequency as the incident wave field via an internally bonded and spatially uniformly excited piezoelectric actuator. The main aim of this work is to examine the performance of a nondiffracting and self-reconstructing zero-order Bessel beam to obtain the full manipulability condition of active carriers in comparison with the case of a plane wave field. The results unveil some unique potentials of the Bessel beams in the company of active carriers, with emphasis on the consumed power of the actuation system. This paper will widen the path toward the single-beam robust acoustic manipulation techniques and may lead to the prospect of combined tweezers and fields, with applications in delivery systems, microswimmers, and trapper designs.

Bubble-generating nano-lipid carriers for ultrasound/CT imaging-guided efficient tumor therapy.

PubMed

Zhang, Nan; Li, Jia; Hou, Ruirui; Zhang, Jiangnan; Wang, Pei; Liu, Xinyang; Zhang, Zhenzhong

2017-12-20

Ideal therapeutic effectiveness of chemotherapy is obtained only when tumor cells are exposed to a maximal drug concentration, which is often hindered by dose-limiting toxicity. We designed a bubble-generating liposomal delivery system by introducing ammonium bicarbonate and gold nanorods into folic acid-conjugated liposomes to allow both multimodal imaging and the local release of drug (doxorubicin) with hyperthermia. The key component, ammonium bicarbonate, allows a controlled, rapid release of doxorubicin to provide an effective drug concentration in the tumor microenvironment. An in vitro temperature-triggered drug release study showed that cumulative release improved more than two-fold. In addition, in vitro and in vivo studies indicated that local heat treatment or ultrasonic cavitation enhanced the therapeutic efficiency greatly. The delivery system could also serve as an excellent contrast agent to allow ultrasonic imaging and computerized tomography imaging simultaneously to further achieve the aim of accurate diagnostics. Results of this study showed that this versatile bubble-generating liposome is a promising system to provide optimal therapeutic effects that are guided by multimodal imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

The delivery of poly(lactic acid)-poly(ethylene glycol) nanoparticles loaded with non-toxic drug to overcome drug resistance for the treatment of neuroblastoma

NASA Astrophysics Data System (ADS)

Dhulekar, Jhilmil

Neuroblastoma is a rare cancer of the sympathetic nervous system. A neuroblastoma tumor develops in the nerve tissue and is diagnosed in infants and children. Approximately 10.2 per million children under the age of 15 are affected in the United States and is slightly more common in boys. Neuroblastoma constitutes 6% of all childhood cancers and has a long-term survival rate of only 15%. There are approximately 700 new cases of neuroblastoma each year in the United States. With such a low rate of survival, the development of more effective treatment methods is necessary. A number of therapies are available for the treatment of these tumors; however, clinicians and their patients face the challenges of systemic side effects and drug resistance of the tumor cells. The application of nanoparticles has the potential to provide a safer and more effective method of delivery drugs to tumors. The advantage of using nanoparticles for drug delivery is the ability to specifically or passively target tumors while reducing the harmful side effects of chemotherapeutics. Drug delivery via nanoparticles can also allow for lower dosage requirements with controlled release of the drugs, which can further reduce systemic toxicity. The aim of this research was to develop a polymeric nanoparticle drug delivery system for the treatment of high-risk neuroblastoma. Nanoparticles composed of a poly(lactic acid)-poly(ethylene glycol) block copolymer were formulated to deliver a non-toxic drug in combination with Temozolomide, a commonly used chemotherapeutic drug for the treatment of neuroblastoma. The non-toxic drug acts as an inhibitor to the DNA-repair protein present in neuroblastoma cells that is responsible for inducing drug resistance in the cells, which would potentially allow for enhanced temozolomide activity. A variety of studies were completed to prove the nanoparticles' low toxicity, loading abilities, and uptake into cells. Additionally, studies were performed to determine the individual effect on cell toxicity of each drug and in combination. Finally, nanoparticles were loaded with the non-toxic drug and delivered with free temozolomide to determine the overall efficacy of the drugs in reducing neuroblastoma cell viability.

Identification of siRNA delivery enhancers by a chemical library screen.

PubMed

Gilleron, Jerome; Paramasivam, Prasath; Zeigerer, Anja; Querbes, William; Marsico, Giovanni; Andree, Cordula; Seifert, Sarah; Amaya, Pablo; Stöter, Martin; Koteliansky, Victor; Waldmann, Herbert; Fitzgerald, Kevin; Kalaidzidis, Yannis; Akinc, Akin; Maier, Martin A; Manoharan, Muthiah; Bickle, Marc; Zerial, Marino

2015-09-18

Most delivery systems for small interfering RNA therapeutics depend on endocytosis and release from endo-lysosomal compartments. One approach to improve delivery is to identify small molecules enhancing these steps. It is unclear to what extent such enhancers can be universally applied to different delivery systems and cell types. Here, we performed a compound library screen on two well-established siRNA delivery systems, lipid nanoparticles and cholesterol conjugated-siRNAs. We identified fifty-one enhancers improving gene silencing 2-5 fold. Strikingly, most enhancers displayed specificity for one delivery system only. By a combination of quantitative fluorescence and electron microscopy we found that the enhancers substantially differed in their mechanism of action, increasing either endocytic uptake or release of siRNAs from endosomes. Furthermore, they acted either on the delivery system itself or the cell, by modulating the endocytic system via distinct mechanisms. Interestingly, several compounds displayed activity on different cell types. As proof of principle, we showed that one compound enhanced siRNA delivery in primary endothelial cells in vitro and in the endocardium in the mouse heart. This study suggests that a pharmacological approach can improve the delivery of siRNAs in a system-specific fashion, by exploiting distinct mechanisms and acting upon multiple cell types. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Biopolymers as transdermal drug delivery systems in dermatology therapy.

PubMed

Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

2010-01-01

The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

Controlled drug delivery systems: past forward and future back.

PubMed

Park, Kinam

2014-09-28

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. Copyright © 2014 Elsevier B.V. All rights reserved.

Research of Ultrasound-Mediated Transdermal Drug Delivery System Using Cymbal-Type Piezoelectric Composite Transducer

NASA Astrophysics Data System (ADS)

Huan, Huiting; Gao, Chunming; Liu, Lixian; Sun, Qiming; Zhao, Binxing; Yan, Laijun

2015-06-01

Transdermal drug delivery (TDD) implemented by especially low-frequency ultrasound is generally known as sonophoresis or phonophoresis which has drawn considerable wide attention. However, TDD has not yet achieved its full potential as an alternative to conventional drug delivery methods due to its bulky instruments. In this paper, a cymbal-type piezoelectric composite transducer (CPCT) which has advantages over a traditional ultrasound generator in weight, flexibility, and power consumption, is used as a substitute ultrasonicator to realize TDD. First, theoretical research on a CPCT based on the finite element analysis was carried out according to which a series of applicable CPCTs with bandwidths of 20 kHz to 100 kHz were elaborated. Second, a TDD experimental setup was built with previously fabricated CPCTs aimed at the administration of glucose. Finally, the TDD performance of glucose molecule transport in porcine skin was measured in vitro by quantifying the concentration of glucose, and the time variation curves were subsequently obtained. During the experiment, the driving wave form, frequency, and power consumption of the transducers were selected as the main elements which determined the efficacy of glucose delivery. The results indicate that the effectiveness of the CPCT-based delivery is constrained more by the frequency and intensity of ultrasound rather than the driving waveform. The light-weight, flexibility, and low-power consumption of a CPCT can potentially achieve effective TDD.

Methods and metrics challenges of delivery-system research

PubMed Central

2012-01-01

Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned). This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not) into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1) modeling intervention context; (2) measuring readiness for change; (3) assessing intervention fidelity and sustainability; (4) assessing complex, multicomponent interventions; and (5) incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory) and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on February 16-17, 2011. The opinions in the paper are those of the author and do not represent the views or recommendations of AHRQ or the US Department of Health and Human Services.1 PMID:22409885

Assembling nanoparticle coatings to improve the drug delivery performance of lipid based colloids

NASA Astrophysics Data System (ADS)

Simovic, Spomenka; Barnes, Timothy J.; Tan, Angel; Prestidge, Clive A.

2012-02-01

Lipid based colloids (e.g. emulsions and liposomes) are widely used as drug delivery systems, but often suffer from physical instabilities and non-ideal drug encapsulation and delivery performance. We review the application of engineered nanoparticle layers at the interface of lipid colloids to improve their performance as drug delivery systems. In addition we focus on the creation of novel hybrid nanomaterials from nanoparticle-lipid colloid assemblies and their drug delivery applications. Specifically, nanoparticle layers can be engineered to enhance the physical stability of submicron lipid emulsions and liposomes, satbilise encapsulated active ingredients against chemical degradation, control molecular transport and improve the dermal and oral delivery characteristics, i.e. increase absorption, bioavailability and facilitate targeted delivery. It is feasible that hybrid nanomaterials composed of nanoparticles and colloidal lipids are effective encapsulation and delivery systems for both poorly soluble drugs and biological drugs and may form the basis for the next generation of medicines. Additional pre-clinical research including specific animal model studies are required to advance the peptide/protein delivery systems, whereas the silica lipid hybrid systems have now entered human clinical trials for poorly soluble drugs.

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.

Ocular delivery systems for topical application of anti-infective agents.

PubMed

Duxfield, Linda; Sultana, Rubab; Wang, Ruokai; Englebretsen, Vanessa; Deo, Samantha; Rupenthal, Ilva D; Al-Kassas, Raida

2016-01-01

For the treatment of anterior eye segment infections using anti-infective agents, topical ocular application is the most convenient route of administration. However, topical delivery of anti-infective agents is associated with a number of problems and challenges owing to the unique structure of the eye and the physicochemical properties of these compounds. Topical ocular drug delivery systems can be classified into two forms: conventional and non-conventional. The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation resulting in low ocular bioavailability. Recently, attention has been focused on improving topical ocular delivery of anti-infective agents using advanced drug delivery systems. This review will focus on the challenges of efficient topical ocular delivery of anti-infective agents and will discuss the various types of delivery systems used to improve the treatment anterior segment infections.

Mucoadhesive and thermogelling systems for vaginal drug delivery.

PubMed

Caramella, Carla M; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria Cristina; Sandri, Giuseppina

2015-09-15

This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. Copyright © 2015 Elsevier B.V. All rights reserved.

Fabrication, Characterization, and Biological Activity of Avermectin Nano-delivery Systems with Different Particle Sizes

NASA Astrophysics Data System (ADS)

Wang, Anqi; Wang, Yan; Sun, Changjiao; Wang, Chunxin; Cui, Bo; Zhao, Xiang; Zeng, Zhanghua; Yao, Junwei; Yang, Dongsheng; Liu, Guoqiang; Cui, Haixin

2018-01-01

Nano-delivery systems for the active ingredients of pesticides can improve the utilization rates of pesticides and prolong their control effects. This is due to the nanocarrier envelope and controlled release function. However, particles containing active ingredients in controlled release pesticide formulations are generally large and have wide size distributions. There have been limited studies about the effect of particle size on the controlled release properties and biological activities of pesticide delivery systems. In the current study, avermectin (Av) nano-delivery systems were constructed with different particle sizes and their performances were evaluated. The Av release rate in the nano-delivery system could be effectively controlled by changing the particle size. The biological activity increased with decreasing particle size. These results suggest that Av nano-delivery systems can significantly improve the controllable release, photostability, and biological activity, which will improve efficiency and reduce pesticide residues.

Including safety-net providers in integrated delivery systems: issues and options for policymakers.

PubMed

Witgert, Katherine; Hess, Catherine

2012-08-01

Health care reform legislation has spurred efforts to develop integrated health care delivery systems that seek to coordinate the continuum of health services. These systems may be of particular benefit to patients who face barriers to accessing care or have multiple health conditions. But it remains to be seen how safety-net providers, including community health centers and public hospitals--which have long experience in caring for these vulnerable populations--will be included in integrated delivery systems. This issue brief explores key considerations for incorporating safety-net providers into integrated delivery systems and discusses the roles of state and federal agencies in sup­porting and testing models of integrated care delivery. The authors conclude that the most important principles in creating integrated delivery systems for vulnerable populations are: (1) an emphasis on primary care; (2) coordination of all care, including behavioral, social, and public health services; and (3) accountability for population health outcomes.

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.

Advances of blood cell-based drug delivery systems.

PubMed

Sun, Yanan; Su, Jing; Liu, Geyi; Chen, Jianjun; Zhang, Xiumei; Zhang, Ran; Jiang, Minhan; Qiu, Mingfeng

2017-01-01

Blood cells, including erythrocytes, leukocytes and platelets are used as drug carriers in a wide range of applications. They have many unique advantages such as long life-span in circulation (especially erythrocytes), target release capacities (especially platelets), and natural adhesive properties (leukocytes and platelets). These properties make blood cell based delivery systems, as well as their membrane-derived carriers, far superior to other drug delivery systems. Despite the advantages, the further development of blood cell-based delivery systems was hindered by limitations in the source, storage, and mass production. To overcome these problems, synthetic biomaterials that mimic blood cell and nanocrystallization of blood cells have been developed and may represent the future direction for blood cell membrane-based delivery systems. In this paper, we review recent progress of the rising blood cell-based drug delivery systems, and also discuss their challenges and future tendency of development. Copyright © 2016. Published by Elsevier B.V.

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape.

PubMed

Zylberberg, Claudia; Matosevic, Sandro

2016-11-01

Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.

Protein-Based Nanomedicine Platforms for Drug Delivery

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

Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong

2009-08-03

Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They aremore » ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein based drug delivery system.« less

Advancements in nano-enabled therapeutics for neuroHIV management.

PubMed

Kaushik, Ajeet; Jayant, Rahul Dev; Nair, Madhavan

This viewpoint is a global call to promote fundamental and applied research aiming toward designing smart nanocarriers of desired properties, novel noninvasive strategies to open the blood-brain barrier (BBB), delivery/release of single/multiple therapeutic agents across the BBB to eradicate neurohuman immunodeficiency virus (HIV), strategies for on-demand site-specific release of antiretroviral therapy, developing novel nanoformulations capable to recognize and eradicate latently infected HIV reservoirs, and developing novel smart analytical diagnostic tools to detect and monitor HIV infection. Thus, investigation of novel nanoformulations, methodologies for site-specific delivery/release, analytical methods, and diagnostic tools would be of high significance to eradicate and monitor neuroacquired immunodeficiency syndrome. Overall, these developments will certainly help to develop personalized nanomedicines to cure HIV and to develop smart HIV-monitoring analytical systems for disease management.

Characterization and evaluation of stabilized particulate formulations as therapeutic oral vaccines for allergy.

PubMed

Kaneko, Kan; McDowell, Arlene; Ishii, Yasuyuki; Hook, Sarah

2017-09-05

Allergic conditions affect more than a quarter of the population in developed countries, but currently available treatments focus more on symptom relief than treating the underlying atopic condition. α-Galactosylceramide (α-GalCer) is a potent immunomodulating compound that has been shown to have a regulatory effect when delivered systemically in nanoparticles. Parenteral delivery is not preferred for chronic conditions, such as allergy, and therefore, the aim of this study was to determine whether a regulatory response could be induced through oral administration in a model of atopy through incorporation of α-GalCer into stable particulate formulations (cationic liposomes, polymerized liposomes and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs)). The formulations showed only minor changes in particle size, polydispersity index and retention of the model antigen ovalbumin (OVA) during incubation in simulated gastrointestinal (GI) conditions. Oral delivery of α-GalCer in cationic liposomes could induce immunostimulating effects systemically, as seen through increases in serum IgG antibody levels, whereas delivery of α-GalCer in polymerized liposomes and PLGA NPs induced local cytokine changes in the mesenteric lymph nodes (MLNs). The generated responses did not exhibit tolerogenic traits which could be useful for immunoregulation, but the responses generated varied between formulations and suggests that further characterization and optimization could lead to the desired immune response.

Solid lipid nanoparticles for the delivery of 1,3,5-triaza-7-phosphaadamantane (PTA) platinum (II) carboxylates.

PubMed

Sguizzato, Maddalena; Cortesi, Rita; Gallerani, Eleonora; Drechsler, Markus; Marvelli, Lorenza; Mariani, Paolo; Carducci, Federica; Gavioli, Riccardo; Esposito, Elisabetta; Bergamini, Paola

2017-05-01

The use of solid lipid nanoparticles (SLN) is a promising route for the delivery of platinum complexes aimed to anticancer activity. This paper describes the production and characterization of SLN suitable for the loading of Pt complexes containing the biocompatible phosphine 1,3,5-triaza-7-phosphaadamantane (PTA) as neutral ligand. After a screening of several lipidic phases, stearic acid-based SLN were identified as the most appropriate for the purpose. They were produced by emulsion-dilution method and then characterized in terms of dimension, polydispersity, time stability, pH balance and morphological aspect. Stearic acid SLN are designed as a system able to coordinate to platinum, acting as anionic carboxylic ligands, replacing the base carbonate of the Pt synthon [PtCO 3 (DMSO) 2 ], where also DMSO can subsequently be substituted by phosphinic ligands, namely PTA. SLN functionalised with Pt-PTA were produced and characterized by this synthetic route. The toxicity of plain SLN and the antiproliferative effect of SLN functionalised with Pt-PTA were evaluated on two human cancer cell lines K562 and A2780. The results indicate that SLN can be exploited as a delivery system for Pt complexes with potential anticancer activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of nanovesicular systems for dermal imiquimod delivery: physicochemical characterization and in vitro/in vivo evaluation.

PubMed

Ma, Man; Wang, Jinping; Guo, Fang; Lei, Mingzhu; Tan, Fengping; Li, Nan

2015-06-01

The aim of the current investigation was to develop and statistically evaluate nanovesicular systems for dermal imiquimod delivery. To this purpose, transethosomes were prepared with phospholipid, ethanol and different permeation enhancers. Conventional ethosomes, with soy phospholipid and ethanol, were used as control. The prepared vesicles were characterized for size, zeta potential, stability and entrapment efficiency. The optimal transethosomal formulation with mean particle size of 82.3 ± 9.5 nm showed the higher entrapment efficiency (68.69 ± 1.7%). In vitro studies, permeation results of accumulated drug and local accumulation efficiency were significantly higher for transethosomes (24.64 µg/cm(2) and 6.70, respectively) than control (14.45 µg/cm(2) and 3.93, respectively). Confocal laser scanning microscopy of rhodamine 6G-loaded transethosomes revealed an enhanced retention into the deeper skin layers as compared to conventional ethosomes. Besides, Fourier-transform infra-red spectroscopy studies were also performed to understand the mechanism of interaction between skin and carriers. What's more, results of in vivo studies indicated the transethosomes of imiquimod providing the most effectiveness for dermal delivery among all of the formulations. These results suggested that transethosomes would be a promising dermal carrier for imiquimod in actinic keratose treatment.

Improved Bioavailability of Levodopa Using Floatable Spray-Coated Microcapsules for the Management of Parkinson's Disease.

PubMed

Baek, Jong-Suep; Tee, Jie Kai; Pang, Yi Yun; Tan, Ern Yu; Lim, Kah Leong; Ho, Han Kiat; Loo, Say Chye Joachim

2018-06-01

Oral administration of levodopa (LD) is the gold standard in managing Parkinson's disease (PD). Although LD is the most effective drug in treating PD, chronic administration of LD induces levodopa-induced dyskinesia. A continuous and sustained provision of LD to the brain could, therefore, reduce peak-dose dyskinesia. In commercial oral formulations, LD is co-administrated with an AADC inhibitor (carbidopa) and a COMT inhibitor (entacapone) to enhance its bioavailability. Nevertheless, patients are known to take up to five tablets a day because of poor sustained-releasing capabilities that lead to fluctuations in plasma concentrations. To achieve a prolonged release of LD with the aim of improving its bioavailability, floatable spray-coated microcapsules containing all three PD drugs were developed. This gastro-retentive delivery system showed sustained release of all PD drugs, at similar release kinetics. Pharmacokinetics study was conducted and this newly developed formulation showed a more plateaued delivery of LD that is void of the plasma concentration fluctuations observed for the control (commercial formulation). At the same time, measurements of LD and dopamine of mice administered with this formulation showed enhanced bioavailability of LD. This study highlights a floatable, sustained-releasing delivery system in achieving improved pharmacokinetics data compared to a commercial formulation.

Safety and feasibility for pediatric cardiac regeneration using epicardial delivery of autologous umbilical cord blood-derived mononuclear cells established in a porcine model system.

PubMed

Cantero Peral, Susana; Burkhart, Harold M; Oommen, Saji; Yamada, Satsuki; Nyberg, Scott L; Li, Xing; O'Leary, Patrick W; Terzic, Andre; Cannon, Bryan C; Nelson, Timothy J

2015-02-01

Congenital heart diseases (CHDs) requiring surgical palliation mandate new treatment strategies to optimize long-term outcomes. Despite the mounting evidence of cardiac regeneration, there are no long-term safety studies of autologous cell-based transplantation in the pediatric setting. We aimed to establish a porcine pipeline to evaluate the feasibility and long-term safety of autologous umbilical cord blood mononuclear cells (UCB-MNCs) transplanted into the right ventricle (RV) of juvenile porcine hearts. Piglets were born by caesarean section to enable UCB collection. Upon meeting release criteria, 12 animals were randomized in a double-blinded fashion prior to surgical delivery of test article (n=6) or placebo (n=6). The UCB-MNC (3×10(6) cells per kilogram) or control (dimethyl sulfoxide, 10%) products were injected intramyocardially into the RV under direct visualization. The cohorts were monitored for 3 months after product delivery with assessments of cardiac performance, rhythm, and serial cardiac biochemical markers, followed by terminal necropsy. No mortalities were associated with intramyocardial delivery of UCB-MNCs or placebo. Two animals from the placebo group developed local skin infection after surgery that responded to antibiotic treatment. Electrophysiological assessments revealed no arrhythmias in either group throughout the 3-month study. Two animals in the cell-therapy group had transient, subclinical dysrhythmia in the perioperative period, likely because of an exaggerated response to anesthesia. Overall, this study demonstrated that autologous UCB-MNCs can be safely collected and surgically delivered in a pediatric setting. The safety profile establishes the foundation for cell-based therapy directed at the RV of juvenile hearts and aims to accelerate cell-based therapies toward clinical trials for CHD. ©AlphaMed Press.

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.

A Comparison of the Six Principles of the Individuals with Disabilities Education Improvement Act of the United States and the Persons with Disability Act of Ghana

ERIC Educational Resources Information Center

Mumuni, Samad Dimbie

2010-01-01

This study compared the six principles of IDEIA of the United States and the Persons with Disability Act of Ghana with the view to determining their similarities and differences. Recommendations were made with the ultimate aim of exploring the need for change in the special education delivery systems in the United States and Ghana. The comparative…

Ciprofloxacin release using natural rubber latex membranes as carrier.

PubMed

Dias Murbach, Heitor; Jaques Ogawa, Guilherme; Azevedo Borges, Felipe; Romeiro Miranda, Matheus Carlos; Lopes, Rute; Roberto de Barros, Natan; Guedes Mazalli, Alexandre Vinicius; Gonçalves da Silva, Rosângela; Ferreira Cinman, José Luiz; de Camargo Drago, Bruno; Donizetti Herculano, Rondinelli

2014-01-01

Natural rubber latex (NRL) from Hevea brasiliensis is easily manipulated, low cost, is of can stimulate natural angiogenesis and cellular adhesion, is a biocompatible, material and presents high mechanical resistance. Ciprofloxacin (CIP) is a synthetic antibiotic (fluoroquinolone) used in the treatment of infection at external fixation screws sites and remote infections, and this use is increasingly frequent in medical practice. The aim of this study was to develop a novel sustained delivery system for CIP based on NRL membranes and to study its delivery system behavior. CIP was found to be adsorbed on the NRL membrane, according to results of energy dispersive X-ray spectroscopy. Results show that the membrane can release CIP for up to 59.08% in 312 hours and the mechanism is due to super case II (non-Fickian). The kinetics of the drug release could be fitted with double exponential function X-ray diffraction and Fourier transform infrared (FTIR) spectroscopy shows some interaction by hydrogen bound, which influences its mechanical behavior.

Curcumin Encapsulated in Milk Exosomes Resists Human Digestion and Possesses Enhanced Intestinal Permeability in Vitro.

PubMed

Vashisht, Monika; Rani, Payal; Onteru, Suneel Kumar; Singh, Dheer

2017-11-01

Exosomes, the extracellular secretary nano-vesicles, act as carriers of biomolecules to the target cells. They exhibit several attributes of an efficient drug delivery system. Curcumin, despite having numerous bioactive and therapeutic properties, has limited pharmaceutical use due to its poor water solubility, stability, and low systemic bioavailability. Hence, this study aims to enhance the therapeutic potential of curcumin, a model hydrophobic drug, by its encapsulation into milk exosomes. In the present study, we investigated the stability of free curcumin and exosomal curcumin in PBS and in vitro digestive processes. Additionally, their uptake and trans-epithelial transport were studied on Caco-2 cells. Curcumin in milk exosomes had higher stability in PBS, sustained harsh digestive processes, and crossed the intestinal barrier than free curcumin. In conclusion, the encapsulation of curcumin into the exosomes enhances its stability, solubility, and bioavailability. Therefore, the present study demonstrated that milk exosomes act as stable oral drug delivery vehicles.

Systematic development of design of experiments (DoE) optimised self-microemulsifying drug delivery system of Zotepine.

PubMed

Dalvadi, Hitesh; Patel, Nikita; Parmar, Komal

2017-05-01

The aim of present investigation is to improve dissolution rate of poor soluble drug Zotepine by a self-microemulsifying drug delivery system (SMEDDS). Ternary phase diagram with oil (Oleic acid), surfactant (Tween 80) and co-surfactant (PEG 400) at apex were used to identify the efficient self-microemulsifying region. Box-Behnken design was implemented to study the influence of independent variables. Principal Component Analysis was used for scrutinising critical variables. The liquid SMEDDS were characterised for macroscopic evaluation, % Transmission, emulsification time and in vitro drug release studies. Optimised formulation OL1 was converted in to S-SMEDDS by using Aerosil ® 200 as an adsorbent in the ratio of 3:1. The S-SMEDDS was characterised by SEM, DSC, globule size (152.1 nm), zeta-potential (-28.1 mV), % transmission study (98.75%), in vitro release (86.57%) at 30 min. The optimised solid SMEDDS formulation showed faster drug release properties as compared to conventional tablet of Zotepine.

Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics.

PubMed

Maier, Martin A; Jayaraman, Muthusamy; Matsuda, Shigeo; Liu, Ju; Barros, Scott; Querbes, William; Tam, Ying K; Ansell, Steven M; Kumar, Varun; Qin, June; Zhang, Xuemei; Wang, Qianfan; Panesar, Sue; Hutabarat, Renta; Carioto, Mary; Hettinger, Julia; Kandasamy, Pachamuthu; Butler, David; Rajeev, Kallanthottathil G; Pang, Bo; Charisse, Klaus; Fitzgerald, Kevin; Mui, Barbara L; Du, Xinyao; Cullis, Pieter; Madden, Thomas D; Hope, Michael J; Manoharan, Muthiah; Akinc, Akin

2013-08-01

In recent years, RNA interference (RNAi) therapeutics, most notably with lipid nanoparticle-based delivery systems, have advanced into human clinical trials. The results from these early clinical trials suggest that lipid nanoparticles (LNPs), and the novel ionizable lipids that comprise them, will be important materials in this emerging field of medicine. A persistent theme in the use of materials for biomedical applications has been the incorporation of biodegradability as a means to improve biocompatibility and/or to facilitate elimination. Therefore, the aim of this work was to further advance the LNP platform through the development of novel, next-generation lipids that combine the excellent potency of the most advanced lipids currently available with biodegradable functionality. As a representative example of this novel class of biodegradable lipids, the lipid evaluated in this work displays rapid elimination from plasma and tissues, substantially improved tolerability in preclinical studies, while maintaining in vivo potency on par with that of the most advanced lipids currently available.

Exploring and validating physicochemical properties of mangiferin through GastroPlus® software

PubMed Central

Khurana, Rajneet Kaur; Kaur, Ranjot; Kaur, Manninder; Kaur, Rajpreet; Kaur, Jasleen; Kaur, Harpreet; Singh, Bhupinder

2017-01-01

Aim: Mangiferin (Mgf), a promising therapeutic polyphenol, exhibits poor oral bioavailability. Hence, apt delivery systems are required to facilitate its gastrointestinal absorption. The requisite details on its physicochemical properties have not yet been well documented in literature. Accordingly, in order to have explicit insight into its physicochemical characteristics, the present work was undertaken using GastroPlus™ software. Results: Aqueous solubility (0.38 mg/ml), log P (-0.65), Peff (0.16 × 10-4 cm/s) and ability to act as P-gp substrate were defined. Potency to act as a P-gp substrate was verified through Caco-2 cells, while Peff was estimated through single pass intestinal perfusion studies. Characterization of Mgf through transmission electron microscopy, differential scanning calorimetry, infrared spectroscopy and powder x-ray diffraction has also been reported. Conclusion: The values of physicochemical properties for Mgf reported in the current manuscript would certainly enable the researchers to develop newer delivery systems for Mgf. PMID:28344830

The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery.

PubMed

Shorter, Susan A; Gollings, Alexander S; Gorringe-Pattrick, Monique A M; Coakley, J Emma; Dyer, Paul D R; Richardson, Simon C W

2017-05-01

The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for 'drug' delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the 'PEG dilemma', balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem. Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking. Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic 'helpers' or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic.

Some engineering aspects of insulin delivery systems.

PubMed

Spencer, W J; Bair, R E; Carlson, G A; Love, J T; Urenda, R S; Eaton, R P; Schade, D S

1980-01-01

The characteristics of electronically controlled insulin delivery systems are presented. Early experiments with an external system have shown promise in providing improved glycemic control over conventional methods of single or multiple subcutaneous insulin injections. The encouraging results with external insulin delivery systems have led to the development and early testing in dogs of an implantable system with remote controls to permit variable insulin flow rates. A number of questions remain to be answered before widespread experimentation with external and implanted insulin delivery systems is possible. There appears to be no major development problems with the engineering aspects of such systems.

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

PubMed Central

Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Atik Badshah, Shaikh; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

2015-01-01

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828

Nomenclature associated with chemical characterization of and compatibility evaluations for medical product delivery systems.

PubMed

Jenke, Dennis R

2003-01-01

Delivery systems are used to store, contain, and/or administer liquid pharmaceutical products. Gaining an understanding of the chemical composition of such a delivery system is necessary with respect to effective system development, registration, and production. Additionally, the ability of the delivery system to impact the chemical composition of the contacted product may define the safety and/or efficacy of the product. Assessing the compatibility of the delivery system and the product is thus both necessary and desirable. The nomenclature associated with compatibility assessments has not been standardized, oftimes leading to conflicting or confusing information. This manuscript puts forth a nomenclature which classifies those chemical entities which participate in the system/product interaction and delineates the various extraction strategies which may be used in compatibility assessments.

Initial steps toward automation of a propellant processor

NASA Technical Reports Server (NTRS)

Schallhorn, Paul; Ramohalli, Kumar

1990-01-01

This paper presents the results from an experimental study aimed at ultimately automating the mixing of propellants in order to minimize unintended variations usually attributed to human error. The water heater and delivery system of a one-pint Baker-Perkins (APV) vertical mixer are automated with computer control. Various innovations are employed to introduce economy and low thermal inertia. Some of these include twin heaters/reservoirs instead of one large reservoir, a compact water mixer for achieving the desired temperature quickly, and thorough insulation of the entire water system. The completed system is tested during two propellant mixes. The temperature uniformly is proven through careful measurements employing several local thermocouples.

Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

PubMed

Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

2016-09-01

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

Caesarean section rate and cost control effectiveness of case payment reform in the new cooperative medical scheme for delivery: evidence from Xi County, China.

PubMed

Liu, Shuang; Wang, Jing; Zhang, Liang; Zhang, Xiang

2018-03-09

In China, increases in both the caesarean section (CS) rates and delivery costs have raised questions regarding the reform of the medical insurance payment system. Case payment is useful for regulating the behaviour of health providers and for controlling the CS rates and excessive increases in medical expenses. New Cooperative Medical Scheme (NCMS) agencies in Xi County in Henan Province piloted a case payment reform (CPR) in delivery for inpatients. We aimed to observe the changes in the CS rates, compare the changes in delivery-related variables, and identify variables related to delivery costs before and after the CPR in Xi County. Overall, 28,314 cases were selected from the Xi County NCMS agency from 2009 to 2010 and from 2014 to 2015. One-way ANOVA and chi-square tests were used to compare the distributions of CS and vaginal delivery (VD) before and after the CPR under different indicators. We applied multivariate linear regressions for the total medical cost of the VD and CS groups and total samples to identify the relationships between medical expenses and variables. The CS rates in Xi County increased from 26.1% to 32.5% after the CPR. The length of stay (LOS), total medical cost, and proportion of county hospitals increased in the CS and VD groups after the CPR, which had significant differences. The total medical cost in the CS and VD groups as well as the total samples was significantly influenced by inpatient age, LOS, and hospital type, and had a significant correlation with the CPR in the VD group and the total samples. The CPR might fail to control the growth of unreasonable medical expenses and regulate the behaviour of providers, which possibly resulted from the unreasonable compensation standard of case payments, prolonged LOS, and the increasing proportion of county hospitals. The NCMS should modify the case payment standard of delivery to inhibit providers' motivation to render CS services. The LOS should be controlled by implementing clinical guidelines, and a reference system should be established to guide patients in choosing reasonable hospitals.

Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

PubMed Central

Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

2016-01-01

Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

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.

Contamination Tracer Testing With Seabed Rock Drills: IODP Expedition 357

NASA Astrophysics Data System (ADS)

Orcutt, B.; Bergenthal, M.; Freudenthal, T.; Smith, D. J.; Lilley, M. D.; Schneiders, L.; Fruh-Green, G. L.

2016-12-01

IODP Expedition 357 utilized seabed rock drills for the first time in the history of the ocean drilling program, with the aim of collecting intact core of shallow mantle sequences from the Atlantis Massif to examine serpentinization processes and the deep biosphere. This new drilling approach required the development of a new system for delivering synthetic tracers during drilling to assess for possible sample contamination. Here, we describe this new tracer delivery system, assess the performance of the system during the expedition, provide an overview of the quality of the core samples collected for deep biosphere investigations based on tracer concentrations, and make recommendations for future applications of the system.

Contamination tracer testing with seabed drills: IODP Expedition 357

NASA Astrophysics Data System (ADS)

Orcutt, Beth N.; Bergenthal, Markus; Freudenthal, Tim; Smith, David; Lilley, Marvin D.; Schnieders, Luzie; Green, Sophie; Früh-Green, Gretchen L.

2017-11-01

IODP Expedition 357 utilized seabed drills for the first time in the history of the ocean drilling program, with the aim of collecting intact sequences of shallow mantle core from the Atlantis Massif to examine serpentinization processes and the deep biosphere. This novel drilling approach required the development of a new remote seafloor system for delivering synthetic tracers during drilling to assess for possible sample contamination. Here, we describe this new tracer delivery system, assess the performance of the system during the expedition, provide an overview of the quality of the core samples collected for deep biosphere investigations based on tracer concentrations, and make recommendations for future applications of the system.

Basics and recent advances in peptide and protein drug delivery

PubMed Central

Bruno, Benjamin J; Miller, Geoffrey D; Lim, Carol S

2014-01-01

While the peptide and protein therapeutic market has developed significantly in the past decades, delivery has limited their use. Although oral delivery is preferred, most are currently delivered intravenously or subcutaneously due to degradation and limited absorption in the gastrointestinal tract. Therefore, absorption enhancers, enzyme inhibitors, carrier systems and stability enhancers are being studied to facilitate oral peptide delivery. Additionally, transdermal peptide delivery avoids the issues of the gastrointestinal tract, but also faces absorption limitations. Due to proteases, opsonization and agglutination, free peptides are not systemically stable without modifications. This review discusses oral and transdermal peptide drug delivery, focusing on barriers and solutions to absorption and stability issues. Methods to increase systemic stability and site-specific delivery are also discussed. PMID:24228993

Closing the delivery gaps in pediatric HIV care in Togo, West Africa: using the care delivery value chain framework to direct quality improvement.

PubMed

Fiori, Kevin; Schechter, Jennifer; Dey, Monica; Braganza, Sandra; Rhatigan, Joseph; Houndenou, Spero; Gbeleou, Christophe; Palerbo, Emmanuel; Tchangani, Elfamozo; Lopez, Andrew; Bensen, Emily; Hirschhorn, Lisa R

2016-03-01

Providing quality care for all children living with HIV/AIDS remains a global challenge and requires the development of new healthcare delivery strategies. The care delivery value chain (CDVC) is a framework that maps activities required to provide effective and responsive care for a patient with a particular disease across the continuum of care. By mapping activities along a value chain, the CDVC enables managers to better allocate resources, improve communication, and coordinate activities. We report on the successful application of the CDVC as a strategy to optimize care delivery and inform quality improvement (QI) efforts with the overall aim of improving care for Pediatric HIV patients in Togo, West Africa. Over the course of 12 months, 13 distinct QI activities in Pediatric HIV/AIDS care delivery were monitored, and 11 of those activities met or exceeded established targets. Examples included: increase in infants receiving routine polymerase chain reaction testing at 2 months (39-95%), increase in HIV exposed children receiving confirmatory HIV testing at 18 months (67-100%), and increase in patients receiving initial CD4 testing within 3 months of HIV diagnosis (67-100%). The CDVC was an effective approach for evaluating existing systems and prioritizing gaps in delivery for QI over the full cycle of Pediatric HIV/AIDS care in three specific ways: (1) facilitating the first comprehensive mapping of Pediatric HIV/AIDS services, (2) identifying gaps in available services, and (3) catalyzing the creation of a responsive QI plan. The CDVC provided a framework to drive meaningful, strategic action to improve Pediatric HIV care in Togo.

Structural design principles for delivery of bioactive components in nutraceuticals and functional foods.

PubMed

McClements, David Julian; Decker, Eric Andrew; Park, Yeonhwa; Weiss, Jochen

2009-06-01

There have been major advances in the design and fabrication of structured delivery systems for the encapsulation of nutraceutical and functional food components. A wide variety of delivery systems is now available, each with its own advantages and disadvantages for particular applications. This review begins by discussing some of the major nutraceutical and functional food components that need to be delivered and highlights the main limitations to their current utilization within the food industry. It then discusses the principles underpinning the rational design of structured delivery systems: the structural characteristics of the building blocks; the nature of the forces holding these building blocks together; and, the different ways of assembling these building blocks into structured delivery systems. Finally, we review the major types of structured delivery systems that are currently available to food scientists: lipid-based (simple, multiple, multilayer, and solid lipid particle emulsions); surfactant-based (simple micelles, mixed micelles, vesicles, and microemulsions) and biopolymer-based (soluble complexes, coacervates, hydrogel droplets, and particles). For each type of delivery system we describe its preparation, properties, advantages, and limitations.

Appraisal of the Effectiveness of CODE; The Coordinated Delivery System for the South Central Research Library Council, January to December 1970.

ERIC Educational Resources Information Center

Faibisoff, Sylvia G.

A major concern of the South Central Research Library Council in establishing an interlibrary loan network was the development of a Coordinated Delivery system (CODE). Several means of delivery were considered--the U.S. mails, commercial trucking (Greyhound, United Parcel Service), and use of the public library system's delivery services. A…

Fiber coupled optical spark delivery system

DOEpatents

Yalin, Azer; Willson, Bryan; Defoort, Morgan

2008-08-12

A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

Smart linkers in polymer-drug conjugates for tumor-targeted delivery.

PubMed

Chang, Minglu; Zhang, Fang; Wei, Ting; Zuo, Tiantian; Guan, Yuanyuan; Lin, Guimei; Shao, Wei

2016-01-01

To achieve effective chemotherapy, many types of drug delivery systems have been developed for the specific environments in tumor tissues. Polymer-drug conjugates are increasingly used in tumor therapy due to several significant advantages over traditional delivery systems. In the fabrication of polymer-drug conjugates, a smart linker is an important component that joins two fragments or molecules together and can be cleared by a specific stimulus, which results in targeted drug delivery and controlled release. By regulating the conjugation between the drug and the nanocarriers, stimulus-sensitive systems based on smart linkers can offer high payloads, certified stability, controlled release and targeted delivery. In this review, we summarize the current state of smart linkers (e.g. disulfide, hydrazone, peptide, azo) used recently in various polymer-drug conjugate-based delivery systems with a primary focus on their sophisticated design principles and drug delivery mechanisms as well as in vivo processes.

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

National healthcare information system in Croatian primary care: the foundation for improvement of quality and efficiency in patient care.

PubMed

Gvozdanović, Darko; Koncar, Miroslav; Kojundzić, Vinko; Jezidzić, Hrvoje

2007-01-01

In order to improve the quality of patient care, while at the same time keeping up with the pace of increased needs of the population for healthcare services that directly impacts on the cost of care delivery processes, the Republic of Croatia, under the leadership of the Ministry of Health and Social Welfare, has formed a strategy and campaign for national public healthcare system reform. The strategy is very comprehensive and addresses all niches of care delivery processes; it is founded on the enterprise information systems that will aim to support end-to-end business processes in the healthcare domain. Two major requirements are in focus: (1) to provide efficient healthcare-related data management in support of decision-making processes; (2) to support a continuous process of healthcare resource spending optimisation. The first project is the Integrated Healthcare Information System (IHCIS) on the primary care level; this encompasses the integration of all primary point-of-care facilities and subjects with the Croatian Institute for Health Insurance and Croatian National Institute of Public Health. In years to come, IHCIS will serve as the main integration platform for connecting all other stakeholders and levels of health care (that is, hospitals, pharmacies, laboratories) into a single enterprise healthcare network. This article gives an overview of Croatian public healthcare system strategy aims and goals, and focuses on properties and characteristics of the primary care project implementation that started in 2003; it achieved a major milestone in early 2007 - the official grand opening of the project with 350 GPs already fully connected to the integrated healthcare information infrastructure based on the IHCIS solution.

An Overview of Clinical and Commercial Impact of Drug Delivery Systems

PubMed Central

Anselmo, Aaron C.; Mitragotri, Samir

2014-01-01

Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. PMID:24747160

Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

PubMed Central

Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

2012-01-01

The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

Dimensions of antenatal care service and the alacrity of mothers towards institutional delivery in South and South East Asia.

PubMed

Dixit, Priyanka; Khan, Junaid; Dwivedi, Laxmi Kant; Gupta, Amrita

2017-01-01

A number of studies have assessed the effectiveness of antenatal care (ANC) on uptake of institutional delivery care. However, none address the issue of association between the different components of ANC i.e. ANC component which is independent of health care delivery systems (timing and number of ANC visits), ANC components which depends on health care delivery systems (specific ANC procedures that women receive) with institutional delivery. Data for the study has been taken from the DHS conducted in the six selected South and South-East Asian countries during 1998-2013. The two dimensions of ANC are the key predictors. The outcome variable is a binary variable, where zero '0' denotes a home delivery and one '1' denotes an institutional delivery. In addition to probit estimation biprobit estimation method has been used to correct for the possible endogeneity. Analysis suggests that both the factors show a positive effect on institutional delivery but the level of associations are different. Probit estimation for each country suggests that the association is higher for the factor- which depends on health care delivery systems than the other factor. After correction of endogeneity through biprobit estimation we get the true associations for both the dimensions and it confirms that the ANC components which depends on health care delivery systems is more associated with the utilization of institutional delivery than the other factor. The content of care may fulfill the women's need and expectations while visiting for ANC care. The study suggests that the quality of antenatal care must be improved which depends on health care delivery systems to motivates the women to utilize the institutional delivery.

Dimensions of antenatal care service and the alacrity of mothers towards institutional delivery in South and South East Asia

PubMed Central

Dixit, Priyanka; Khan, Junaid; Dwivedi, Laxmi Kant; Gupta, Amrita

2017-01-01

Background A number of studies have assessed the effectiveness of antenatal care (ANC) on uptake of institutional delivery care. However, none address the issue of association between the different components of ANC i.e. ANC component which is independent of health care delivery systems (timing and number of ANC visits), ANC components which depends on health care delivery systems (specific ANC procedures that women receive) with institutional delivery. Methods Data for the study has been taken from the DHS conducted in the six selected South and South-East Asian countries during 1998–2013. The two dimensions of ANC are the key predictors. The outcome variable is a binary variable, where zero '0' denotes a home delivery and one '1' denotes an institutional delivery. In addition to probit estimation biprobit estimation method has been used to correct for the possible endogeneity. Findings Analysis suggests that both the factors show a positive effect on institutional delivery but the level of associations are different. Probit estimation for each country suggests that the association is higher for the factor- which depends on health care delivery systems than the other factor. After correction of endogeneity through biprobit estimation we get the true associations for both the dimensions and it confirms that the ANC components which depends on health care delivery systems is more associated with the utilization of institutional delivery than the other factor. Conclusions The content of care may fulfill the women’s need and expectations while visiting for ANC care. The study suggests that the quality of antenatal care must be improved which depends on health care delivery systems to motivates the women to utilize the institutional delivery. PMID:28742809

Spray-Dried Nanoparticle-in-Microparticle Delivery Systems (NiMDS) for Gene Delivery, Comprising Polyethylenimine (PEI)-Based Nanoparticles in a Poly(Vinyl Alcohol) Matrix.

PubMed

Schulze, Jan; Kuhn, Stephanie; Hendrikx, Stephan; Schulz-Siegmund, Michaela; Polte, Tobias; Aigner, Achim

2018-03-01

Nucleic acid-based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid-based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready-to-use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine-based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray-dried nanoparticle-in-microparticle delivery system is presented for the encapsulation of polyethylenimine-based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy-to-handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine-based nanoparticles from the nanoparticle-in-microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle-in-microparticle delivery system is demonstrated as ready-to-use dry powder to be an efficient device for the inhalative delivery of polyethylenimine-based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Understanding the organization of public health delivery systems: an empirical typology.

PubMed

Mays, Glen P; Scutchfield, F Douglas; Bhandari, Michelyn W; Smith, Sharla A

2010-03-01

Policy discussions about improving the U.S. health care system increasingly recognize the need to strengthen its capacities for delivering public health services. A better understanding of how public health delivery systems are organized across the United States is critical to improvement. To facilitate the development of such evidence, this article presents an empirical method of classifying and comparing public health delivery systems based on key elements of their organizational structure. This analysis uses data collected through a national longitudinal survey of local public health agencies serving communities with at least 100,000 residents. The survey measured the availability of twenty core public health activities in local communities and the types of organizations contributing to each activity. Cluster analysis differentiated local delivery systems based on the scope of activities delivered, the range of organizations contributing, and the distribution of effort within the system. Public health delivery systems varied widely in organizational structure, but the observed patterns of variation suggested that systems adhere to one of seven distinct configurations. Systems frequently migrated from one configuration to another over time, with an overall trend toward offering a broader scope of services and engaging a wider range of organizations. Public health delivery systems exhibit important structural differences that may influence their operations and outcomes. The typology developed through this analysis can facilitate comparative studies to identify which delivery system configurations perform best in which contexts.

Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

PubMed

Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

2016-07-30

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

Co-delivery of vascular endothelial growth factor and angiopoietin-1 using injectable microsphere/hydrogel hybrid systems for therapeutic angiogenesis.

PubMed

Shin, Seung-Hwa; Lee, Jangwook; Ahn, Dong-Gyun; Lee, Kuen Yong

2013-08-01

We hypothesized that combined delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) using microsphere/hydrogel hybrid systems could enhance mature vessel formation compared with administration of each factor alone. Hybrid delivery systems composed of alginate hydrogels and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres containing angiogenic factors were prepared. The release behavior of angiogenic factors from hybrid systems was monitored in vitro. The hybrid systems were injected into an ischemic rodent model, and blood vessel formation at the ischemic site was evaluated. The sustained release over 4 weeks of both VEGF and Ang-1 from hybrid systems was achieved in vitro. Co-delivery of VEGF and Ang-1 was advantageous to retain muscle tissues and significantly induced vessel enlargement at the ischemic site, compared to mice treated with either VEGF or Ang-1 alone. Sustained and combined delivery of VEGF and Ang-1 significantly enhances vessel enlargement at the ischemic site, compared with sustained delivery of either factor alone. Microsphere/hydrogel hybrid systems may be a promising vehicle for delivery of multiple drugs for many therapeutic applications.

Extended ocular drug delivery systems for the anterior and posterior segments: biomaterial options and applications.

PubMed

Kang-Mieler, Jennifer J; Dosmar, Emily; Liu, Wenqiang; Mieler, William F

2017-05-01

The development of new therapies for treating various eye conditions has led to a demand for extended release delivery systems, which would lessen the need for frequent application while still achieving therapeutic drug levels in the target tissues. Areas covered: Following an overview of the different ocular drug delivery modalities, this article surveys the biomaterials used to develop sustained release drug delivery systems. Microspheres, nanospheres, liposomes, hydrogels, and composite systems are discussed in terms of their primary materials. The advantages and disadvantages of each drug delivery system are discussed for various applications. Recommendations for modifications and strategies for improvements to these basic systems are also discussed. Expert opinion: An ideal sustained release drug delivery system should be able to encapsulate and deliver the necessary drug to the target tissues at a therapeutic level without any detriment to the drug. Drug encapsulation should be as high as possible to minimize loss and unless it is specifically desired, the initial burst of drug release should be kept to a minimum. By modifying various biomaterials, it is possible to achieve sustained drug delivery to both the anterior and posterior segments of the eye.

Comparative distribution of pilocarpine in ocular tissues of the rabbit during administration by eyedrop or by membrane-controlled delivery systems.

PubMed

Sendelbeck, L; Moore, D; Urquhart, J

1975-08-01

We compared the patterns of pilocarpine distribution in the rabbit eye during two regimens that were comparably efficacious in human clinical use: an administration of 2% pilocarpine nitrate eyedrops, every six hours, for four and eight days, and a continuous delivery of pilocarpine for as long as eight days, at 20 mug/hr, from a membrane-controlled delivery system in the inferior cul-de-sac. Pilocarpine labeled with radioactive carbon (14C) was used as a tracer. With administration of eyedrops, 14C levels in ocular tissues rose and fell within each six-hour interval between eyedrops, but with the delivery system, 14C levels remained constant over the two- to eight-day period. In each tissue, the 14C level within the first hour after the most recently administered eyedrop always exceeded the constant level maintained by the delivery system. Three to six hours after eyedrop administration, the 14C levels in cornea, iris, and sclera were approximately equal to those maintained by the delivery system. However, in lens, vitreous humor, and conjunctiva, the 14C levels were always two to five times higher with eyedrop administration than with the delivery system. Only aqueous humor showed a significantly lower 14C level with eyedrops than with the delivery system, occurring late in the interval between eyedrops. Compared to eyedrop administration, the membrane-controlled delivery system produced drug levels in ocular tissues that were constant rather than variable with time, and appreciably lower in tissues where the drug made no known contribution to the reduction of pressure.

Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs

PubMed Central

Ezzati Nazhad Dolatabadi, Jafar; Valizadeh, Hadi; Hamishehkar, Hamed

2015-01-01

In recent years, nanomaterials have been widely applied as advanced drug and gene delivery nanosystems. Among them, solid lipid nanoparticles (SLNs) have attracted great attention as colloidal drug delivery systems for incorporating hydrophilic or lipophilic drugs and various macromolecules as well as proteins and nucleic acids. Therefore, SLNs offer great promise for controlled and site specific drug and gene delivery. This article includes general information about SLN structures and properties, production procedures, characterization. In addition, recent progress on development of drug and gene delivery systems using SLNs was reviewed. PMID:26236652

Apoptosis induction and anti-cancer activity of LeciPlex formulations.

PubMed

Dhawan, Vivek V; Joshi, Ganesh V; Jain, Ankitkumar S; Nikam, Yuvraj P; Gude, Rajiv P; Mulherkar, Rita; Nagarsenker, Mangal S

2014-10-01

Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery. Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential. In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system. Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Smart Drug Delivery Systems in Cancer Therapy.

PubMed

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Determining the feasibility of robotic courier medication delivery in a hospital setting.

PubMed

Kirschling, Thomas E; Rough, Steve S; Ludwig, Brad C

2009-10-01

The feasibility of a robotic courier medication delivery system in a hospital setting was evaluated. Robotic couriers are self-guiding, self-propelling robots that navigate hallways and elevators to pull an attached or integrated cart to a desired destination. A robotic courier medication delivery system was pilot tested in two patient care units at a 471-bed tertiary care academic medical center. Average transit for the existing manual medication delivery system hourly hospitalwide deliveries was 32.6 minutes. Of this, 32.3% was spent at the patient care unit and 67.7% was spent pushing the cart or waiting at an elevator. The robotic courier medication delivery system traveled as fast as 1.65 ft/sec (52% speed of the manual system) in the absence of barriers but moved at an average rate of 0.84 ft/sec (26% speed of the manual system) during the study, primarily due to hallway obstacles. The robotic courier was utilized for 50% of the possible 1750 runs during the 125-day pilot due to technical or situational difficulties. Of the runs that were sent, a total of 79 runs failed, yielding an overall 91% success rate. During the final month of the pilot, the success rate reached 95.6%. Customer satisfaction with the traditional manual delivery system was high. Customer satisfaction with deliveries declined after implementation of the robotic courier medication distribution system. A robotic courier medication delivery system was implemented but was not expanded beyond the two pilot units. Challenges of implementation included ongoing education on how to properly move the robotic courier and keeping the hallway clear of obstacles.

AcademyHealth's Delivery System Science Fellowship: Training Embedded Researchers to Design, Implement, and Evaluate New Models of Care.

PubMed

Kanani, Nisha; Hahn, Erin; Gould, Michael; Brunisholz, Kimberly; Savitz, Lucy; Holve, Erin

2017-07-01

AcademyHealth's Delivery System Science Fellowship (DSSF) provides a paid postdoctoral pragmatic learning experience to build capacity within learning healthcare systems to conduct research in applied settings. The fellowship provides hands-on training and professional leadership opportunities for researchers. Since its inception in 2012, the program has grown rapidly, with 16 health systems participating in the DSSF to date. In addition to specific projects conducted within health systems (and numerous publications associated with those initiatives), the DSSF has made several broader contributions to the field, including defining delivery system science, identifying a set of training objectives for researchers working in delivery systems, and developing a national collaborative network of care delivery organizations, operational leaders, and trainees. The DSSF is one promising approach to support higher-value care by promoting continuous learning and improvement in health systems. © 2017 Society of Hospital Medicine.

The role of intracochlear drug delivery devices in the management of inner ear disease.

PubMed

Ayoob, Andrew M; Borenstein, Jeffrey T

2015-03-01

Diseases of the inner ear include those of the auditory and vestibular systems, and frequently result in disabling hearing loss or vertigo. Despite a rapidly expanding pipeline of potential cochlear therapeutics, the inner ear remains a challenging organ for targeted drug delivery, and new technologies are required to deliver these therapies in a safe and efficacious manner. In addition to traditional approaches for direct inner ear drug delivery, novel microfluidics-based systems are under development, promising improved control over pharmacokinetics over longer periods of delivery, ultimately with application towards hair cell regeneration in humans. Advances in the development of intracochlear drug delivery systems are reviewed, including passive systems, active microfluidic technologies and cochlear prosthesis-mediated delivery. This article provides a description of novel delivery systems and their potential future clinical applications in treating inner ear disease. Recent progresses in microfluidics and miniaturization technologies are enabling the development of wearable and ultimately implantable drug delivery microsystems. Progress in this field is being spurred by the convergence of advances in molecular biology, microfluidic flow control systems and models for drug transport in the inner ear. These advances will herald a new generation of devices, with near-term applications in preclinical models, and ultimately with human clinical use for a range of diseases of the inner ear.

Calcium silicate-based drug delivery systems.

PubMed

Zhu, Ying-Jie; Guo, Xiao-Xuan; Sham, Tsun-Kong

2017-02-01

Compared with other inorganic materials such as silica, metal oxides, noble metals and carbon, calcium silicate-based materials, especially nanostructured calcium silicate materials, have high biocompatibility, bioactivity and biodegradability, high specific surface area, nanoporous/hollow structure, high drug-loading capacity, pH-responsive drug release behavior and desirable drug release properties, and thus they are promising for the application in drug delivery. Calcium silicate-based drug delivery systems have a long drug-release time, which can significantly prolong the therapeutic effect of drugs. Another advantage of calcium silicate-based drug delivery systems is their pH-responsive drug release property, which can act as an ideal platform for targeted drug delivery. Areas covered: In recent years, studies have been carried out on calcium silicate-based drug delivery systems, and important results and insights have been documented. This article is not intended to offer a comprehensive review on the research on calcium silicate-based drug delivery systems, but presents some examples reported in the literature, and includes new insights obtained by tracking the interactions between drug molecules and calcium silicate carriers on the molecular level using the synchrotron-based X-ray spectroscopy. Expert opinion: Finally, our opinions on calcium silicate-based drug delivery systems are provided, and several research directions for the future studies are proposed.

[Advances of tumor targeting peptides drug delivery system with pH-sensitive activities].

PubMed

Ma, Yin-yun; Li, Li; Huang, Hai-feng; Gou, San-hu; Ni, Jing-man

2016-05-01

The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism,type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

Adenosine-Associated Delivery Systems

PubMed Central

Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

2016-01-01

Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

Organic-inorganic hybrid nanocomposites based on chitosan derivatives and layered double hydroxides with intercalated phacolysin as ocular delivery system

NASA Astrophysics Data System (ADS)

Qin, Zhiguo; Zhang, Jie; Chi, Huibo; Cao, Feng

2015-12-01

This study was mainly aimed to evaluate the potential use of a novel ocular drug delivery system, organic-inorganic hybrid nanocomposites based on chitosan derivatives and layered double hydroxides (LDH). Organic polymers of chitosan-glutathione (CG) and pre-activated chitosan-glutathione (CG-2MNA) were successfully synthesized and characterized. LDH with intercalated phacolysin (PCL), including larger hexagonal LDH-PCL (Lh-LDH-PCL), larger spherical LDH-PCL (Ls-LDH-PCL), smaller hexagonal LDH-PCL (Sh-LDH-PCL), CG hybrid LDH-PCL (LDH-PCL-CG), and CG-2MNA hybrid LDH-PCL (LDH-PCL-CG-2MNA), were prepared. The nanocomposites with particle size of 107.2-274.9 nm were characterized by powder X-ray diffraction, Fourier transform infrared, transmission electron micrographs, etc. In vivo precorneal retention studies showed that the detectable time of all nanocomposites was prolonged from 2 to 6 h in comparison to PCL saline. Accordingly, the AUC0-6h values of Lh-LDH-PCL, Ls-LDH-PCL, Sh-LDH-PCL, LDH-PCL-CG, and LDH-PCL-CG-2MNA nanocomposites were increased by 2.27-, 2.08-, 3.08-, 4.67-, and 3.36-fold, respectively. The Draize test and hematoxylin and eosin staining demonstrated that modified LDH had no eye irritation after single and repeated administration. These results indicated that chitosan derivatives-LDH hybrid nanocomposite dispersion could be a promising ocular drug delivery system to improve precorneal retention time of drugs.