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

Light-switchable systems for remotely controlled drug delivery.

PubMed

Shim, Gayong; Ko, Seungbeom; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Lee, Jaiwoo; Kwon, Taekhyun; Choi, Han-Gon; Kim, Young Bong; Oh, Yu-Kyoung

2017-12-10

Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines. We need a paradigm shift in drug delivery. One strategy that may overcome the limitations of pathophysiology-based drug delivery is the use of remotely controlled delivery technology. Unlike pathophysiology-based active drug targeting strategies, light-switchable systems are not affected by the heterogeneity of cells, tissue types, and/or microenvironments. Instead, they are triggered by remote light (i.e., near-infrared) stimuli, which are absorbed by photoresponsive molecules or three-dimensional nanostructures. The sequential conversion of light to heat or reactive oxygen species can activate drug release and allow it to be spatio-temporally controlled. Light-switchable systems have been used to activate endosomal drug escape, modulate the release of chemical and biological drugs, and alter nanoparticle structures to control the release rates of drugs. This review will address the limitations of pathophysiology-based drug delivery systems, the current status of light-based remote-switch systems, and future directions in the application of light-switchable systems for remotely controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

PubMed

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-06-01

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review.

PubMed

Singh, Jagdeep; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-08-11

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

Candesartan cilexetil loaded nanodelivery systems for improved oral bioavailability.

PubMed

Dudhipala, Narendar; Veerabrahma, Kishan

2017-02-01

Candesartan cilexetil (CC), an antihypertensive drug, has low oral bioavailability due to poor solubility and hepatic first-pass metabolism. These are major limitations in oral delivery of CC. Several approaches are known to reduce the problems of solubility and improve the bioavailability of CC. Among various approaches, nanotechnology-based delivery of CC has potential to overcome the challenges associated with the oral administration. This review focuses on various nano-based delivery systems available and tried for improving the aqueous solubility, dissolution and consequently bioavailability of CC upon oral administration. Of all, solid lipid nanoparticles appear to be promising delivery system, based on current reported results, for delivery of CC, as this system improved the oral bioavailability and possessed prolonged pharmacodynamic effect.

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.

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.

[Smart drug delivery systems based on nanoscale ZnO].

PubMed

Huang, Xiao; Chen, Chun; Yi, Caixia; Zheng, Xi

2018-04-01

In view of the excellent biocompatibility as well as the low cost, nanoscale ZnO shows great potential for drug delivery application. Moreover, The charming character enable nanoscale ZnO some excellent features (e.g. dissolution in acid, ultrasonic permeability, microwave absorbing, hydrophobic/hydrophilic transition). All of that make nanoscale ZnO reasonable choices for smart drug delivery. In the recent decade, more and more studies have focused on controlling the drug release behavior via smart drug delivery systems based on nanoscale ZnO responsive to some certain stimuli. Herein, we review the recent exciting progress on the pH-responsive, ultrasound-responsive, microwave-responsive and UV-responsive nanoscale ZnO-based drug delivery systems. A brief introduction of the drug controlled release behavior and its effect of the drug delivery systems is presented. The biocompatibility of nanoscale ZnO is also discussed. Moreover, its development prospect is looked forward.

Polymer-lipid hybrid systems: merging the benefits of polymeric and lipid-based nanocarriers to improve oral drug delivery.

PubMed

Rao, Shasha; Prestidge, Clive A

2016-01-01

A number of biobarriers limit efficient oral drug absorption; both polymer-based and lipid-based nanocarriers have demonstrated properties and delivery mechanisms to overcome these biobarriers in preclinical settings. Moreover, in order to address the multifaceted oral drug delivery challenges, polymer-lipid hybrid systems are now being designed to merge the beneficial features of both polymeric and lipid-based nanocarriers. Recent advances in the development of polymer-lipid hybrids with a specific focus on their viability in oral delivery are reviewed. Three classes of polymer-lipid hybrids have been identified, i.e. lipid-core polymer-shell systems, polymer-core lipid-shell systems, and matrix-type polymer-lipid hybrids. We focus on their application to overcome the various biological barriers to oral drug absorption, as exemplified by selected preclinical studies. Numerous studies have demonstrated the superiority of polymer-lipid hybrid systems to their non-hybrid counterparts in providing improved drug encapsulation, modulated drug release, and improved cellular uptake. These features have encouraged their applications in the delivery of chemotherapeutics, proteins, peptides, and vaccines. With further research expected to optimize the manufacturing and scaling up processes and in-depth pre-clinical pharmacological and toxicological assessments, these multifaceted drug delivery systems will have significant clinical impact on the oral delivery of pharmaceuticals and biopharmaceuticals.

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

PubMed

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

2013-09-01

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

Elastin-Like Recombinamers As Smart Drug Delivery Systems.

PubMed

Arias, F Javier; Santos, Mercedes; Ibanez-Fonseca, Arturo; Pina, Maria Jesus; Serrano, Sofía

2018-02-19

Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Applications of lipid based formulation technologies in the delivery of biotechnology-based therapeutics.

PubMed

du Plessis, Lissinda H; Marais, Etienne B; Mohammed, Faruq; Kotzé, Awie F

2014-01-01

In the last decades several new biotechnologically-based therapeutics have been developed due to progress in genetic engineering. A growing challenge facing pharmaceutical scientists is formulating these compounds into oral dosage forms with adequate bioavailability. An increasingly popular approach to formulate biotechnology-based therapeutics is the use of lipid based formulation technologies. This review highlights the importance of lipid based drug delivery systems in the formulation of oral biotechnology based therapeutics including peptides, proteins, DNA, siRNA and vaccines. The different production procedures used to achieve high encapsulation efficiencies of the bioactives are discussed, as well as the factors influencing the choice of excipient. Lipid based colloidal drug delivery systems including liposomes and solid lipid nanoparticles are reviewed with a focus on recent advances and updates. We further describe microemulsions and self-emulsifying drug delivery systems and recent findings on bioactive delivery. We conclude the review with a few examples on novel lipid based formulation technologies.

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.

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.

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

Multilayer engineered nanoliposomes as a novel tool for oral delivery of lipopeptide-based vaccines against group A Streptococcus.

PubMed

Marasini, Nirmal; Giddam, Ashwini K; Ghaffar, Khairunnisa A; Batzloff, Michael R; Good, Michael F; Skwarczynski, Mariusz; Toth, Istvan

2016-05-01

To develop an oral nanovaccine delivery system for lipopeptide-based vaccine candidate against group A Streptococcus. Lipid-core peptide-1-loaded nanoliposomes were prepared as a template and coated with opposite-charged polyelectrolytes to produce particles with size <200 nm. Efficacy of this oral nanovaccine delivery system was evaluated in mice model. Polymer-coated liposomes produced significantly higher antigen-specific mucosal IgA and systemic IgG titers in comparison to vaccine formulated with a strong mucosal adjuvant upon oral immunization in mice. Moreover, high levels of systemic antibody titers were retained even at day 185 postprimary immunization. Efficient oral delivery platform for lipopeptide-based vaccines has been developed.

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…

Environmentally friendly, one-pot synthesis of folic acid-decorated graphene oxide-based drug delivery system

NASA Astrophysics Data System (ADS)

Lin, Quankui; Huang, Xiaojie; Tang, Junmei; Han, Yuemei; Chen, Hao

2013-12-01

A targeted drug delivery system based on graphene oxide (GO) was produced via one-pot synthesis method, taking advantages of the self-polymerization of the dopamine (DA). The polymerization of dopamine resulted in polydopamine capped GO nanocomposite. Meanwhile, the anti-tumor drug doxorubicin (DOX) can be loaded in the nanocomposite and the tumor cell targeting molecule folic acid (FA) can also been immobilized on the nanocomposite surface simultaneously. The size of the obtained FA-decorated GO-based drug delivery system (DA/GO(DOX)-FA) is about 600 nm. It renders a sustained drug release manner. The cell culture results reveal that the FA-decorated GO-based drug delivery system (DA/GO(DOX)-FA) via one-pot method shows property of targeted killing of cancer cells in vitro. This one-pot method just needs the pH adjusting to induce the self-polymerization of DA, but excludes the fussy chemical grafting process and the organic solvents, which make it an environmentally friendly method to synthesize FA-decorated GO-based drug delivery system.

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.

Self-assembling nucleic acid delivery vehicles via linear, water-soluble, cyclodextrin-containing polymers.

PubMed

Davis, M E; Pun, S H; Bellocq, N C; Reineke, T M; Popielarski, S R; Mishra, S; Heidel, J D

2004-01-01

Non-viral (synthetic) nucleic acid delivery systems have the potential to provide for the practical application of nucleic acid-based therapeutics. We have designed and prepared a tunable, non-viral nucleic acid delivery system that self-assembles with nucleic acids and centers around a new class of polymeric materials; namely, linear, water-soluble cyclodextrin-containing polymers. The relationships between polymer structure and gene delivery are illustrated, and the roles of the cyclodextrin moieties for minimizing toxicity and forming inclusion complexes in the self-assembly processes are highlighted. This vehicle is the first example of a polymer-based gene delivery system formed entirely by self-assembly.

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.

Nasal-nanotechnology: revolution for efficient therapeutics delivery.

PubMed

Kumar, Amrish; Pandey, Aditya Nath; Jain, Sunil Kumar

2016-01-01

In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose. The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration. Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration. The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.

Silk-based delivery systems of bioactive molecules

PubMed Central

Numata, Keiji; Kaplan, David L

2010-01-01

Silks are biodegradable, biocompatible, self-assemblying proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes are reviewed. PMID:20298729

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.

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.

Novel biorelevant dissolution medium as a prognostic tool for polysaccharide-based colon-targeted drug delivery system.

PubMed

Yadav, Ankit Kumar; Sadora, Manik; Singh, Sachin Kumar; Gulati, Monica; Maharshi, Peddi; Sharma, Abhinav; Kumar, Bimlesh; Rathee, Harish; Ghai, Deepak; Malik, Adil Hussain; Garg, Varun; Gowthamrajan, K

2017-01-01

To overcome the limitations of the conventionally used methods for evaluation of orally administered colon-targeted delivery systems, a novel dissolution method using probiotics has been recently reported. In the present study, universal suitability of this medium composed of five different probiotics is established. Different delivery systems - mini tablets, liquisolid compacts, and microspheres coated with different polysaccharides - were prepared and subjected to sequential dissolution testing in medium with and without microbiota. The results obtained from fluid thioglycollate medium (FTM)-based probiotic medium for all the polysaccharide-based formulations showed statistically similar dissolution profile to that in the rat and goat cecal content media. Hence, it can be concluded that the developed FTM-based probiotic medium, once established, may eliminate the need for further animal sacrifice in the dissolution testing of polysaccharide-based colon-targeted delivery system.

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.

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

Prototype system of secure VOD

NASA Astrophysics Data System (ADS)

Minemura, Harumi; Yamaguchi, Tomohisa

1997-12-01

Secure digital contents delivery systems are to realize copyright protection and charging mechanism, and aim at secure delivery service of digital contents. Encrypted contents delivery and history (log) management are means to accomplish this purpose. Our final target is to realize a video-on-demand (VOD) system that can prevent illegal usage of video data and manage user history data to achieve a secure video delivery system on the Internet or Intranet. By now, mainly targeting client-server systems connected with enterprise LAN, we have implemented and evaluated a prototype system based on the investigation into the delivery method of encrypted video contents.

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.

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

PubMed

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

2015-06-01

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

Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs.

PubMed

Dahan, Arik; Hoffman, Amnon

2008-07-02

As a consequence of modern drug discovery techniques, there has been a consistent increase in the number of new pharmacologically active lipophilic compounds that are poorly water soluble. A great challenge facing the pharmaceutical scientist is making these molecules into orally administered medications with sufficient bioavailability. One of the most popular approaches to improve the oral bioavailability of these molecules is the utilization of a lipid based drug delivery system. Unfortunately, current development strategies in the area of lipid based delivery systems are mostly empirical. Hence, there is a need for a simplified in vitro method to guide the selection of a suitable lipidic vehicle composition and to rationalize the delivery system design. To address this need, a dynamic in vitro lipolysis model, which provides a very good simulation of the in vivo lipid digestion process, has been developed over the past few years. This model has been extensively used for in vitro assessment of different lipid based delivery systems, leading to enhanced understanding of the suitability of different lipids and surfactants as a delivery system for a given poorly water soluble drug candidate. A key goal in the development of the dynamic in vitro lipolysis model has been correlating the in vitro data of various drug-lipidic delivery system combinations to the resultant in vivo drug profile. In this paper, we discuss and review the need for this model, its underlying theory, practice and limitations, and the available data accumulated in the literature. Overall, the dynamic in vitro lipolysis model seems to provide highly useful initial guidelines in the development process of oral lipid based drug delivery systems for poorly water soluble drugs, and it predicts phenomena that occur in the pre-enterocyte stages of the intestinal absorption cascade.

Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities.

PubMed

Li, Ling; Hu, Shuo; Chen, Xiaoyuan

2018-07-01

In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome editing systems have become one of the most robust platforms in basic biomedical research and therapeutic applications. To date, efficient in vivo delivery of the CRISPR/Cas9 system to the targeted cells remains a challenge. Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo, their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications. Alternative non-viral delivery systems for CRISPR/Cas9 are urgently needed. With the rapid development of non-viral vectors, lipid- or polymer-based nanocarriers have shown great potential for CRISPR/Cas9 delivery. In this review, we analyze the pros and cons of delivering CRISPR/Cas9 systems in the form of plasmid, mRNA, or protein and then discuss the limitations and challenges of CRISPR/Cas9-based genome editing. Furthermore, current non-viral vectors that have been applied for CRISPR/Cas9 delivery in vitro and in vivo are outlined in details. Finally, critical obstacles for non-viral delivery of CRISPR/Cas9 system are highlighted and promising strategies to overcome these barriers are proposed. Published by Elsevier Ltd.

Recent Advances in Nanoparticle-Based Targeted Drug-Delivery Systems Against Cancer and Role of Tumor Microenvironment.

PubMed

Ashfaq, Usman Ali; Riaz, Muhammad; Yasmeen, Erum; Yousaf, Muhammad Zubair

2017-01-01

Cancer is one of the major causes of death worldwide. The silent activation of cellular factors responsible for deviation from normal regulatory pathways leads to the development of cancer. Nano-biotechnology is a novel drug-delivery system with high potential of efficacy and accuracy to target lethal cancers. Various biocompatible nanoparticle (NP)-based drug-delivery systems such as liposomes, dendrimers, micelles, silica, quantum dots, and magnetic, gold, and carbon nanotubes have already been reported for successful targeted cancer treatment. NPs are functionalized with different biological molecules, peptides, antibody, and protein ligands for targeted drug delivery. These systems include a hydrophilic central core, a target-oriented biocompatible outer layer, and a middle hydrophobic core where the drug destined to reach target site resides. Most of the NPs have the ability to maintain their structural shape and are constructed according to the cancer microenvironment. The self-assembling and colloidal properties of NPs have caused them to become the best vehicles for targeted drug delivery. The tumor microenvironment (TME) plays a major role in cancer progression, detection, and treatment. Due to its continuous complex behavior, the TME can hinder delivery systems, thus halting cancer treatment. Nonetheless, a successful biophysiological interaction between the NPs and the TME results in targeted release of drugs. Currently, a number of drugs and NP-based delivery systems against cancer are in clinical and preclinical trials and a few have been approved by Food and Drug Administration (FDA); for example: taxol, doxil, cerubidine, and adrucil. This review summarizes topical advances about the drugs being used for cancer treatment, their targeted delivery systems based on NPs, and the role of TME in this connection.

Exploring the role of peptides in polymer-based gene delivery.

PubMed

Sun, Yanping; Yang, Zhen; Wang, Chunxi; Yang, Tianzhi; Cai, Cuifang; Zhao, Xiaoyun; Yang, Li; Ding, Pingtian

2017-09-15

Polymers are widely studied as non-viral gene vectors because of their strong DNA binding ability, capacity to carry large payload, flexibility of chemical modifications, low immunogenicity, and facile processes for manufacturing. However, high cytotoxicity and low transfection efficiency substantially restrict their application in clinical trials. Incorporating functional peptides is a promising approach to address these issues. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we systematically summarize the role of peptides in polymer-based gene delivery, and elaborate how to rationally design polymer-peptide based gene delivery vectors. Polymers are widely studied as non-viral gene vectors, but suffer from high cytotoxicity and low transfection efficiency. Incorporating short, bioactive peptides into polymer-based gene delivery systems can address this issue. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we highlight the peptides' roles in polymer-based gene delivery, and elaborate how to utilize various functional peptides to enhance the transfection efficiency of polymers. The optimized peptide-polymer vectors should be able to alter their structures and functions according to biological microenvironments and utilize inherent intracellular pathways of cells, and consequently overcome the barriers during gene delivery to enhance transfection efficiency. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Application of Chitosan and its Derivatives in Nanocarrier Based Pulmonary Drug Delivery Systems.

PubMed

Dua, Kamal; Bebawy, Mary; Awasthi, Rajendra; Tekade, Rakesh K; Tekade, Muktika; Gupta, Gaurav; De Jesus Andreoli Pinto, Terezinha; Hansbro, Philip M

2017-01-01

The respiratory tract as a non-invasive route of drug administration is gaining increasing attention in the present time on achieving both local and the systemic therapeutic effects. Success in achieving pulmonary delivery, requires overcoming barriers including mucociliary clearance and uptake by macrophages. An effective drug delivery system delivers the therapeutically active moieties at the right time and rate to target sites. A major limitation associated with most of the currently available conventional and controlled release drug delivery devices is that not all the drug candidates are well absorbed uniformly locally or systemically. We searched and reviewed the literature focusing on chitosan and chitosan derivative based nanocarrier systems used in pulmonary drug delivery. We focused on the applications of chitosan in the development of nanoparticles for this purpose. Chitosan, a natural linear bio-polyaminosaccharide is central in the development of novel drug delivery systems (NDDS) including nanoparticles for use in the treatment of various respiratory diseases. It achieves this through its unique properties of biodegradability, biocompatibility, mucoadhesivity and its ability to enhance macromolecule permeation across membranes. It also achieves sustained and targeted effects, primary requirements for an effective pulmonary drug delivery system. This review highlights the applications and importance of chitosan with special emphasis on nanotechnology, employed in the management of respiratory diseases such as asthma, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis. This review will be of interest to both the biological and formulation scientists as it provides a summary on the utility of chitosan in pulmonary drug delivery systems. At present, there are no patented chitosan based controlled release products available for pulmonary drug delivery and so this area has enormous potential in the field of respiratory science. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Advances in drug delivery system for platinum agents based combination therapy.

PubMed

Kang, Xiang; Xiao, Hai-Hua; Song, Hai-Qin; Jing, Xia-Bin; Yan, Le-San; Qi, Ruo-Gu

2015-12-01

Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.

Exploring information systems outsourcing in U.S. hospital-based health care delivery systems.

PubMed

Diana, Mark L

2009-12-01

The purpose of this study is to explore the factors associated with outsourcing of information systems (IS) in hospital-based health care delivery systems, and to determine if there is a difference in IS outsourcing activity based on the strategic value of the outsourced functions. IS sourcing behavior is conceptualized as a case of vertical integration. A synthesis of strategic management theory (SMT) and transaction cost economics (TCE) serves as the theoretical framework. The sample consists of 1,365 hospital-based health care delivery systems that own 3,452 hospitals operating in 2004. The findings indicate that neither TCE nor SMT predicted outsourcing better than the other did. The findings also suggest that health care delivery system managers may not be considering significant factors when making sourcing decisions, including the relative strategic value of the functions they are outsourcing. It is consistent with previous literature to suggest that the high cost of IS may be the main factor driving the outsourcing decision.

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.

Silk-based delivery systems of bioactive molecules.

PubMed

Numata, Keiji; Kaplan, David L

2010-12-30

Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed. Copyright © 2010 Elsevier B.V. All rights reserved.

Microneedles for enhanced transdermal and intraocular drug delivery.

PubMed

Moffatt, Kurtis; Wang, Yujing; Raj Singh, Thakur Raghu; Donnelly, Ryan F

2017-10-01

Microneedle mediated delivery based research has garnered great interest in recent years. In the past, the initial focus was delivery of macromolecules of biological origin, however the field has now broadened its scope to include transdermal delivery of conventional low molecular weight drug molecules. Great success has been demonstrated utilising this approach, particularly in the field of vaccine delivery. Current technological advances have permitted an enhancement in design formulation, allowing delivery of therapeutic doses of small molecule drugs and biomolecules, aided by larger patch sizes and scalable manufacture. In addition, it has been recently shown that microneedles are beneficial in localisation of drug delivery systems within targeted ocular tissues. Microneedles have the capacity to modify the means in which therapeutics and formulations are delivered to the eye. However, further research is still required due to potential drawbacks and challenges. Indeed, no true microneedle-based transdermal or ocular drug delivery system has yet been marketed. Some concerns have been raised regarding regulatory issues and manufacturing processes of such systems, and those in the field are now actively working to address them. Microneedle-based transdermal and ocular drug delivery systems have the potential to greatly impact not only patient benefits, but also industry, and through diligence, innovation and collaboration, their true potential will begin to be realised within the next 3-5 years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gold nanoparticle-DNA aptamer composites as a universal carrier for in vivo delivery of biologically functional proteins.

PubMed

Ryou, Sang-Mi; Yeom, Ji-Hyun; Kang, Hyo Jung; Won, Miae; Kim, Jin-Sik; Lee, Boeun; Seong, Maeng-Je; Ha, Nam-Chul; Bae, Jeehyeon; Lee, Kangseok

2014-12-28

Although the delivery of biologically functional protein(s) into mammalian cells could be of tremendous value to biomedical research, the development of such technology has been hindered by the lack of a safe and effective delivery method. Here, we present a simple, efficient, and versatile gold nanoparticle-DNA aptamer conjugate (AuNP-Apt)-based system, with nanoblock-like properties, that allows any recombinant protein to be loaded without additional modifications and delivered into mammalian living systems. AuNP-Apt-based protein delivery system was able to deliver various proteins into variety of cell types in vitro without showing cytotoxicity. This AuNP-Apt system was also effective for the local and systemic targeted delivery of proteins in vivo. A local injection of the AuNP-Apt loaded with the apoptosis-inducing BIM protein efficiently inhibited the growth of xenograft tumors in mice. Furthermore, an intravenous injection of AuNP-Apt loaded with both epidermal growth factor (EGF) and BIM resulted in the targeted delivery of BIM into a xenograft tumor derived from EGF receptor-overexpressing cancer cells with no detectable systemic toxicity. Our findings show that this system can serve as an innovative platform for the development of protein-based biomedical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Crystals and crystallization in oil-in-water emulsions: implications for emulsion-based delivery systems.

PubMed

McClements, David Julian

2012-06-15

Many bioactive components intended for oral ingestion (pharmaceuticals and nutraceuticals) are hydrophobic molecules with low water-solubilities and high melting points, which poses considerable challenges to the formulation of oral delivery systems. Oil-in-water emulsions are often suitable vehicles for the encapsulation and delivery of this type of bioactive component. The bioactive component is usually dissolved in a carrier lipid phase by either dilution and/or heating prior to homogenization, and then the carrier lipid and water phases are homogenized to form an emulsion consisting of small oil droplets dispersed in water. The successful development of this kind of emulsion-based delivery system depends on a good understanding of the influence of crystals on the formation, stability, and properties of emulsions. This review article addresses the physicochemical phenomena associated with the encapsulation, retention, crystallization, release, and absorption of hydrophobic bioactive components within emulsions. This knowledge will be useful for the rational formulation of effective emulsion-based delivery systems for oral delivery of crystalline hydrophobic bioactive components in the food, health care, and pharmaceutical industries. Copyright © 2012 Elsevier B.V. All rights reserved.

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment

PubMed Central

Chen, Binlong; Dai, Wenbing; He, Bing; Zhang, Hua; Wang, Xueqing; Wang, Yiguang; Zhang, Qiang

2017-01-01

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects. PMID:28255348

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment.

PubMed

Chen, Binlong; Dai, Wenbing; He, Bing; Zhang, Hua; Wang, Xueqing; Wang, Yiguang; Zhang, Qiang

2017-01-01

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects.

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

Engaging Faculty in Telecommunications-Based Instructional Delivery Systems.

ERIC Educational Resources Information Center

Swalec, John J.

In the design and development of telecommunications-based instructional delivery systems, attention to faculty involvement and training is often overlooked until the system is operational. The Waubonsee Telecommunications Instructional Consortium (TIC), in Illinois, is one network that benefited from early faculty input. Even before the first…

Evaluating Student Response to WeBWorK, a Web-Based Homework Delivery and Grading System

ERIC Educational Resources Information Center

Roth, Vicki; Ivanchenko, Volodymyr; Record, Nicholas

2008-01-01

As the use of web-based homework delivery and checking systems expands, we have greater need to evaluate how students engage with these systems and how changes in the systems influence student behavior. Reported here is the assessment of WeBWorK, an open-source web-based homework program used largely in postsecondary math and science courses, with…

Development of small RNA delivery systems for lung cancer therapy.

PubMed

Fujita, Yu; Kuwano, Kazuyoshi; Ochiya, Takahiro

2015-03-06

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

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.

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

PubMed Central

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

2013-01-01

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

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.

Malaria treatment using novel nano-based drug delivery systems.

PubMed

Baruah, Uday Krishna; Gowthamarajan, Kuppusamy; Vanka, Ravisankar; Karri, Veera Venkata Satyanarayana Reddy; Selvaraj, Kousalya; Jojo, Gifty M

2017-08-01

We reside in an era of technological innovation and advancement despite which infectious diseases like malaria remain to be one of the greatest threats to the humans. Mortality rate caused by malaria disease is a huge concern in the twenty-first century. Multiple drug resistance and nonspecific drug targeting of the most widely used drugs are the main reasons/drawbacks behind the failure in malarial therapy. Dose-related toxicity because of high doses is also a major concern. Therefore, to overcome these problems nano-based drug delivery systems are being developed to facilitate site-specific or target-based drug delivery and hence minimizing the development of resistance progress and dose-dependent toxicity issues. In this review, we discuss about the shortcomings in treating malaria and how nano-based drug delivery systems can help in curtailing the infectious disease malaria.

Vision and Reality for Technology-Based Delivery Systems in Postsecondary Education.

ERIC Educational Resources Information Center

Mingle, James R.

This paper explores the implications of technological advancement and telecommunications services on postsecondary education, especially in relation to educational effectiveness, costs, increasing deregulation, and financing. Four scenarios illustrate different educational delivery modes. Common elements of educational delivery systems of the…

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

PubMed

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

2015-01-01

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

Designing polymers with sugar-based advantages for bioactive delivery applications.

PubMed

Zhang, Yingyue; Chan, Jennifer W; Moretti, Alysha; Uhrich, Kathryn E

2015-12-10

Sugar-based polymers have been extensively explored as a means to increase drug delivery systems' biocompatibility and biodegradation. Here,we review he use of sugar-based polymers for drug delivery applications, with a particular focus on the utility of the sugar component(s) to provide benefits for drug targeting and stimuli responsive systems. Specifically, numerous synthetic methods have been developed to reliably modify naturally-occurring polysaccharides, conjugate sugar moieties to synthetic polymer scaffolds to generate glycopolymers, and utilize sugars as a multifunctional building block to develop sugar-linked polymers. The design of sugar-based polymer systems has tremendous implications on both the physiological and biological properties imparted by the saccharide units and are unique from synthetic polymers. These features include the ability of glycopolymers to preferentially target various cell types and tissues through receptor interactions, exhibit bioadhesion for prolonged residence time, and be rapidly recognized and internalized by cancer cells. Also discussed are the distinct stimuli-sensitive properties of saccharide-modified polymers to mediate drug release under desired conditions. Saccharide-based systems with inherent pH- and temperature-sensitive properties, as well as enzyme-cleavable polysaccharides for targeted bioactive delivery, are covered. Overall, this work emphasizes inherent benefits of sugar-containing polymer systems for bioactive delivery.

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.

A community-based event delivery protocol in publish/subscribe systems for delay tolerant sensor networks.

PubMed

Liu, Nianbo; Liu, Ming; Zhu, Jinqi; Gong, Haigang

2009-01-01

The basic operation of a Delay Tolerant Sensor Network (DTSN) is to finish pervasive data gathering in networks with intermittent connectivity, while the publish/subscribe (Pub/Sub for short) paradigm is used to deliver events from a source to interested clients in an asynchronous way. Recently, extension of Pub/Sub systems in DTSNs has become a promising research topic. However, due to the unique frequent partitioning characteristic of DTSNs, extension of a Pub/Sub system in a DTSN is a considerably difficult and challenging problem, and there are no good solutions to this problem in published works. To ad apt Pub/Sub systems to DTSNs, we propose CED, a community-based event delivery protocol. In our design, event delivery is based on several unchanged communities, which are formed by sensor nodes in the network according to their connectivity. CED consists of two components: event delivery and queue management. In event delivery, events in a community are delivered to mobile subscribers once a subscriber comes into the community, for improving the data delivery ratio. The queue management employs both the event successful delivery time and the event survival time to decide whether an event should be delivered or dropped for minimizing the transmission overhead. The effectiveness of CED is demonstrated through comprehensive simulation studies.

Mesoporous carbon nanomaterials in drug delivery and biomedical application.

PubMed

Zhao, Qinfu; Lin, Yuanzhe; Han, Ning; Li, Xian; Geng, Hongjian; Wang, Xiudan; Cui, Yu; Wang, Siling

2017-01-01

Recent development of nano-technology provides highly efficient and versatile treatment methods to achieve better therapeutic efficacy and lower side effects of malignant cancer. The exploration of drug delivery systems (DDSs) based on nano-material shows great promise in translating nano-technology to clinical use to benefit patients. As an emerging inorganic nanomaterial, mesoporous carbon nanomaterials (MCNs) possess both the mesoporous structure and the carbonaceous composition, endowing them with superior nature compared with mesoporous silica nanomaterials and other carbon-based materials, such as carbon nanotube, graphene and fullerene. In this review, we highlighted the cutting-edge progress of carbon nanomaterials as drug delivery systems (DDSs), including immediate/sustained drug delivery systems and controlled/targeted drug delivery systems. In addition, several representative biomedical applications of mesoporous carbon such as (1) photo-chemo synergistic therapy; (2) delivery of therapeutic biomolecule and (3) in vivo bioimaging are discussed and integrated. Finally, potential challenges and outlook for future development of mesoporous carbon in biomedical fields have been discussed in detail.

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.

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

PubMed

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

2009-12-01

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

An overview of clinical and commercial impact of drug delivery systems.

PubMed

Anselmo, Aaron C; Mitragotri, Samir

2014-09-28

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Liposomal Drug Delivery System for Cancer Therapy: Advancement and Patents.

PubMed

Jha, Sheetal; Sharma, Pramod K; Malviya, Rishabha

2016-01-01

In this review article, authors reviewed about the liposomes which are amongst various drug delivering systems for the delivery of the therapeutic agents at the target site. Advances in liposomal drug delivery systems for the cancer therapy have enhanced the therapeutic levels of the anticancer moieties. Liposomes show promising action on the tumor by incorporating less amount of drug at the target site, with minimum toxic effect and maximum therapeutic effect and thereby enhancing the bioavailability. Liposome-based drug delivery systems provide the potential to elevate the effect of drug concentration in tumor cells. Manuscript briefly describes the role of liposomes in cancer therapy and various patents based on the same. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The implications of recent advances in carboxymethyl chitosan based targeted drug delivery and tissue engineering applications.

PubMed

Upadhyaya, Laxmi; Singh, Jay; Agarwal, Vishnu; Tewari, Ravi Prakash

2014-07-28

Over the last decade carboxymethyl chitosan (CMCS) has emerged as a promising biopolymer for the development of new drug delivery systems and improved scaffolds along with other tissue engineering devices for regenerative medicine that is currently one of the most rapidly growing fields in the life sciences. CMCS is amphiprotic ether, derived from chitosan, exhibiting enhanced aqueous solubility, excellent biocompatibility, controllable biodegradability, osteogenesis ability and numerous other outstanding physicochemical and biological properties. More strikingly, it can load hydrophobic drugs and displays strong bioactivity which highlight its suitability and extensive usage for preparing different drug delivery and tissue engineering formulations respectively. This review provides a comprehensive introduction to various types of CMCS based formulations for delivery of therapeutic agents and tissue regeneration and further describes their preparation procedures and applications in different tissues/organs. Detailed information of CMCS based nano/micro systems for targeted delivery of drugs with emphasis on cancer specific and organ specific drug delivery have been described. Further, we have discussed various CMCS based tissue engineering biomaterials along with their preparation procedures and applications in different tissues/organs. The article then, gives a brief account of therapy combining drug delivery and tissue engineering. Finally, identification of major challenges and opportunities for current and ongoing application of CMCS based systems in the field are summarised. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

PubMed

Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

2016-02-10

Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

A sight on protein-based nanoparticles as drug/gene delivery systems.

PubMed

Salatin, Sara; Jelvehgari, Mitra; Maleki-Dizaj, Solmaz; Adibkia, Khosro

2015-01-01

Polymeric nanomaterials have extensively been applied for the preparation of targeted and controlled release drug/gene delivery systems. However, problems involved in the formulation of synthetic polymers such as using of the toxic solvents and surfactants have limited their desirable applications. In this regard, natural biomolecules including proteins and polysaccharide are suitable alternatives due to their safety. According to literature, protein-based nanoparticles possess many advantages for drug and gene delivery such as biocompatibility, biodegradability and ability to functionalize with targeting ligands. This review provides a general sight on the application of biodegradable protein-based nanoparticles in drug/gene delivery based on their origins. Their unique physicochemical properties that help them to be formulated as pharmaceutical carriers are also discussed.

Recent trends in drug delivery system using protein nanoparticles.

PubMed

Sripriyalakshmi, S; Jose, Pinkybel; Ravindran, Aswathy; Anjali, C H

2014-09-01

Engineered nanoparticles that can facilitate drug formulation and passively target tumours have been under extensive research in recent years. These successes have driven a new wave of significant innovation in the generation of advanced particles. The fate and transport of diagnostic nanoparticles would significantly depend on nonselective drug delivery, and hence the use of high drug dosage is implemented. In this perspective, nanocarrier-based drug targeting strategies can be used which improve the selective delivery of drugs to the site of action, i.e. drug targeting. Pharmaceutical industries majorly focus on reducing the toxicity and side effects of drugs but only recently it has been realised that carrier systems themselves may pose risks to the patient. Proteins are compatible with biological systems and they are biodegradable. They offer a multitude of moieties for modifications to tailor drug binding, imaging or targeting entities. Thus, protein nanoparticles provide outstanding contributions as a carrier for drug delivery systems. This review summarises recent progress in particle-based therapeutic delivery and discusses important concepts in particle design and biological barriers for developing the next generation of particles drug delivery systems.

Theranostic system for drug delivery and pharmacokinetic imaging based on nanosecond pulsed light-induced photomechanical and photoacoustic effects

NASA Astrophysics Data System (ADS)

Tsunoi, Yasuyuki; Sato, Shunichi; Kawauchi, Satoko; Akutsu, Yusuke; Miyagawa, Yoshihiro; Araki, Koji; Shiotani, Akihiro; Terakawa, Mitsuhiro

2015-11-01

For efficient and side effects-free pharmacological treatment, we here propose a theranostic system that enables transvascular drug delivery by photomechanical waves (PMWs) and photoacoustic (PA) imaging of the drug distribution; both functions are based on nanosecond laser pulses and can therefore be integrated in one system. Through optical fibers arranged around an ultrasound sensor, low-energy and high-energy nanosecond light pulses were transmitted respectively for PA imaging and PMW-based drug delivery by temporal switching. With the system, we delivered a test drug (Evans blue) to tumors in mice and visualized distributions of both the blood vessels and drug in the tissue in vivo, showing the validity of the system.

[Integrated delivery systems in California--success and failure determining factors for the first 10 years and impetus for Germany].

PubMed

Janus, K; Amelung, V E

2004-10-01

Since the coming into effect of the Health Care Modernization Act (Gesundheitsmodernisierungsgesetz) the conditions for integrated health care delivery are favourable in Germany. However, comprehensive approaches are a long time in coming. In contrast, integrated health care delivery as an integral part of the spreading of managed care entered a further stage of development, which enables health care decision makers to draw conclusions regarding the further development of integrated health care delivery in Germany. Based on case studies integrated delivery systems in the San Francisco Bay Area have been analyzed with the objective to evaluate pitfalls and successful strategies for integrated health care delivery. The major pitfalls refer to an insufficient local focus, a lack of actual integration and the application of per capita reimbursement (which is a key subject on the political agenda in Germany as well) within integrated delivery systems. On the contrary, successful strategies include achieving a dynamic tension between centralized and decentralized coordination, internal and external relationship management, well organised human resource management including a well-defined corporate policy and a comprehensive implementation of information technology. Based on US experiences with integrated delivery systems implications for the design of integrated health care delivery in Germany are discussed.

Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells.

PubMed

Taratula, Olena; Dani, Raj Kumar; Schumann, Canan; Xu, Hong; Wang, Andrew; Song, Han; Dhagat, Pallavi; Taratula, Oleh

2013-12-15

A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40°C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach. Copyright © 2013 Elsevier B.V. All rights reserved.

A novel gene delivery composite system based on biodegradable folate-poly (ester amine) polymer and thermosensitive hydrogel for sustained gene release

PubMed Central

Yang, Yi; Zhao, Hang; Jia, YanPeng; Guo, QingFa; Qu, Ying; Su, Jing; Lu, XiaoLing; Zhao, YongXiang; Qian, ZhiYong

2016-01-01

Local anti-oncogene delivery providing high local concentration of gene, increasing antitumor effect and decreasing systemic side effects is currently attracting interest in cancer therapy. In this paper, a novel local sustained anti-oncogene delivery system, PECE thermoresponsive hydrogel containing folate-poly (ester amine) (FA-PEA) polymer/DNA (tumor suppressor) complexes, is demonstrated. First, a tumor-targeted biodegradable folate-poly (ester amine) (FA-PEA) polymer based on low-molecular-weight polyethyleneimine (PEI) was synthesized and characterized, and the application for targeted gene delivery was investigated. The polymer had slight cytotoxicity and high transfection efficiency in vitro compared with PEI 25k, which indicated that FA-PEA was a potential vector for targeted gene delivery. Meanwhile, we successfully prepared a thermoresponsive PECE hydrogel composite containing FA-PEA/DNA complexes which could contain the genes and slowly release the genes into cells. We concluded the folate-poly (ester amine) (FA-PEA) polymer would be useful for targeted gene delivery, and the novel gene delivery composite based on biodegradable folate-poly (ester amine) polymer and thermosensitive PECE hydrogel showed potential for sustained gene release. PMID:26883682

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.

Lecithin-based nanostructured gels for skin delivery: an update on state of art and recent applications.

PubMed

Elnaggar, Yosra S R; El-Refaie, Wessam M; El-Massik, Magda A; Abdallah, Ossama Y

2014-04-28

Conventional carriers for skin delivery encounter obstacles of drug leakage, scanty permeation and low entrapment efficiency. Phospholipid nanogels have recently been recognized as prominent delivery systems to circumvent such obstacles and impart easier application. The current review provides an overview on different types of lecithin nanostructured gels, with particular emphasis on liposomal versus microemulsion gelled systems. Liposomal gels investigated encompassed classic liposomal hydrogel, modified liposomal gels (e.g. Transferosomal, Ethosomal, Pro-liposomal and Phytosomal gels), Microgel in liposomes (M-i-L) and Vesicular phospholipid gel (VPG). Microemulsion gelled systems encompassed Lecithin microemulsion-based organogels (LMBGs), Pluronic lecithin organogels (PLOs) and Lecithin-stabilized microemulsion-based hydrogels. All systems were reviewed regarding matrix composition, state of art, characterization and updated applications. Different classes of lecithin nanogels exhibited crucial impact on transdermal delivery regarding drug permeation, drug loading and stability aspects. Future perspectives of this theme issue are discussed based on current laboratory studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: a review.

PubMed

Xinming, Li; Yingde, Cui; Lloyd, Andrew W; Mikhalovsky, Sergey V; Sandeman, Susan R; Howel, Carol A; Liewen, Liao

2008-04-01

Only about 5% of drugs administrated by eye drops are bioavailable, and currently eye drops account for more than 90% of all ophthalmic formulations. The bioavailability of ophthalmic drugs can be improved by a soft contact lens-based ophthalmic drug delivery system. Several polymeric hydrogels have been investigated for soft contact lens-based ophthalmic drug delivery systems: (i) polymeric hydrogels for conventional contact lens to absorb and release ophthalmic drugs; (ii) polymeric hydrogels for piggyback contact lens combining with a drug plate or drug solution; (iii) surface-modified polymeric hydrogels to immobilize drugs on the surface of contact lenses; (iv) polymeric hydrogels for inclusion of drugs in a colloidal structure dispersed in the lens; (v) ion ligand-containing polymeric hydrogels; (vi) molecularly imprinted polymeric hydrogels which provide the contact lens with a high affinity and selectivity for a given drug. Polymeric hydrogels for these contact lens-based ophthalmic drug delivery systems, their advantages and drawbacks are critically analyzed in this review.

Overcoming the Challenges of siRNA Delivery: Nanoparticle Strategies.

PubMed

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

2017-01-01

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

Responsive materials for self-regulated insulin delivery.

PubMed

Wu, Weitai; Zhou, Shuiqin

2013-11-01

With diabetes mellitus becoming an important public health concern, insulin-delivery systems are attracting increasing interest from both scientific and technological researchers. This feature article covers the present state-of-the-art glucose-responsive insulin-delivery system (denoted as GRIDS), based on responsive polymer materials, a promising system for self-regulated insulin delivery. Three types of GRIDS are discussed, based on different fundamental mechanisms of glucose-recognition, with: a) glucose enzyme, b) glucose binding protein, and c) synthetic boronic acid as the glucose-sensitive component. At the end, a personal perspective on the major issues yet to be worked out in future research is provided. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

Adamantane in Drug Delivery Systems and Surface Recognition.

PubMed

Štimac, Adela; Šekutor, Marina; Mlinarić-Majerski, Kata; Frkanec, Leo; Frkanec, Ruža

2017-02-16

The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application.

Towards an Innovative Web-Based Lab Delivery System for a Management Information Systems Course

ERIC Educational Resources Information Center

Breimer, Eric; Cotler, Jami; Yoder, Robert

2011-01-01

While online systems are an essential component of distance learning, they can also play a critical role in improving the delivery of activities in a traditional laboratory setting. The quality and effectiveness of online course delivery is often compared to equivalent face-to-face alternatives. In our approach, we have harnessed what we feel to…

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

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.

Injectable hydrogels for delivering biotherapeutic molecules.

PubMed

Mathew, Ansuja Pulickal; Uthaman, Saji; Cho, Ki-Hyun; Cho, Chong-Su; Park, In-Kyu

2018-04-15

To date, numerous delivery systems based on either organic or inorganic material have been developed to achieve efficient and sustained delivery of therapeutics. Hydrogels, which are three dimensional networks of crosslinked hydrophilic polymers, have a significant role in solving the clinical and pharmacological limitations of present systems because of their biocompatibility, ease of preparation and unique physical properties such as a tunable porous nature and affinity for biological fluids. Development of an in situ forming injectable hydrogel system has allowed excellent spatial and temporal control, unlike systemically administered therapeutics. Injectable hydrogel systems can offset difficulties with conventional hydrogel-based drug delivery systems in the clinic by forming a drug/gene delivery or cell-growing depot in the body with a single injection, thereby enabling patient compliance and comfort. Carbohydrate polymers are widely used for the synthesis of injectable in situ-forming hydrogels because of ready availability, presence of modifiable functional groups, biocompatibility and other physiochemical properties. In this review, we discuss different aspects of injectable hydrogels, such as bulk hydrogels/macrogels, microgels, and nanogels derived from natural polymers, and their importance in the delivery of therapeutics such as genes, drugs, cells or other biomolecules and how these revolutionary systems can complement existing therapeutic delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

PubMed

Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

2015-11-01

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Utilisation of maternal health care in western rural China under a new rural health insurance system (New Co-operative Medical System).

PubMed

Long, Qian; Zhang, Tuohong; Xu, Ling; Tang, Shenglan; Hemminki, Elina

2010-10-01

To investigate factors influencing maternal health care utilisation in western rural China and its relation to income before (2002) and after (2007) introducing a new rural health insurance system (NCMS). Data from cross-sectional household-based health surveys carried out in ten western rural provinces of China in 2003 and 2008 were used in the study. The study population comprised women giving birth in 2002 or 2007, with 917 and 809 births, respectively. Correlations between outcomes and explanatory variables were studied by logistic regression models and a log-linear model. Between 2002 and 2007, having no any pre-natal visit decreased from 25% to 12% (difference 13%, 95% CI 10-17%); facility-based delivery increased from 45% to 80% (difference 35%, 95% CI 29-37%); and differences in using pre-natal and delivery care between the income groups narrowed. In a logistic regression analysis, women with lower education, from minority groups, or high parity were less likely to use pre-natal and delivery care in 2007. The expenditure for facility-based delivery increased over the period, but the out-of-pocket expenditure for delivery as a percentage of the annual household income decreased. In 2007, it was 14% in the low-income group. NCMS participation was found positively correlated with lower out-of-pocket expenditure for facility-based delivery (coefficient -1.14 P < 0.05) in 2007. Facility-based delivery greatly increased between 2002 and 2007, coinciding with the introduction of the NCMS. The rural poor were still facing substantial payment for facility-based delivery, although NCMS participation reduced the out-of-pocket expenditure on average. © 2010 Blackwell Publishing Ltd.

Oral delivery of peptides and proteins using lipid-based drug delivery systems.

PubMed

Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

2012-10-01

In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism by which intestinal absorption of peptides and proteins is promoted. The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides and proteins. Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve the design and development of lipid-based DDS with the desired bioavailability and therapeutic profile.

Carrier-Based Drug Delivery System for Treatment of Acne

PubMed Central

Vyas, Amber; Kumar Sonker, Avinesh

2014-01-01

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

Controlled Drug Delivery Using Microdevices

PubMed Central

Sanjay, Sharma T.; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

2016-01-01

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems. PMID:26813304

Controlled Drug Delivery Using Microdevices.

PubMed

Sanjay, Sharma T; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems.

Nanobiotechnology: Cell Membrane-Based Delivery Systems.

PubMed

Zhang, Pengfei; Liu, Gang; Chen, Xiaoyuan

2017-04-01

The increasingly rapid pace of research in the field of bioinspired drug delivery systems is revealing the promise of cell membrane-based nanovesicles for biomedical applications. Those cell membrane-based nanoparticles combine the natural functionalities of cell plasma membranes and the bioengineering flexibility of synthetic nanomaterials, and such versatility provides a means of designing exciting new drug formulations for personalized treatment in future nanomedicine.

Radiation delivery system and method

DOEpatents

Sorensen, Scott A.; Robison, Thomas W.; Taylor, Craig M. V.

2002-01-01

A radiation delivery system and method are described. The system includes a treatment configuration such as a stent, balloon catheter, wire, ribbon, or the like, a portion of which is covered with a gold layer. Chemisorbed to the gold layer is a radiation-emitting self-assembled monolayer or a radiation-emitting polymer. The radiation delivery system is compatible with medical catheter-based technologies to provide a therapeutic dose of radiation to a lesion following an angioplasty procedure.

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.

An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

PubMed Central

Salvador, Aiala; Igartua, Manoli; Hernández, Rosa Maria; Pedraz, José Luis

2011-01-01

The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity. PMID:21773041

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.

PubMed

Szunerits, Sabine; Boukherroub, Rabah

2018-01-01

Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of examples of thermal technologies for local and systemic transdermal drug delivery will be discussed and put into perspective.

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

PubMed Central

Szunerits, Sabine; Boukherroub, Rabah

2018-01-01

Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of examples of thermal technologies for local and systemic transdermal drug delivery will be discussed and put into perspective. PMID:29497609

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

PubMed

Malhi, Sarandeep; Gu, Xiaochen

2015-07-01

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

Intracellular Protein Delivery System Using a Target-Specific Repebody and Translocation Domain of Bacterial Exotoxin.

PubMed

Kim, Hee-Yeon; Kang, Jung Ae; Ryou, Jeong-Hyun; Lee, Gyeong Hee; Choi, Dae Seong; Lee, Dong Eun; Kim, Hak-Sung

2017-11-17

With the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform. The delivery platform was revealed to efficiently translocate a protein cargo to the cytosol in a target-specific manner. We demonstrate the utility and potential of the delivery platform by showing a remarkable tumor regression with negligible toxicity in a xenograft mice model when gelonin was used as the cytotoxic protein cargo. The present platform can find wide applications to the cell-selective cytosolic delivery of diverse proteins in many areas.

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

PubMed

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

2017-02-01

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

Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle.

PubMed

Wendel, Sebastian O; Menon, Sailesh; Alshetaiwi, Hamad; Shrestha, Tej B; Chlebanowski, Lauren; Hsu, Wei-Wen; Bossmann, Stefan H; Narayanan, Sanjeev; Troyer, Deryl L

2015-01-01

The recent WHO report on antibiotic resistances shows a dramatic increase of microbial resistance against antibiotics. With only a few new antibiotics in the pipeline, a different drug delivery approach is urgently needed. We have obtained evidence demonstrating the effectiveness of a cell based drug delivery system that utilizes the innate immune system as targeting carrier for antibacterial drugs. In this study we show the efficient loading of neutrophil granulocytes with chlorhexidine and the complete killing of E. coli as well as Fusobacterium necrophorum in in-vitro studies. Fusobacterium necrophorum causes hepatic abscesses in cattle fed high grain diets. We also show in a mouse model that this delivery system targets infections of F. necrophorum in the liver and reduces the bacterial burden by an order of magnitude from approximately 2•106 to 1•105.

Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

PubMed Central

Lohani, Alka; Singh, Garima; Bhattacharya, Shiv Sankar; Verma, Anurag

2014-01-01

Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs. PMID:24949205

Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

NASA Astrophysics Data System (ADS)

Dawidczyk, Charlene; Russell, Luisa; Searson, Peter

2014-08-01

The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics and tumor accumulation. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

Modular reservoir concept for MEMS-based transdermal drug delivery systems

NASA Astrophysics Data System (ADS)

Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.

2014-11-01

While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.

RNA Replicon Delivery via Lipid-Complexed PRINT Protein Particles

PubMed Central

Xu, Jing; Luft, J. Christopher; Yi, Xianwen; Tian, Shaomin; Owens, Gary; Wang, Jin; Johnson, Ashley; Berglund, Peter; Smith, Jonathan; Napier, Mary E.; DeSimone, Joseph M.

2013-01-01

Herein we report the development of a non-viral lipid-complexed PRINT® (particle replication in non-wetting templates) protein particle system (LPP particle) for RNA replicon delivery with a view towards RNA replicon-based vaccination. Cylindrical bovine serum albumin (BSA) particles (diameter (d) 1 µm, height (h) 1 µm) loaded with RNA replicon and stabilized with a fully reversible disulfide cross-linker were fabricated using PRINT technology. Highly efficient delivery of the particles to Vero cells was achieved by complexing particles with a mixture of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipids. Our data suggest that: 1) this lipid-complexed protein particle is a promising system for delivery of RNA replicon-based vaccines, and 2) it is necessary to use a degradable cross-linker for successful delivery of RNA replicon via protein-based particles. PMID:23924216

Physically facilitating drug-delivery systems

PubMed Central

Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

2012-01-01

Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

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

PubMed

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

2018-05-01

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

Outcomes for Youth with Severe Emotional Disturbance: A Repeated Measures Longitudinal Study of a Wraparound Approach of Service Delivery in Systems of Care

ERIC Educational Resources Information Center

Painter, Kirstin

2012-01-01

Background: Systems of care is a family centered, strengths-based service delivery model for treating youth experiencing a serious emotional disturbance. Wraparound is the most common method of service delivery adopted by states and communities as a way to adhere to systems of care philosophy. Objective: The purpose of this study was to evaluate…

Robust and High Order Computational Method for Parachute and Air Delivery and MAV System

DTIC Science & Technology

2017-11-01

Report: Robust and High Order Computational Method for Parachute and Air Delivery and MAV System The views, opinions and/or findings contained in this...University Title: Robust and High Order Computational Method for Parachute and Air Delivery and MAV System Report Term: 0-Other Email: xiaolin.li...model coupled with an incompressible fluid solver through the impulse method . Our approach to simulating the parachute system is based on the front

Cell-Based Biohybrid Drug Delivery Systems: The Best of the Synthetic and Natural Worlds.

PubMed

Banskota, Samagya; Yousefpour, Parisa; Chilkoti, Ashutosh

2017-01-01

The goal of drug delivery is to deliver therapeutics to the site of disease while reducing unwanted side effects. In recent years, a diverse variety of synthetic nano and microparticles have been developed as drug delivery systems. The success of these systems for drug delivery lies in their ability to overcome biological barriers such as the blood-brain barrier, to evade immune clearance and avoid nonspecific biodistribution. This Review provides an overview of recent advances in the design of biohybrid drug delivery systems, which combine cells with synthetic systems to overcome some of these biological hurdles. Examples include eukaryotic cells, such as stem cells, red blood cells, immune cells, platelets, and cancer cells that are used to carry drug-loaded synthetic particles. Synthetic particles can also be cloaked with naturally derived cell membranes and thereby evade immune clearance, exhibit prolonged systemic circulation, and target specific tissues by capitalizing on the interaction/homing tendency of certain cells and their membrane components to particular tissues. Different designs of cell-based biohybrid systems and their applications, as well as their promise and limitations, are discussed herein. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Erythrocyte membrane based cationic polymer-mcDNA complexes as an efficient gene delivery system.

PubMed

Huang, Ping; Zhao, Jing; Wei, Chiju; Hou, Xiaohu; Chen, Pingzhang; Tan, Yan; He, Cheng-Yi; Wang, Zhiyong; Chen, Zhi-Ying

2016-12-20

Gene therapy has great promise for the treatment of obtained and inherited serious diseases. However, the lack of safe and efficient gene delivery systems remains a barrier for their clinical application. Here, we reported a potential gene delivery vehicle composed of the erythrocyte membrane and cationic polymers, for example the XtremeGENE from Roche and the ε-caprolactone modified polyethylenimine. In addition to high efficiency, this system showed negligible cytotoxicity compared to the two cationic polymers alone in various cell lines, including human embryonic kidney cells (293T), human liver cancer cells (Huh7 and HepG2), murine dendritic cells (DC2.4) and human umbilical cord mesenchymal stem cells (Hu-MSCs). Moreover, the results of confocal laser scanning microscopy and flow cytometry suggested that the cell uptake of this gene vector was improved and might be introduced by the fusion interaction between the erythrocyte membrane and targeted cells.Thus, all the results revealed that the erythrocyte membrane based gene delivery system might be able to serve as an excellent gene delivery system.

From conventional towards new - natural surfactants in drug delivery systems design: current status and perspectives.

PubMed

Savić, Snezana; Tamburić, Slobodanka; Savić, Miroslav M

2010-03-01

Surfactants play an important role in the development of both conventional and advanced (colloidal) drug delivery systems. There are several commercial surfactants, but a proportionally small group of them is approved as pharmaceutical excipients, recognized in various pharmacopoeias and therefore widely accepted by the pharmaceutical industry. The review covers some of the main categories of natural, sugar-based surfactants (alkyl polyglucosides and sugar esters) as prospective pharmaceutical excipients. It provides analysis of the physicochemical characteristics of sugar-based surfactants and their possible roles in the design of conventional or advanced drug delivery systems for different routes of administration. Summary and analysis of recent data on functionality, applied concentrations and formulation improvements produced by alkyl polyglucosides and sugar esters in different conventional and advanced delivery systems could be of interest to researchers dealing with drug formulation. Recent FDA certification of an alkyl polyglucoside surfactant for topical formulation presents a significant step in the process of recognition of this relatively new group of surfactants. This could trigger further research into the potential benefits of naturally derived materials in both conventional and new drug delivery systems.

Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug.

PubMed

Shim, Gayong; Han, Su-Eun; Yu, Yong-Hee; Lee, Sangbin; Lee, Han Young; Kim, Kwangmeyung; Kwon, Ick Chan; Park, Tae Gwan; Kim, Young Bong; Choi, Yong Seok; Kim, Chan-Wha; Oh, Yu-Kyoung

2011-10-10

Oligolysine-based cationic lipid derivatives were synthesized for delivery of siRNA, and formulated into cationic liposomes. Among various oligolysine-based lipid derivatives differing in lysine residue number and lipid moiety, trilysinoyl oleylamide (TLO)-based liposomes (TLOL) showed the highest delivery efficiency combined with minimal cytotoxicity. Delivery of siRNA using TLOL silenced target genes both in vitro and in vivo. In green fluorescent protein (GFP)-expressing tumor tissue, a significant reduction of fluorescence was observed after intratumoral administration of siGFP using TLOL compared with control siGL2. Intravenous administration of siMcl1 employing pegylated TLOL (pTLOL) reduced the expression of human Mcl1 protein in KB-xenografted tumor tissue. Despite the reduction in target protein Mcl1 expression following such systemic delivery, tumor growth was only slightly reduced compared to a siGL2-treated control group. To potentiate the anticancer activity of siMcl1, the anticancer drug suberoylanilide hydroxamic acid (SAHA) was additionally encapsulated in pTLOL. After intravenous administration of siMcl1 using SAHA-loaded pTLOL (pSTLOL), a significant reduction in tumor growth was observed compared to that seen in animals treated with free SAHA or siGL2 complexed with pSTLOL. The results indicate that pTLOL could be further developed as a systemic delivery system for synergistic anticancer siRNA and a drug. Copyright © 2010 Elsevier B.V. All rights reserved.

Noncovalent interaction-assisted drug delivery system with highly efficient uptake and release of paclitaxel for anticancer therapy.

PubMed

Wei, Yuping; Ma, Liang; Zhang, Liang; Xu, Xia

2017-01-01

An effective drug delivery system requires efficient drug uptake and release inside cancer cells. Here, we report a novel drug delivery system, in which paclitaxel (PTX) interacts with a novel cell penetrating peptide (CPP) through noncovalent interaction designed based on molecular simulations. This CPP/PTX complex confers high efficiency in delivering PTX into cancer cells not by endocytosis but by an energy-independent pathway. Once inside cells, the noncovalent interaction between PTX and the CPP may allow fast release of PTX within cells due to the direct translocation of CPP/PTX. This drug delivery system exhibits strong capacity for inhibition of tumor growth and offers a new avenue for the development of advanced drug delivery systems for anticancer therapy.

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

A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine.

PubMed

Jahangirian, Hossein; Lemraski, Ensieh Ghasemian; Webster, Thomas J; Rafiee-Moghaddam, Roshanak; Abdollahi, Yadollah

2017-01-01

This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed "green nanomedicine". Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms) are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2017-06-01

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

Curb Challenges of the “Trojan Horse” Approach: Smart Strategies in Achieving Effective yet Safe Cell-penetrating Peptide-based Drug Delivery

PubMed Central

Huang, Yongzhuo; Jiang, Yifan; Wang, Huiyuan; Wang, Jianxin; Shin, Meong Cheol; Byun, Youngro; He, Huining; Liang, Yanqin; Yang, Victor C.

2013-01-01

Cell-penetrating peptide (CPP)-mediated intracellular drug delivery system, often specifically termed as “the Trojan horse approach”, has become the “holy grail” in achieving effective delivery of macromolecular compounds such as proteins, DNA, siRNAs, and drug carriers. It is characterized by the unique cell- (or receptor-), temperature-, and payload-independent mechanisms, therefore offering potent means to improve poor cellular uptake of a variety of macromolecular drugs. Nevertheless, this “Trojan horse” approach also acts like a double-edged sword, causing serious safety and toxicity concerns to normal tissues or organs for in vivo application, due to lack of target selectivity of the powerful cell penetrating activity. To overcome this problem of potent yet non-selective penetration vs. targeting delivery, a number of “smart” strategies have been developed in recent years, including controllable CPP-based drug delivery systems based on various stimuli-responsive mechanisms. This review article provides a fundamental understanding of these smart systems, as well as a discussion of their real-time in vivo applicability. PMID:23369828

Resource Consumption of a Diffusion Model for Prevention Programs: The PROSPER Delivery System

PubMed Central

Crowley, Daniel M.; Jones, Damon E.; Greenberg, Mark T.; Feinberg, Mark E.; Spoth, Richard L.

2012-01-01

Purpose To prepare public systems to implement evidence-based prevention programs for adolescents, it is necessary to have accurate estimates of programs’ resource consumption. When evidence-based programs are implemented through a specialized prevention delivery system, additional costs may be incurred during cultivation of the delivery infrastructure. Currently, there is limited research on the resource consumption of such delivery systems and programs. In this article, we describe the resource consumption of implementing the PROSPER (PROmoting School–Community–University Partnerships to Enhance Resilience) delivery system for a period of 5 years in one state, and how the financial and economic costs of its implementation affect local communities as well as the Cooperative Extension and University systems. Methods We used a six-step framework for conducting cost analysis, using a Cost–Procedure–Process–Outcome Analysis model (Yates, Analyzing costs, procedures, processes, and outcomes in human services: An introduction, 1996; Yates, 2009). This method entails defining the delivery System; bounding cost parameters; identifying, quantifying, and valuing systemic resource Consumption, and conducting sensitivity analysis of the cost estimates. Results Our analyses estimated both the financial and economic costs of the PROSPER delivery system. Evaluation of PROSPER illustrated how costs vary over time depending on the primacy of certain activities (e.g., team development, facilitator training, program implementation). Additionally, this work describes how the PROSPER model cultivates a complex resource infrastructure and provides preliminary evidence of systemic efficiencies. Conclusions This work highlights the need to study the costs of diffusion across time and broadens definitions of what is essential for successful implementation. In particular, cost analyses offer innovative methodologies for analyzing the resource needs of prevention systems. PMID:22325131

Graphene as multifunctional delivery platform in cancer therapy.

PubMed

Nejabat, Mojgan; Charbgoo, Fahimeh; Ramezani, Mohammad

2017-08-01

The biomedical applications of graphene-based nanomaterials including drug and gene delivery have grown rapidly in the past few years. This is due to its high surface area that results in high cargo loading capacity. It is demonstrated that graphene can improve drug efficacy without increasing the dose of the chemotherapeutic agent in cancer treatment. Considering these valuable benefits of graphene, this review focused on the newest advancements in drug and gene delivery systems using graphene and unveiling advantages and disadvantages of different graphene-based materials in introducing an effective cargo delivery system for cancer therapy. Different approaches for reducing cytotoxic impacts of graphene oxide and production of biocompatible delivery platform were also reviewed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2355-2367, 2017. © 2017 Wiley Periodicals, Inc.

Systems modeling and simulation applications for critical care medicine

PubMed Central

2012-01-01

Critical care delivery is a complex, expensive, error prone, medical specialty and remains the focal point of major improvement efforts in healthcare delivery. Various modeling and simulation techniques offer unique opportunities to better understand the interactions between clinical physiology and care delivery. The novel insights gained from the systems perspective can then be used to develop and test new treatment strategies and make critical care delivery more efficient and effective. However, modeling and simulation applications in critical care remain underutilized. This article provides an overview of major computer-based simulation techniques as applied to critical care medicine. We provide three application examples of different simulation techniques, including a) pathophysiological model of acute lung injury, b) process modeling of critical care delivery, and c) an agent-based model to study interaction between pathophysiology and healthcare delivery. Finally, we identify certain challenges to, and opportunities for, future research in the area. PMID:22703718

Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment.

PubMed

Barhate, Ganesh; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Pokharkar, Varsha

2014-11-01

Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Enhanced blood-brain barrier transport of vinpocetine by oral delivery of mixed micelles in combination with a message guider.

PubMed

Ding, Jiaojiao; Sun, Yujiao; Li, Jinfeng; Wang, Huimin; Mao, Shirui

2017-07-01

The blood-brain barrier represents an insurmountable obstacle for the therapy of central nervous system related diseases. Polymeric micelles have many desirable properties for brain targeting by oral delivery, but the stability and targeting efficiency needs to be improved. In this study, it was demonstrated that binary micelle system can compensate the drawbacks of mono system by preparing mixed micelles in combination with PEG-based copolymers. Here, we explored a brain targeting drug delivery system via facile approaches using P123 based mixed micelles in combination with a message guider from traditional Chinese medicine, borneol, for oral delivery. With higher drug-loading, improved stability, prolonged in vitro release profile, increased bioavailability and enhanced brain targeting effect was achieved after peroral delivery of the mixed micelles. More importantly, without extra structure modification for active targeting, it was demonstrated for the first time that oral delivery of vinpocetine loaded mixed micelles together with borneol is an effective way to increase drug concentration in the brain and the targeting efficiency is borneol dose dependent. Such a "simple but effective" modality may shed light on the potential use of polymeric micelles in combination with a message drug to achieve drug brain targeting or other targeting sites via oral delivery.

42 CFR 457.1005 - Cost-effective coverage through a community-based health delivery system.

Code of Federal Regulations, 2013 CFR

2013-10-01

... requirements of § 457.618 (the 10 percent limit on expenditures not used for health benefits coverage for... health care delivery system, such as through contracts with health centers receiving funds under section... 42 Public Health 4 2013-10-01 2013-10-01 false Cost-effective coverage through a community-based...

42 CFR 457.1005 - Cost-effective coverage through a community-based health delivery system.

Code of Federal Regulations, 2014 CFR

2014-10-01

... requirements of § 457.618 (the 10 percent limit on expenditures not used for health benefits coverage for... health care delivery system, such as through contracts with health centers receiving funds under section... 42 Public Health 4 2014-10-01 2014-10-01 false Cost-effective coverage through a community-based...

42 CFR 457.1005 - Cost-effective coverage through a community-based health delivery system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... requirements of § 457.618 (the 10 percent limit on expenditures not used for health benefits coverage for... health care delivery system, such as through contracts with health centers receiving funds under section... 42 Public Health 4 2010-10-01 2010-10-01 false Cost-effective coverage through a community-based...

42 CFR 457.1005 - Cost-effective coverage through a community-based health delivery system.

Code of Federal Regulations, 2012 CFR

2012-10-01

... requirements of § 457.618 (the 10 percent limit on expenditures not used for health benefits coverage for... health care delivery system, such as through contracts with health centers receiving funds under section... 42 Public Health 4 2012-10-01 2012-10-01 false Cost-effective coverage through a community-based...

42 CFR 457.1005 - Cost-effective coverage through a community-based health delivery system.

Code of Federal Regulations, 2011 CFR

2011-10-01

... requirements of § 457.618 (the 10 percent limit on expenditures not used for health benefits coverage for... health care delivery system, such as through contracts with health centers receiving funds under section... 42 Public Health 4 2011-10-01 2011-10-01 false Cost-effective coverage through a community-based...

Cyclodextrin-based supramolecular systems for drug delivery: Recent progress and future perspective

PubMed Central

Zhang, Jianxiang; Ma, Peter X

2013-01-01

The excellent biocompatibility and unique inclusion capability as well as powerful functionalization capacity of cyclodextrins and their derivatives make them especially attractive for engineering novel functional materials for biomedical applications. There has been increasing interest recently to fabricate supramolecular systems for drug and gene delivery based on cyclodextrin materials. This review focuses on state of the art and recent advances in the construction of cyclodextrin-based assemblies and their applications for controlled drug delivery. First, we introduce cyclodextrin materials utilized for self-assembly. The fabrication technologies of supramolecular systems including nanoplatforms and hydrogels as well as their applications in nanomedicine and pharmaceutical sciences are then highlighted. At the end, the future directions of this field are discussed. PMID:23673149

Anti-Cancer Drug Delivery Using Carbohydrate-Based Polymers.

PubMed

Ranjbari, Javad; Mokhtarzadeh, Ahad; Alibakhshi, Abbas; Tabarzad, Maryam; Hejazi, Maryam; Ramezani, Mohammad

2018-02-12

Polymeric drug delivery systems in the form of nanocarriers are the most interesting vehicles in anticancer therapy. Among different types of biocompatible polymers, carbohydrate-based polymers or polysaccharides are the most common natural polymers with complex structures consisting of long chains of monosaccharide or disaccharide units bound by glycosidic linkages. Their appealing properties such as availability, biocompatibility, biodegradability, low toxicity, high chemical reactivity, facile chemical modification and low cost led to their extensive applications in biomedical and pharmaceutical fields including development of nano-vehicles for delivery of anti-cancer therapeutic agents. Generally, reducing systemic toxicity, increasing short half-lives and tumor localization of agents are the top priorities for a successful cancer therapy. Polysaccharide-based or - coated nanosystems with respect to their advantageous features as well as accumulation in tumor tissue due to enhanced permeation and retention (EPR) effect can provide promising carrier systems for the delivery of noblest impressive agents. Most challenging factor in cancer therapy was the toxicity of anti-cancer therapeutic agents for normal cells and therefore, targeted delivery of these drugs to the site of action can be considered as an interesting therapeutic strategy. In this regard, several polysaccharides exhibited selective affinity for specific cell types, and so they can act as a targeting agent in drug delivery systems. Accordingly, different aspects of polysaccharide applications in cancer treatment or diagnosis were reviewed in this paper. In this regard, after a brief introduction of polysaccharide structure and its importance, the pharmaceutical usage of carbohydrate-based polymers was considered according to the identity of accompanying active pharmaceutical agents. It was also presented that the carbohydrate based polymers have been extensively considered as promising materials in the design of efficient nanocarriers for anti-cancer biopharmaceuticals including peptide and proteins or nucleic acid-based therapeutics. Then, the importance of various polysaccharide co-polymers in the drug delivery approaches was illustrated. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A comparison of organized and traditional health care: implications for health promotion and prospective medicine.

PubMed

Lawrence, D M

2005-01-01

To compare organized and traditional health care delivery systems and their ability to meet several major challenges facing health care in the next 25 years. Analysis of traditional and organized health care systems based on a career spent in organized health care systems. The traditional health care system based on independent autonomous physicians is not able to meet the challenges of current healthcare. Stronger integration and coordination, i.e., organized health care delivery systems are required.

Bacteriophage T4 as a Nanoparticle Platform to Display and Deliver Pathogen Antigens: Construction of an Effective Anthrax Vaccine.

PubMed

Tao, Pan; Li, Qin; Shivachandra, Sathish B; Rao, Venigalla B

2017-01-01

Protein-based subunit vaccines represent a safer alternative to the whole pathogen in vaccine development. However, limitations of physiological instability and low immunogenicity of such vaccines demand an efficient delivery system to stimulate robust immune responses. The bacteriophage T4 capsid-based antigen delivery system can robustly elicit both humoral and cellular immune responses without any adjuvant. Therefore, it offers a strong promise as a novel antigen delivery system. Currently Bacillus anthracis, the causative agent of anthrax, is a serious biothreat agent and no FDA-approved anthrax vaccine is available for mass vaccination. Here, we describe a potential anthrax vaccine using a T4 capsid platform to display and deliver the 83 kDa protective antigen, PA, a key component of the anthrax toxin. This T4 vaccine platform might serve as a universal antigen delivery system that can be adapted to develop vaccines against any infectious disease.

A Transdermal Drug Delivery System Based on LIGA Technology and Soft Lithography

NASA Astrophysics Data System (ADS)

Matteucci, Marco; Perennes, Frederic; Marmiroli, Benedetta; Di Fabrizio, Enzo

2007-01-01

This report presents a transdermal drug delivery system based on LIGA fabricated microparts. It is a portable device combining a magnetically actuated micro gear pump with a microneedle array. The fluidic behaviour of the system is analyzed in order to predict its performance according to the dimension of the microparts and then compared to experimental data. The manufacturing process of both micropump and microneedle array are described.

Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery.

PubMed

Li, Zixian; de Barros, Andre Luis Branco; Soares, Daniel Cristian Ferreira; Moss, Sara Nicole; Alisaraie, Laleh

2017-05-30

The unique properties of single-walled carbon nanotubes (SWNTs) enable them to play important roles in many fields. One of their functional roles is to transport cargo into cell. SWNTs are able to traverse amphipathic cell membranes due to their large surface area, flexible interactions with cargo, customizable dimensions, and surface chemistry. The cargoes delivered by SWNTs include peptides, proteins, nucleic acids, as well as drug molecules for therapeutic purpose. The drug delivery functions of SWNTs have been explored over the past decade. Many breakthrough studies have shown the high specificity and potency of functionalized SWNT-based drug delivery systems for the treatment of cancers and other diseases. In this review, we discuss different aspects of drug delivery by functionalized SWNT carriers, diving into the cellular uptake mechanisms, biodistribution of the delivery system, and safety concerns on degradation of the carriers. We emphasize the delivery of several common drugs to highlight the recent achievements of SWNT-based drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Nano-scale gene delivery systems; current technology, obstacles, and future directions.

PubMed

Garcia-Guerra, Antonio; Dunwell, Thomas L; Trigueros, Sonia

2018-01-07

Within the different applications of nanomedicine currently being developed, nano-gene delivery is appearing as an exciting new technique with the possibility to overcome recognised hurdles and fulfill several biological and medical needs. The central component of all delivery systems is the requirement for the delivery of genetic material into cells, and for them to eventually reside in the nucleus where their desired function will be exposed. However, genetic material does not passively enter cells; thus, a delivery system is necessary. The emerging field of nano-gene delivery exploits the use of new materials and the properties that arise at the nanometre-scale to produce delivery vectors that can effectively deliver genetic material into a variety of different types of cells. The novel physicochemical properties of the new delivery vectors can be used to address the current challenges existing in nucleic acid delivery in vitro and in vivo. While there is a growing interest in nanostructure-based gene delivery, the field is still in its infancy, and there is yet much to discover about nanostructures and their physicochemical properties in a biological context. We carry out an organized and focused search of bibliographic databases. Our results suggest that despite new breakthroughs in nanostructure synthesis and advanced characterization techniques, we still face many barriers in producing highly efficient and non-toxic delivery systems. In this review, we overview the types of systems currently used for clinical and biomedical research applications along with their advantages and disadvantages, as well as discussing barriers that arise from nano-scale interactions with biological material. In conclusion, we hope that by bringing the far reaching multidisciplinary nature of nano-gene delivery to light, new targeted nanotechnology-bases strategies are developed to overcome the major challenges covered in this review. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

A New Carbon Nanotube-Based Breast Cancer Drug Delivery System: Preparation and In Vitro Analysis Using Paclitaxel.

PubMed

Shao, Wei; Paul, Arghya; Rodes, Laetitia; Prakash, Satya

2015-04-01

Paclitaxel (PTX) is one of the most important drugs for breast cancer; however, the drug effects are limited by its systematic toxicity and poor water solubility. Nanoparticles have been applied for delivery of cancer drugs to overcome their limitations. Toward this goal, a novel single-walled carbon nanotube (SWNT)-based drug delivery system was developed by conjugation of human serum albumin (HSA) nanoparticles for loading of antitumor agent PTX. The nanosized macromolecular SWNT-drug carrier (SWNT-HSA) was characterized by TEM, UV-Vis-NIR spectrometry, and TGA. The SWNT-based drug carrier displayed high intracellular delivery efficiency (cell uptake rate of 80%) in breast cancer MCF-7 cells, as examined by fluorescence-labeled drug carriers, suggesting the needle-shaped SWNT-HSA drug carrier was able to transport drugs across cell membrane despite its macromolecular structure. The drug loading on SWNT-based drug carrier was through high binding affinity of PTX to HSA proteins. The PTX formulated with SWNT-HSA showed greater growth inhibition activity in MCF-7 breast cancer cells than PTX formulated with HSA nanoparticle only (cell viability of 63 vs 70% in 48 h and 53 vs 62% in 72 h). The increased drug efficacy could be driven by SWNT-mediated cell internalization. These data suggest that the developed SWNT-based antitumor agent is functional and effective. However, more studies for in vivo drug delivery efficacy and other properties are needed before this delivery system can be fully realized.

Using grey literature to prepare pharmacy students for an evolving healthcare delivery system.

PubMed

Happe, Laura E; Walker, Desiree'

2013-05-13

To assess the impact of using "grey literature" (information internally produced in print or electronic format by agencies such as hospitals, government, businesses, etc) rather than a textbook in a course on healthcare delivery systems on students' perception of the relevance of healthcare delivery system topics and their ability to identify credible sources of this information. A reading from the grey literature was identified and assigned to the students for each topic in the course. Pre- and post-course survey instruments were used for the assessment. Students reported healthcare delivery systems topics to be moderately relevant to the profession of pharmacy on both the pre- and post-course survey instruments. Students' knowledge of current and credible sources of information on healthcare delivery system topics significantly improved based on self-reports and scores on objective assessments (p<0.05). Assignment of grey literature in a course on healthcare delivery systems can be used to ensure that information in the pharmacy school curriculum is the most current and credible information available.

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

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

Assessment of Alternative Student Aid Delivery Systems: Assessment of the Current Delivery System.

ERIC Educational Resources Information Center

Advanced Technology, Inc., Reston, VA.

The effects of the current system for delivering federal financial assistance to students under the Pell Grant, Guaranteed Student Loan (GSL), and campus-based programs are analyzed. Information is included on the use of the assessment model, which combines program evaluation, systems research, and policy analysis methodologies.…

Microneedles As a Delivery System for Gene Therapy

PubMed Central

Chen, Wei; Li, Hui; Shi, De; Liu, Zhenguo; Yuan, Weien

2016-01-01

Gene delivery systems can be divided to two major types: vector-based (either viral vector or non-viral vector) and physical delivery technologies. Many physical carriers, such as electroporation, gene gun, ultrasound start to be proved to have the potential to enable gene therapy. A relatively new physical delivery technology for gene delivery consists of microneedles (MNs), which has been studied in many fields and for many molecule types and indications. Microneedles can penetrate the stratum corneum, which is the main barrier for drug delivery through the skin with ease of administration and without significant pain. Many different kinds of MNs, such as metal MNs, coated MNs, dissolving MNs have turned out to be promising in gene delivery. In this review, we discussed the potential as well as the challenges of utilizing MNs to deliver nucleic acids for gene therapy. We also proposed that a combination of MNs and other gene delivery approaches may lead to a better delivery system for gene therapy. PMID:27303298

Advancement of multifunctional hybrid nanogel systems: Construction and application in drug co-delivery and imaging technique.

PubMed

Ma, Yakun; Ge, Yanxiu; Li, Lingbing

2017-02-01

Nanogel-based multifunctional drug delivery systems, especially hybrid nanogels and multicompartment nanogels have drawn more and more extensive attention from the researchers in pharmacy because it can result in achieving a superior functionality through the synergistic property enhancement of each component. The unique hybrid and compartmentalized structures provide the great potential for co-delivery of multiple agents even the multiple agents with different physicochemical properties. Otherwise the hybrid nanogel encapsulating optical and magnetic resonance imaging contrast can be utilized in imaging technique for disease diagnosis. More importantly through nanogel-based multifunctional drug delivery systems the stimuli-responsive features might be easily employed for the design of targeted release of drug. This review summarizes the construction of diverse hybrid nanogels and multicompartment nanogels. The application in co-delivery of multiple agents and imaging agents for diagnosis as well as the application in the design of stimuli-responsive multifunctional nanogels as drug delivery are also reviewed and discussed. The future prospects in application of multifunctional nanogels will be also discussed in this review. Copyright © 2016 Elsevier B.V. All rights reserved.

Dendrimers as Carriers for siRNA Delivery and Gene Silencing: A Review

PubMed Central

Huang, Weizhe; He, Ziying

2013-01-01

RNA interference (RNAi) was first literaturally reported in 1998 and has become rapidly a promising tool for therapeutic applications in gene therapy. In a typical RNAi process, small interfering RNAs (siRNA) are used to specifically downregulate the expression of the targeted gene, known as the term “gene silencing.” One key point for successful gene silencing is to employ a safe and efficient siRNA delivery system. In this context, dendrimers are emerging as potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have attracted intense interest since their emanating research in the 1980s and are extensively studied as efficient DNA delivery vectors in gene transfer applications, due to their unique features based on the well-defined and multivalent structures. Knowing that DNA and RNA possess a similar structure in terms of nucleic acid framework and the electronegative nature, one can also use the excellent DNA delivery properties of dendrimers to develop effective siRNA delivery systems. In this review, the development of dendrimer-based siRNA delivery vectors is summarized, focusing on the vector features (siRNA delivery efficiency, cytotoxicity, etc.) of different types of dendrimers and the related investigations on structure-activity relationship to promote safe and efficient siRNA delivery system. PMID:24288498

Nanoliposome is a Promising Carrier of Protein and Peptide Biomolecule for the Treatment of Cancer.

PubMed

Kumar Giri, Tapan; Giri, Ayan; Kumar Barman, Tapan; Maity, Subhasis

2016-01-01

Nano-liposomes are the newly developed delivery systems for cancer therapy that are finding a position particularly suitable as peptide and protein carriers. These are three-layered self-assembled structures with nanoparticulate carrier systems. The overall pharmacological properties of commonly used protein and peptide in cancer therapy can be improved by the incorporation of protein and peptide into the nano-liposome. The surface modifications can be made liposomes to make compatible with targeting ligands has made these nanocarriers for targeted delivery. This review discusses the method of preparation and characterization of liposome based protein peptide delivery for the treatment of cancer. This review also explores latest work intended for targeted treatment of cancer by nano-liposomal protein and peptide delivery system. This type of delivery is targeting protein and peptide to tumor site by avoiding the reticuloendothelial system. Methods of nano-liposome delivery containing protein and peptide are also highlighted.

Bioresorbable polyelectrolytes for smuggling drugs into cells.

PubMed

Jaganathan, Sripriya

2016-06-01

There is ample evidence that biodegradable polyelectrolyte nanocapsules are multifunctional vehicles which can smuggle drugs into cells, and release them upon endogenous activation. A large number of endogenous stimuli have already been tested in vitro, and in vivo research is escalating. Thus, the interest in the design of intelligent polyelectrolyte multilayer (PEM) drug delivery systems is clear. The need of the hour is a systematic translation of PEM-based drug delivery systems from the lab to clinical studies. Reviews on multifarious stimuli that can trigger the release of drugs from such systems already exist. This review summarizes the available literature, with emphasis on the recent progress in PEM-based drug delivery systems that are receptive in the presence of endogenous stimuli, including enzymes, glucose, glutathione, pH, and temperature, and addresses different active and passive drug targeting strategies. Insights into the current knowledge on the diversified endogenous approaches and methodological challenges may bring inspiration to resolve issues that currently bottleneck the successful implementation of polyelectrolytes into the catalog of third-generation drug delivery systems.

Simulation of a Schema Theory-Based Knowledge Delivery System for Scientists.

ERIC Educational Resources Information Center

Vaughan, W. S., Jr.; Mavor, Anne S.

A future, automated, interactive, knowledge delivery system for use by researchers was tested using a manual cognitive model. Conceptualized from schema/frame/script theories in cognitive psychology and artificial intelligence, this hypothetical system was simulated by two psychologists who interacted with four researchers in microbiology to…

A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine

PubMed Central

Jahangirian, Hossein; Lemraski, Ensieh Ghasemian; Webster, Thomas J; Rafiee-Moghaddam, Roshanak; Abdollahi, Yadollah

2017-01-01

This review discusses the impact of green and environmentally safe chemistry on the field of nanotechnology-driven drug delivery in a new field termed “green nanomedicine”. Studies have shown that among many examples of green nanotechnology-driven drug delivery systems, those receiving the greatest amount of attention include nanometal particles, polymers, and biological materials. Furthermore, green nanodrug delivery systems based on environmentally safe chemical reactions or using natural biomaterials (such as plant extracts and microorganisms) are now producing innovative materials revolutionizing the field. In this review, the use of green chemistry design, synthesis, and application principles and eco-friendly synthesis techniques with low side effects are discussed. The review ends with a description of key future efforts that must ensue for this field to continue to grow. PMID:28442906

Sustained, Controlled and Stimuli-Responsive Drug Release Systems Based on Nanoporous Anodic Alumina with Layer-by-Layer Polyelectrolyte

NASA Astrophysics Data System (ADS)

Porta-i-Batalla, Maria; Eckstein, Chris; Xifré-Pérez, Elisabet; Formentín, Pilar; Ferré-Borrull, J.; Marsal, Lluis F.

2016-08-01

Controlled drug delivery systems are an encouraging solution to some drug disadvantages such as reduced solubility, deprived biodistribution, tissue damage, fast breakdown of the drug, cytotoxicity, or side effects. Self-ordered nanoporous anodic alumina is an auspicious material for drug delivery due to its biocompatibility, stability, and controllable pore geometry. Its use in drug delivery applications has been explored in several fields, including therapeutic devices for bone and dental tissue engineering, coronary stent implants, and carriers for transplanted cells. In this work, we have created and analyzed a stimuli-responsive drug delivery system based on layer-by-layer pH-responsive polyelectrolyte and nanoporous anodic alumina. The results demonstrate that it is possible to control the drug release using a polyelectrolyte multilayer coating that will act as a gate.

Water Delivery--It's All about Pressure

ERIC Educational Resources Information Center

Roman, Harry T.

2005-01-01

There is a great deal of wisdom in the old saying "water seeks its level." In fact, the concept has bearing on a very practical side of human life as well, since the public water delivery system is based on it. In this article, the author discusses the concept behind water pressure and describes how the water systems work based on this concept.…

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.

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

Porous silicon for drug delivery applications and theranostics: recent advances, critical review and perspectives.

PubMed

Kumeria, Tushar; McInnes, Steven J P; Maher, Shaheer; Santos, Abel

2017-12-01

Porous silicon (pSi) engineered by electrochemical etching has been used as a drug delivery vehicle to address the intrinsic limitations of traditional therapeutics. Biodegradability, biocompatibility, and optoelectronic properties make pSi a unique candidate for developing biomaterials for theranostics and photodynamic therapies. This review presents an updated overview about the recent therapeutic systems based on pSi, with a critical analysis on the problems and opportunities that this technology faces as well as highlighting pSi's growing potential. Areas covered: Recent progress in pSi-based research includes drug delivery systems, including biocompatibility studies, drug delivery, theranostics, and clinical trials with the most relevant examples of pSi-based systems presented here. A critical analysis about the technical advantages and disadvantages of these systems is provided along with an assessment on the challenges that this technology faces, including clinical trials and investors' support. Expert opinion: pSi is an outstanding material that could improve existing drug delivery and photodynamic therapies in different areas, paving the way for developing advanced theranostic nanomedicines and incorporating payloads of therapeutics with imaging capabilities. However, more extensive in-vivo studies are needed to assess the feasibility and reliability of this technology for clinical practice. The technical and commercial challenges that this technology face are still uncertain.

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.

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.

Photoacoustic microscopy imaging for microneedle drug delivery

NASA Astrophysics Data System (ADS)

Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

2018-02-01

The recent development of novel transdermal drug delivery systems (TDDS) using microneedle technology allows micron-sized conduits to be formed within the outermost skin layers attracting keen interest in skin as an interface for localized and systemic delivery of therapeutics. In light of this, researchers are using microneedles as tools to deliver nanoparticle formulations to targeted sites for effective therapy. However, in such studies the use of traditional histological methods are employed for characterization and do not allow for the in vivo visualization of drug delivery mechanism. Hence, this study presents a novel imaging technology to characterize microneedle based nanoparticle delivery systems using optical resolution-photoacoustic microscopy (OR-PAM). In this study in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and the spatial distribution of the nanoparticles in the tissue was successfully illustrated. Characterization of parameters that are relevant in drug delivery studies such as penetration depth, efficiency of delivered gold nanoparticles were monitored using the system. Photoacoustic microscopy proves an ideal tool for the characterization studies of microneedle properties and the studies shows microneedles as an ideal tool for precise and controlled drug delivery.

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

Silk-Based Biomaterials for Sustained Drug Delivery

PubMed Central

Yucel, Tuna; Lovett, Michael L.; Kaplan, David L.

2014-01-01

Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk’s well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products. PMID:24910193

Transdermal patches: history, development and pharmacology

PubMed Central

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-01-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

DNA nanostructure-based drug delivery nanosystems in cancer therapy.

PubMed

Wu, Dandan; Wang, Lei; Li, Wei; Xu, Xiaowen; Jiang, Wei

2017-11-25

DNA as a novel biomaterial can be used to fabricate different kinds of DNA nanostructures based on its principle of GC/AT complementary base pairing. Studies have shown that DNA nanostructure is a nice drug carrier to overcome big obstacles existing in cancer therapy such as systemic toxicity and unsatisfied drug efficacy. Thus, different types of DNA nanostructure-based drug delivery nanosystems have been designed in cancer therapy. To improve treating efficacy, they are also developed into more functional drug delivery nanosystems. In recent years, some important progresses have been made. The objective of this review is to make a retrospect and summary about these different kinds of DNA nanostructure-based drug delivery nanosystems and their latest progresses: (1) active targeting; (2) mutidrug co-delivery; (3) construction of stimuli-responsive/intelligent nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Augmentative Communication Services in the Schools.

ERIC Educational Resources Information Center

Blackstone, Sarah W.

1989-01-01

The article considers current issues concerning service delivery systems and practices concerning augmentative and alternative communication (AAC) services in U.S. schools. Concerns in AAC program development are noted and service delivery models (center-based, community-based, or collaborative) are compared. (DB)

Inhalable particulate drug delivery systems for lung cancer therapy: Nanoparticles, microparticles, nanocomposites and nanoaggregates.

PubMed

Abdelaziz, Hadeer M; Gaber, Mohamed; Abd-Elwakil, Mahmoud M; Mabrouk, Moustafa T; Elgohary, Mayada M; Kamel, Nayra M; Kabary, Dalia M; Freag, May S; Samaha, Magda W; Mortada, Sana M; Elkhodairy, Kadria A; Fang, Jia-You; Elzoghby, Ahmed O

2018-01-10

There is progressive evolution in the use of inhalable drug delivery systems (DDSs) for lung cancer therapy. The inhalation route offers many advantages, being non-invasive method of drug administration as well as localized delivery of anti-cancer drugs to tumor tissue. This article reviews various inhalable colloidal systems studied for tumor-targeted drug delivery including polymeric, lipid, hybrid and inorganic nanocarriers. The active targeting approaches for enhanced delivery of nanocarriers to lung cancer cells were illustrated. This article also reviews the recent advances of inhalable microparticle-based drug delivery systems for lung cancer therapy including bioresponsive, large porous, solid lipid and drug-complex microparticles. The possible strategies to improve the aerosolization behavior and maintain the critical physicochemical parameters for efficient delivery of drugs deep into lungs were also discussed. Therefore, a strong emphasis is placed on the approaches which combine the merits of both nanocarriers and microparticles including inhalable nanocomposites and nanoaggregates and on the optimization of such formulations using the proper techniques and carriers. Finally, the toxicological behavior and market potential of the inhalable anti-cancer drug delivery systems are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system

PubMed Central

Thakkar, Hetal; Nangesh, Jitesh; Parmar, Mayur; Patel, Divyakant

2011-01-01

Background: Raloxifene, a second-generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods: In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in vitro intestinal permeability. Results: The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion: Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation. PMID:21966167

Opportunities and Challenges for Niosomes as Drug Delivery Systems.

PubMed

Thakkar, Miloni; Brijesh, S

2016-01-01

With the increase in drug resistance observed in most infectious diseases as well as some forms of cancer, and with the chances of development of new drug molecules to address this issue looking bleak, one of the most plausible ways to disease treatment is combination therapy. Combination therapy would ensure delay in drug resistance, if utilized rationally. However, the biggest difficulty in employing combination therapy are adverse effects due to potential drug-drug interactions and patient compliance due to multiple routes of administration or multiple dosing that may be required. To overcome these issues, researchers have utilized nanoparticle-based systems that can hold multiple drugs in a single carrier. There are several nanocarrier systems available for such purposes. However, the focus of this review will be non-ionic surfactant-based systems (niosomes) for delivery of multiple therapeutic agents. Niosomes are artificially prepared drug delivery carriers. They are structurally similar to liposomes albeit more stable than them. Literature pertaining to combination drug delivery and various drug delivery systems was reviewed. It was conceptualized that many of the methods used to prepare various types of carriers for combination delivery of drugs may be used for niosomal systems as well. We envisage that niosomes may effectively be utilized to package older drugs in newer ways. The review will thus focus on techniques that may be used for the formulation of niosomes, ways to encapsulate multiple-drug moieties, and challenges associated in preparing and optimizing such systems.

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.

Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

NASA Astrophysics Data System (ADS)

Shalviri, Alireza

The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in controlled delivery applications of larger molecular size compounds. The starch based hydrogels, polymers and nanoparticles developed in this work have shown great potentials for controlled drug delivery and biomedical imaging applications.

Surfactant-based drug delivery systems for treating drug-resistant lung cancer.

PubMed

Kaur, Prabhjot; Garg, Tarun; Rath, Goutam; Murthy, R S R; Goyal, Amit K

2016-01-01

Among all cancers, lung cancer is the major cause of deaths. Lung cancer can be categorized into two classes for prognostic and treatment purposes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Both categories of cancer are resistant to certain drugs. Various mechanisms behind drug resistance are over-expression of superficial membrane proteins [glycoprotein (P-gp)], lung resistance-associated proteins, aberration of the intracellular enzyme system, enhancement of the cell repair system and deregulation of cell apoptosis. Structure-performance relationships and chemical compatibility are consequently major fundamentals in surfactant-based formulations, with the intention that a great deal investigation is committed to this region. With the purpose to understand the potential of P-gp in transportation of anti-tumor drugs to cancer cells with much effectiveness and specificity, several surfactant-based delivery systems have been developed which may include microspheres, nanosized drug carriers (nanoparticles, nanoemulsions, stealth liposomes, nanogels, polymer-drug conjugates), novel powders, hydrogels and mixed micellar systems intended for systemic and/or localized delivery.

Microemulsions based transdermal drug delivery systems.

PubMed

Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

2014-01-01

Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.

Nanoemulsion-based delivery systems for polyunsaturated (ω-3) oils: formation using a spontaneous emulsification method.

PubMed

Gulotta, Alessandro; Saberi, Amir Hossein; Nicoli, Maria Cristina; McClements, David Julian

2014-02-19

Nanoemulsion-based delivery systems are finding increasing utilization to encapsulate lipophilic bioactive components in food, personal care, cosmetic, and pharmaceutical applications. In this study, a spontaneous emulsification method was used to fabricate nanoemulsions from polyunsaturated (ω-3) oils, that is, fish oil. This low-energy method relies on formation of fine oil droplets when an oil/surfactant mixture is added to an aqueous solution. The influence of surfactant-to-oil ratio (SOR), oil composition (lemon oil and MCT), and cosolvent composition (glycerol, ethanol, propylene glycol, and water) on the formation and stability of the systems was determined. Optically transparent nanoemulsions could be formed by controlling SOR, oil composition, and aqueous phase composition. The spontaneous emulsification method therefore has considerable potential for fabricating nanoemulsion-based delivery systems for incorporating polyunsatured oils into clear food, personal care, and pharmaceutical products.

Solubility enhancement and delivery systems of curcumin a herbal medicine: a review.

PubMed

Hani, Umme; Shivakumar, H G

2014-01-01

Curcumin diferuloylmethane is a main yellow bioactive component of turmeric, possess wide spectrum of biological actions. It was found to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. However, the benefits are curtailed by its extremely poor aqueous solubility, which subsequently limits the bioavailability and therapeutic effects of curcumin. Nanotechnology is the available approach in solving these issues. Therapeutic efficacy of curcumin can be utilized effectively by doing improvement in formulation properties or delivery systems. Numerous attempts have been made to design a delivery system of curcumin. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of curcumin. This review focuses on the methods to increase solubility of curcumin and various nanotechnologies based delivery systems and other delivery systems of curcumin.

A fluorescence-based imaging approach to pharmacokinetic analysis of intracochlear drug delivery.

PubMed

Ayoob, Andrew M; Peppi, Marcello; Tandon, Vishal; Langer, Robert; Borenstein, Jeffrey T

2018-04-05

Advances in microelectromechanical systems (MEMS) technologies are enhancing the development of intracochlear delivery devices for the treatment of hearing loss with emerging pharmacological therapies. Direct intracochlear delivery addresses the limitations of systemic and intratympanic delivery. However, optimization of delivery parameters for these devices requires pharmacokinetic assessment of the spatiotemporal drug distribution inside the cochlea. Robust methods of measuring drug concentration in the perilymph have been developed, but lack spatial resolution along the tonotopic axis or require complex physiological measurements. Here we describe an approach for quantifying distribution of fluorescent drug-surrogate probe along the cochlea's sensory epithelium with high spatial resolution enabled by confocal fluorescence imaging. Fluorescence from FM 1-43 FX, a fixable endocytosis marker, was quantified using confocal fluorescence imaging of whole mount sections of the organ of Corti from cochleae resected and fixed at several time points after intracochlear delivery. Intracochlear delivery of FM 1-43 FX near the base of the cochlea produces a base-apex gradient of fluorescence in the row of inner hair cells after 1 h post-delivery that is consistent with diffusion-limited transport along the scala tympani. By 3 h post-delivery there is approximately an order of magnitude decrease in peak average fluorescence intensity, suggesting FM 1-43 FX clearance from both the perilymph and inner hair cells. The increase in fluorescence intensity at 72 h post-delivery compared to 3 h post-delivery may implicate a potential radial transport pathway into the scala media. Copyright © 2018 Elsevier B.V. All rights reserved.

Lactococcus lactis-based vaccines: current status and future perspectives.

PubMed

Bahey-El-Din, Mohammed; Gahan, Cormac G M

2011-01-01

Lactococcus lactis offers significant potential as a platform for the delivery of vaccines especially via mucosal routes of administration. The organism has an established history of safe use in the food industry and is highly amenable to genetic manipulation, with many systems available for efficient production of secreted and surface-expressed proteins. Here we describe the benefits of using this organism as a vaccine delivery platform and outline how L. lactis based antigen delivery may be improved. Finally we discuss the safe use of L. lactis vectors and outline the potential for use of biological containment systems and killed lactococcal preparations.

Lipid based delivery and immuno-stimulatory systems: Master tools to combat leishmaniasis.

PubMed

Sabur, Abdus; Asad, Mohammad; Ali, Nahid

2016-11-01

Disease management of leishmaniasis is appalling due to lack of a human vaccine and the toxicity and resistance concerns with limited therapeutic drugs. The challenges in development of a safe vaccine for generation and maintenance of robust antileishmanial protective immunity through a human administrable route of immunization can be addressed through immunomodulation and targeted delivery. The versatility of lipid based particulate system for deliberate delivery of diverse range of molecules including immunomodulators, antigens and drugs have essentially found pivotal role in design of proficient vaccination and therapeutic strategies against leishmaniasis. The prospects of lipid based preventive and curative formulations for leishmaniasis have been highlighted in this review. Copyright © 2016. Published by Elsevier Inc.

Capsid-like supramolecular dendritic systems as pH-responsive nanocarriers for drug penetration and site-specific delivery.

PubMed

Li, Yachao; Lai, Yusi; Xu, Xianghui; Zhang, Xiao; Wu, Yahui; Hu, Cheng; Gu, Zhongwei

2016-02-01

Supramolecular dendritic systems emerge as a promising new-generation bioinspired nanoplatform for nanomedicine. Herein, we report capsid-like mimics self-assembled from peptide dendrimers and functionalized peptides to enhance drug penetration and site-specific delivery for tumor therapy. These drug-loaded supramolecular dendritic systems are endowed with capsid-like component and nanostructure by a facile supramolecular approach. As expected, the drug-loaded capsid-like nanocarriers show some desirable advantages for antitumor drug delivery: a) well-defined nanostructure to improve drug location at tumor site, b) capsid-like architecture to enhance drug penetration, c) high internalization, pH-controlled release and nuclear delivery to jointly achieve site-specific delivery. Based on these merits, the drug-loaded capsid nanocarriers provide efficient tumor suppression to 4T1 tumor bearing BALB/c mice and decrease the DOX-induced toxicity during treatment course. Dendrimers have been tested in many clinical trials as nanocarriers, without great success due to many limitations. Here, the authors attempted to address these issues by developing supramolecular dendritic systems, which mimic capsids in viruses. Both in-vitro and in-vivo studies showed promising results. This work should provide a platform for further development of dendrimer-based nanocarriers for drug delivery. Copyright © 2015 Elsevier Inc. All rights reserved.

Advancements in ocular drug delivery.

PubMed

Weiner, Alan L; Gilger, Brian C

2010-11-01

This review covers both noninvasive and invasive ophthalmic drug delivery systems that can have application to therapy of veterinary ophthalmic diseases. Noninvasive approaches include gel technologies, permeation enhancement via pro-drug development, solubilization agents and nanoparticle technologies, iontophoresis, microneedles, drug-eluting contact lenses and eye misters, and microdroplets. More invasive systems include both eroding implants and noneroding technologies that encompass diffusion based systems, active pumps, intraocular lenses, suprachoroidal drug delivery, and episcleral reservoirs. In addition to addressing the physiologic challenges of achieving the necessary duration of delivery, tissue targeting and patient compliance, the commercial development factors of biocompatibility, sterilization, manufacturability and long-term stability will be discussed. © 2010 American College of Veterinary Ophthalmologists.

[Training and challenges for the health care system in Brazil: an analysis of investments to expand health care service delivery].

PubMed

Soares, Adilson

2007-07-01

The goal of this study is to discuss the investments made by the Brazilian government to expand health care service delivery in the Unified National Health System (SUS) from 1995 to 2001. The data indicate a mismatch between investments to increase service delivery and maintenance and optimization of the health service network's capacity. The paper concludes that there is a need to guarantee financial maintenance of the system and conduct new investments based on an analysis of the installed capacity and the financial possibilities to guarantee resources for continuous delivery of this additional services supply.

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.

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

Production Functions for Water Delivery Systems: Analysis and Estimation Using Dual Cost Function and Implicit Price Specifications

NASA Astrophysics Data System (ADS)

Teeples, Ronald; Glyer, David

1987-05-01

Both policy and technical analysis of water delivery systems have been based on cost functions that are inconsistent with or are incomplete representations of the neoclassical production functions of economics. We present a full-featured production function model of water delivery which can be estimated from a multiproduct, dual cost function. The model features implicit prices for own-water inputs and is implemented as a jointly estimated system of input share equations and a translog cost function. Likelihood ratio tests are performed showing that a minimally constrained, full-featured production function is a necessary specification of the water delivery operations in our sample. This, plus the model's highly efficient and economically correct parameter estimates, confirms the usefulness of a production function approach to modeling the economic activities of water delivery systems.

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

Martino, Mikaël M.; Briquez, Priscilla S.; Maruyama, Kenta

Growth factors are very promising molecules to enhance bone regeneration. However, their translation to clinical use has been seriously limited, facing issues related to safety and cost-effectiveness. These problems derive from the vastly supra-physiological doses of growth factor used without optimized delivery systems. Therefore, these issues have motivated the development of new delivery systems allowing better control of the spatio-temporal release and signaling of growth factors. Because the extracellular matrix (ECM) naturally plays a fundamental role in coordinating growth factor activity in vivo, a number of novel delivery systems have been inspired by the growth factor regulatory function of themore » ECM. After introducing the role of growth factors during the bone regeneration process, this review exposes different issues that growth factor-based therapies have encountered in the clinic and highlights recent delivery approaches based on the natural interaction between growth factor and the ECM.« less

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.

Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation

PubMed Central

Kim, Sungwoo; Kang, Yunqing; Krueger, Chad A.; Sen, Milan; Holcomb, John B.; Chen, Di; Wenke, Joseph C.; Yang, Yunzhi

2012-01-01

The purpose of this study was to develop and characterize a chitosan gel/gelatin microspheres (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1 containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system than other treatments (p<0.05) after a week of culture. PMID:22293583

Development In Drug Targeting And Delivery In Cervical Cancer.

PubMed

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

2017-10-09

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

PLGA: a unique polymer for drug delivery.

PubMed

Kapoor, Deepak N; Bhatia, Amit; Kaur, Ripandeep; Sharma, Ruchi; Kaur, Gurvinder; Dhawan, Sanju

2015-01-01

Biodegradable polymers have played an important role in the delivery of drugs in a controlled and targeted manner. Polylactic-co-glycolic acid (PLGA) is one of the extensively researched synthetic biodegradable polymers due to its favorable properties. It is also known as a 'Smart Polymer' due to its stimuli sensitive behavior. A wide range of PLGA-based drug delivery systems have been reported for the treatment or diagnosis of various diseases and disorders. The present review provides an overview of the chemistry, physicochemical properties, biodegradation behavior, evaluation parameters and applications of PLGA in drug delivery. Different drug-polymer combinations developed into drug delivery or carrier systems are enumerated and discussed.

Enhancing endosomal escape for nanoparticle mediated siRNA delivery

NASA Astrophysics Data System (ADS)

Ma, Da

2014-05-01

Gene therapy with siRNA is a promising biotechnology to treat cancer and other diseases. To realize siRNA-based gene therapy, a safe and efficient delivery method is essential. Nanoparticle mediated siRNA delivery is of great importance to overcome biological barriers for systemic delivery in vivo. Based on recent discoveries, endosomal escape is a critical biological barrier to be overcome for siRNA delivery. This feature article focuses on endosomal escape strategies used for nanoparticle mediated siRNA delivery, including cationic polymers, pH sensitive polymers, calcium phosphate, and cell penetrating peptides. Work has been done to develop different endosomal escape strategies based on nanoparticle types, administration routes, and target organ/cell types. Also, enhancement of endosomal escape has been considered along with other aspects of siRNA delivery to ensure target specific accumulation, high cell uptake, and low toxicity. By enhancing endosomal escape and overcoming other biological barriers, great progress has been achieved in nanoparticle mediated siRNA delivery.

Zein-based Nanocarriers as Potential Natural Alternatives for Drug and Gene Delivery: Focus on Cancer Therapy.

PubMed

Elzoghby, Ahmed; Freag, May; Mamdouh, Hadeer; Elkhodairy, Kadria

2017-01-01

Protein nanocarriers possess unique merits including minimal cytotoxicity, numerous renewable sources, and high drug-binding capability. In opposition to delivery carriers utilizing hydrophilic animal proteins, hydrophobic plant proteins (e.g, zein) have great tendency in fabricating controlled-release particulate carriers without additional chemical modification to stiffen them, which in turn evades the use of toxic chemical crosslinkers. Moreover, zein is related to a class of alcohol-soluble prolamins and generally recognized as safe (GRAS) carrier for drug delivery. Various techniques have been adopted to fabricate zein-based nanoparticulate systems including phase separation coacervation, spray-drying, supercritical anti-solvent approach, electrospinning and self-assembly. This manuscript reviews the recent advances in the zein-based colloidal nano-carrier systems such as nanospheres, nanocapsules, micelles and nanofibers with a special focus on their physicochemical characteristics and drug delivery applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Formation and stabilization of nanoemulsion-based vitamin E delivery systems using natural biopolymers: Whey protein isolate and gum arabic.

PubMed

Ozturk, Bengu; Argin, Sanem; Ozilgen, Mustafa; McClements, David Julian

2015-12-01

Natural biopolymers, whey protein isolate (WPI) and gum arabic (GA), were used to fabricate emulsion-based delivery systems for vitamin E-acetate. Stable delivery systems could be formed when vitamin E-acetate was mixed with sufficient orange oil prior to high pressure homogenization. WPI (d32=0.11 μm, 1% emulsifier) was better than GA (d32=0.38 μm, 10% emulsifier) at producing small droplets at low emulsifier concentrations. However, WPI-stabilized nanoemulsions were unstable to flocculation near the protein isoelectric point (pH 5.0), at high ionic strength (>100mM), and at elevated temperatures (>60 °C), whereas GA-stabilized emulsions were stable. This difference was attributed to differences in emulsifier stabilization mechanisms: WPI by electrostatic repulsion; GA by steric repulsion. These results provide useful information about the emulsifying and stabilizing capacities of natural biopolymers for forming food-grade vitamin-enriched delivery systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanoparticles in the clinic

PubMed Central

Anselmo, Aaron C.

2016-01-01

Abstract Nanoparticle/microparticle‐based drug delivery systems for systemic (i.e., intravenous) applications have significant advantages over their nonformulated and free drug counterparts. For example, nanoparticle systems are capable of delivering therapeutics and treating areas of the body that other delivery systems cannot reach. As such, nanoparticle drug delivery and imaging systems are one of the most investigated systems in preclinical and clinical settings. Here, we will highlight the diversity of nanoparticle types, the key advantages these systems have over their free drug counterparts, and discuss their overall potential in influencing clinical care. In particular, we will focus on current clinical trials for nanoparticle formulations that have yet to be clinically approved. Additional emphasis will be on clinically approved nanoparticle systems, both for their currently approved indications and their use in active clinical trials. Finally, we will discuss many of the often overlooked biological, technological, and study design challenges that impact the clinical success of nanoparticle delivery systems. PMID:29313004

Local delivery of fluorescent dye for fiber-optics confocal microscopy of the living heart.

PubMed

Huang, Chao; Kaza, Aditya K; Hitchcock, Robert W; Sachse, Frank B

2014-01-01

Fiber-optics confocal microscopy (FCM) is an emerging imaging technology with various applications in basic research and clinical diagnosis. FCM allows for real-time in situ microscopy of tissue at sub-cellular scale. Recently FCM has been investigated for cardiac imaging, in particular, for discrimination of cardiac tissue during pediatric open-heart surgery. FCM relies on fluorescent dyes. The current clinical approach of dye delivery is based on systemic injection, which is associated with high dye consumption, and adverse clinical events. In this study, we investigated approaches for local dye delivery during FCM imaging based on dye carriers attached to the imaging probe. Using three-dimensional confocal microscopy, automated bench tests, and FCM imaging we quantitatively characterized dye release of carriers composed of open-pore foam only and foam loaded with agarose hydrogel. In addition, we compared local dye delivery with a model of systemic dye delivery in the isolated perfused rodent heart. We measured the signal-to-noise ratio (SNR) of images acquired in various regions of the heart. Our evaluations showed that foam-agarose dye carriers exhibited a prolonged dye release vs. foam-only carriers. Foam-agarose dye carriers allowed reliable imaging of 5-9 lines, which is comparable to 4-8 min of continuous dye release. Our study in the living heart revealed that the SNR of FCM images using local and systemic dye delivery is not different. However, we observed differences in the imaged tissue microstructure with the two approaches. Structural features characteristic of microvasculature were solely observed for systemic dye delivery. Our findings suggest that local dye delivery approach for FCM imaging constitutes an important alternative to systemic dye delivery. We suggest that the approach for local dye delivery will facilitate clinical translation of FCM, for instance, for FCM imaging during pediatric heart surgery.

Polymer-Mediated Delivery of siRNAs to Hepatocellular Carcinoma: Variables Affecting Specificity and Effectiveness.

PubMed

Farra, Rossella; Musiani, Francesco; Perrone, Francesca; Čemažar, Maja; Kamenšek, Urška; Tonon, Federica; Abrami, Michela; Ručigaj, Aleš; Grassi, Mario; Pozzato, Gabriele; Bonazza, Deborah; Zanconati, Fabrizio; Forte, Giancarlo; El Boustani, Maguie; Scarabel, Lucia; Garziera, Marica; Russo Spena, Concetta; De Stefano, Lucia; Salis, Barbara; Toffoli, Giuseppe; Rizzolio, Flavio; Grassi, Gabriele; Dapas, Barbara

2018-03-28

Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs), are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work.

In vitro and ex vivo strategies for intracellular delivery

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Technology-mediated therapy for chronic pain management: the challenges of adapting behavior change interventions for delivery with pervasive communication technology.

PubMed

Rosser, Benjamin A; McCullagh, Paul; Davies, Richard; Mountain, Gail A; McCracken, Lance; Eccleston, Christopher

2011-04-01

Adapting therapeutic practice from traditional face-to-face exchange to remote technology-based delivery presents challenges for the therapist, patient, and technical writer. This article documents the process of therapy adaptation and the resultant specification for the SMART2 project-a technology-based self-management system for assisting long-term health conditions, including chronic pain. Focus group discussions with healthcare professionals and patients were conducted to inform selection of therapeutic objectives and appropriate technology. Pertinent challenges are identified, relating to (1) reduction and definition of therapeutic objectives, and (2) how to approach adaptation of therapy to a form suited to technology delivery. The requirement of the system to provide dynamic and intelligent responses to patient experience and behavior is also emphasized. Solutions to these challenges are described in the context of the SMART2 technology-based intervention. More explicit discussion and documentation of therapy adaptation to technology-based delivery within the literature is encouraged.

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

On-Chip Laser-Power Delivery System for Dielectric Laser Accelerators

NASA Astrophysics Data System (ADS)

Hughes, Tyler W.; Tan, Si; Zhao, Zhexin; Sapra, Neil V.; Leedle, Kenneth J.; Deng, Huiyang; Miao, Yu; Black, Dylan S.; Solgaard, Olav; Harris, James S.; Vuckovic, Jelena; Byer, Robert L.; Fan, Shanhui; England, R. Joel; Lee, Yun Jo; Qi, Minghao

2018-05-01

We propose an on-chip optical-power delivery system for dielectric laser accelerators based on a fractal "tree-network" dielectric waveguide geometry. This system replaces experimentally demanding free-space manipulations of the driving laser beam with chip-integrated techniques based on precise nanofabrication, enabling access to orders-of-magnitude increases in the interaction length and total energy gain for these miniature accelerators. Based on computational modeling, in the relativistic regime, our laser delivery system is estimated to provide 21 keV of energy gain over an acceleration length of 192 μ m with a single laser input, corresponding to a 108-MV/m acceleration gradient. The system may achieve 1 MeV of energy gain over a distance of less than 1 cm by sequentially illuminating 49 identical structures. These findings are verified by detailed numerical simulation and modeling of the subcomponents, and we provide a discussion of the main constraints, challenges, and relevant parameters with regard to on-chip laser coupling for dielectric laser accelerators.

Online Instruction: An Alternative Delivery System for Higher Education

ERIC Educational Resources Information Center

Wronkovich, Michael

2003-01-01

In an increasingly technological society, delivery systems for professional development and higher education have greatly expanded. Video conferencing and web-based alternatives provide opportunities to extend the college campus far beyond the boundaries traditionally considered feasible. Adult learners have found the convenience of web-based…

State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines.

PubMed

Dawidczyk, Charlene M; Kim, Chloe; Park, Jea Ho; Russell, Luisa M; Lee, Kwan Hyi; Pomper, Martin G; Searson, Peter C

2014-08-10

The ability to efficiently deliver a drug to a tumor site is dependent on a wide range of physiologically imposed design constraints. Nanotechnology provides the possibility of creating delivery vehicles where these design constraints can be decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing targeting efficiency and efficacy. Here we review the design strategies of the two FDA-approved antibody-drug conjugates (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and Abraxane) in the context of the challenges associated with systemic targeted delivery of a drug to a solid tumor. The lessons learned from these nanomedicines provide an important insight into the key challenges associated with the development of new platforms for systemic delivery of anti-cancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and infectious diseases.

PubMed

Bolhassani, Azam; Javanzad, Shabnam; Saleh, Tayebeh; Hashemi, Mehrdad; Aghasadeghi, Mohammad Reza; Sadat, Seyed Mehdi

2014-01-01

Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids. Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems.

Exosomes as nanocarriers for siRNA delivery: paradigms and challenges.

PubMed

Shahabipour, Fahimeh; Banach, Maciej; Sahebkar, Amirhossein

2016-12-01

Exosomes are nano-sized vesicles that facilitate intercellular communications through carrying genetic materials and functional biomolecules. Owing to their unique size and structure, exosomes have emerged as a useful tool to overcome the limitations of siRNA delivery. The use of exosomes as siRNA delivery vehicles lacks certain disadvantages of the existing foreign delivery systems such as viruses, polycationic polymers and liposomes, and introduces several advantages including inherent capacity to pass through biological barriers and escape from phagocytosis by the reticuloendothelial system, as well as being biocompatible, non-toxic, and immunologically inert. Different strategies have been employed to harness exosome-based delivery systems, including surface modification with targeting ligands, and using exosome-display technology, virus-modified exosomes, and exosome-mimetic vesicles. The present review provides a capsule summary of the recent advances and current challenges in the field of exosome-mediated siRNA delivery.

Pharmacosomes: An Emerging Novel Vesicular Drug Delivery System for Poorly Soluble Synthetic and Herbal Drugs

PubMed Central

2013-01-01

In the arena of solubility enhancement, several problems are encountered. A novel approach based on lipid drug delivery system has evolved, pharmacosomes. Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the form of hexagonal assembly of colloidal drug dispersions attached covalently to the phospholipid. They act as befitting carrier for delivery of drugs quite precisely owing to their unique properties like small size, amphiphilicity, active drug loading, high entrapment efficiency, and stability. They help in controlled release of drug at the site of action as well as in reduction in cost of therapy, drug leakage and toxicity, increased bioavailability of poorly soluble drugs, and restorative effects. There has been advancement in the scope of this delivery system for a number of drugs used for inflammation, heart diseases, cancer, and protein delivery along with a large number of herbal drugs. Hence, pharmacosomes open new challenges and opportunities for improved novel vesicular drug delivery system. PMID:24106615

Chitosan nanoparticle based delivery systems for sustainable agriculture.

PubMed

Kashyap, Prem Lal; Xiang, Xu; Heiden, Patricia

2015-01-01

Development of technologies that improve food productivity without any adverse impact on the ecosystem is the need of hour. In this context, development of controlled delivery systems for slow and sustained release of agrochemicals or genetic materials is crucial. Chitosan has emerged as a valuable carrier for controlled delivery of agrochemicals and genetic materials because of its proven biocompatibility, biodegradability, non-toxicity, and adsorption abilities. The major advantages of encapsulating agrochemicals and genetic material in a chitosan matrix include its ability to function as a protective reservoir for the active ingredients, protecting the ingredients from the surrounding environment while they are in the chitosan domain, and then controlling their release, allowing them to serve as efficient gene delivery systems for plant transformation or controlled release of pesticides. Despite the great progress in the use of chitosan in the area of medical and pharmaceutical sciences, there is still a wide knowledge gap regarding the potential application of chitosan for encapsulation of active ingredients in agriculture. Hence, the present article describes the current status of chitosan nanoparticle-based delivery systems in agriculture, and to highlight challenges that need to be overcome. Copyright © 2015 Elsevier B.V. All rights reserved.

Newly Engineered Magnetic Erythrocytes for Sustained and Targeted Delivery of Anti-Cancer Therapeutic Compounds

PubMed Central

Taranta, Monia; Naldi, Ilaria

2011-01-01

Cytotoxic chemotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can they be selectively improved? Alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. These formulations are associated with problems like severe toxic side effects on healthy organs, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site-specific controlled drug delivery systems. In response to these concerns, we have developed a new drug delivery system based on magnetic erythrocytes engineered with a viral spike fusion protein. This new erythrocyte-based drug delivery system has the potential for magnetic-controlled site-specific localization and highly efficient fusion capability with the targeted cells. Here we show that the erythro-magneto-HA virosomes drug delivery system is able to attach and fuse with the target cells and to efficiently release therapeutic compounds inside the cells. The efficacy of the anti-cancer drug employed is increased and the dose required is 10 time less than that needed with conventional therapy. PMID:21373641

Nanosponge Carriers- An Archetype Swing in Cancer Therapy: A Comprehensive Review.

PubMed

Osmani, Riyaz Ali M; Hani, Umme; Bhosale, Rohit R; Kulkarni, Parthasarathi K; Shanmuganathan, Seetharaman

2017-01-01

Nanotechnology and nanomedicines are emerging research meadows; which chiefly focuses on creating and manipulating materials at a nanometer level for the betterment in imaging, diagnosis and treatment of a range of diseases together with cancer. Cyclodextrin-based nanosponges, anticipated as a new-fangled nanosized delivery system, are ground-breaking hyper-crosslinked cyclodextrin polymers nanostructured within a three-dimensional network. Nanosponges based systems hold the potential of elevating the solubility, absorption, penetration, bioavailability, in vivo stability, targeted as well as sustained delivery, and therapeutic efficiency of numerous anticancer agents. The extension of nanosponges based drug delivery systems is an exhilarating and demanding research pasture, predominantly to overcome aforementioned problems allied to existing anticancer formulations and for the further progressions in cancer therapies. Nanosponges in cancer therapy, particularly cyclodextrin based nanosponges are brought up in this review. By quoting diverse attempts made in pertinent direction, efforts have been made to exemplify the characteristics, suitability and versatility of cyclodextrin based nanosponges for their promising applications in cancer treatment.

A targeted drug delivery system based on dopamine functionalized nano graphene oxide

NASA Astrophysics Data System (ADS)

Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

2017-01-01

The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

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.

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

Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers.

PubMed

Chen, Wei; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

2014-09-28

Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention (EPR) effect, and degradation in vivo into nontoxic products after completing their tasks. The current biodegradable drug and gene delivery systems exhibit, however, typically low in vivo therapeutic efficacy, due to issues of low loading capacity, inadequate in vivo stability, premature cargo release, poor uptake by target cells, and slow release of therapeutics inside tumor cells. To overcome these problems, a variety of advanced drug and gene delivery systems has recently been designed and developed based on functional biodegradable polycarbonates and copolymers. Notably, polycarbonates and copolymers with diverse functionalities such as hydroxyl, carboxyl, amine, alkene, alkyne, halogen, azido, acryloyl, vinyl sulfone, pyridyldisulfide, and saccharide, could be readily obtained by controlled ring-opening polymerization. In this paper, we give an overview on design concepts and recent developments of functional polycarbonate-based nanocarriers including stimuli-sensitive, photo-crosslinkable, or active targeting polymeric micelles, polymersomes and polyplexes for enhanced drug and gene delivery in vitro and in vivo. These multifunctional biodegradable nanosystems might be eventually developed for safe and efficient cancer chemotherapy and gene therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Protamine-based nanoparticles as new antigen delivery systems.

PubMed

González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

2015-11-01

The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Micro/nanoparticle adjuvants for antileishmanial vaccines: present and future trends.

PubMed

Badiee, Ali; Heravi Shargh, Vahid; Khamesipour, Ali; Jaafari, Mahmoud Reza

2013-01-21

Leishmania infection continues to have a major impact on public health inducing significant morbidity and mortality mostly in the poorest populations. Drug resistance, toxicity and side effects associated with expensive chemotherapeutic treatments and difficult reservoir control emphasize the need for a safe and effective vaccine which is not available yet. Although, Leishmanization (LZ) was shown to be effective against cutaneous leishmaniasis, standardization and safety are the main problems of LZ. First generation killed parasites demonstrated limited efficacy in phase 3 trials and moreover well defined molecules have not reached to phase 3 yet. Limited efficacy in vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Hence, the use of particulate delivery systems as carriers for antigen and/or immunostimulatory adjuvants for effective delivery to the antigen-presenting cells (APCs) is a valuable strategy to enhance vaccine efficacies. Particle-based delivery systems such as emulsions, liposomes, virosomes, and polymeric microspheres have the potential for successfully delivering antigens, which can then be further improved via incorporation of additional antigenic or immustimulatory adjuvant components in or onto the particle carrier system. In this review, we have attempted to provide a list of particulate vaccine delivery systems involved in the production of candidate leishmaniasis vaccines and introduced some potentially useful vaccine delivery systems for leishmaniasis in future experiments. In conclusion, combination vaccines (adjuvant systems) composed of candidate antigens and more importantly well-developed particulate delivery systems, such as lipid-based particles containing immunostimulatory adjuvants, have a chance to succeed as antileishmanial vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

PubMed

Labib, Gihan

2018-01-01

Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

PubMed

Zandstra, Jurjen; van Beuge, Marike M; Zuidema, Johan; Petersen, Arjen H; Staal, Mark; Duque, Luisa F; Rodriguez, Sergio; Lathuile, Audrey A R; Veldhuis, Gert J; Steendam, Rob; Bank, Ruud A; Popa, Eliane R

2015-10-01

The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney. We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs. Using a rat model of acute kidney injury, subcapsular injection of placebo and rapamycin monodisperse microspheres (monospheres) was compared to subcutaneous injection, mimicking systemic administration. We did not find any adverse effects related to the delivery method. Irrespective of the injection site, a similar low dose of rapamycin was present in the circulation. However, only local intrarenal delivery of rapamycin from monospheres led to decreased macrophage infiltration and a significantly lower amount of myofibroblasts in the kidney, where systemic administration did not. Local delivery of rapamycin did cause a transient increase in the deposition of collagen I, but not of collagen III. We conclude that therapeutic effects can be increased when rapamycin is delivered subcapsularly by monospheres, which, combined with low systemic concentrations, may lead to an effective intrarenal delivery method.

A Promising Combo Gene Delivery System Developed from (3-Aminopropyl)triethoxysilane-Modified Iron Oxide Nanoparticles and Cationic Polymers

NASA Astrophysics Data System (ADS)

Zhang, Zubin; Song, Lina; Dong, Jinlai; Guo, Dawei; Du, Xiaolin; Cao, Biyin; Zhang, Yu; Gu, Ning; Mao, Xinliang

2013-05-01

(3-Aminopropyl)triethoxysilane-modified iron oxide nanoparticles (APTES-IONPs) have been evaluated for various biomedical applications, including medical imaging and drug delivery. Cationic polymers (CPs) such as Lipofectamine and TurboFect are widely used for research in gene delivery, but their toxicity and low in vivo efficiency limited their further application. In the present study, we synthesized water-soluble APTES-IONPs and developed a combo gene delivery system based on APTES-IONPs and CPs. This system significantly increased gene-binding capacity, protected genes from degradation, and improved gene transfection efficiency for DNA and siRNA in both adherent and suspension cells. Because of its great biocompatibility, high gene-carrying ability, and very low cytotoxicity, this combo gene delivery system will be expected for a wide application, and it might provide a new method for gene therapy.

RNase non-sensitive and endocytosis independent siRNA delivery system: delivery of siRNA into tumor cells and high efficiency induction of apoptosis

NASA Astrophysics Data System (ADS)

Jiang, Xinglu; Wang, Guobao; Liu, Ru; Wang, Yaling; Wang, Yongkui; Qiu, Xiaozhong; Gao, Xueyun

2013-07-01

To date, RNase degradation and endosome/lysosome trapping are still serious problems for siRNA-based molecular therapy, although different kinds of delivery formulations have been tried. In this report, a cell penetrating peptide (CPP, including a positively charged segment, a linear segment, and a hydrophobic segment) and a single wall carbon nanotube (SWCNT) are applied together by a simple method to act as a siRNA delivery system. The siRNAs first form a complex with the positively charged segment of CPP via electrostatic forces, and the siRNA-CPP further coats the surface of the SWCNT via hydrophobic interactions. This siRNA delivery system is non-sensitive to RNase and can avoid endosome/lysosome trapping in vitro. When this siRNA delivery system is studied in Hela cells, siRNA uptake was observed in 98% Hela cells, and over 70% mRNA of mammalian target of rapamycin (mTOR) is knocked down, triggering cell apoptosis on a significant scale. Our siRNA delivery system is easy to handle and benign to cultured cells, providing a very efficient approach for the delivery of siRNA into the cell cytosol and cleaving the target mRNA therein.

A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy.

PubMed

Johnsen, Kasper Bendix; Gudbergsson, Johann Mar; Skov, Martin Najbjerg; Pilgaard, Linda; Moos, Torben; Duroux, Meg

2014-08-01

Exosomes denote a class of secreted nanoparticles defined by size, surface protein and lipid composition, and the ability to carry RNA and proteins. They are important mediators of intercellular communication and regulators of the cellular niche, and their altered characteristics in many diseases, such as cancer, suggest them to be important both for diagnostic and therapeutic purposes, prompting the idea of using exosomes as drug delivery vehicles, especially for gene therapy. This review covers the current status of evidence presented in the field of exosome-based drug delivery systems. Components for successful exosome-based drug delivery, such as choice of donor cell, therapeutic cargo, use of targeting peptide, loading method and administration route are highlighted and discussed with a general focus pertaining to the results obtained in models of different cancer types. In addition, completed and on-going clinical trials are described, evaluating exosome-based therapies for the treatment of different cancer types. Due to their endogenous origin, exosome-based drug delivery systems may have advantages in the treatment of cancer, but their design needs further refinement to justify their usage on the clinical scale. Copyright © 2014 Elsevier B.V. All rights reserved.

Insights on Localized and Systemic Delivery of Redox-Based Therapeutics

PubMed Central

Batrakova, Elena V.; Mota, Roberto

2018-01-01

Reactive oxygen and nitrogen species are indispensable in cellular physiology and signaling. Overproduction of these reactive species or failure to maintain their levels within the physiological range results in cellular redox dysfunction, often termed cellular oxidative stress. Redox dysfunction in turn is at the molecular basis of disease etiology and progression. Accordingly, antioxidant intervention to restore redox homeostasis has been pursued as a therapeutic strategy for cardiovascular disease, cancer, and neurodegenerative disorders among many others. Despite preliminary success in cellular and animal models, redox-based interventions have virtually been ineffective in clinical trials. We propose the fundamental reason for their failure is a flawed delivery approach. Namely, systemic delivery for a geographically local disease limits the effectiveness of the antioxidant. We take a critical look at the literature and evaluate successful and unsuccessful approaches to translation of redox intervention to the clinical arena, including dose, patient selection, and delivery approach. We argue that when interpreting a failed antioxidant-based clinical trial, it is crucial to take into account these variables and importantly, whether the drug had an effect on the redox status. Finally, we propose that local and targeted delivery hold promise to translate redox-based therapies from the bench to the bedside. PMID:29636836

Considering retail health clinics.

PubMed

Mullin, Kathy

2009-12-01

By gaining increasing acceptance from consumers and traditional providers, retail-based convenient care clinics have moved from the innovative fringe into the mainstream of healthcare delivery. Nationwide, resourceful administrators are experimenting with retail-based delivery systems, using the clinic's unique attributes to promote wellness, expand accessibility, reduce delivery costs, and enhance brand recognition. This article takes an in-depth look at the convenient care business model, pertinent regulatory issues, and some of the associated benefits and concerns.

Transdermal patches: history, development and pharmacology.

PubMed

Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

2015-05-01

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. © 2015 The British Pharmacological Society.

Course Evaluation: Reconfigurations for Learning with Learning Management Systems

ERIC Educational Resources Information Center

Park, Ji Yong

2014-01-01

The introduction of online delivery platforms such as learning management systems (LMS) in tertiary education has changed the methods and modes of curriculum delivery and communication. While course evaluation methods have also changed from paper-based in-class-administered methods to largely online-administered methods, the data collection…

Automating Document Delivery: A Conference Report.

ERIC Educational Resources Information Center

Ensor, Pat

1992-01-01

Describes presentations made at a forum on automation, interlibrary loan (ILL), and document delivery sponsored by the Houston Area Library Consortium. Highlights include access versus ownership; software for ILL; fee-based services; automated management systems for ILL; and electronic mail and online systems for end-user-generated ILL requests.…

Nanoscale platforms for messenger RNA delivery.

PubMed

Li, Bin; Zhang, Xinfu; Dong, Yizhou

2018-05-04

Messenger RNA (mRNA) has become a promising class of drugs for diverse therapeutic applications in the past few years. A series of clinical trials are ongoing or will be initiated in the near future for the treatment of a variety of diseases. Currently, mRNA-based therapeutics mainly focuses on ex vivo transfection and local administration in clinical studies. Efficient and safe delivery of therapeutically relevant mRNAs remains one of the major challenges for their broad applications in humans. Thus, effective delivery systems are urgently needed to overcome this limitation. In recent years, numerous nanoscale biomaterials have been constructed for mRNA delivery in order to protect mRNA from extracellular degradation and facilitate endosomal escape after cellular uptake. Nanoscale platforms have expanded the feasibility of mRNA-based therapeutics, and enabled its potential applications to protein replacement therapy, cancer immunotherapy, therapeutic vaccines, regenerative medicine, and genome editing. This review focuses on recent advances, challenges, and future directions in nanoscale platforms designed for mRNA delivery, including lipid and lipid-derived nanoparticles, polymer-based nanoparticles, protein derivatives mRNA complexes, and other types of nanomaterials. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures. © 2018 Wiley Periodicals, Inc.

Nanocarriers in ocular drug delivery: an update review.

PubMed

Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani Rai; Vyas, S P

2009-01-01

Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.

Uniform Surface Modification of 3D Bioglass®-Based Scaffolds with Mesoporous Silica Particles (MCM-41) for Enhancing Drug Delivery Capability

PubMed Central

Boccardi, Elena; Philippart, Anahí; Juhasz-Bortuzzo, Judith A.; Beltrán, Ana M.; Novajra, Giorgia; Vitale-Brovarone, Chiara; Spiecker, Erdmann; Boccaccini, Aldo R.

2015-01-01

The design and characterization of a new family of multifunctional scaffolds based on bioactive glass (BG) of 45S5 composition for bone tissue engineering and drug delivery applications are presented. These BG-based scaffolds are developed via a replication method of polyurethane packaging foam. In order to increase the therapeutic functionality, the scaffolds were coated with mesoporous silica particles (MCM-41), which act as an in situ drug delivery system. These sub-micron spheres are characterized by large surface area and pore volume with a narrow pore diameter distribution. The solution used for the synthesis of the silica mesoporous particles was designed to obtain a high-ordered mesoporous structure and spherical shape – both are key factors for achieving the desired controlled drug release. The MCM-41 particles were synthesized directly inside the BG-based scaffolds, and the drug-release capability of this combined system was evaluated. Moreover, the effect of MCM-41 particle coating on the bioactivity of the BG-based scaffolds was assessed. The results indicate that it is possible to obtain a multifunctional scaffold system characterized by high and interconnected porosity, high bioactivity, and sustained drug delivery capability. PMID:26594642

Early childhood education: Status trends, and issues related to electronic delivery

NASA Technical Reports Server (NTRS)

Rothenberg, D.

1973-01-01

The status of, and trends and issues within, early childhood education which are related to the possibilities of electronic delivery of educational service are considered in a broader investigation of the role of large scale, satellite based educational telecommunications systems. Data are analyzed and trends and issues discussed to provide information useful to the system designer who wishes to identify and assess the opportunities for large scale electronic delivery in early childhood education.

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.

Pharmacogenomics in the preclinical development of vaccines: evaluation of efficacy and systemic toxicity in the mouse using array technology.

PubMed

Regnström, Karin J

2008-01-01

The development of vaccines, conventional protein based as well as nucleic acid based vaccines, and their delivery systems has been largely empirical and ineffective. This is partly due to a lack of methodology, since traditionally only a few markers are studied. By introducing gene expression analysis and bioinformatics into the design of vaccines and their delivery systems, vaccine development can be improved and accelerated considerably. Each vaccine antigen and delivery system combination is characterized by a unique genomic profile, a "fingerprint" that will give information of not only immunological and toxicological responses but also other related cellular responses e.g. cell cycle, apoptosis and carcinogenic effects. The resulting unique genomic fingerprint facilitates the establishment of molecular structure--pharmacological activity relationships and therefore leads to optimization of vaccine development.

Glucose-Responsive Supramolecular Vesicles Based on Water-Soluble Pillar[5]arene and Pyridylboronic Acid Derivatives for Controlled Insulin Delivery.

PubMed

Gao, Lei; Wang, Tingting; Jia, Keke; Wu, Xuan; Yao, Chenhao; Shao, Wei; Zhang, Dongmei; Hu, Xiao-Yu; Wang, Leyong

2017-05-11

The stimuli-responsive behavior of supramolecular nanocarriers is crucial for their potential applications as smart drug delivery systems. We hereby constructed a glucose-responsive supramolecular drug delivery system based on the host-guest interaction between a water-soluble pillar[5]arene (WP5) and a pyridylboronic acid derivative (G) for insulin delivery and controlled release under physiological conditions. The approach represents the ideal treatment of diabetes mellitus. The drug loading and in vitro drug release experiments demonstrated that large molecular weight insulin could be encapsulated into the vesicles with high loading efficiency, which, to our knowledge, is the first example of small-size supramolecular vesicles with excellent encapsulation capacity of a large protein molecule. Moreover, FITC-labeled insulin was used to evaluate the release behavior of insulin, and it was demonstrated that high glucose concentration could facilitate the quick release of insulin, suggesting a smart drug delivery system for potential application in controlled insulin release only under hyperglycemic conditions. Finally, we demonstrated that these supramolecular nanocarriers have good cytocompatibility, which is essential for their further biomedical applications. The present study provides a novel strategy for the construction of glucose-responsive smart supramolecular drug delivery systems, which has potential applications for the treatment of diabetes mellitus. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology.

PubMed

Meng, Jianing; Agrahari, Vivek; Youm, Ibrahima

2017-03-01

At present, brain tumor is among the most challenging diseases to treat and the therapy is limited by the lack of effective methods to deliver anticancer agents across the blood-brain barrier (BBB). BBB is a selective barrier that separates the circulating blood from the brain extracellular fluid. In its neuroprotective function, BBB prevents the entry of toxins, as well as most of anticancer agents and is the main impediment for brain targeted drug delivery approaches. Nanotechnology-based delivery systems provide an attractive strategy to cross the BBB and reach the central nervous system (CNS). The incorporation of anticancer agents in various nanovehicles facilitates their delivery across the BBB. Moreover, a more powerful tool in brain tumor therapy has relied surface modifications of nanovehicles with specific ligands that can promote their passage through the BBB and favor the accumulation of the drug in CNS tumors. This review describes the physiological and anatomical features of the brain tumor and the BBB, and summarizes the recent advanced approaches to deliver anticancer drugs into brain tumor using nanobiotechnology-based drug carrier systems. The role of specific ligands in the design of functionalized nanovehicles for targeted delivery to brain tumor is reviewed. The current trends and future approaches in the CNS delivery of therapeutic molecules to tumors are also discussed.

Academic Institutionalization of Community Health Services: Way Ahead in Medical Education Reforms

PubMed Central

Kumar, Raman

2012-01-01

Policy on medical education has a major bearing on the outcome of health care delivery system. Countries plan and execute development of human resource in health, based on the realistic assessments of health system needs. A closer observation of medical education and its impact on the delivery system in India reveals disturbing trends. Primary care forms backbone of any system for health care delivery. One of the major challenges in India has been chronic deficiency of trained human resource eager to work in primary care setting. Attracting talent and employing skilled workforce seems a distant dream. Talking specifically of the medical education, there are large regional variations, urban - rural divide and issues with financing of the infrastructure. The existing design of medical education is not compatible with the health care delivery system of India. Impact is visible at both qualitative as well as quantitative levels. Medical education and the delivery system are working independent of each other, leading outcomes which are inequitable and unjust. Decades of negligence of medical education regulatory mechanism has allowed cropping of multiple monopolies governed by complex set of conflict of interest. Primary care physicians, supposed to be the community based team leaders stand disfranchised academically and professionally. To undo the distorted trajectory, a paradigm shift is required. In this paper, we propose expansion of ownership in medical education with academic institutionalization of community health services. PMID:24478994

Recent progress on nanoparticle-based drug delivery systems for cancer therapy

PubMed Central

Xin, Yanru; Yin, Mingming; Zhao, Liyuan; Meng, Fanling; Luo, Liang

2017-01-01

The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years. PMID:28884040

Naphthalocyanine as a New Photothermal Actuator for Lipid-Based Drug Delivery Systems.

PubMed

Du, Joanne D; Hong, Linda; Tan, Angel; Boyd, Ben J

2018-02-08

One approach to address the substantial global burden of ocular diseases such as aged related macular degeneration is using light-activated drug delivery to obviate the need for highly invasive and frequent, costly intravitreal injections. To enable such systems, new light responsive materials are required. This communication reports the use of silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (SiNC), a small molecule photosensitizer, as a new actuator for triggering light responsive lipid-based drug delivery systems. Small-angle X-ray scattering was used to confirm that the addition of SiNC imparted light sensitivity to the lipid systems, resulting in a complete phase transition within 20 s of near-infrared irradiation. The phase transition was also reversible, suggesting the potential for on-demand drug delivery. When compared to the phase transitions induced using alternative light responsive actuators, gold nanorods and graphene, there were some differences in phase behavior. Namely, the phytantriol with SiNC system transitioned directly to the inverse micellar phase, skipping the intermediate inverse hexagonal structure. The photodynamic properties and efficiency in controlling the release of drug suggest that SiNC-actuated lipid systems have the potential to reduce the burden of repeated intravitreal injections.

Pluronic-Functionalized Silica-Lipid Hybrid Microparticles: Improving the Oral Delivery of Poorly Water-Soluble Weak Bases.

PubMed

Rao, Shasha; Richter, Katharina; Nguyen, Tri-Hung; Boyd, Ben J; Porter, Christopher J H; Tan, Angel; Prestidge, Clive A

2015-12-07

A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

PubMed

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

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.

MicroRNA delivery for regenerative medicine.

PubMed

Peng, Bo; Chen, Yongming; Leong, Kam W

2015-07-01

MicroRNA (miRNA) directs post-transcriptional regulation of a network of genes by targeting mRNA. Although relatively recent in development, many miRNAs direct differentiation of various stem cells including induced pluripotent stem cells (iPSCs), a major player in regenerative medicine. An effective and safe delivery of miRNA holds the key to translating miRNA technologies. Both viral and nonviral delivery systems have seen success in miRNA delivery, and each approach possesses advantages and disadvantages. A number of studies have demonstrated success in augmenting osteogenesis, improving cardiogenesis, and reducing fibrosis among many other tissue engineering applications. A scaffold-based approach with the possibility of local and sustained delivery of miRNA is particularly attractive since the physical cues provided by the scaffold may synergize with the biochemical cues induced by miRNA therapy. Herein, we first briefly cover the application of miRNA to direct stem cell fate via replacement and inhibition therapies, followed by the discussion of the promising viral and nonviral delivery systems. Next we present the unique advantages of a scaffold-based delivery in achieving lineage-specific differentiation and tissue development. Copyright © 2015 Elsevier B.V. All rights reserved.

Microfabrication for Drug Delivery

PubMed Central

Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

2016-01-01

This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

Design and optimization of a flexible high-peak-power laser-to-fiber coupled illumination system used in digital particle image velocimetry

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

Robinson, Ronald A.; Ilev, Ilko K.

We present a study on the design and parameter optimization of a flexible high-peak-power fiber-optic laser delivery system using commercially available solid-core silica fibers and an experimental glass hollow waveguide (HW). The fiber-optic delivery system provides a flexible, safe, and easily and precisely positioned laser irradiation for many applications including uniform illumination for digital particle image velocimetry (DPIV). The delivery fibers, when coupled through a line-generating lens, produce a uniform thin laser sheet illumination for accurate and repeatable DPIV two-dimensional velocity measurements. We report experimental results on homogenizing the laser beam profile using various mode-mixing techniques. Furthermore, because a fundamentalmore » problem for fiber-optic-based high-peak-power laser delivery systems is the possible damage effects of the fiber material, we determine experimentally the peak power density damage threshold of various delivery fibers designed for the visible spectral range at a typical DPIV laser wavelength of 532 nm. In the case of solid-core silica delivery fibers using conventional lens-based laser-to-fiber coupling, the damage threshold varies from 3.7 GW/cm{sup 2} for a 100-{mu}m-core-diameter high-temperature fiber to 3.9 GW/cm{sup 2} for a 200-{mu}m-core-diameter high-power delivery fiber, with a total output laser energy delivered of at least 3-10 mJ for those respective fibers. Therefore, these fibers are marginally suitable for most macro-DPIV applications. However, to improve the high-power delivery capability for close-up micro-DPIV applications, we propose and validate an experimental fiber link with much higher laser power delivery capability than the solid-core fiber links. We use an uncoated grazing-incidence-based tapered glass funnel coupled to a glass HW with hollow air-core diameter of 700 {mu}m, a low numerical aperture of 0.05, and a thin inside cladding of cyclic olefin polymer coating for optimum transmission at 532 nm. Because of the mode homogenizing effect and lower power density, the taper-waveguide laser delivery technique ensured high damage threshold for the delivery HW, and as a result, no damage occurred at the maximum measured input laser energy of 33 mJ used in this study.« less

Nanofibers based tissue engineering and drug delivery approaches for myocardial regeneration.

PubMed

Joshi, Jyotsna; Kothapalli, Chandrasekhar R

2015-01-01

Human heart has endogenous regenerative capability; however, the intrinsic repair mechanism is not sufficient to overcome the impact placed by adverse pathological conditions, such as myocardial infarction (MI). In such circumstances, the damaged tissue initiates a series of remodeling process which results in the deterioration of structural, functional, and mechanical properties of the myocardium. To address such adverse conditions, clinical approaches ranging from surgical interventions, pharmaceutical drugs, and device implantation are administered which have played significant role in reducing the mortality rate. However, these approaches do not replace the lost cardiomyocytes, or restore the degraded structure-function relationship of the myocardium. In this aspect, cell-based therapy has gained substantial interest as a potential clinical approach for myocardial regeneration; however this method is impeded by lower graft retention and poor cell viability. To overcome these limitations, biomaterials are being developed as "trojan horses", i.e., vehicles for homing and deploying cells, and as matrices for delivering specific biological, mechanical, and chemical cues intended for tissue regeneration. Similarly, several candidate drugs, potent synthetic and biological molecules, and advanced drug delivery systems are being examined to provide exogenous cues in a controlled fashion to the diseased myocardium. In this article, we review biomaterials-based drug delivery systems for myocardial regeneration, specifically on the applications of hydrogels, microgels, nanoparticles, and nanofibers in the field. The prime focus of the article is on nanofibers-based drug delivery systems that is gaining considerable attention as a biomimetic pharmacological approach. We highlight literature on fabrication methods of self-assembling and electrospun nanofibers, drug incorporation methods and release kinetics, and in vitro and in vivo outcomes from nanofiber-based drug delivery systems in cardiac regeneration.

Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential.

PubMed

Vij, Neeraj

2011-09-01

The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept.

PubMed

Kara, Adnane; Rouillard, Camille; Mathault, Jessy; Boisvert, Martin; Tessier, Frédéric; Landari, Hamza; Melki, Imene; Laprise-Pelletier, Myriam; Boisselier, Elodie; Fortin, Marc-André; Boilard, Eric; Greener, Jesse; Miled, Amine

2016-05-28

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μ M was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an "intelligent" drug delivery system based on a feedback loop to monitor drug delivery.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept

PubMed Central

Kara, Adnane; Rouillard, Camille; Mathault, Jessy; Boisvert, Martin; Tessier, Frédéric; Landari, Hamza; Melki, Imene; Laprise-Pelletier, Myriam; Boisselier, Elodie; Fortin, Marc-André; Boilard, Eric; Greener, Jesse; Miled, Amine

2016-01-01

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 μM was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an “intelligent” drug delivery system based on a feedback loop to monitor drug delivery. PMID:27240377

Development of a general-purpose, integrated knowledge capture and delivery system

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

Roberts, A.G.; Freer, E.B.

1991-01-01

KATIE (Knowledge-Based Assistant for Troubleshooting Industrial Equipment) was first conceived as a solution for maintenance problems. In the area of process control, maintenance technicians have become responsible for increasingly complicated equipment and an overwhelming amount of associated information. The sophisticated distributed control systems have proven to be such a drastic change for technicians that they are forced to rely on the engineer for troubleshooting guidance. Because it is difficult for a knowledgeable engineer to be readily available for troubleshooting,maintenance personnel wish to capture the information provided by the engineer. The solution provided has two stages. First, a specific complicated systemmore » was chosen as a test case. An effort was made to gather all available system information in some form. Second, a method of capturing and delivering this collection of information was developed. Several features were desired for this knowledge capture/delivery system (KATIE). Creation of the knowledge base needed to be independent of the delivery system. The delivery path need to be as simple as possible for the technician, and the capture, or authoring, system could provide very sophisticated features. It was decided that KATIE should be as general as possible, not internalizing specifics about the first implementation. The knowledge bases created needed to be completely separate from KATIE needed to have a modular structure so that each type of information (rules, procedures, manuals, symptoms) could be encapsulated individually.« less

In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

PubMed

Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

2013-12-28

Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the varying electric pulse amplitude, the amount of topical and transdermal drug delivery to the skin can be controlled. Furthermore, the newly developed monitoring system provides a tool for rapid real-time determination of both, transdermal and topical delivery, when the delivered molecule is fluorescent. © 2013 Elsevier B.V. All rights reserved.

Osmotic Drug Delivery System as a Part of Modified Release Dosage Form

PubMed Central

Keraliya, Rajesh A.; Patel, Chirag; Patel, Pranav; Keraliya, Vipul; Soni, Tejal G.; Patel, Rajnikant C.; Patel, M. M.

2012-01-01

Conventional drug delivery systems are known to provide an immediate release of drug, in which one can not control the release of the drug and can not maintain effective concentration at the target site for longer time. Controlled drug delivery systems offer spatial control over the drug release. Osmotic pumps are most promising systems for controlled drug delivery. These systems are used for both oral administration and implantation. Osmotic pumps consist of an inner core containing drug and osmogens, coated with a semipermeable membrane. As the core absorbs water, it expands in volume, which pushes the drug solution out through the delivery ports. Osmotic pumps release drug at a rate that is independent of the pH and hydrodynamics of the dissolution medium. The historical development of osmotic systems includes development of the Rose-Nelson pump, the Higuchi-Leeper pumps, the Alzet and Osmet systems, the elementary osmotic pump, and the push-pull system. Recent advances include development of the controlled porosity osmotic pump, and systems based on asymmetric membranes. This paper highlights the principle of osmosis, materials used for fabrication of pumps, types of pumps, advantages, disadvantages, and marketed products of this system. PMID:22852100

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

PubMed Central

Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon

2015-01-01

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy. PMID:26078967

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review.

PubMed

Rigon, Roberta Balansin; Oyafuso, Márcia Helena; Fujimura, Andressa Terumi; Gonçalez, Maíra Lima; do Prado, Alice Haddad; Gremião, Maria Palmira Daflon; Chorilli, Marlus

2015-01-01

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

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.

Integration of e-Management, e-Development and e-Learning Technologies for Blended Course Delivery

ERIC Educational Resources Information Center

Johnson, Lynn E.; Tang, Michael

2005-01-01

This paper describes and assesses a pre-engineering curriculum development project called Foundations of Engineering, Science and Technology (FEST). FEST integrates web-based technologies into an inter-connected system to enable delivery of a blended program at multiple institutions. Tools and systems described include 1) technologies to deliver…

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

PubMed Central

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

2018-01-01

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

Rationalising polymer selection for supersaturated film forming systems produced by an aerosol spray for the transdermal delivery of methylphenidate.

PubMed

Edwards, A; Qi, S; Liu, F; Brown, M B; McAuley, W J

2017-05-01

Film forming systems offer a number of advantages for topical and transdermal drug delivery, in particular enabling production of a supersaturated state which can greatly improve drug absorption and bioavailability. However the suitability of individual film forming polymers to stabilise the supersaturated state and optimise delivery of drugs is not well understood. This study reports the use of differential scanning calorimetry (DSC) to measure the solubility of methylphenidate both as the free base and as the hydrochloride salt in two polymethacrylate copolymers, Eudragit RS (EuRS) and Eudragit E (EuE) and relates this to the ability of films formed using these polymers to deliver methylphenidate across a model membrane. EuRS provided greater methylphenidate delivery when the drug was formulated as the free base in comparison EuE because the lower solubility of the drug in EuRS provided a higher degree of drug saturation in the polymeric film. In contrast EuE provided greater delivery of methylphenidate hydrochloride as EuRS could not prevent its crystallisation from a supersaturated state. Methylphenidate flux across the membrane could be directly related to degree of saturation of the drug in the film formulation as estimated by the drug solubility in the individual polymers demonstrating the importance of drug solubility in the polymer included in film forming systems for topical/transdermal drug delivery. In addition DSC has been demonstrated to be a useful tool for determining the solubility of drugs in polymers used in film forming systems and the approaches outlined here are likely to be useful for predicting the suitability of polymers for particular drugs in film forming transdermal drug delivery systems. Copyright © 2017. Published by Elsevier B.V.

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.

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

PubMed

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

2018-05-01

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

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

PubMed

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

2017-02-01

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

pH-Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid-Based Delivery Systems.

PubMed

Oumzil, Khalid; Benizri, Sébastien; Tonelli, Giovanni; Staedel, Cathy; Appavoo, Ananda; Chaffanet, Max; Navailles, Laurence; Barthélémy, Philippe

2015-11-01

Lipid-based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3'-orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH-sensitive liposomes. ONL-based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH-cleavable nucleolipids to control the stability of lipid-based delivery systems represents a promising approach for the intracellular delivery of drug cargos. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Reflections on CD-ROM: Bridging the Gap between Technology and Purpose.

ERIC Educational Resources Information Center

Saviers, Shannon Smith

1987-01-01

Provides a technological overview of CD-ROM (Compact Disc-Read Only Memory), an optically-based medium for data storage offering large storage capacity, computer-based delivery system, read-only medium, and economic mass production. CD-ROM database attributes appropriate for information delivery are also reviewed, including large database size,…

Functionally engineered nanosized particles in pharmaceutics: improved oral delivery of poorly water-soluble drugs.

PubMed

Ozeki, Tetsuya; Tagami, Tatsuaki

2013-01-01

The development of drug nanoparticles has attracted substantial attention because of their potential to improve the dissolution rate and oral availability of poorly water-soluble drugs. This review summarizes the recent articles that discussed nanoparticle-based oral drug delivery systems. The preparation methods were categorized as top-down and bottom-up methods, which are common methods for preparing drug nanoparticles. In addition, methods of handling drug nanoparticles (e.g., one-step preparation of nanocomposites which are microparticles containing drug nanoparticles) were introduced for the effective preservation of drug nanoparticles. The carrier-based preparation of drug nanoparticles was also introduced as a potentially promising oral drug delivery system.

Safe delivery and newborn care practices in Sindh, Pakistan: a community-based investigation of mothers and health workers.

PubMed

Hassan, Hamid; Jokhio, Abdul Hakeem; Winter, Heather; Macarthur, Christine

2012-08-01

to determine the prevalence of specific intrapartum practices in Sindh province, Pakistan. a cross-sectional, questionnaire based study. 6 health clinics in Mirpurkhas, Sindh province, rural Pakistan. 225 mothers and 82 health workers. outcome measures were indicators of safe delivery practices and referral following an obstetric complication. Prevalence of unhygienic and unsafe practices in deliveries attended by Traditional Birth Attendants (TBAs) was common. Deliveries by skilled attendants were significantly safer but with some failures in hygienic practices. 29% of women who had experienced an obstetric complication had not received emergency obstetric care. safe delivery practices and newborn care needs to be improved in rural Pakistan. This may be achieved by training health workers and TBAs in safe delivery practices, using safe delivery kits and with an effective referral system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges.

PubMed

Ha, Dinh; Yang, Ningning; Nadithe, Venkatareddy

2016-07-01

Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

Autonomous Rhythmic Drug Delivery Systems Based on Chemical and Biochemomechanical Oscillators

NASA Astrophysics Data System (ADS)

Siegel, Ronald A.

While many drug delivery systems target constant, or zero-order drug release, certain drugs and hormones must be delivered in rhythmic pulses in order to achieve their optimal effect. Here we describe studies with two model autonomous rhythmic delivery systems. The first system is driven by a pH oscillator that modulates the ionization state of a model drug, benzoic acid, which can permeate through a lipophilic membrane when the drug is uncharged. The second system is based on a nonlinear negative feedback instability that arises from coupling of swelling of a hydrogel membrane to an enzymatic reaction, with the hydrogel controlling access of substrate to the enzyme, and the enzyme's product controlling the hydrogel's swelling state. The latter system, whose autonomous oscillations are driven by glucose at constant external activity, is shown to deliver gonadotropin releasing hormone (GnRH) in rhythmic pulses, with periodicity of the same order as observed in sexually mature adult humans. Relevant experimental results and some mathematical models are reviewed.

Development of a Microfluidics-Based Intracochlear Drug Delivery Device

PubMed Central

Sewell, William F.; Borenstein, Jeffrey T.; Chen, Zhiqiang; Fiering, Jason; Handzel, Ophir; Holmboe, Maria; Kim, Ernest S.; Kujawa, Sharon G.; McKenna, Michael J.; Mescher, Mark M.; Murphy, Brian; Leary Swan, Erin E.; Peppi, Marcello; Tao, Sarah

2009-01-01

Background Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases. PMID:19923811

Strategies for transporting nanoparticles across the blood-brain barrier.

PubMed

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

2016-02-01

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

Tribological investigation of a functional medical textile with lubricating drug-delivery finishing.

PubMed

Gerhardt, L-C; Lottenbach, R; Rossi, R M; Derler, S

2013-08-01

Textile-based drug delivery systems have a high potential for innovative medical and gerontechnological applications. In this study, the tribological behaviour and lubrication properties of a novel textile with drug delivery function/finishing was investigated by means of friction experiments that simulated cyclic dynamic contacts with skin under dry and wet conditions. The textile drug delivery system is based on a loadable biopolymer dressing on a polyester (PES) woven fabric. The fabrics were finished with low (LC) and highly cross-linked (HC) polysaccharide dressings and investigated in the unloaded condition as well as loaded with phytotherapeutic substances. The mechanical resistance and possible abrasion of the functional coatings on the textile substrate were assessed by friction measurements and scanning electron microscopical analyses. Under dry contact conditions, all investigated fabrics (PES substrate alone and textiles with loaded and unloaded dressings) showed generally low friction coefficients (0.20-0.26). Under wet conditions, the measured friction coefficients were typically higher (0.34-0.51) by a factor of 1.5-2. In the wet condition, both loaded drug delivery textiles exhibited 7-29% lower friction (0.34-0.41) than the PES fabric with unloaded dressings (0.42-0.51), indicating pronounced lubrication effects. The lubrication effects as well as the abrasion resistance of the studied textiles with drug delivery function depended on the degree of dilution of the phytotherapeutic substances. Lubricating formulations of textile-based drug delivery systems which reduce friction against the skin might be promising candidates for advanced medical textile finishes in connection with skin care and wound (decubitus ulcer) prevention. Copyright © 2013 Elsevier B.V. All rights reserved.

Photo-synthesis of protein-based nanoparticles and the application in drug delivery

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

Xie, Jinbing; Wang, Hongyang; Cao, Yi

Recently, protein-based nanoparticles as drug delivery systems have attracted great interests due to the excellent behavior of high biocompatibility and biodegradability, and low toxicity. However, the synthesis techniques are generally costly, chemical reagents introduced, and especially present difficulties in producing homogeneous monodispersed nanoparticles. Here, we introduce a novel physical method to synthesize protein nanoparticles which can be accomplished under physiological condition only through ultraviolet (UV) illumination. By accurately adjusting the intensity and illumination time of UV light, disulfide bonds in proteins can be selectively reduced and the subsequent self-assembly process can be well controlled. Importantly, the co-assembly can also bemore » dominated when the proteins mixed with either anti-cancer drugs, siRNA, or active targeting molecules. Both in vitro and in vivo experiments indicate that our synthesized protein–drug nanoparticles (drug-loading content and encapsulation efficiency being ca. 8.2% and 70%, respectively) not only possess the capability of traditional drug delivery systems (DDS), but also have a greater drug delivery efficiency to the tumor sites and a better inhibition of tumor growth (only 35% of volume comparing to the natural growing state), indicating it being a novel drug delivery system in tumor therapy.« less

Directed transport of bacteria-based drug delivery vehicles: bacterial chemotaxis dominates particle shape.

PubMed

Sahari, Ali; Traore, Mahama A; Scharf, Birgit E; Behkam, Bahareh

2014-10-01

Several attenuated and non-pathogenic bacterial species have been demonstrated to actively target diseased sites and successfully deliver plasmid DNA, proteins and other therapeutic agents into mammalian cells. These disease-targeting bacteria can be employed for targeted delivery of therapeutic and imaging cargos in the form of a bio-hybrid system. The bio-hybrid drug delivery system constructed here is comprised of motile Escherichia coli MG1655 bacteria and elliptical disk-shaped polymeric microparticles. The transport direction for these vehicles can be controlled through biased random walk of the attached bacteria in presence of chemoattractant gradients in a process known as chemotaxis. In this work, we utilize a diffusion-based microfluidic platform to establish steady linear concentration gradients of a chemoattractant and investigate the roles of chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles. Our experimental results demonstrate for the first time that bacterial chemotactic response dominates the effect of body shape in extravascular transport; thus, the non-spherical system could be more favorable for drug delivery applications owing to the known benefits of using non-spherical particles for vascular transport (e.g. relatively long circulation time).

An emerging platform for drug delivery: aerogel based systems.

PubMed

Ulker, Zeynep; Erkey, Can

2014-03-10

Over the past few decades, advances in "aerogel science" have provoked an increasing interest for these materials in pharmaceutical sciences for drug delivery applications. Because of their high surface areas, high porosities and open pore structures which can be tuned and controlled by manipulation of synthesis conditions, nanostructured aerogels represent a promising class of materials for delivery of various drugs as well as enzymes and proteins. Along with biocompatible inorganic aerogels and biodegradable organic aerogels, more complex systems such as surface functionalized aerogels, composite aerogels and layered aerogels have also been under development and possess huge potential. Emphasis is given to the details of the aerogel synthesis and drug loading methods as well as the influence of synthesis parameters and loading methods on the adsorption and release of the drugs. Owing to their ability to increase the bioavailability of low solubility drugs, to improve both their stability and their release kinetics, there are an increasing number of research articles concerning aerogels in different drug delivery applications. This review presents an up to date overview of the advances in all kinds of aerogel based drug delivery systems which are currently under investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.

PubMed

Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça

2017-05-01

In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.

Polymeric nanoparticles

PubMed Central

Bolhassani, Azam; Javanzad, Shabnam; Saleh, Tayebeh; Hashemi, Mehrdad; Aghasadeghi, Mohammad Reza; Sadat, Seyed Mehdi

2014-01-01

Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids. Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems. PMID:24128651

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.

Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma.

PubMed

Chang, Le; Wang, Guojing; Jia, Tingting; Zhang, Lei; Li, Yulong; Han, Yanxi; Zhang, Kuo; Lin, Guigao; Zhang, Rui; Li, Jinming; Wang, Lunan

2016-04-26

Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide. However, the treatment of patients with HCC is particularly challenging. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a potential suppressor of several types of tumors, but the delivery of long RNA remains problematic, limiting its applications. In the present study, we designed a novel delivery system based on MS2 virus-like particles (VLPs) crosslinked with GE11 polypeptide. This vector was found to be fast, effective and safe for the targeted delivery of lncRNA MEG3 RNA to the epidermal growth factor receptor (EGFR)-positive HCC cell lines without the activation of EGFR downstream pathways, and significantly attenuated both in vitro and in vivo tumor cell growth. Our study also revealed that the targeted delivery was mainly dependent on clathrin-mediated endocytosis and MEG3 RNA suppresses tumor growth mainly via increasing the expression of p53 and its downstream gene GDF15, but decreasing the expression of MDM2. Thus, this vector is promising as a novel delivery system and may facilitate a new approach to lncRNA based cancer therapy.

Harnessing the privatisation of China's fragmented health-care delivery.

PubMed

Yip, Winnie; Hsiao, William

2014-08-30

Although China's 2009 health-care reform has made impressive progress in expansion of insurance coverage, much work remains to improve its wasteful health-care delivery. Particularly, the Chinese health-care system faces substantial challenges in its transformation from a profit-driven public hospital-centred system to an integrated primary care-based delivery system that is cost effective and of better quality to respond to the changing population needs. An additional challenge is the government's latest strategy to promote private investment for hospitals. In this Review, we discuss how China's health-care system would perform if hospital privatisation combined with hospital-centred fragmented delivery were to prevail--population health outcomes would suffer; health-care expenditures would escalate, with patients bearing increasing costs; and a two-tiered system would emerge in which access and quality of care are decided by ability to pay. We then propose an alternative pathway that includes the reform of public hospitals to pursue the public interest and be more accountable, with public hospitals as the benchmarks against which private hospitals would have to compete, with performance-based purchasing, and with population-based capitation payment to catalyse coordinated care. Any decision to further expand the for-profit private hospital market should not be made without objective assessment of its effect on China's health-policy goals. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Medical Education and Health Care Delivery: A Call to Better Align Goals and Purposes.

PubMed

Sklar, David P; Hemmer, Paul A; Durning, Steven J

2018-03-01

The transformation of the U.S. health care system is under way, driven by the needs of an aging population, rising health care spending, and the availability of health information. However, the speed and effectiveness of the transformation of health care delivery will depend, in large part, upon engagement of the health professions community and changes in clinicians' practice behaviors. Current efforts to influence practice behaviors emphasize changes in the health payment system with incentives to move from fee-for-service to alternative payment models.The authors describe the potential of medical education to augment payment incentives to make changes in clinical practice and the importance of aligning the purpose and goals of medical education with those of the health care delivery system. The authors discuss how curricular and assessment changes and faculty development can align medical education with the transformative trends in the health care delivery system. They also explain how the theory of situated cognition offers a shared conceptual framework that could help address the misalignment of education and clinical care. They provide examples of how quality improvement, health care innovation, population care management, and payment alignment could create bridges for joining health care delivery and medical education to meet the health care reform goals of a high-performing health care delivery system while controlling health care spending. Finally, the authors illustrate how current payment incentives such as bundled payments, value-based purchasing, and population-based payments can work synergistically with medical education to provide high-value care.

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.

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.

Using exosomes, naturally-equipped nanocarriers, for drug delivery.

PubMed

Batrakova, Elena V; Kim, Myung Soo

2015-12-10

Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell-cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neurodegenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations. Published by Elsevier B.V.

Polysaccharides based nanomaterials for targeted anti-cancer drug delivery.

PubMed

Dheer, Divya; Arora, Divya; Jaglan, Sundeep; Rawal, Ravindra K; Shankar, Ravi

2017-01-01

Polysaccharides, an important class of biological polymers, are effectively bioactive, nontoxic, hydrophilic, biodegradable and offer a wide diversity in structure and properties. These can be easily modified chemically and biochemically to enhance the bioadhesion with biological tissues, better stability and can improve bioavailability of drugs. Most of the chemotherapeutic drugs have a narrow therapeutic index, slow drug delivery systems and poor water solubility that usually proves toxic to human bodies. The inherent biocompatibility of these biopolymers have shown enhancement of solubility of some chemotherapeutic drugs which also leads to the preparation of nanomaterials for the delivery of antibiotics, anticancer, proteins, peptides and nucleic acids using several routes of administration. Recently, synthesis and research on polysaccharides based nanomaterials have gained enormous attention as one of the most applicable resources in nanomedicine area. This review article will provide a specific emphasis on polysaccharides as natural biomaterials for targeted anticancer drug delivery system.

Examining fiscal federalism, regionalization and community-based initiatives in Canada's health care delivery system.

PubMed

Forest, Pierre-Gerlier; Palley, Howard A

2008-01-01

This study focuses on the ability of Canadian provinces to shape in different ways the development of various provincial health delivery systems within the constraints of the mandates of the federal Canada Health Act of 1984 and the fiscal revenues that the provinces receive if they comply with these mandates. In so doing, it will examine the operation of Canadian federalism with respect to various provincial health systems. This study applies a comparative analysis framework developed by Heisler and Peters to facilitate an understanding of the dimensionality of provincial health delivery systems as applied to the case of provincial regionalization and community-based initiatives. The three sets of relationships touched upon are: first, the levels of government and the nature of their involvement in public policy concerning the provincial health care delivery systems; and secondly, understanding of the factors influencing provincial governments' political dispositions to act in various directions. A third dimension that is taken are the factors influencing the "timing" of particular decisions. A fourth area noted by Heisler and Peters and other comparative analysts is the nature and characteristics of public and private sector activities in health care and other social policy areas. While the evolving nature of public and private sector health care delivery activities within Canada's provincial and territorial systems is a significant policy matter in the Canadian context, due to the space limitations of this article, they are not discussed herein.

Exploiting Nanotechnology for the Development of MicroRNA-Based Cancer Therapeutics.

PubMed

Tyagi, Nikhil; Arora, Sumit; Deshmukh, Sachin K; Singh, Seema; Marimuthu, Saravanakumar; Singh, Ajay P

2016-01-01

MicroRNAs (miRNAs/miRs) represent a novel class of small non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with complementary sequences in the 3' untranslated region (UTR) of target mRNAs. Functional studies suggest that miRNAs control almost every biological process, and their aberrant expression leads to a disease state, such as cancer. Differential expression of miRNAs in cancerous versus normal cells have generated enormous interest for the development of miRNA-based cancer cell-targeted therapeutics. Depending on the miRNA function and expression in cancer, two types of miRNA-based therapeutic strategies can be utilized that either restore or inhibit miRNA function through exogenous delivery of miRNAs mimics or inhibitors (anti-miRs). However, hydrophilic nature of miRNA mimics/anti-miRs, sensitivity to nuclease degradation in serum, poor penetration and reduced uptake by the tumor cells are chief hurdles in accomplishing their efficient in vivo delivery. To overcome these barriers, several nanotechnology-based systems are being developed and tested for delivery efficacy. This review summarizes the importance of miRNAs-based therapeutics in cancer, associated translational challenges and novel nanotechnology-assisted delivery systems that hold potential for next-generation miRNA-based cancer therapeutics.

[Efficacy of a new fenbendazole formulation produced by nanotechnology-based drug delivery system against nematodosis].

PubMed

Varlamova, A I; Arkhipov, I A; Odoevskaia, I M; Danilevskaia, N V; Khalikov, S S; Chistiachenko, Iu S; Dushkin, A V

2014-01-01

The efficacy of a new fenbendazile formulation produced by nanotechnology-based drug delivery system was investigated in45 sheep naturally infected with gastrointestinal nematodes. The formulation showed 95.6% efficacy against Nematodes spp. at a dose of 1.0 mg/kg dw of its active ingredient and 100% efficacy against other species of gastrointestinal nematodes. Given at a dose of 10 mg/kg dw, the basic drug--fenbendazole (substance) displayed 96.39 and 100% efficacy, respectively.

Polysaccharide-Based Micelles for Drug Delivery

PubMed Central

Zhang, Nan; Wardwell, Patricia R.; Bader, Rebecca A.

2013-01-01

Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date. PMID:24300453

Particle-based platforms for malaria vaccines.

PubMed

Wu, Yimin; Narum, David L; Fleury, Sylvain; Jennings, Gary; Yadava, Anjali

2015-12-22

Recombinant subunit vaccines in general are poor immunogens likely due to the small size of peptides and proteins, combined with the lack or reduced presentation of repetitive motifs and missing complementary signal(s) for optimal triggering of the immune response. Therefore, recombinant subunit vaccines require enhancement by vaccine delivery vehicles in order to attain adequate protective immunity. Particle-based delivery platforms, including particulate antigens and particulate adjuvants, are promising delivery vehicles for modifying the way in which immunogens are presented to both the innate and adaptive immune systems. These particle delivery platforms can also co-deliver non-specific immunostimodulators as additional adjuvants. This paper reviews efforts and advances of the Particle-based delivery platforms in development of vaccines against malaria, a disease that claims over 600,000 lives per year, most of them are children under 5 years of age in sub-Sahara Africa. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concepts and practices used to develop functional PLGA-based nanoparticulate systems.

PubMed

Sah, Hongkee; Thoma, Laura A; Desu, Hari R; Sah, Edel; Wood, George C

2013-01-01

The functionality of bare polylactide-co-glycolide (PLGA) nanoparticles is limited to drug depot or drug solubilization in their hard cores. They have inherent weaknesses as a drug-delivery system. For instance, when administered intravenously, the nanoparticles undergo rapid clearance from systemic circulation before reaching the site of action. Furthermore, plain PLGA nanoparticles cannot distinguish between different cell types. Recent research shows that surface functionalization of nanoparticles and development of new nanoparticulate dosage forms help overcome these delivery challenges and improve in vivo performance. Immense research efforts have propelled the development of diverse functional PLGA-based nanoparticulate delivery systems. Representative examples include PEGylated micelles/nanoparticles (PEG, polyethylene glycol), polyplexes, polymersomes, core-shell-type lipid-PLGA hybrids, cell-PLGA hybrids, receptor-specific ligand-PLGA conjugates, and theranostics. Each PLGA-based nanoparticulate dosage form has specific features that distinguish it from other nanoparticulate systems. This review focuses on fundamental concepts and practices that are used in the development of various functional nanoparticulate dosage forms. We describe how the attributes of these functional nanoparticulate forms might contribute to achievement of desired therapeutic effects that are not attainable using conventional therapies. Functional PLGA-based nanoparticulate systems are expected to deliver chemotherapeutic, diagnostic, and imaging agents in a highly selective and effective manner.

Concepts and practices used to develop functional PLGA-based nanoparticulate systems

PubMed Central

Sah, Hongkee; Thoma, Laura A; Desu, Hari R; Sah, Edel; Wood, George C

2013-01-01

The functionality of bare polylactide-co-glycolide (PLGA) nanoparticles is limited to drug depot or drug solubilization in their hard cores. They have inherent weaknesses as a drug-delivery system. For instance, when administered intravenously, the nanoparticles undergo rapid clearance from systemic circulation before reaching the site of action. Furthermore, plain PLGA nanoparticles cannot distinguish between different cell types. Recent research shows that surface functionalization of nanoparticles and development of new nanoparticulate dosage forms help overcome these delivery challenges and improve in vivo performance. Immense research efforts have propelled the development of diverse functional PLGA-based nanoparticulate delivery systems. Representative examples include PEGylated micelles/nanoparticles (PEG, polyethylene glycol), polyplexes, polymersomes, core-shell–type lipid-PLGA hybrids, cell-PLGA hybrids, receptor-specific ligand-PLGA conjugates, and theranostics. Each PLGA-based nanoparticulate dosage form has specific features that distinguish it from other nanoparticulate systems. This review focuses on fundamental concepts and practices that are used in the development of various functional nanoparticulate dosage forms. We describe how the attributes of these functional nanoparticulate forms might contribute to achievement of desired therapeutic effects that are not attainable using conventional therapies. Functional PLGA-based nanoparticulate systems are expected to deliver chemotherapeutic, diagnostic, and imaging agents in a highly selective and effective manner. PMID:23459088

Computer-Based Educational Software System. Final Report.

ERIC Educational Resources Information Center

Brandt, Richard C.; Davis, Bradley N.

CBESS (Computer-Based Educational Software System) is a set of 22 programs addressing authoring, instructional delivery, and instructional management. The programs are divided into five groups: (1) Computer-Based Memorization System (CBMS), which helps students acquire and maintain declarative (factual) knowledge (11 programs); (2) Language Skills…

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…

WATGIS: A GIS-Based Lumped Parameter Water Quality Model

Treesearch

Glenn P. Fernandez; George M. Chescheir; R. Wayne Skaggs; Devendra M. Amatya

2002-01-01

A Geographic Information System (GIS)­based, lumped parameter water quality model was developed to estimate the spatial and temporal nitrogen­loading patterns for lower coastal plain watersheds in eastern North Carolina. The model uses a spatially distributed delivery ratio (DR) parameter to account for nitrogen retention or loss along a drainage network. Delivery...

Some Useful Cost-Benefit Criteria for Evaluating Computer-Based Test Delivery Models and Systems

ERIC Educational Resources Information Center

Luecht, Richard M.

2005-01-01

Computer-based testing (CBT) is typically implemented using one of three general test delivery models: (1) multiple fixed testing (MFT); (2) computer-adaptive testing (CAT); or (3) multistage testing (MSTs). This article reviews some of the real cost drivers associated with CBT implementation--focusing on item production costs, the costs…

Mechanism-Based Tumor-Targeting Drug Delivery System. Validation of Efficient Vitamin Receptor-Mediated Endocytosis and Drug Release

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

Chen, S.; Wong, S.; Zhao, X.

An efficient mechanism-based tumor-targeting drug delivery system, based on tumor-specific vitamin-receptor mediated endocytosis, has been developed. The tumor-targeting drug delivery system is a conjugate of a tumor-targeting molecule (biotin: vitamin H or vitamin B-7), a mechanism-based self-immolative linker and a second-generation taxoid (SB-T-1214) as the cytotoxic agent. This conjugate (1) is designed to be (i) specific to the vitamin receptors overexpressed on tumor cell surface and (ii) internalized efficiently through receptor-mediated endocytosis, followed by smooth drug release via glutathione-triggered self-immolation of the linker. In order to monitor and validate the sequence of events hypothesized, i.e., receptor-mediated endocytosis of the conjugate,more » drug release, and drug-binding to the target protein (microtubules), three fluorescent/fluorogenic molecular probes (2, 3, and 4) were designed and synthesized. The actual occurrence of these processes was unambiguously confirmed by means of confocal fluorescence microscopy (CFM) and flow cytometry using L1210FR leukemia cells, overexpressing biotin receptors. The molecular probe 4, bearing the taxoid linked to fluorescein, was also used to examine the cell specificity (i.e., efficacy of receptor-based cell targeting) for three cell lines, L1210FR (biotin receptors overexpressed), L1210 (biotin receptors not overexpressed), and WI38 (normal human lung fibroblast, biotin receptor negative). As anticipated, the molecular probe 4 exhibited high specificity only to L1210FR. To confirm the direct correlation between the cell-specific drug delivery and anticancer activity of the probe 4, its cytotoxicity against these three cell lines was also examined. The results clearly showed a good correlation between the two methods. In the same manner, excellent cell-specific cytotoxicity of the conjugate 1 (without fluorescein attachment to the taxoid) against the same three cell lines was confirmed. This mechanism-based tumor-targeting drug delivery system will find a range of applications.« less

Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies.

PubMed

Jang, Bora; Kwon, Hyokyoung; Katila, Pramila; Lee, Seung Jin; Lee, Hyukjin

2016-03-01

Cancer causes >8.2 million deaths annually worldwide; thus, various cancer treatments have been investigated over the past decades. Among them, combination drug therapy has become extremely popular, and treatment with more than one drug is often necessary to achieve appropriate anticancer efficacy. With the development of nanoformulations and nanoparticulate-based drug delivery, researchers have explored the feasibility of dual delivery of biological therapeutics to overcome the current drawbacks of cancer therapy. Compared with the conventional single drug therapy, dual delivery of therapeutics has provided various synergistic effects in addition to offering multimodality to cancer treatment. In this review, we highlight and summarize three aspects of dual-delivery systems for cancer therapy. These include (1) overcoming drug resistance by the dual delivery of chemical drugs with biological therapeutics for synergistic therapy, (2) targeted and controlled drug release by the dual delivery of drugs with stimuli-responsive nanomaterials, and (3) multimodal theranostics by the dual delivery of drugs and molecular imaging probes. Furthermore, recent developments, perspectives, and new challenges regarding dual-delivery systems for cancer therapy are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Prospective multicenter study of ultrasound-based measurements of fetal head station and position throughout labor.

PubMed

Vitner, D; Paltieli, Y; Haberman, S; Gonen, R; Ville, Y; Nizard, J

2015-11-01

To assess the relationship between fetal head position and head station during labor, as measured using an ultrasound-based system, and the occurrence of occiput posterior (OP) position at delivery. This was an international prospective observational study including women who delivered between January 2009 and September 2013 in four centers: one in Brooklyn, NY, USA; one in Haifa, Israel; and two in Paris, France. We used an ultrasound-based system (LaborPro) to monitor fetal head station and position non-invasively throughout labor. We collected data on demographics, labor parameters and outcome. A total of 595 women were included. In 563 (94.6%) women, fetal head position at delivery was occiput anterior (OA), in 31 (5.2%) it was OP and in one (0.2%) it was occiput transverse. In 89% of pregnancies with intrapartum OP when fetal head station was above -2, the head position turned to OA at delivery; the equivalent figures were 74% and 63% OA at delivery when intrapartum OP was diagnosed at head stations of -2 to < 0, and 0 and below, respectively. Cesarean delivery was performed in 35% of pregnancies with fetal head in OP position at delivery, as opposed to 10% of those with non-OP position at delivery. On retrospective analysis, all deliveries in OP were already in OP at station -2 and below. In this first assessment of fetal head position at delivery according to fetal head position at various station levels, our data show that 100% of OP positions at delivery were already in OP position at station -2 and below. We did not observe rotation from a non-OP to an OP position from station -2 and below. Nearly two-thirds of fetuses in OP at station 0 and below will rotate to an OA position for delivery. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Clinical experience with drug delivery systems as tools to decrease the toxicity of anticancer chemotherapeutic agents.

PubMed

Maranhão, Raul C; Vital, Carolina G; Tavoni, Thauany M; Graziani, Silvia R

2017-10-01

The toxicity of chemotherapeutic agents, resulting from their low pharmacological index, introduces considerable discomfort and risk to cancer patients. Among several strategies to reduce the toxicity of chemotherapeutic agents, targeted drug delivery is the most promising one. Areas covered: Liposomes, micelles, albumin-based, polymeric, dendritic and lipid core nanoparticles have been used as carriers to concentrate anticancer drugs in neoplastic tissues, and clinical studies of those preparations are reviewed. In most clinical studies, drug delivery systems reduced drug toxicity. Lipid core nanoparticles (LDE) that bind to cell lipoprotein receptors have the ability to concentrate in neoplastic tissues and were the first artificial non-liposomal system shown in in vivo studies to possess targeting properties. The toxicity reduction achieved by LDE as vehicle of carmustine, etoposide and paclitaxel was singularly strong. Expert opinion: The reduced toxicity offered by drug delivery systems has expanded treatment population that may benefit from chemotherapy including feeble, overtreated and elderly patients that would otherwise be offered palliative therapy. Drug delivery systems may either prolong the duration of treatments or allow increases in drug dose.

Redox-sensitive dendrimersomes assembled from amphiphilic Janus dendrimers for siRNA delivery.

PubMed

Du, Xiao-Jiao; Wang, Ze-Yu; Wang, Yu-Cai

2018-06-14

The development of delivery systems for small interfering RNA (siRNA) plays a key role in its clinical application. As the major delivery systems for siRNA, cationic polymer- or lipid-based vehicles are plagued by inherent issues. As proof of concept, a disulfide bond-containing amphiphilic Janus dendrimer (ssJD), which could be conveniently synthesized and readily scaled up with high reproducibility, was explored as a siRNA delivery system to circumvent these issues. The cationic hydrophilic head of this Janus dendrimer ensured strong and stable binding with negatively charged siRNA via electrostatic interactions, and the loaded siRNA was rapidly released from the obtained complexes under a redox environment. Therefore, after efficient internalization into tumor cells, redox-sensitive dendrimersome (RSDs)/siRNA exhibited significantly improved gene silencing efficacy.

Physician practice management companies: implications for hospital-based integrated delivery systems.

PubMed

Burns, L R; Robinson, J C

1997-01-01

Physician practice management companies (PPMCs) are one of the most visible entrants into the industry of managing physician practices, and anywhere from 100-150 are already in operation. Although PPMCs and hospital-based integrated delivery systems (IDSs) differ from each other in many ways, they share a number of common features, including the pursuit of capitation contracts from payors. As a result, PPMCs pose a growing, direct threat to hospital systems in competing for managed care contracts that cover physician service. PPMCs also provide an alternative to hospital-based IDSs at the local market level for physician group consolidation. This article looks at the structure, operation, and strategy of PPMCs and examines what implications their growth will have for hospital-based IDSs.

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

PubMed

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

2017-11-01

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

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

NASA Astrophysics Data System (ADS)

Wang, Huaimin; Yang, Zhimou

2012-08-01

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

Liquid Crystalline Systems Based on Glyceryl Monooleate and Penetration Enhancers for Skin Delivery of Celecoxib: Characterization, In Vitro Drug Release, and In Vivo Studies.

PubMed

Dante, Mariane de Cássia Lima; Borgheti-Cardoso, Livia Neves; Fantini, Marcia Carvalho de Abreu; Praça, Fabíola Silva Garcia; Medina, Wanessa Silva Garcia; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

2018-03-01

Celecoxib (CXB) is a widely used anti-inflammatory drug that also acts as a chemopreventive agent against several types of cancer, including skin cancer. As the long-term oral administration of CXB has been associated with severe side effects, the skin delivery of this drug represents a promising alternative for the treatment of skin inflammatory conditions and chemoprevention of skin cancer. We prepared and characterized liquid crystalline systems based on glyceryl monooleate and water containing penetration enhancers which were primarily designed to promote skin delivery of CXB. Analysis of their phase behavior revealed the formation of cubic and hexagonal phases depending on the systems' composition. The systems' structure and composition markedly affected the in vitro CXB release profile. Oleic acid reduced CXB release rate, but association oleic acid/propylene glycol increased the drug release rate. The developed systems significantly reduced inflammation in an aerosil-induced rat paw edema model. The systems' composition and liquid crystalline structure influenced their anti-inflammatory potency. Cubic phase systems containing oleic acid/propylene glycol association reduced edema in a sustained manner, indicating that they modulate CXB release and permeation. Our findings demonstrate that the developed liquid crystalline systems are potential carriers for the skin delivery of CXB. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Nanobiotechnology-based drug delivery in brain targeting.

PubMed

Dinda, Subas C; Pattnaik, Gurudutta

2013-01-01

Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity of specific receptors expressed across the BBB. It is found that the low density lipoproteins related protein (LPR) with engineered peptide compound (EpiC) formed the platform incorporating the Angiopep peptide as a new effective therapeutics. The current challenges are to design and develop the drug delivery careers, which must be able to deliver the drug across the BBB at a safe and effective manner. Nanoparticles are found to be effective careers in delivery of conventional drugs, recombinant proteins, vaccines as well as nucleotides. Nanoparticlulate drug delivery systems are found to be improving in the pharmacokinetic strategies of the drug molecules such as biodistribution, bioavailability and drug release characteristics in a controlled and effective manner with site specific drug delivery targeting to tissue or cell with reduction in toxic manifestation. Therefore, the use of nanotechnology in the field of pharmaceutical biotechnology helps in improving the drug delivery strategy including the kinetics and therapeutic index to solve the delivery problems of some biotech drugs including the recombinant proteins and oligonucleotides. This review is made to provide an insight to the role of nanobiotechnology in drug delivery and drug targeting to brain and its recent advances in the field of drug delivery systems.

Microchips and controlled-release drug reservoirs.

PubMed

Staples, Mark

2010-01-01

This review summarizes and updates the development of implantable microchip-containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro- and nanoelectromechanical systems (MEMS or NEMS)-based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip-based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug-medical device combinations may protect labile active ingredients within hermetically sealed reservoirs. Copyright (c) 2010 John Wiley & Sons, Inc.

Carbohydrate-Based Host-Guest Complexation of Hydrophobic Antibiotics for the Enhancement of Antibacterial Activity.

PubMed

Jeong, Daham; Joo, Sang-Woo; Shinde, Vijay Vilas; Cho, Eunae; Jung, Seunho

2017-08-08

Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release.

Interview with faz chowdhury.

PubMed

Chowdhury, Faz

2014-06-01

Faz Chowdhury is the Chief Executive Officer of Nemaura Pharma (Loughborough, UK), a pharmaceutical drug-delivery company developing patented formulation technologies alongside transdermal systems. Having originally trained as a pharmaceutical scientist, Dr Chowdhury received his PhD in Nanomedicine from the University of Oxford (Oxford, UK). With recognized expertise in the pharmaceutical industry and the holder of more than 15 patents on drug-delivery systems, Dr Chowdhury discussed the challenges faced in microneedle-based drug delivery, an area widely expected to revolutionize the transdermal field over the coming years. Interview conducted by James Potticary, Commissioning Editor.

Preparation, characterization and in vivo evaluation of a combination delivery system based on hyaluronic acid/jeffamine hydrogel loaded with PHBV/PLGA blend nanoparticles for prolonged delivery of Teriparatide.

PubMed

Bahari Javan, Nika; Montazeri, Hamed; Rezaie Shirmard, Leila; Jafary Omid, Nersi; Barbari, Ghullam Reza; Amini, Mohsen; Ghahremani, Mohammad Hossein; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid

2017-04-01

In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD 50 of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

SU-E-T-649: Quality Assurances for Proton Therapy Delivery Equipment

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

Arjomandy, B; Kase, Y; Flanz, J

2015-06-15

Purpose: The number of proton therapy centers has increased dramatically over the past decade. Currently, there is no comprehensive set of guidelines that addresses quality assurance (QA) procedures for the different technologies used for proton therapy. The AAPM has charged task group 224 (TG-224) to provide recommendations for QA required for accurate and safe dose delivery, using existing and next generation proton therapy delivery equipment. Methods: A database comprised of QA procedures and tolerance limits was generated from many existing proton therapy centers in and outside of the US. These consist of proton therapy centers that possessed double scattering, uniformmore » scanning, and pencil beams delivery systems. The diversity in beam delivery systems as well as the existing devices to perform QA checks for different beam parameters is the main subject of TG-224. Based on current practice at the clinically active proton centers participating in this task group, consensus QA recommendations were developed. The methodologies and requirements of the parameters that must be verified for consistency of the performance of the proton beam delivery systems are discussed. Results: TG-224 provides procedures and QA checks for mechanical, imaging, safety and dosimetry requirements for different proton equipment. These procedures are categorized based on their importance and their required frequencies in order to deliver a safe and consistent dose. The task group provides daily, weekly, monthly, and annual QA check procedures with their tolerance limits. Conclusions: The procedures outlined in this protocol provide sufficient information to qualified medical physicists to perform QA checks for any proton delivery system. Execution of these procedures should provide confidence that proton therapy equipment is functioning as commissioned for patient treatment and delivers dose safely and accurately within the established tolerance limits. The report will be published in late 2015.« less

Additive Construction with Mobile Emplacement (ACME) / Automated Construction of Expeditionary Structures (ACES) Materials Delivery System (MDS)

NASA Technical Reports Server (NTRS)

Mueller, R. P.; Townsend, I. I.; Tamasy, G. J.; Evers, C. J.; Sibille, L. J.; Edmunson, J. E.; Fiske, M. R.; Fikes, J. C.; Case, M.

2018-01-01

The purpose of the Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) project is to incorporate the Liquid Goods Delivery System (LGDS) into the Dry Goods Delivery System (DGDS) structure to create an integrated and automated Materials Delivery System (MDS) for 3D printing structures with ordinary Portland cement (OPC) concrete. ACES 3 is a prototype for 3-D printing barracks for soldiers in forward bases, here on Earth. The LGDS supports ACES 3 by storing liquid materials, mixing recipe batches of liquid materials, and working with the Dry Goods Feed System (DGFS) previously developed for ACES 2, combining the materials that are eventually extruded out of the print nozzle. Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) is a project led by the US Army Corps of Engineers (USACE) and supported by NASA. The equivalent 3D printing system for construction in space is designated Additive Construction with Mobile Emplacement (ACME) by NASA.

Reframing HIV care: putting people at the centre of antiretroviral delivery.

PubMed

Duncombe, Chris; Rosenblum, Scott; Hellmann, Nicholas; Holmes, Charles; Wilkinson, Lynne; Biot, Marc; Bygrave, Helen; Hoos, David; Garnett, Geoff

2015-04-01

The delivery of HIV care in the initial rapid scale-up of HIV care and treatment was based on existing clinic-based models, which are common in highly resourced settings and largely undifferentiated for individual needs. A new framework for treatment based on variable intensities of care tailored to the specific needs of different groups of individuals across the cascade of care is proposed here. Service intensity is characterised by four delivery components: (i) types of services delivered, (ii) location of service delivery, (iii) provider of health services and (iv) frequency of health services. How these components are developed into a service delivery framework will vary across countries and populations, with the intention being to improve acceptability and care outcomes. The goal of getting more people on treatment before they become ill will necessitate innovative models of delivering both testing and care. As HIV programmes expand treatment eligibility, many people entering care will not be 'patients' but healthy, active and productive members of society. To take the framework to scale, it will be important to: (i) define which individuals can be served by an alternative delivery framework; (ii) strengthen health systems that support decentralisation, integration and task shifting; (iii) make the supply chain more robust; and (iv) invest in data systems for patient tracking and for programme monitoring and evaluation. © 2015 The Authors. Tropical Medicine & International Health published by John Wiley & Sons Ltd.

Application of three-dimensional printing for colon targeted drug delivery systems

PubMed Central

Charbe, Nitin B.; McCarron, Paul A.; Lane, Majella E.; Tambuwala, Murtaza M.

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems. PMID:28929046

Application of three-dimensional printing for colon targeted drug delivery systems.

PubMed

Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

2017-01-01

Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

Hyaluronic Acid-Based pH-Sensitive Polymer-Modified Liposomes for Cell-Specific Intracellular Drug Delivery Systems.

PubMed

Miyazaki, Maiko; Yuba, Eiji; Hayashi, Hiroshi; Harada, Atsushi; Kono, Kenji

2018-01-17

For the enhancement of therapeutic effects and reduction of side effects derived from anticancer drugs in cancer chemotherapy, it is imperative to develop drug delivery systems with cancer-specificity and controlled release function inside cancer cells. pH-sensitive liposomes are useful as an intracellular drug delivery system because of their abilities to transfer their contents into the cell interior through fusion or destabilization of endosome, which has weakly acidic environment. We earlier reported liposomes modified with various types of pH-sensitive polymers based on synthetic polymers and biopolymers as vehicles for intracellular drug delivery systems. In this study, hyaluronic acid (HA)-based pH-sensitive polymers were designed as multifunctional polymers having not only pH-sensitivity but also targeting properties to cells expressing CD44, which is known as a cancer cell surface marker. Carboxyl group-introduced HA derivatives of two types, MGlu-HA and CHex-HA, which have a more hydrophobic side chain structure than that of MGlu-HA, were synthesized by reaction with various dicarboxylic anhydrides. These polymer-modified liposomes were stable at neutral pH, but showed content release under weakly acidic conditions. CHex-HA-modified liposomes delivered their contents into CD44-expressing cells more efficiently than HA-modified or MGlu-HA-modified liposomes or unmodified liposomes, whereas the same liposomes were taken up only slightly by cells expressing CD44 proteins less. Competition assay using free HA or other polymers revealed that HA derivative-modified liposomes might be recognized by CD44. Therefore, HA-derivative-modified liposomes are useful as cell-specific intracellular drug delivery systems.

Secreted phospholipase A(2) as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue.

PubMed

Davidsen, Jesper; Jørgensen, Kent; Andresen, Thomas L; Mouritsen, Ole G

2003-01-10

Polymer-coated liposomes can act as versatile drug-delivery systems due to long vascular circulation time and passive targeting by leaky blood vessels in diseased tissue. We present an experimental model system illustrating a new principle for improved and programmable drug-delivery, which takes advantage of an elevated activity of secretory phospholipase A(2) (PLA(2)) at the diseased target tissue. The secretory PLA(2) hydrolyses a lipid-based proenhancer in the carrier liposome, producing lyso-phospholipids and free fatty acids, which are shown in a synergistic way to lead to enhanced liposome destabilization and drug release at the same time as the permeability of the target membrane is enhanced. Moreover, the proposed system can be made thermosensitive and offers a rational way for developing smart liposome-based drug delivery systems. This can be achieved by incorporating specific lipid-based proenhancers or prodestabilisers into the liposome carrier, which automatically becomes activated by PLA(2) only at the diseased target sites, such as inflamed or cancerous tissue.

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.

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.

Development and Application of a Systems Engineering Framework to Support Online Course Design and Delivery

ERIC Educational Resources Information Center

Bozkurt, Ipek; Helm, James

2013-01-01

This paper develops a systems engineering-based framework to assist in the design of an online engineering course. Specifically, the purpose of the framework is to provide a structured methodology for the design, development and delivery of a fully online course, either brand new or modified from an existing face-to-face course. The main strength…

Rethinking the service delivery system of psychological interventions in low and middle income countries.

PubMed

Murray, L K; Jordans, M J D

2016-07-12

Global mental health is a growing field intricately connected to broader health, violence and economic issues. Despite the high prevalence and cost of mental health disorders, an estimated 75 % of those with need in lower resource settings do not receive intervention. Most studies to date have examined the effectiveness of single-disorder mental health treatments - an approach that may be a significant challenge to scale-up and sustainability in lower resource settings. This paper presents a brief overview of the scientific progress in global mental health, and suggests consideration of an internal stepped care delivery approach. An internal stepped care model is one idea of a delivery system, utilizing a common elements approach, where the same provider could navigate between different elements based on severity and type of problems of the client. It is distinct from traditional stepped care models in that clients remain with the same provider, rather than relying on referral systems. An internal stepped care delivery system based on a simplified common elements approach could be more efficient, scalable, sustainable, and reduce the loss of clients to referrals in lower resource settings.

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

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release.

PubMed

Cunningham, Alexander J; Robinson, Mattieu; Banquy, Xavier; Leblond, Jeanne; Zhu, X X

2018-03-05

Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed toward breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG) 4 ) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC 50 and highest cellular internalization, indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.

siRNA delivery targeting to the lung via agglutination-induced accumulation and clearance of cationic tetraamino fullerene.

PubMed

Minami, Kosuke; Okamoto, Koji; Doi, Kent; Harano, Koji; Noiri, Eisei; Nakamura, Eiichi

2014-05-12

The efficient treatment of lung diseases requires lung-selective delivery of agents to the lung. However, lung-selective delivery is difficult because the accumulation of micrometer-sized carriers in the lung often induces inflammation and embolization-related toxicity. Here we demonstrate a lung-selective delivery system of small interfering RNA (siRNA) by controlling the size of carrier vehicle in blood vessels. The carrier is made of tetra(piperazino)fullerene epoxide (TPFE), a water-soluble cationic tetraamino fullerene. TPFE and siRNA form sub-micrometer-sized complexes in buffered solution and these complexes agglutinate further with plasma proteins in the bloodstream to form micrometer-sized particles. The agglutinate rapidly clogs the lung capillaries, releases the siRNA into lung cells to silence expression of target genes, and is then cleared rapidly from the lung after siRNA delivery. We applied our delivery system to an animal model of sepsis, indicating the potential of TPFE-based siRNA delivery for clinical applications.

siRNA delivery targeting to the lung via agglutination-induced accumulation and clearance of cationic tetraamino fullerene

NASA Astrophysics Data System (ADS)

Minami, Kosuke; Okamoto, Koji; Doi, Kent; Harano, Koji; Noiri, Eisei; Nakamura, Eiichi

2014-05-01

The efficient treatment of lung diseases requires lung-selective delivery of agents to the lung. However, lung-selective delivery is difficult because the accumulation of micrometer-sized carriers in the lung often induces inflammation and embolization-related toxicity. Here we demonstrate a lung-selective delivery system of small interfering RNA (siRNA) by controlling the size of carrier vehicle in blood vessels. The carrier is made of tetra(piperazino)fullerene epoxide (TPFE), a water-soluble cationic tetraamino fullerene. TPFE and siRNA form sub-micrometer-sized complexes in buffered solution and these complexes agglutinate further with plasma proteins in the bloodstream to form micrometer-sized particles. The agglutinate rapidly clogs the lung capillaries, releases the siRNA into lung cells to silence expression of target genes, and is then cleared rapidly from the lung after siRNA delivery. We applied our delivery system to an animal model of sepsis, indicating the potential of TPFE-based siRNA delivery for clinical applications.

siRNA delivery targeting to the lung via agglutination-induced accumulation and clearance of cationic tetraamino fullerene

PubMed Central

MINAMI, Kosuke; OKAMOTO, Koji; DOI, Kent; HARANO, Koji; NOIRI, Eisei; NAKAMURA, Eiichi

2014-01-01

The efficient treatment of lung diseases requires lung-selective delivery of agents to the lung. However, lung-selective delivery is difficult because the accumulation of micrometer-sized carriers in the lung often induces inflammation and embolization-related toxicity. Here we demonstrate a lung-selective delivery system of small interfering RNA (siRNA) by controlling the size of carrier vehicle in blood vessels. The carrier is made of tetra(piperazino)fullerene epoxide (TPFE), a water-soluble cationic tetraamino fullerene. TPFE and siRNA form sub-micrometer-sized complexes in buffered solution and these complexes agglutinate further with plasma proteins in the bloodstream to form micrometer-sized particles. The agglutinate rapidly clogs the lung capillaries, releases the siRNA into lung cells to silence expression of target genes, and is then cleared rapidly from the lung after siRNA delivery. We applied our delivery system to an animal model of sepsis, indicating the potential of TPFE-based siRNA delivery for clinical applications. PMID:24814863

Effect of amino groups of mesoporous silica nanoparticles on CpG oligodexynucleotide delivery

NASA Astrophysics Data System (ADS)

Xu, Yi; Claiden, Peter; Zhu, Yufang; Morita, Hiromi; Hanagata, Nobutaka

2015-08-01

In this study, we proposed to modify mesoporous silica nanoparticles (MSNs) with 3-aminopropyltriethoxysilane (NH2-TES), aminoethylaminopropyltriethoxysilane (2NH2-TES) and 3-[2-(2-aminoethylamino)ethylamino] propyl-trimethoxysilane (3NH2-TES) for binding of cytosine-phosphate-guanosine oligodexynucleotides (CpG ODN), and investigated the effect of different amino groups of MSNs on the CpG ODN delivery. Serum stability, in vitro cytotoxicity, and cytokine interleukin-6 (IL-6) induction by MSN-NH2/CpG, MSN-2NH2/CpG and MSN-3NH2/CpG complexes were investigated in detail. The results showed that three kinds of aminated-MSN-based CpG ODN delivery systems had no cytotoxicity to RAW264.7 cells, and binding of CpG ODN to MSN-NH2, MSN-2NH2 and MSN-3NH2 nanoparticles enhanced the serum stability of CpG ODN due to protection by the nanoparticles. However, three aminated MSN-based CpG ODN delivery systems exhibited different CpG ODN delivery efficiency, and MSN-NH2/CpG complexes had the highest ability to induce IL-6 secretion.

Porous silicon-cyclodextrin based polymer composites for drug delivery applications.

PubMed

Hernandez-Montelongo, J; Naveas, N; Degoutin, S; Tabary, N; Chai, F; Spampinato, V; Ceccone, G; Rossi, F; Torres-Costa, V; Manso-Silvan, M; Martel, B

2014-09-22

One of the main applications of porous silicon (PSi) in biomedicine is drug release, either as a single material or as a part of a composite. PSi composites are attractive candidates for drug delivery systems because they can display new chemical and physical characteristics, which are not exhibited by the individual constituents alone. Since cyclodextrin-based polymers have been proven efficient materials for drug delivery, in this work β-cyclodextrin-citric acid in-situ polymerization was used to functionalize two kinds of PSi (nanoporous and macroporous). The synthesized composites were characterized by microscopy techniques (SEM and AFM), physicochemical methods (ATR-FTIR, XPS, water contact angle, TGA and TBO titration) and a preliminary biological assay was performed. Both systems were tested as drug delivery platforms with two different model drugs, namely, ciprofloxacin (an antibiotic) and prednisolone (an anti-inflammatory), in two different media: pure water and PBS solution. Results show that both kinds of PSi/β-cyclodextrin-citric acid polymer composites, nano- and macro-, provide enhanced release control for drug delivery applications than non-functionalized PSi samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

An implantable thermoresponsive drug delivery system based on Peltier device.

PubMed

Yang, Rongbing; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Rochev, Yury

2013-04-15

Locally dropping the temperature in vivo is the main obstacle to the clinical use of a thermoresponsive drug delivery system. In this paper, a Peltier electronic element is incorporated with a thermoresponsive thin film based drug delivery system to form a new drug delivery device which can regulate the release of rhodamine B in a water environment at 37 °C. Various current signals are used to control the temperature of the cold side of the Peltier device and the volume of water on top of the Peltier device affects the change in temperature. The pulsatile on-demand release profile of the model drug is obtained by turning the current signal on and off. The work has shown that the 2600 mAh power source is enough to power this device for 1.3 h. Furthermore, the excessive heat will not cause thermal damage in the body as it will be dissipated by the thermoregulation of the human body. Therefore, this simple novel device can be implanted and should work well in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

Fluid delivery control system

DOEpatents

Hoff, Brian D.; Johnson, Kris William; Algrain, Marcelo C.; Akasam, Sivaprasad

2006-06-06

A method of controlling the delivery of fluid to an engine includes receiving a fuel flow rate signal. An electric pump is arranged to deliver fluid to the engine. The speed of the electric pump is controlled based on the fuel flow rate signal.

Cellulose based polymeric systems in drug delivery

USDA-ARS?s Scientific Manuscript database

The pharmaceutical industry requires the development of biodegradable, biocompatible, non toxic, site specific drug delivery polymers, which can be easily coupled with drugs to be delivered orally, topically, locally, or parenterally. The use of the most abundant biopolymer, cellulose along with its...

7 CFR 400.701 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., unique policy provisions or endorsements, the delivery process of the submission, and the process of... information is based, such data may include, but is not limited to, focus group results, market research studies, qualitative market estimates, effects upon the delivery system or ancillary participants...

7 CFR 400.701 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., unique policy provisions or endorsements, the delivery process of the submission, and the process of... information is based, such data may include, but is not limited to, focus group results, market research studies, qualitative market estimates, effects upon the delivery system or ancillary participants...

7 CFR 400.701 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., unique policy provisions or endorsements, the delivery process of the submission, and the process of... information is based, such data may include, but is not limited to, focus group results, market research studies, qualitative market estimates, effects upon the delivery system or ancillary participants...

7 CFR 400.701 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., unique policy provisions or endorsements, the delivery process of the submission, and the process of... information is based, such data may include, but is not limited to, focus group results, market research studies, qualitative market estimates, effects upon the delivery system or ancillary participants...

Therapeutic applications of hydrogels in oral drug delivery

PubMed Central

Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

2015-01-01

Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

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.

Optical levitation particle delivery system for a dual beam fiber optic trap.

PubMed

Gauthier, R C; Frangioudakis, A

2000-01-01

We combine a radiation-pressure-based levitation system with a dual fiber, laser trapping system to demonstrate the potential of delivering single particles into the fiber trap. The forces versus position and the trajectory of the particle subjected to the laser beams are examined with an enhanced ray optics model. A sequence of video images taken from the experimental apparatus demonstrates the principle of particle delivery, trapping, and further manipulation.

Increase in facility-based deliveries associated with a maternal health voucher programme in informal settlements in Nairobi, Kenya.

PubMed

Bellows, Ben; Kyobutungi, Catherine; Mutua, Martin Kavao; Warren, Charlotte; Ezeh, Alex

2013-03-01

To measure whether there was an association between the introduction of an output-based voucher programme and the odds of a facility-based delivery in two Nairobi informal settlements. Nairobi Urban Health and Demographic Surveillance System (NUHDSS) and two cross-sectional household surveys in Korogocho and Viwandani informal settlements in 2004-05 and 2006-08. Odds of facility-based delivery were estimated before and after introduction of an output-based voucher. Supporting NUHDSS data were used to determine whether any trend in maternal health care was coincident with immunizations, a non-voucher outpatient service. As part of NUHDSS, households in Korogocho and Viwandani reported place of delivery and the presence of a skilled birth attendant (2003-10) and vaccination coverage (2003-09). A detailed maternal and child health (MCH) tool was added to NUHDSS (September 2006-10). Prospective enrolment in NUHDSS-MCH was conditional on having a newborn after September 2006. In addition to recording mother's place of delivery, NUHDSS-MCH recorded the use of the voucher. There were significantly greater odds of a facility-based delivery among respondents during the voucher programme compared with similar respondents prior to voucher launch. Testing whether unrelated outpatient care also increased, a falsification exercise found no significant increase in immunizations for children 12-23 months of age in the same period. Although the proportion completing any antenatal care (ANC) visit remained above 95% of all reported pregnancies and there was a significant increase in facility-based deliveries, the proportion of women completing 4+ ANC visits was significantly lower during the voucher programme. A positive association was observed between vouchers and facility-based deliveries in Nairobi. Although there is a need for higher quality evidence and validation in future studies, this statistically significant and policy relevant finding suggests that increases in facility-based deliveries can be achieved through output-based finance models that target subsidies to underserved populations.

Designing Online Learning. Knowledge Series: A Topical, Start-Up Guide to Distance Education Practice and Delivery.

ERIC Educational Resources Information Center

Mishra, Sanjaya

The term "online learning" refers to an Internet- or intranet-based teaching and learning system designed for World Wide Web-based delivery without face-to-face contact between teacher and learner. The Internet is the backbone of online learning. The following media are available to designers of online courses: text; graphics and images;…

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.

Mononuclear phagocytes as a target, not a barrier, for drug delivery.

PubMed

Yong, Seok-Beom; Song, Yoonsung; Kim, Hyung Jin; Ain, Qurrat Ul; Kim, Yong-Hee

2017-08-10

Mononuclear phagocytes have been generally recognized as a barrier to drug delivery. Recently, a new understanding of mononuclear phagocytes (MPS) ontogeny has surfaced and their functions in disease have been unveiled, demonstrating the need for re-evaluation of perspectives on mononuclear phagocytes in drug delivery. In this review, we described mononuclear phagocyte biology and focus on their accumulation mechanisms in disease sites with explanations of monocyte heterogeneity. In the 'MPS as a barrier' section, we summarized recent studies on mechanisms to avoid phagocytosis based on two different biological principles: protein adsorption and self-recognition. In the 'MPS as a target' section, more detailed descriptions were given on mononuclear phagocyte-targeted drug delivery systems and their applications to various diseases. Collectively, we emphasize in this review that mononuclear phagocytes are potent targets for future drug delivery systems. Mononuclear phagocyte-targeted delivery systems should be created with an understanding of mononuclear phagocyte ontogeny and pathology. Each specific subset of phagocytes should be targeted differently by location and function for improved disease-drug delivery while avoiding RES clearance such as Kupffer cells and splenic macrophages. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Air Force Journal of Logistics: Logistics Dimensions Improving Bare Base Agile Combat Support, The Path to Integration. Volume 28, Number 2

DTIC Science & Technology

2004-01-01

the system is balanced, there is the right flow of new pilots to match the availability of instructors for initial training missions, the right mix of...which attempted to redesign and streamline the DoD global distribution system , significantly improved delivery time to test locations.4 During its...somewhat confusing priority system that does not guarantee cargo delivery at a specific time and a pricing system that does not adequately differentiate

Material processing with fiber based ultrafast pulse delivery

NASA Astrophysics Data System (ADS)

Baumbach, S.; Stockburger, R.; Führa, B.; Zoller, S.; Thum, S.; Moosmann, J.; Maier, D.; Kanal, F.; Russ, S.; Kaiser, E.; Budnicki, A.; Sutter, D. H.; Pricking, S.; Killi, A.

2018-02-01

We report on TRUMPF's ultrafast laser systems equipped with industrialized hollow core fiber laser light cables. Beam guidance in general by means of optical fibers, e.g. for multi kilowatt cw laser systems, has become an integral part of laser-based material processing. One advantage of fiber delivery, among others, is the mechanical separation between laser and processing head. An equally important benefit is given by the fact that the fiber end acts as an opto-mechanical fix-point close to successive optical elements in the processing head. Components like lenses, diffractive optical elements etc. can thus be designed towards higher efficiency which results in better material processing. These aspects gain increasing significance when the laser system operates in fundamental mode which is usually the case for ultrafast lasers. Through the last years beam guidance of ultrafast laser pulses by means of hollow core fiber technology established very rapidly. The combination of TRUMPF's long-term stable ultrafast laser sources, passive fiber coupling, connector and packaging forms a flexible and powerful system for laser based material processing well suited for an industrial environment. In this article we demonstrate common material processing applications with ultrafast lasers realized with TRUMPF's hollow core fiber delivery. The experimental results are contrasted and evaluated against conventional free space propagation in order to illustrate the performance of flexible ultrafast beam delivery.

Dropwise additive manufacturing of pharmaceutical products for amorphous and self emulsifying drug delivery systems.

PubMed

Içten, Elçin; Purohit, Hitesh S; Wallace, Chelsey; Giridhar, Arun; Taylor, Lynne S; Nagy, Zoltan K; Reklaitis, Gintaras V

2017-05-30

The improvements in healthcare systems and the advent of the precision medicine initiative have created the need to develop more innovative manufacturing methods for the delivery and production of individualized dosing and personalized treatments. In accordance with the changes observed in healthcare systems towards more innovative therapies, this paper presents dropwise additive manufacturing of pharmaceutical products (DAMPP) for small scale, distributed manufacturing of individualized dosing as an alternative to conventional manufacturing methods A dropwise additive manufacturing process for amorphous and self-emulsifying drug delivery systems is reported, which utilizes drop-on-demand printing technology for automated and controlled deposition of melt-based formulations onto inert tablets. The advantages of drop on demand technology include reproducible production of droplets with adjustable sizing and high placement accuracy, which enable production of individualized dosing even for low dose and high potency drugs. Flexible use of different formulations, such as lipid-based formulations, allows enhancement of the solubility of poorly water soluble and highly lipophilic drugs with DAMPP. Here, DAMPP is used to produce solid oral dosage forms from melts of an active pharmaceutical ingredient and a surfactant. The dosage forms are analyzed to show the amorphous nature, self-emulsifying drug delivery system characteristics and dissolution behavior of these formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of free delivery policy on utilization of maternal health services in county referral hospitals in Kenya.

PubMed

Njuguna, John; Kamau, Njoroge; Muruka, Charles

2017-06-21

Kenya has a high maternal mortality rate. Provision of skilled delivery plays a major role in reducing maternal mortality. Cost is a hindrance to the utilization of skilled delivery. The Government of Kenya introduced a policy of free delivery services in government facilities beginning June 2013. We sought to determine the impact of this intervention on facility based deliveries in Kenya. We compared deliveries and antenatal attendance in 47 county referral hospitals and 30 low cost private hospitals not participating in the free delivery policy for 2013 and 2014 respectively. The data was extracted from the Kenya Health Information System. Multiple regression was done to assess factors influencing increase in number of deliveries among the county referral hospitals. The number of deliveries and antenatal attendance increased by 26.8% and 16.2% in county referral hospitals and decreased by 11.9% and 5.4% respectively in low cost private hospitals. Increase in deliveries among county referral hospitals was influenced by population size of county and type of county referral hospital. Counties with level 5 hospitals recorded more deliveries compared to those with level 4 hospitals. This intervention increased the number of facility based deliveries. Policy makers may consider incorporating low cost private hospitals so as to increase the coverage of this intervention.

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

Passarge, M; Fix, M K; Manser, P

Purpose: To create and test an accurate EPID-frame-based VMAT QA metric to detect gross dose errors in real-time and to provide information about the source of error. Methods: A Swiss cheese model was created for an EPID-based real-time QA process. The system compares a treatmentplan- based reference set of EPID images with images acquired over each 2° gantry angle interval. The metric utilizes a sequence of independent consecutively executed error detection Methods: a masking technique that verifies infield radiation delivery and ensures no out-of-field radiation; output normalization checks at two different stages; global image alignment to quantify rotation, scaling andmore » translation; standard gamma evaluation (3%, 3 mm) and pixel intensity deviation checks including and excluding high dose gradient regions. Tolerances for each test were determined. For algorithm testing, twelve different types of errors were selected to modify the original plan. Corresponding predictions for each test case were generated, which included measurement-based noise. Each test case was run multiple times (with different noise per run) to assess the ability to detect introduced errors. Results: Averaged over five test runs, 99.1% of all plan variations that resulted in patient dose errors were detected within 2° and 100% within 4° (∼1% of patient dose delivery). Including cases that led to slightly modified but clinically equivalent plans, 91.5% were detected by the system within 2°. Based on the type of method that detected the error, determination of error sources was achieved. Conclusion: An EPID-based during-treatment error detection system for VMAT deliveries was successfully designed and tested. The system utilizes a sequence of methods to identify and prevent gross treatment delivery errors. The system was inspected for robustness with realistic noise variations, demonstrating that it has the potential to detect a large majority of errors in real-time and indicate the error source. J. V. Siebers receives funding support from Varian Medical Systems.« less

Comparison of life cycle emissions and energy consumption for environmentally adapted metalworking fluid systems.

PubMed

Clarens, Andres F; Zimmerman, Julie B; Keoleian, Greg A; Hayes, Kim F; Skerlos, Steven J

2008-11-15

A number of environmentally adapted lubricants have been proposed in response to the environmental and health impacts of metalworking fluids (MWFs). The alternatives typically substitute petroleum with vegetable-based components and/or deliver minimum quantities of lubricant in gas rather than water, with the former strategy being more prevalent than the latter. A comparative life cycle assessment of water- and gas-based systems has shown that delivery of lubricants in air rather than water can reduce solid waste by 60%, water use by 90%, and aquatic toxicity by 80%, while virtually eliminating occupational health concerns. However, air-delivery of lubricants cannot be used for severe machining operations due to limitations of cooling and lubricant delivery. For such operations, lubricants delivered in supercritical carbon dioxide (scCO2) are effective while maintaining the health and environmental advantages of air-based systems. Although delivery conditions were found to significantly influence the environmental burdens of all fluids, energy consumption was relatively constant under expected operating conditions. Global warming potential (GWP) increased when delivering lubricants in gas rather than water though all classes of MWFs have low GWP compared with other factory operations. It is therefore concluded that the possibility of increased GWP when switching to gas-based MWFs is a reasonable tradeoff for definite and large reductions in aquatic toxicity, water use, solid waste, and occupational health risks.

Lipid-associated Oral Delivery: Mechanisms and Analysis of Oral Absorption Enhancement

PubMed Central

Rezhdo, Oljora; Speciner, Lauren; Carrier, Rebecca L.

2016-01-01

The majority of newly discovered oral drugs are poorly water soluble, and co-administration with lipids has proven effective in significantly enhancing bioavailability of some compounds with low aqueous solubility. Yet, lipid-based delivery technologies have not been widely employed in commercial oral products. Lipids can impact drug transport and fate in the gastrointestinal (GI) tract through multiple mechanisms including enhancement of solubility and dissolution kinetics, enhancement of permeation through the intestinal mucosa, and triggering drug precipitation upon lipid emulsion depletion (e.g., by digestion). The effect of lipids on drug absorption is currently not quantitatively predictable, in part due to the multiple complex dynamic processes that can be impacted by lipids. Quantitative mechanistic analysis of the processes significant to lipid system function and overall impact on drug absorption can aid understanding of drug-lipid interactions in the GI tract and exploitation of such interactions to achieve optimal lipid-based drug delivery. In this review, we discuss the impact of co-delivered lipids and lipid digestion on drug dissolution, partitioning, and absorption in the context of the experimental tools and associated kinetic expressions used to study and model these processes. The potential benefit of a systems-based consideration of the concurrent multiple dynamic processes occurring upon co-dosing lipids and drugs to predict the impact of lipids on drug absorption and enable rational design of lipid-based delivery systems is presented. PMID:27520734

Single-step assembly of cationic lipid-polymer hybrid nanoparticles for systemic delivery of siRNA.

PubMed

Yang, Xian-Zhu; Dou, Shuang; Wang, Yu-Cai; Long, Hong-Yan; Xiong, Meng-Hua; Mao, Cheng-Qiong; Yao, Yan-Dan; Wang, Jun

2012-06-26

The clinical success of therapeutics of small interfering RNA (siRNA) is still hindered by its delivery systems. Cationic polymer or lipid-based vehicles as the major delivery systems of siRNA cannot sufficiently satisfy siRNA therapeutic applications. It is hypothesized that cationic lipid-polymer hybrid nanoparticles may take advantage of both polymeric and lipid-based nanoparticles for siRNA delivery, while diminishing the shortcomings of both. In this study, cationic lipid-polymer hybrid nanoparticles were prepared by a single-step nanoprecipitation of a cationic lipid (N,N-bis(2-hydroxyethyl)-N-methyl-N-(2-cholesteryloxycarbonyl aminoethyl) ammonium bromide, BHEM-Chol) and amphiphilic polymers for systemic delivery of siRNA. The formed hybrid nanoparticles comprised a hydrophobic polylactide core, a hydrophilic poly(ethylene glycol) shell, and a cationic lipid monolayer at the interface of the core and the shell. Such hybrid nanoparticles exhibited excellent stability in serum and showed significantly improved biocompatibility compared to that of pure BHEM-Chol particles. The hybrid nanoparticles were capable of delivering siRNA into BT474 cells and facilitated the escape of loaded siRNA from the endosome into the cytoplasm. The hybrid nanoparticles carrying polo-like kinase 1 (Plk1)-specific siRNA (siPlk1) remarkably and specifically downregulated expression of the oncogene Plk1 and induced cancer cell apoptosis both in vitro and in vivo and significantly suppressed tumor growth following systemic administration. We demonstrate that this system is stable, nontoxic, highly efficient, and easy to scale up, bringing the clinical application of siRNA therapy one important step closer to reality.

Fabrication of functional PLGA-based electrospun scaffolds and their applications in biomedical engineering.

PubMed

Zhao, Wen; Li, Jiaojiao; Jin, Kaixiang; Liu, Wenlong; Qiu, Xuefeng; Li, Chenrui

2016-02-01

Electrospun PLGA-based scaffolds have been applied extensively in biomedical engineering, such as tissue engineering and drug delivery system. Due to lack of the recognition sites on cells, hydropholicity and single-function, the applications of PLGA fibrous scaffolds are limited. In order to tackle these issues, many works have been done to obtain functional PLGA-based scaffolds, including surface modifications, the fabrication of PLGA-based composite scaffolds and drug-loaded scaffolds. The functional PLGA-based scaffolds have significantly improved cell adhesion, attachment and proliferation. Moreover, the current study has summarized the applications of functional PLGA-based scaffolds in wound dressing, vascular and bone tissue engineering area as well as drug delivery system. Copyright © 2015 Elsevier B.V. All rights reserved.

Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo

NASA Astrophysics Data System (ADS)

Liu, Yun; Ding, Xingwei; Li, Jinghua; Luo, Zhong; Hu, Yan; Liu, Junjie; Dai, Liangliang; Zhou, Jun; Hou, Changjun; Cai, Kaiyong

2015-04-01

To reduce the toxic side effects of traditional chemotherapeutics in vivo, we designed and constructed a biocompatible, matrix metalloproteinases (MMPs) responsive drug delivery system based on mesoporous silica nanoparticles (MSNs). MMPs substrate peptide containing PLGLAR (sensitive to MMPs) was immobilized onto the surfaces of amino-functionalized MSNs via an amidation reaction, serving as MMPs sensitive intermediate linker. Bovine serum albumin was then covalently coupled to linker as end-cap for sealing the mesopores of MSNs. Lactobionic acid was further conjugated to the system as targeting motif. Doxorubicin hydrochloride was used as the model anticancer drug in this study. A series of characterizations revealed that the system was successfully constructed. The peptide-functionalized MSNs system demonstrated relatively high sensitivity to MMPs for triggering drug delivery, which was potentially important for tumor therapy since the tumor’s microenvironment overexpressed MMPs in nature. The in vivo experiments proved that the system could efficiently inhibit the tumor growth with minimal side effects. This study provides an approach for the development of the next generation of nanotherapeutics toward efficient cancer treatment.

Recent progress on fabrication and drug delivery applications of nanostructured hydroxyapatite.

PubMed

Mondal, Sudip; Dorozhkin, Sergy V; Pal, Umapada

2018-07-01

Through this brief review, we provide a comprehensive historical background of the development of nanostructured hydroxyapatite (nHAp), and its application potentials for controlled drug delivery, drug conjugation, and other biomedical treatments. Aspects associated with efficient utilization of hydroxyapatite (HAp) nanostructures such as their synthesis, interaction with drug molecules, and other concerns, which need to be resolved before they could be used as a potential drug carrier in body system, are discussed. This review focuses on the evolution of perceptions, practices, and accomplishments in providing improved delivery systems for drugs until date. The pioneering developments that have presaged today's fascinating state of the art drug delivery systems based on HAp and HAp-based composite nanostructures are also discussed. Special emphasis has been given to describe the application and effectiveness of modified HAp as drug carrier agent for different diseases such as bone-related disorders, carriers for antibiotics, anti-inflammatory, carcinogenic drugs, medical imaging, and protein delivery agents. As only a very few published works made comprehensive evaluation of HAp nanostructures for drug delivery applications, we try to cover the three major areas: concepts, practices and achievements, and applications, which have been consolidated and patented for their practical usage. The review covers a broad spectrum of nHAp and HAp modified inorganic drug carriers, emphasizing some of their specific aspects those needed to be considered for future drug delivery applications. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Nanotechnology Approaches to Biology > Cells at the Nanoscale. © 2017 Wiley Periodicals, Inc.

Qualification of the GASGUARD® SAS GGT Arsine Sub-Atmospheric Gas Delivery System for Ion Implantation

NASA Astrophysics Data System (ADS)

Dunn, James P.; Rolland, James L.; Grim, James S.; Machado, Reinaldo M.; Hartz, Christopher L.

2006-11-01

A beta level evaluation of the GASGUARD® SAS GGT Arsine ion implant dopant supply developed by Air Products and Chemicals, Inc. was conducted by Atmel Corporation. The evaluation included characterization of the normalized wafer yield, mass spectra, ionization efficiency, flow rate, beam current, extraction of usable material and cylinder lifetime. This new and novel sub-atmospheric dopant gas delivery system utilizes a unique electrochemical process, which can generate, on demand, high flows of arsine at a constant 400 torr pressure while limiting net inventory of arsine to only 1 gram. This paper illustrates how Atmel Corporation evaluated and released this new arsine dopant delivery system for commercial production and verified high delivery capacity, resulting in reduced gas costs and increased cylinder life compared to the traditional adsorbent based technology.

DNA/RNA-based formulations for treatment of breast cancer.

PubMed

Xie, Zhaolu; Zeng, Xianghui

2017-12-01

To develop a successful formulation for the gene therapy of breast cancer, an effective therapeutic nucleic acid and a proper delivery system are essential. Increased understanding of breast cancer, and developments in biotechnology, material science and nanotechnology have provided a major impetus in the development of effective formulations for the gene therapy of breast cancer. Areas covered: We discuss DNA/RNA-based formulations that can inhibit the growth of breast cancer cells and control the progress of breast cancer. Targets for the gene therapy of breast cancer, DNA/RNA-based therapeutics and delivery systems are summarized. And examples of successful DNA/RNA-based formulations for breast cancer gene therapy are reviewed. Expert opinion: Several challenges remain in developing effective DNA/RNA-based formulations for treatment of breast cancer. Firstly, most of the currently utilized targets are not effective enough as monotherapy for breast cancer. Secondly, the requirements for co-delivery system make the preparation of formulation more complicated. Thirdly, nanoparticles with the modification of tumor-targeting ligands could be more unstable in circulation and normal tissues. Lastly, immune responses against the viral vectors are unfavorable for the gene therapy of breast cancer because of the damage to the host and the impaired therapeutic ability.

Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.

PubMed

Caccavo, D; Barba, A A; d'Amore, M; De Piano, R; Lamberti, G; Rossi, A; Colombo, P

2017-12-01

The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting and synergistic action of an antifungal peptide in an antibiotic drug-delivery system.

PubMed

Park, Seong-Cheol; Kim, Young-Min; Lee, Jong-Kook; Kim, Nam-Hong; Kim, Eun-Ji; Heo, Hun; Lee, Min-Young; Lee, Jung Ro; Jang, Mi-Kyeong

2017-06-28

Amphotericin B (AmB) has been widely used against fungal infections throughout almost the entire body, including the skin, nails, oral cavity, respiratory tract, and urinary tract. However, the development of AmB-loaded nanoparticles demands a novel technique that reduces its toxicity and other associated problems. Here, we developed a pH-responsive and redox-sensitive polymer-based AmB-delivery carrier system. In particular, this system was functionalized by conjugation with the antifungal peptide histatin 5, which acts both as a targeting ligand and a synergistic antifungal molecule against Candida albicans, a major systemic fungal pathogen of humans. Our results in vitro and in vivo suggest that this drug-delivery system may serve as a novel tool to facilitate the use of antimicrobial peptides as targeting ligands to pathogenic microbes, which would open new avenues of investigation in the field of drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhaled nano- and microparticles for drug delivery

PubMed Central

El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

2015-01-01

The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

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.

Synthesis and characterization of novel amphiphilic copolymer stearic acid-coupled F127 nanoparticles for nano-technology based drug delivery system.

PubMed

Gao, Qihe; Liang, Qing; Yu, Fei; Xu, Jian; Zhao, Qihua; Sun, Baiwang

2011-12-01

Pluronic, F127, amphiphilic block copolymers, are used for several applications, including drug delivery systems. The critical micelle concentration (CMC) of F127 is about 0.26-0.8 wt% so that the utility of F127 in nano-technology based drug delivery system is limited since the nano-sized micelles could dissociate upon dilution. Herein, stearic acid (SA) was simply coupled to F127 between the carboxyl group of SA and the hydroxyl group of F127, which formed a novel copolymer named as SA-coupled F127, with significantly lower CMC. Above the CMC 6.9 × 10(-5)wt%, SA-coupled F127 self-assembled stable nanoparticles with Zeta potential -36 mV. Doxorubicin (DOX)-loaded nanoparticles were made, with drug loading (DL) 5.7 wt% and Zeta potential -36 to -39 mV, and the nanoparticles exhibited distinct shape with the size distribution from 20 to 50 nm. DOX-loaded nanoparticles were relatively stable and exhibited DOX dependant cytotoxicity toward MCF-7 cells in vitro. These results suggest that SA-coupled F127 potentially could be applied as a nano-technology based drug delivery method. Copyright © 2011 Elsevier B.V. All rights reserved.

Current trends in the use of vitamin E-based micellar nanocarriers for anticancer drug delivery.

PubMed

Muddineti, Omkara Swami; Ghosh, Balaram; Biswas, Swati

2017-06-01

Owing to the complexity of cancer pathogenesis, conventional chemotherapy can be an inadequate method of killing cancer cells effectively. Nanoparticle-based drug delivery systems have been widely exploited pre-clinically in recent years. Areas covered: Incorporation of vitamin-E in nanocarriers have the advantage of (1) improving the hydrophobicity of the drug delivery system, thereby improving the solubility of the loaded poorly soluble anticancer drugs, (2) enhancing the biocompatibility of the polymeric drug carriers, and (3) improving the anticancer potential of the chemotherapeutic agents by reversing the cellular drug resistance via simultaneous administration. In addition to being a powerful antioxidant, vitamin E demonstrated its anticancer potential by inducing apoptosis in various cancer cell lines. Various vitamin E analogs have proven their ability to cause marked inhibition of drug efflux transporters. Expert opinion: The review discusses the potential of incorporating vitamin E in the polymeric micelles which are designed to carry poorly water-soluble anticancer drugs. Current applications of various vitamin E-based polymeric micelles with emphasis on the use of α-tocopherol, D-α-tocopheryl succinate (α-TOS) and its conjugates such as D-α-tocopheryl polyethylene glycol-succinate (TPGS) in micellar system is delineated. Advantages of utilizing polymeric micelles for drug delivery and the challenges to treat cancer, including multiple drug resistance have been discussed.

Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

PubMed

Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

2015-05-15

Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Polymer based drug delivery systems for mycobacterial infections.

PubMed

Pandey, Rajesh; Khuller, G K

2004-07-01

In the last decade, polymer based technologies have found wide biomedical applications. Polymers, whether synthetic (e.g. polylactide-co-glycolide or PLG) or natural (e.g. alginate, chitosan etc.), have the property of encapsulating a diverse range of molecules of biological interest and bear distinct therapeutic advantages such as controlled release of drugs, protection against the premature degradation of drugs and reduction in drug toxicity. These are important considerations in the long-duration treatment of chronic infectious diseases such as tuberculosis in which patient non-compliance is the major obstacle to successful chemotherapy. Antitubercular drugs, singly or in combination, have been encapsulated in polymers to provide controlled drug release and the system also offers the flexibility of selecting various routes of administration such as oral, subcutaneous and aerosol. The present review highlights the approaches towards the preparation of polymeric antitubercular drug delivery systems, emphasizing how the route of administration may influence drug bioavailability as well as the chemotherapeutic efficacy. In addition, the pros and cons of the various delivery systems are also discussed.

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.

Integrating mitosis, toxicity, and transgene expression in a telecommunications packet-switched network model of lipoplex-mediated gene delivery.

PubMed

Martin, Timothy M; Wysocki, Beata J; Beyersdorf, Jared P; Wysocki, Tadeusz A; Pannier, Angela K

2014-08-01

Gene delivery systems transport exogenous genetic information to cells or biological systems with the potential to directly alter endogenous gene expression and behavior with applications in functional genomics, tissue engineering, medical devices, and gene therapy. Nonviral systems offer advantages over viral systems because of their low immunogenicity, inexpensive synthesis, and easy modification but suffer from lower transfection levels. The representation of gene transfer using models offers perspective and interpretation of complex cellular mechanisms,including nonviral gene delivery where exact mechanisms are unknown. Here, we introduce a novel telecommunications model of the nonviral gene delivery process in which the delivery of the gene to a cell is synonymous with delivery of a packet of information to a destination computer within a packet-switched computer network. Such a model uses nodes and layers to simplify the complexity of modeling the transfection process and to overcome several challenges of existing models. These challenges include a limited scope and limited time frame, which often does not incorporate biological effects known to affect transfection. The telecommunication model was constructed in MATLAB to model lipoplex delivery of the gene encoding the green fluorescent protein to HeLa cells. Mitosis and toxicity events were included in the model resulting in simulation outputs of nuclear internalization and transfection efficiency that correlated with experimental data. A priori predictions based on model sensitivity analysis suggest that increasing endosomal escape and decreasing lysosomal degradation, protein degradation, and GFP-induced toxicity can improve transfection efficiency by three-fold. Application of the telecommunications model to nonviral gene delivery offers insight into the development of new gene delivery systems with therapeutically relevant transfection levels.

Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging.

PubMed

Li, Yunkun; Li, Yachao; Zhang, Xiao; Xu, Xianghui; Zhang, Zhijun; Hu, Cheng; He, Yiyan; Gu, Zhongwei

2016-01-01

Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum-based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms.

Nanocrystal for ocular drug delivery: hope or hype.

PubMed

Sharma, Om Prakash; Patel, Viral; Mehta, Tejal

2016-08-01

The complexity of the structure and nature of the eye emanates a challenge for drug delivery to formulation scientists. Lower bioavailability concern of conventional ocular formulation provokes the interest of researchers in the development of novel drug delivery system. Nanotechnology-based formulations have been extensively investigated and found propitious in improving bioavailability of drugs by overcoming ocular barriers prevailing in the eye. The advent of nanocrystals helped in combating the problem of poorly soluble drugs specifically for oral and parenteral drug delivery and led to development of various marketed products. Nanocrystal-based formulations explored for ocular drug delivery have been found successful in achieving increase in retention time, bioavailability, and permeability of drugs across the corneal and conjunctival epithelium. In this review, we have highlighted the ocular physiology and barriers in drug delivery. A comparative analysis of various nanotechnology-based ocular formulations is done with their pros and cons. Consideration is also given to various methods of preparation of nanocrystals with their patented technology. This article highlights the success achieved in conquering various challenges of ocular delivery by the use of nanocrystals while emphasizing on its advantages and application for ocular formulation. The perspectives of nanocrystals as an emerging flipside to explore the frontiers of ocular drug delivery are discussed.

Laser based synthesis of nanofunctionalized particulates for pulmonary based controlled drug delivery applications

NASA Astrophysics Data System (ADS)

Singh, R. K.; Kim, W.-S.; Ollinger, M.; Craciun, V.; Coowantwong, I.; Hochhaus, G.; Koshizaki, N.

2002-09-01

There is an urgent need to develop controlled drug release systems for the delivery of drugs via the pulmonary route. A key issue in pulmonary dry delivery systems is to reduce the amount of biodegradable polymers that are added to control the drug release. We have synthesized nanofunctionalized drug particles using the pulsed laser deposition on particles (PLDP) (e.g. budesonide) in an effort to control the architecture and thickness of a nanoscale polymer coating on the drug particles. In vitro studies indicated that the dry half-life release for budesonide can be enhanced from 1.2 to over 60 min by a nanoscale coating on the drug particle. Extensive studies have been conducted to characterize the bonding and composition of the polymer film deposited on drug particles.

Selective gene silencing by viral delivery of short hairpin RNA

PubMed Central

2010-01-01

RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells. PMID:20858246

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.

Toward an evidence-based system for innovation support for implementing innovations with quality: tools, training, technical assistance, and quality assurance/quality improvement.

PubMed

Wandersman, Abraham; Chien, Victoria H; Katz, Jason

2012-12-01

An individual or organization that sets out to implement an innovation (e.g., a new technology, program, or policy) generally requires support. In the Interactive Systems Framework for Dissemination and Implementation, a Support System should work with Delivery Systems (national, state and/or local entities such as health and human service organizations, community-based organizations, schools) to enhance their capacity for quality implementation of innovations. The literature on the Support System [corrected] has been underresearched and under-developedThis article begins to conceptualize theory, research, and action for an evidence-based system for innovation support (EBSIS). EBSIS describes key priorities for strengthening the science and practice of support. The major goal of EBSIS is to enhance the research and practice of support in order to build capacity in the Delivery System for implementing innovations with quality, and thereby, help the Delivery System achieve outcomes. EBSIS is guided by a logic model that includes four key support components: tools, training, technical assistance, and quality assurance/quality improvement. EBSIS uses the Getting To Outcomes approach to accountability to aid the identification and synthesis of concepts, tools, and evidence for support. We conclude with some discussion of the current status of EBSIS and possible next steps, including the development of collaborative researcher-practitioner-funder-consumer partnerships to accelerate accumulation of knowledge on the Support System.

Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system.

PubMed

Liu, Quan; Fassihi, Reza

2008-02-04

A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244nm, with automatic sampling over a 24h period using a marketed product as a reference to calculate the "f(2)" factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with "f(2)" of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine.

Inorganic Nanomaterials as Carriers for Drug Delivery.

PubMed

Chen, Shizhu; Hao, Xiaohong; Liang, Xingjie; Zhang, Qun; Zhang, Cuimiao; Zhou, Guoqiang; Shen, Shigang; Jia, Guang; Zhang, Jinchao

2016-01-01

For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study.

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.

Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

PubMed

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

2016-01-01

Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

Enhancing School-Based Mental Health Services with a Preventive and Promotive Approach to Universal Screening for Complete Mental Health

ERIC Educational Resources Information Center

Dowdy, Erin; Furlong, Michael; Raines, Tara C.; Bovery, Bibliana; Kauffman, Beth; Kamphaus, Randy W.; Dever, Bridget V.; Price, Martin; Murdock, Jan

2015-01-01

Universal screening for complete mental health is proposed as a key step in service delivery reform to move school-based psychological services from the back of the service delivery system to the front, which will increase emphasis on prevention, early intervention, and promotion. A sample of 2,240 high school students participated in a schoolwide…

Regulating plant physiology with organic electronics.

PubMed

Poxson, David J; Karady, Michal; Gabrielsson, Roger; Alkattan, Aziz Y; Gustavsson, Anna; Doyle, Siamsa M; Robert, Stéphanie; Ljung, Karin; Grebe, Markus; Simon, Daniel T; Berggren, Magnus

2017-05-02

The organic electronic ion pump (OEIP) provides flow-free and accurate delivery of small signaling compounds at high spatiotemporal resolution. To date, the application of OEIPs has been limited to delivery of nonaromatic molecules to mammalian systems, particularly for neuroscience applications. However, many long-standing questions in plant biology remain unanswered due to a lack of technology that precisely delivers plant hormones, based on cyclic alkanes or aromatic structures, to regulate plant physiology. Here, we report the employment of OEIPs for the delivery of the plant hormone auxin to induce differential concentration gradients and modulate plant physiology. We fabricated OEIP devices based on a synthesized dendritic polyelectrolyte that enables electrophoretic transport of aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana seedlings in vivo was monitored in real time via dynamic fluorescent auxin-response reporters and induced physiological responses in roots. Our results provide a starting point for technologies enabling direct, rapid, and dynamic electronic interaction with the biochemical regulation systems of plants.

Regulating plant physiology with organic electronics

PubMed Central

Poxson, David J.; Karady, Michal; Alkattan, Aziz Y.; Gustavsson, Anna; Robert, Stéphanie; Grebe, Markus; Berggren, Magnus

2017-01-01

The organic electronic ion pump (OEIP) provides flow-free and accurate delivery of small signaling compounds at high spatiotemporal resolution. To date, the application of OEIPs has been limited to delivery of nonaromatic molecules to mammalian systems, particularly for neuroscience applications. However, many long-standing questions in plant biology remain unanswered due to a lack of technology that precisely delivers plant hormones, based on cyclic alkanes or aromatic structures, to regulate plant physiology. Here, we report the employment of OEIPs for the delivery of the plant hormone auxin to induce differential concentration gradients and modulate plant physiology. We fabricated OEIP devices based on a synthesized dendritic polyelectrolyte that enables electrophoretic transport of aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana seedlings in vivo was monitored in real time via dynamic fluorescent auxin-response reporters and induced physiological responses in roots. Our results provide a starting point for technologies enabling direct, rapid, and dynamic electronic interaction with the biochemical regulation systems of plants. PMID:28420793

Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi

2011-01-01

An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

A novel local anti-colorectal cancer drug delivery system: negative lipidoid nanoparticles with a passive target via a size-dependent pattern

NASA Astrophysics Data System (ADS)

Ding, Weifeng; Wang, Feng; Zhang, Jianfeng; Guo, Yibing; Ju, Shaoqing; Wang, Huimin

2013-09-01

The nontoxic, targeted and effective delivery of nucleic acid drugs remains an important challenge for clinical development. Here, we describe a novel negative lipidoid nanoparticle delivery system, providing entrapment-based transfection agents for local delivery of siRNA to the colorectal cancer focus. The delivery system was synthesized with lipidoid material 98N12-5(1), mPEG2000-C12/C14 glyceride and cholesterol at a desired molar ratio to realize the anionic surface charge of particles, which could alleviate to a larger degree the inflammatory response and immune stimulation of the organism, embodying dramatic biocompatibility. In particular, mPEG2000-C12/C14 glyceride was selected to ameliorate the stability of the delivery system and protection of nucleic acids by extending the tail length of the carbons, crucial also to neutralize the positive charge of 98N12-5(1) to form a resultant anionic particle. In vivo experiments revealed that a particle size of 90 nm perfectly realized a passive target in a size-dependent manner and did not affect the function of the liver and kidneys by a local delivery method, enema. We clarified that the uptake of negative lipidoid nanoparticles internalized through a lipid raft endocytotic pathway with low cytotoxicity, strong biocompatibility and high efficacy. This study suggests that negative lipidoid nanoparticles with enema delivery costitute, uniquely and appropriately, a local anti-colorectal cancer nucleic acid drug delivery platform, and the application of similar modes may be feasible in other therapeutic settings.

Paclitaxel loaded phospholipid-based gel as a drug delivery system for local treatment of glioma.

PubMed

Chen, Tijia; Gong, Ting; Zhao, Ting; Liu, Xing; Fu, Yao; Zhang, Zhirong; Gong, Tao

2017-08-07

Paclitaxel (PTX) is a chemotherapeutic agent and has been widely used in clinic against human cancer. However, it has limited application in brain tumor treatment due to the poor penetration of blood brain barrier. Local delivery system is a promising carrier of PTX in the treatment of glioma. A biodegradable phospholipid-based gel (PG) system was developed for intratumoral injection and evaluated in brain glioma-bearing mice model. PTX loaded PG was composed of phospholipid, ethanol, medium chain triglyceride, triacetin and PTX. It was prepared by a very simple method. The system was a transparent solution with good fluidity, while turned into a gel after phase-transition when ethanol diffused. Both in vitro dissolution and in vivo imaging study proved the sustained release effect of PG system. In vivo tolerability study showed a better tolerability after mice treated with PTX PG compared with free PTX. The survival time of brain glioma-bearing mice after treatment with PTX PG was significantly prolonged compared with mice treated by free PTX (P<0.05). In conclusion, this study developed a novel PG based local PTX delivery system with simple preparation method, good tolerability and high therapeutic efficacy. It has a great potential to improve the clinical management of glioma. Copyright © 2017 Elsevier B.V. All rights reserved.

Cesarean Delivery in the United States 2005 - 2014: A Population-Based Analysis Using the Robson Ten Group Classification System.

PubMed

Hehir, Mark P; Ananth, Cande V; Siddiq, Zainab; Flood, Karen; Friedman, Alexander M; D'Alton, Mary E

2018-04-12

Cesarean delivery has increased steadily in the United States over recent decades with significant downstream health consequences. The World Health Organization has endorsed the Robson Ten Group Classification System (TGCS) as a global standard to facilitate analysis and comparison of cesarean delivery rates. Our objective was to apply the TGCS to a nationwide cohort in the United States over a 10-year period. This population-based analysis applied the TGCS to all births in the United States from 2005-2014, recorded in the 2003-revised birth certificate format. Over the study 10-year period 27,044,217 deliveries met inclusion criteria. Five parameters (parity including previous cesarean, gestational age, labor onset, fetal presentation and plurality), identifiable on presentation for delivery, were used to classify all women included into one of ten groups. The overall cesarean rate was 31.6%. Group 3 births (singleton, term, cephalic multiparas in spontaneous labor) were most common, while Group 5 births (those with a previous cesarean) accounted for the most cesarean deliveries increasing from 27% of all cesareans in 2005-06 to over 34% in 2013-14. Breech pregnancies (Groups 6 and 7) had cesarean rates above 90%. Primiparous and multiparous women who had a prelabor cesarean [Groups 2(b) and 4(b)] accounted for over one quarter of all cesarean deliveries. Women with a previous cesarean delivery represent an increasing proportion of cesarean deliveries. Use of the Robson criteria allows standardised comparisons of data and identifies clinical scenarios driving changes in cesarean rates. Hospitals and health organisations can use the TGCS to evaluate quality and processes associated with cesarean delivery. Copyright © 2018 Elsevier Inc. All rights reserved.

In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain.

PubMed

Modarres, Hassan Pezeshgi; Janmaleki, Mohsen; Novin, Mana; Saliba, John; El-Hajj, Fatima; RezayatiCharan, Mahdi; Seyfoori, Amir; Sadabadi, Hamid; Vandal, Milène; Nguyen, Minh Dang; Hasan, Anwarul; Sanati-Nezhad, Amir

2018-03-10

The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Potential applications for halloysite nanotubes based drug delivery systems

NASA Astrophysics Data System (ADS)

Sun, Lin

Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery. In this study, a drug delivery system was built based on halloysite via three different fabrication methods: physical adsorption, vacuum loading and layer-by-layer coating. Methotrexate was used as the model drug. Factors that may affect performance in both drug loading and release were tested. Results showed that methotrexate could be incorporated within the HNTs system and released in a sustained manner. Layer-by-layer coating showed a better potential than the other two methods in both MTX loading and release. Besides, lower pH could greatly improve MTX loading and release while the increased number of polyelectrolytes bilayers had a limited impact. Osteosarcoma is the most common primary bone malignancy in children and adolescents. Postoperative recurrence and metastasis has become one of the leading causes for patient death after surgical remove of the tumor mass. A strategy could be a sustained release of chemotherapeutics directly at the primary tumor sites where recurrence would mostly occur. Then, this HNTs based system was tested with osteosarcoma cells in vitro to show the potential of delivering chemotherapeutics in the treatment of osteosarcoma. Methotrexate was incorporated within HNTs with a layer-bylayer coating technique, and drug coated HNTs were filled into nylon-6 which is a common material for surgical sutures in industry. Results showed that (1) methotrexate could be released in a sustained manner; (2) cytotoxicity test confirmed the biocompatibility of HNTs and methotrexate coated HNTs; (3) proliferation test confirmed the growth inhibition of released methotrexate on osteosarcoma cells; and (4) nylon-6 could prolong the sustained release of methotrexate from polyelectrolytes coated HNTs. Another application comes from the prevention of surgical site infection. It is a common complication in surgery, which may prolong hospital stay, increase mortality rate, and cause additional financial burden for patients. By directly releasing antibiotics at the surgical site, it is supposed to enhance the drug efficacy and improve the treatment outcome. Therefore, the same HNTs based system was tested with E. coli in vitro to show the potential of delivering antibiotics to enhance the prevention of surgical site infection. Nitrofurantoin was incorporated within HNTs using the layer-by-layer coating technique, and the drug coated HNTs were filled into nylon-6 again. Results showed that (1) nitrofurantoin could be incorporated with this HNTs based drug delivery system, and released in a sustained manner; (2) nylon-6 could prolong the sustained release of nitrofurantoin from polyelectrolytes coated HNTs; and (3) released nitrofurantoin could severely inhibit E. coil growth. Therefore, a tunable drug delivery system based on HNTs was developed, and a great potential of medical application in drug delivery was shown.

Versatile types of polysaccharide-based supramolecular polycation/pDNA nanoplexes for gene delivery

NASA Astrophysics Data System (ADS)

Hu, Yang; Zhao, Nana; Yu, Bingran; Liu, Fusheng; Xu, Fu-Jian

2014-06-01

Different polysaccharide-based supramolecular polycations were readily synthesized by assembling multiple β-cyclodextrin-cored star polycations with an adamantane-functionalized dextran via host-guest interaction in the absence or presence of bioreducible linkages. Compared with nanoplexes of the starting star polycation and pDNA, the supramolecular polycation/pDNA nanoplexes exhibited similarly low cytotoxicity, improved cellular internalization and significantly higher gene transfection efficiencies. The incorporation of disulfide linkages imparted the supramolecular polycation/pDNA nanoplexes with the advantage of intracellular bioreducibility, resulting in better gene delivery properties. In addition, the antitumor properties of supramolecular polycation/pDNA nanoplexes were also investigated using a suicide gene therapy system. The present study demonstrates that the proper assembly of cyclodextrin-cored polycations with adamantane-functionalized polysaccharides is an effective strategy for the production of new nanoplex delivery systems.Different polysaccharide-based supramolecular polycations were readily synthesized by assembling multiple β-cyclodextrin-cored star polycations with an adamantane-functionalized dextran via host-guest interaction in the absence or presence of bioreducible linkages. Compared with nanoplexes of the starting star polycation and pDNA, the supramolecular polycation/pDNA nanoplexes exhibited similarly low cytotoxicity, improved cellular internalization and significantly higher gene transfection efficiencies. The incorporation of disulfide linkages imparted the supramolecular polycation/pDNA nanoplexes with the advantage of intracellular bioreducibility, resulting in better gene delivery properties. In addition, the antitumor properties of supramolecular polycation/pDNA nanoplexes were also investigated using a suicide gene therapy system. The present study demonstrates that the proper assembly of cyclodextrin-cored polycations with adamantane-functionalized polysaccharides is an effective strategy for the production of new nanoplex delivery systems. Electronic supplementary information (ESI) available: 1H NMR assay and synthetic route of Dex-Ad and Dex-SS-Ad. See DOI: 10.1039/c4nr01590h

Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts.

PubMed

Emmert, Maximilian Y; Weber, Benedikt; Behr, Luc; Sammut, Sebastien; Frauenfelder, Thomas; Wolint, Petra; Scherman, Jacques; Bettex, Dominique; Grünenfelder, Jürg; Falk, Volkmar; Hoerstrup, Simon P

2014-01-01

While transcatheter aortic valve implantation (TAVI) has rapidly evolved for the treatment of aortic valve disease, the currently used bioprostheses are prone to continuous calcific degeneration. Thus, autologous, cell-based, living, tissue-engineered heart valves (TEHVs) with regeneration potential have been suggested to overcome these limitations. We investigate the technical feasibility of combining the concept of TEHV with transapical implantation technology using a state-of-the-art transcatheter delivery system facilitating the exact anatomical position in the systemic circulation. Trileaflet TEHVs fabricated from biodegradable synthetic scaffolds were sewn onto self-expanding Nitinol stents seeded with autologous marrow stromal cells, crimped and transapically delivered into the orthotopic aortic valve position of adult sheep (n = 4) using the JenaValve transapical TAVI System (JenaValve, Munich, Germany). Delivery, positioning and functionality were assessed by angiography and echocardiography before the TEHV underwent post-mortem gross examination. For three-dimensional reconstruction of the stent position of the anatomically oriented system, a computed tomography analysis was performed post-mortem. Anatomically oriented, transapical delivery of marrow stromal cell-based TEHV into the orthotopic aortic valve position was successful in all animals (n = 4), with a duration from cell harvest to TEHV implantation of 101 ± 6 min. Fluoroscopy and echocardiography displayed sufficient positioning, thereby entirely excluding the native leaflets. There were no signs of coronary obstruction. All TEHV tolerated the loading pressure of the systemic circulation and no acute ruptures occurred. Animals displayed intact and mobile leaflets with an adequate functionality. The mean transvalvular gradient was 7.8 ± 0.9 mmHg, and the mean effective orifice area was 1.73 ± 0.02 cm(2). Paravalvular leakage was present in two animals, and central aortic regurgitation due to a single-leaflet prolapse was detected in two, which was primarily related to the leaflet design. No stent dislocation, migration or affection of the mitral valve was observed. For the first time, we demonstrate the technical feasibility of a transapical TEHV delivery into the aortic valve position using a commercially available and clinically applied transapical implantation system that allows for exact anatomical positioning. Our data indicate that the combination of TEHV and a state-of-the-art transapical delivery system is feasible, representing an important step towards translational, transcatheter-based TEHV concepts.

Application of optical coherence tomography for assessment of transcutaneous vaccine delivery

NASA Astrophysics Data System (ADS)

Kamali, T.; Rattanapak, T.; Hook, S.; Meglinski, I.

2012-03-01

Immunization is one of the most efficient and cost-effective means for the prevention of diseases, but most vaccines have to be administered invasively. A novel strategy of inducing an immune response is topical application of vaccines to intact skin. Apart from being a non-invasive route of drug delivery, skin delivery also offers an advantageous mode of immunization due to the ability of skin immune cells to present antigens to the immune system. Topical vaccine penetration through the outermost layers of skin is based on the percutaneous diffusion of lipid-based nano-particles. In the current study we investigate the applicability of Optical Coherence Tomography for monitoring transcutaneous delivery of a peptide vaccine into the skin in vivo.

Insulin delivery and nocturnal glucose control in children and adolescents with type 1 diabetes.

PubMed

Tauschmann, Martin; Hovorka, Roman

2017-12-01

Nocturnal glucose control remains challenging in children and adolescents with type 1 diabetes due to highly variable overnight insulin requirements. The issue may be addressed by glucose responsive insulin delivery based on real-time continuous glucose measurements. Areas covered: This review outlines recent developments of glucose responsive insulin delivery systems from a paediatric perspective. We cover threshold-based suspend application, predictive low glucose suspend, and more advanced single hormone and dual-hormone closed-loop systems. Approaches are evaluated in relation to nocturnal glucose control particularly during outpatient randomised controlled trials. Expert opinion: Significant progress translating research from controlled clinical centre settings to free-living unsupervised home studies have been achieved over the past decade. Nocturnal glycaemic control can be improved whilst reducing the risk of hypoglycaemia with closed-loop systems. Following the US regulatory approval of the first hybrid closed-loop system in non-paediatric population, large multinational closed-loop clinical trials and pivotal studies including paediatric populations are underway or in preparation to facilitate the use of closed-loop systems in clinical practice.

Preparation and evaluation of a phospholipid-based injectable gel for the long term delivery of leuprolide acetaterrh.

PubMed

Long, Danhong; Gong, Tao; Zhang, Zhirong; Ding, Rui; Fu, Yao

2016-07-01

A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-a-month injection of LA-loaded SPME (SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.

Recent perspectives on the delivery of biologics to back of the eye

PubMed Central

Joseph, Mary; Trinh, Hoang M.; Cholkar, Kishore; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Introduction Biologics are generally macromolecules, large in size with poor stability in biological environments. Delivery of biologics to tissues at the back of the eye remains a challenge. To overcome these challenges and treat posterior ocular diseases, several novel approaches have been developed. Nanotechnology-based delivery systems, like drug encapsulation technology, macromolecule implants and gene delivery are under investigation. We provide an overview of emerging technologies for biologics delivery to back of the eye tissues. Moreover, new biologic drugs currently in clinical trials for ocular neovascular diseases have been discussed. Areas Covered Anatomy of the eye, posterior segment disease and diagnosis, barriers to biologic delivery, ocular pharmacokinetic, novel biologic delivery system Expert Opinion Anti-VEGF therapy represents a significant advance in developing biologics for the treatment of ocular neovascular diseases. Various strategies for biologic delivery to posterior ocular tissues are under development with some in early or late stages of clinical trials. Despite significant progress in the delivery of biologics, there is unmet need to develop sustained delivery of biologics with nearly zero-order release kinetics to the back of the eye tissues. In addition, elevated intraocular pressure associated with frequent intravitreal injections of macromolecules is another concern that needs to be addressed. PMID:27573097

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.

Optical transfection using an endoscope-like system.

PubMed

Ma, Nan; Gunn-Moore, Frank; Dholakia, Kishan

2011-02-01

Optical transfection is a powerful method for targeted delivery of therapeutic agents to biological cells. A tightly focused pulsed laser beam may transiently change the permeability of a cell membrane to facilitate the delivery of foreign genetic material into cells. We report the first realization of an endoscope-like integrated system for optical transfection. An imaging fiber (coherent optical fiber bundle) with ∼ 6000 cores (pixels) embedded in a fiber cladding of ∼ 300 μm in diameter, produces an image circle (area) of ∼ 270 μm diam. This imaging fiber, with an ordered axicon lens array chemically etched at its exit face, is used for the delivery of a femtosecond laser to the cell membrane for optical transfection along with subcellular resolution imaging. A microcapillary-based microfluidic system for localized drug delivery was also combined in this miniature, flexible system. Using this novel system, a plasmid transfection efficiency up to ∼ 72% was obtained for CHO-K1 cells. This endoscope-like system opens a range of exciting applications, in particular, in the targeted in vivo optical microsurgery area.

Gene delivery with viral vectors for cerebrovascular diseases

PubMed Central

Gan, Yu; Jing, Zheng; Stetler, R. Anne; Cao, Guodong

2017-01-01

Recent achievements in the understanding of molecular events involved in the pathogenesis of central nervous system (CNS) injury have made gene transfer a promising approach for various neurological disorders, including cerebrovascular diseases. However, special obstacles, including the post-mitotic nature of neurons and the blood-brain barrier (BBB), constitute key challenges for gene delivery to the CNS. Despite the various limitations in current gene delivery systems, a spectrum of viral vectors has been successfully used to deliver genes to the CNS. Furthermore, recent advancements in vector engineering have improved the safety and delivery of viral vectors. Numerous viral vector-based clinical trials for neurological disorders have been initiated. This review will summarize the current implementation of viral gene delivery in the context of cerebrovascular diseases including ischemic stroke, hemorrhagic stroke and subarachnoid hemorrhage (SAH). In particular, we will discuss the potentially feasible ways in which viral vectors can be manipulated and exploited for use in neural delivery and therapy. PMID:23276981

Harnessing the potential of biomaterials for brain repair after stroke

NASA Astrophysics Data System (ADS)

Tuladhar, Anup; Payne, Samantha L.; Shoichet, Molly S.

2018-03-01

Stroke is a devastating disease for which no clinical treatment exists to regenerate lost tissue. Strategies for brain repair in animal models of stroke include the delivery of drug or cell-based therapeutics; however, the complex anatomy and functional organization of the brain presents many challenges. Biomaterials may alleviate some of these challenges by providing a scaffold, localizing the therapy to the site of action, and/or modulating cues to brain cells. Here, the challenges associated with delivery of therapeutics to the brain and the biomaterial strategies used to overcome these challenges are described. For example, innovative hydrogel delivery systems have been designed to provide sustained trophic factor delivery for endogenous repair and to support transplanted cell survival and integration. Novel treatments, such as electrical stimulation of transplanted cells and the delivery of factors for the direct reprogramming of astrocytes into neurons, may be further enhanced by biomaterial delivery systems. Ultimately, improved clinical translation will be achieved by combining clinically relevant therapies with biomaterials strategies.

Novel Strategies for Anterior Segment Ocular Drug Delivery

PubMed Central

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

2013-01-01

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

Gelatin device for the delivery of growth factors involved in endochondral ossification.

PubMed

Ahrens, Lucas A J; Vonwil, Daniel; Christensen, Jon; Shastri, V Prasad

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo.

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

PubMed Central

Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang

2016-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520

Gelatin device for the delivery of growth factors involved in endochondral ossification

PubMed Central

Ahrens, Lucas A. J.; Vonwil, Daniel; Christensen, Jon

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo. PMID:28380024

Chlorotoxin-conjugated graphene oxide for targeted delivery of an anticancer drug

PubMed Central

Wang, Hao; Gu, Wei; Xiao, Ning; Ye, Ling; Xu, Qunyuan

2014-01-01

Current chemotherapy for glioma is rarely satisfactory due to low therapeutic efficiency and systemic side effects. We have developed a glioma-targeted drug delivery system based on graphene oxide. Targeted peptide chlorotoxin-conjugated graphene oxide (CTX-GO) sheets were successfully synthesized and characterized. Doxorubicin was loaded onto CTX-GO (CTX-GO/DOX) with high efficiency (570 mg doxorubicin per gram CTX-GO) via noncovalent interactions. Doxorubicin release was pH-dependent and showed sustained-release properties. Cytotoxicity experiments demonstrated that CTX-GO/DOX mediated the highest rate of death of glioma cells compared with free doxorubicin or graphene oxide loaded with doxorubicin only. Further, conjugation with chlorotoxin enhanced accumulation of doxorubicin within glioma cells. These findings indicate that CTX-GO is a promising platform for drug delivery and provide a rationale for developing a glioma-specific drug delivery system. PMID:24672236

Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment.

PubMed

Liu, Jia; Qi, Chao; Tao, Kaixiong; Zhang, Jinxiang; Zhang, Jian; Xu, Luming; Jiang, Xulin; Zhang, Yunti; Huang, Lei; Li, Qilin; Xie, Hongjian; Gao, Jinbo; Shuai, Xiaoming; Wang, Guobin; Wang, Zheng; Wang, Lin

2016-03-01

Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross-linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericin's photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems.

Lipid Nanoparticles Enabling Gene Therapies: From Concepts to Clinical Utility.

PubMed

Kulkarni, Jayesh A; Cullis, Pieter R; van der Meel, Roy

2018-04-23

Genetic drugs based on RNA or DNA have remarkable therapeutic potential as virtually any disease can be treated by silencing a pathological gene, expressing a beneficial protein, or by editing defective genes. However, therapies based on nucleic acid polymers require sophisticated delivery systems to deliver these macromolecules to the interior of target cells. In this study, we review progress in developing nonviral lipid nanoparticle (LNP) delivery systems that have attractive properties, including ease of manufacture, reduced immune responses, multidosing capabilities, larger payloads, and flexibility of design. LNP systems represent the most advanced delivery systems for genetic drugs as it is expected that an LNP-short interfering RNA (siRNA) formulation will receive clinical approval from the Food and Drug Administration (FDA) in 2018 for treatment of the hereditary condition transthyretin-mediated amyloidosis, a fatal condition for which there is currently no treatment. This achievement is largely due to the development of optimized ionizable cationic lipids, arguably the most important factor in the clinical success of LNP-siRNA. In addition, we highlight potential LNP applications, including targeting tissues beyond the liver and therapeutic approaches based on messenger RNA or Clustered Regularly Interspaced Short Palindromic Repeats/Cas.

Recent advances in inorganic nanoparticle-based drug delivery systems.

PubMed

Murakami, Tatsuya; Tsuchida, Kunihiro

2008-02-01

Drug delivery systems, designed to enhance drug efficacy and reduce their adverse effects, have evolved accompanied by the development of novel materials. Nanotechnology is an emerging scientific area that has created a variety of intriguing inorganic nanoparticles. In this review, we focus on the feasibility of inorganic nanoparticles, including iron oxide nanoparticles, gold nanoparticles, fullerenes and carbon nanohorns, as drug carriers, and summarize recent advances in this field.

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.

Targeted Drug Delivery Based on Gold Nanoparticle Derivatives.

PubMed

Gholipourmalekabadi, Mazaher; Mobaraki, Mohammadmahdi; Ghaffari, Maryam; Zarebkohan, Amir; Omrani, Vahid Fallah; Urbanska, Aleksandra M; Seifalian, Alexander

2017-01-01

Drug delivery systems are effective and attractive methods which allow therapeutic substances to be introduced into the body more effectively and safe by having tunable delivery rate and release target site. Gold nanoparticles (AuNPs) have a myriad of favorable physical, chemical, optical, thermal and biological properties that make them highly suitable candidates as non-toxic carriers for drug and gene delivery. The surface modifications of AuNPs profoundly improve their circulation, minimize aggregation rates, enhance attachment to therapeutic molecules and target agents due to their nano range size which further increases their ability to cross cell membranes and reduce overall cytotoxicity. This comprehensive article reviews the applications of the AuNPs in drug delivery systems along with their corresponding surface modifications. The highlighting results obtained from the preclinical trial are promising and next five years have huge possibility move to the clinical setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Current Status of Messenger RNA Delivery Systems.

PubMed

Stanton, Matthew G

2018-06-01

Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy. The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results. The use of mRNA for prolonged and repeated expression of proteins and enzymes to treat rare, typically monogenic disease is nearing clinical entry. These uses of mRNA require delivery solutions, and the application of and improvement to existing nanoparticle nucleic acid delivery systems have jump started the pace of development and reenergized the field of particle based nucleic acid delivery. The current status of mRNA delivery is reviewed in this article with an eye toward clinical tractability.

Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems

PubMed Central

Chen, Yulin; Ma, Ping; Gui, Shuangying

2014-01-01

Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed. PMID:24995330

Multilayered materials based on biopolymers as drug delivery systems.

PubMed

Vilela, Carla; Figueiredo, Ana R P; Silvestre, Armando J D; Freire, Carmen S R

2017-02-01

The design of efficient therapeutic delivery devices has become a tremendously active area of research with a strong contribution from the layer-by-layer (LbL) technology. The application of this simple yet firmly established technique for the design of drug reservoirs originates a multitude of multilayered systems of tailored architecture and with a high level of control of drug administration. Areas covered: This review will focus on the most recent and original research on LbL assemblies based on biopolymers including polysaccharides, polypeptides and proteins, with potential use in drug delivery. Herein, drug reservoirs consisting of multilayered planar films and capsules will be examined with emphasis on the ones benefiting from the non-cytotoxic and biocompatible nature of biopolymers, which are suitable to load, protect and release a high payload of toxic and fragile drugs. Expert opinion: The combination of biopolymers with LbL technology has undergone extensive research, still, there is a multitude of R&D opportunities for the design of smart drug delivery systems with distinct multilayered morphologies, low immunological response, non-invasive drug release devices, as well as the design of theranostic systems combining diagnostics and therapeutic features. Further developments in terms of scaling towards mass production in the pharmaceutical industry are expected in the long-term.

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.

Fabrication, Physicochemical Characterization, and Performance Evaluation of Biodegradable Polymeric Microneedle Patch System for Enhanced Transcutaneous Flux of High Molecular Weight Therapeutics.

PubMed

Shah, Viral; Choudhury, Bijaya Krushna

2017-11-01

A revolutionary paradigm shift is being observed currently, towards the use of therapeutic biologics for disease management. The present research was focused on designing an efficient dosage form for transdermal delivery of α-choriogonadotropin (high molecular weight biologic), through biodegradable polymeric microneedles. Polyvinylpyrrolidone-based biodegradable microneedle arrays loaded with high molecular weight polypeptide, α-choriogonadotropin, were fabricated for its systemic delivery via transdermal route. Varied process and formulation parameters were optimized for fabricating microneedle array, which in turn was expected to temporally rupture the stratum corneum layer of the skin, acting as a major barrier to drug delivery through transdermal route. The developed polymeric microneedles were optimized on the basis of quality attributes like mechanical strength, axial strength, insertion ratio, and insertion force analysis. The optimized polymeric microneedle arrays were characterized for in vitro drug release studies, ex vivo drug permeation studies, skin resealing studies, and in vivo pharmacokinetic studies. Results depicted that fabricated polymeric microneedle arrays with mechanical strength of above 5 N and good insertion ratio exhibited similar systemic bioavailability of α-choriogonadotropin in comparison to marketed subcutaneous injection formulation of α-choriogonadotropin. Thus, it was ultimately concluded that the designed drug delivery system can serve as an efficient tool for systemic delivery of therapeutic biologics, with an added benefit of overcoming the limitations of parenteral delivery, achieving better patient acceptability and compliance.

Clinical applications of advanced rotational radiation therapy

NASA Astrophysics Data System (ADS)

Nalichowski, Adrian

Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates. Methods and Materials: An anthropomorphic phantom was used to create TMI plans using the new GPU based treatment planning system and the existing CPU cluster based system. Optimization parameters were selected based on clinically used values for field width, modulation factor and pitch. Treatment plans were also created on Eclipse treatment planning system (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) for dose delivery on IX treatment unit. A retrospective review was performed of 42 publications that reported IP rates along with lung dose, fractionation regimen, dose rate and chemotherapy. The analysis consisted of nearly thirty two hundred patients and 34 unique radiation regimens. Multivariate logistic regression was performed to determine parameters associated with IP and establish does response function. Results: The results showed very good dosimetric agreement between the GPU and CPU calculated plans. The results from SBRT study show that GPU planning system can maintain 90% target coverage while meeting all the constraints of RTOG 0631 protocol. Beam on time for Tomotherapy and flattening filter free RapidArc was much faster than for Vero or Cyberknife. Retrospective data analysis showed that lung dose and Cyclophosphomide (Cy) are both predictors of IP in TBI/TMI treatments. The dose rate was not found to be an independent risk factor for IP. The model failed to establish accurate dose response function, but the discrete data indicated a radiation dose threshold of 7.6Gy (EQD2_repair) and 120 mg/kg of Cy below which no IP cases were reported. Conclusion: The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation. The new system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing when compared to Eclipse treatment planning system for VMAT delivery. The machine optimization parameters tested for TMI cases provide a comprehensive overview of the capabilities of the treatment planning station and associated helical delivery system. The new system also proved to be dosimetrically compatible with other leading modalities for treatments of small and complicated target volumes and was even superior when treatment delivery times were compared. These finding demonstrate that the advanced treatment planning and delivery system from TomoTherapy is well suitable for treatments of complicated cases such as TMI and SRS and it's often dosimetrically and/or logistically superior to other modalities. The new planning system can easily meet the constraint of threshold lung dose established in this study. The results presented here on the capabilities of Tomotherapy and on the identified lung dose threshold provide an opportunity to explore alternative fractionation schemes without sacrificing target coverage or lung toxicity. (Abstract shortened by ProQuest.).

Monolithic natural gas storage delivery system based on sorbents

DOEpatents

Hornbostel, Marc; Krishnan, Gopala N.; Sanjurjo, Angel

2016-09-27

The invention provides methods for producing a strong, light, sorbent-based storage/dispenser system for gases and fuels. The system comprises a porous monolithic material with an adherent strong impervious skin that is capable of storing a gas under pressure in a safe and usable manner.

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

NASA Astrophysics Data System (ADS)

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

2016-06-01

This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites.This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07206a

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.

Polycation-based gene therapy: current knowledge and new perspectives.

PubMed

Tiera, Marcio J; Shi, Qin; Winnik, Françoise M; Fernandes, Julio C

2011-08-01

At present, gene transfection insufficient efficiency is a major drawback of non-viral gene therapy. The 2 main types of delivery systems deployed in gene therapy are based on viral or non-viral gene carriers. Several non-viral modalities can transfer foreign genetic material into the human body. To do so, polycation-based gene delivery methods must achieve sufficient efficiency in the transportation of therapeutic genes across various extracellular and intracellular barriers. These barriers include interactions with blood components, vascular endothelial cells and uptake by the reticuloendothelial system. Furthermore, the degradation of therapeutic DNA by serum nucleases is a potential obstacle for functional delivery to target cells. Cationic polymers constitute one of the most promising approaches to the use of viral vectors for gene therapy. A better understanding of the mechanisms by which DNA can escape from endosomes and traffic to enter the nucleus has triggered new strategies of synthesis and has revitalized research into new polycation-based systems. The objective of this review is to address the state of the art in gene therapy with synthetic and natural polycations and the latest advances to improve gene transfer efficiency in cells.

Candidate Mission from Planet Earth control and data delivery system architecture

NASA Technical Reports Server (NTRS)

Shapiro, Phillip; Weinstein, Frank C.; Hei, Donald J., Jr.; Todd, Jacqueline

1992-01-01

Using a structured, experienced-based approach, Goddard Space Flight Center (GSFC) has assessed the generic functional requirements for a lunar mission control and data delivery (CDD) system. This analysis was based on lunar mission requirements outlined in GSFC-developed user traffic models. The CDD system will facilitate data transportation among user elements, element operations, and user teams by providing functions such as data management, fault isolation, fault correction, and link acquisition. The CDD system for the lunar missions must not only satisfy lunar requirements but also facilitate and provide early development of data system technologies for Mars. Reuse and evolution of existing data systems can help to maximize system reliability and minimize cost. This paper presents a set of existing and currently planned NASA data systems that provide the basic functionality. Reuse of such systems can have an impact on mission design and significantly reduce CDD and other system development costs.

A telemedicine health care delivery system

NASA Technical Reports Server (NTRS)

Sanders, Jay H.

1991-01-01

The Interactive Telemedicine Systems (ITS) system was specifically developed to address the ever widening gap between our medical care expertise and our medical care delivery system. The frustrating reality is that as our knowledge of how to diagnose and treat medical conditions has continued to advance, the system to deliver that care has remained in an embryonic stage. This has resulted in millions of people being denied their most basic health care needs. Telemedicine utilizes an interactive video system integrated with biomedical telemetry that allows a physician at a base station specialty medical complex or teaching hospital to examine and treat a patient at multiple satellite locations, such as rural hospitals, ambulatory health centers, correctional institutions, facilities caring for the elderly, community hospital emergency departments, or international health facilities. Based on the interactive nature of the system design, the consulting physician at the base station can do a complete history and physical examination, as if the patient at the satellite site was sitting in the physician's office. This system is described.

A method for defining value in healthcare using cancer care as a model.

PubMed

Feeley, Thomas W; Fly, Helen Shafer; Albright, Heidi; Walters, Ronald; Burke, Thomas W

2010-01-01

Value-based healthcare delivery is being discussed in a variety of healthcare forums. This concept is of great importance in the reform of the US healthcare delivery system. Defining and applying the principles of value-based competition in healthcare delivery models will permit future evaluation of various delivery applications. However, there are relatively few examples of how to apply these principles to an existing care delivery system. In this article, we describe an approach for assessing the value created when treating cancer patients in a multidisciplinary care setting within a comprehensive cancer center. We describe the analysis of a multidisciplinary care center that treats head and neck cancers, and we attempt to examine how this center integrates with Porter and Teisberg's (2006) concept of value-based competition based on the results analysis. Using the relationship between outcomes and costs as the definition of value, we developed a methodology to analyze proposed outcomes for a population of patients treated using a multidisciplinary approach, and we matched those outcomes to the costs of the care provided. We present this work as a model for defining value for a subset of patients undergoing active treatment. The method can be applied not only to head and neck treatments, but to other modalities as well. Public reporting of this type of data for a variety of conditions can lead to improved competition in the healthcare marketplace and, as a result, improve outcomes and decrease health expenditures.

Biodegradable polymers as non-viral carriers for plasmid DNA delivery.

PubMed

Luten, Jordy; van Nostrum, Cornelus F; De Smedt, Stefaan C; Hennink, Wim E

2008-03-03

Gene therapy holds a great promise for the treatment of acquired and inherited diseases with a genetic origin that are currently incurable. Non-viral gene delivery systems are gaining recognition as an alternative to viral gene vectors for their potential in avoiding immunogenicity and toxicity problems inherently associated with the use of viral systems. Many cationic polymers have been studied both in vitro and in vivo for gene delivery purposes. However, in recent years there has been a focus on biodegradable carrier systems. The potential advantage of biodegradable carriers as compared to their non-degradable counterparts is their reduced toxicity and the avoidance of accumulation of the polymer in the cells after repeated administration. Also, the degradation of the polymer can be used as a tool to release the plasmid DNA into the cytosol. In this article the recent results obtained with two classes of degradable gene delivery systems, namely those based on water-soluble cationic polymers and on micro- and nanoparticles will be summarized and discussed.

Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin.

PubMed

Kong, Bong Ju; Kim, Ayoung; Park, Soo Nam

2016-08-20

In the present study, the properties of hydrogel systems based on hyaluronic acid (HA)-hydroxyethyl cellulose (HEC) were investigated for effective transdermal delivery of isoliquiritigenin (ILTG). Hydrogels were synthesized by chemical cross-linking, and network structures were characterised using scanning electron microscopy (SEM) and surface area analyser. Texture properties and swelling of HA-HEC hydrogels were found to be closely linked to cross-linker concentration and swelling medium. Water in HA-HEC hydrogels was found to exist mostly in the form of free water. The viscoelasticity and the network stabilization of the hydrogels were analysed via rheological studies. The release kinetics of the hydrogel followed Fickian diffusion mechanism. In an in vitro skin penetration study, the system substantially improved the delivery of ILTG into the skin. These results indicate that the hydrogel system composed of HA and HEC has potential as a transdermal delivery system, with cross-linking density and the swelling medium influencing the properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Insight to drug delivery aspects for colorectal cancer.

PubMed

Gulbake, Arvind; Jain, Aviral; Jain, Ashish; Jain, Ankit; Jain, Sanjay K

2016-01-14

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapies are the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor (epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC.

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

PubMed

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

2016-09-01

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

Engineering liposomal nanoparticles for targeted gene therapy.

PubMed

Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

2017-08-01

Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

How controlled release technology can aid gene delivery.

PubMed

Jo, Jun-Ichiro; Tabata, Yasuhiko

2015-01-01

Many types of gene delivery systems have been developed to enhance the level of gene expression. Controlled release technology is a feasible gene delivery system which enables genes to extend the expression duration by maintaining and releasing them at the injection site in a controlled manner. This technology can reduce the adverse effects by the bolus dose administration and avoid the repeated administration. Biodegradable biomaterials are useful as materials for the controlled release-based gene delivery technology and various biodegradable biomaterials have been developed. Controlled release-based gene delivery plays a critical role in a conventional gene therapy and genetic engineering. In the gene therapy, the therapeutic gene is released from biodegradable biomaterial matrices around the tissue to be treated. On the other hand, the intracellular controlled release of gene from the sub-micro-sized matrices is required for genetic engineering. Genetic engineering is feasible for cell transplantation as well as research of stem cells biology and medicine. DNA hydrogel containing a sequence of therapeutic gene and the exosome including the individual specific nucleic acids may become candidates for controlled release carriers. Technologies to deliver genes to cell aggregates will play an important role in the promotion of regenerative research and therapy.

Elements of Network-Based Assessment

ERIC Educational Resources Information Center

Gibson, David

2007-01-01

Elements of network-based assessment systems are envisioned based on recent advances in knowledge and practice in learning theory, assessment design and delivery, and semantic web interoperability. The architecture takes advantage of the meditating role of technology as well as recent models of assessment systems. This overview of the elements…

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

Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System.

PubMed

Onishi, Hiraku; Tokuyasu, Ayako

2016-09-13

The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Microparticles (MP) were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA), trimethyl-chitosan (TMC), and chitosan (Ch). Using salmon calcitonin (sCT) as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1)-, and Ch-based MP were produced, and their Eudragit L100 (Eud)-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. All microparticles before and after enteric coating had a submicron size (600-800 nm) and micrometer size (1300-1500 nm), respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs.

Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System

PubMed Central

Onishi, Hiraku; Tokuyasu, Ayako

2016-01-01

Background: The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Methods: Microparticles (MP) were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA), trimethyl-chitosan (TMC), and chitosan (Ch). Using salmon calcitonin (sCT) as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1)-, and Ch-based MP were produced, and their Eudragit L100 (Eud)-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. Results: All microparticles before and after enteric coating had a submicron size (600–800 nm) and micrometer size (1300–1500 nm), respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. Conclusion: The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs. PMID:27649146

Integration mechanisms and hospital efficiency in integrated health care delivery systems.

PubMed

Wan, Thomas T H; Lin, Blossom Yen-Ju; Ma, Allen

2002-04-01

This study analyzes integration mechanisms that affect system performances measured by indicators of efficiency in integrated delivery systems (IDSs) in the United States. The research question is, do integration mechanisms improve IDSs' efficiency in hospital care? American Hospital Association's Annual Survey (1998) and Dorenfest's Survey on Information Systems in Integrated Healthcare Delivery Systems (1998) were used to conduct the study, using IDS as the unit of analysis. A covariance structure equation model of the effects of system integration mechanisms on IDS performance was formulated and validated by an empirical examination of IDSs. The study sample includes 973 hospital-based integrated health care delivery systems operating in the United States, carried in the list of Dorenfests Survey on Information Systems in Integrated Health care Delivery Systems. The measurement indicators of system integration mechanisms are categorized into six related domains: informatic integration, case management, hybrid physician-hospital integration, forward integration, backward integration, and high tech medical services. The multivariate analysis reveals that integration mechanisms in system operation are positively correlated and positively affect IDSs' efficiency. The six domains of integration mechanisms account for 58.9% of the total variance in hospital performance. The service differentiation strategy such as having more high tech medical services have much stronger influences on efficiency than other integration mechanisms do. The beneficial effects of integration mechanisms have been realized in IDS performance. High efficiency in hospital care can be achieved by employing proper integration strategies in operations.

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.

Cyclodextrin based nanosponges for pharmaceutical use: a review.

PubMed

Tejashri, Gursalkar; Amrita, Bajaj; Darshana, Jain

2013-09-01

Nanosponges are a novel class of hyper-crosslinked polymer based colloidal structures consisting of solid nanoparticles with colloidal sizes and nanosized cavities. These nano-sized colloidal carriers have been recently developed and proposed for drug delivery, since their use can solubilize poorly water-soluble drugs and provide prolonged release as well as improve a drug's bioavailability by modifying the pharmacokinetic parameters of actives. Development of nanosponges as drug delivery systems, with special reference to cyclodextrin based nanosponges, is presented in this article. In the current review, attempts have been made to illustrate the features of cyclodextrin based nanosponges and their applications in pharmaceutical formulations. Special emphasis has been placed on discussing the methods of preparation, characterization techniques and applications of these novel drug delivery carriers for therapeutic purposes. Nanosponges can be referred to as solid porous particles having a capacity to load drugs and other actives into their nanocavity; they can be formulated as oral, parenteral, topical or inhalation dosage forms. Nanosponges offer high drug loading compared to other nanocarriers and are thus suitable for solving issues related to stability, solubility and delayed release of actives. Controlled release of the loaded actives and solubility enhancement of poorly water-soluble drugs are major advantages of nanosponge drug delivery systems.

Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions'.

PubMed

Akhtar, Naseem; Khan, Riaz A

2016-10-01

Skin cancer is among one of the most common human malignancies wide-spread world-over with mortality statistics rising continuously at an alarming rate. The increasing frequency of these malignancies has marked the need for adopting effective treatment plan coupled with better and site-specific delivery options for the desired therapeutic agent's availability at the affected site. The concurrent delivery approaches to cancerous tissues are under constant challenge and, as a result, are evolving and gaining advancements in terms of delivery modes, therapeutic agents and site-specificity of the therapeutics delivery. The lipid-based liposomal drug delivery is an attractive and emerging option, and which is meticulously shaping up beyond a threshold level to a promising, and viable route for the effective delivery of therapeutic agents and other required injuctions to the skin cancer. An update on liposomal delivery of chemotherapeutic agents, natural-origin compounds, photosensitizer, and DNA repair enzymes as well as other desirable and typical delivery modes employed in drug delivery and in the treatment of skin cancers is discussed in details. Moreover, liposomal delivery of nucleic acid-based therapeutics, i.e., small interfering RNA (siRNA), mRNA therapy, and RGD-linked liposomes are among the other promising novel technology under constant development. The current clinical applicability, viable clinical plans, future prospects including transport feasibility of delivery vesicles and imaging techniques in conjunction with the therapeutic agents is also discussed. The ongoing innovations in liposomal drug delivery technology for skin cancers hold promise for further development of the methodology for better, more effective and site-specific delivery as part of the better treatment plan by ensuring faster drug transport, better and full payload delivery with enough and required concentration of the dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Intrapartum fetal heart rate monitoring: evaluation of a standardized system of interpretation for prediction of metabolic acidosis at delivery and neonatal neurological morbidity.

PubMed

Soncini, Emanuele; Paganelli, Simone; Vezzani, Cristina; Gargano, Giancarlo; Giovanni Battista, La Sala

2014-09-01

To assess the ability of the intrapartum fetal heart rate interpretation system developed in 2008 by the National Institute of Child Health and Human Development (NICHD) to predict fetal metabolic acidosis at delivery and neonatal neurological morbidity. We analyzed the intrapartum fetal heart rate tracings of 314 singleton fetuses at ≥ 37 weeks using the NICHD three-tier system of interpretation: Category I (normal), Category II (indeterminate) and Category III (abnormal). Category II was further divided into Category IIA, with moderate fetal heart rate variability or accelerations, and Category IIB, with minimal/absent fetal heart rate variability and no accelerations. The presence and duration of the different patterns were compared with several clinical neonatal outcomes and with umbilical artery acid-base balance at birth. The mean values of pH and base excess decreased proportionally as tracings worsened (p < 0.001). The duration of at least 30 min for Category III tracings was highly predictive of a pH <7.00 and a base excess ≤-12 mmol/L. The same was true for the duration of Category IIB tracings that lasted for at least 50 min. Our study demonstrates that the interpretation of fetal heart rate tracings based on a strictly standardized system is closely associated with umbilical artery acid-base status at delivery.

DOD Hotline Allegations on Army Use of A Computer Contract

DTIC Science & Technology

1993-10-29

Army, the Navy, and the Defense Logistics Agency central order processing offices and reviewed delivery orders issued on the EDS contract. A...o The contracting officers used the EDS contract line item number and the description when completing a delivery order. o The central order ... processing offices used an automated data base system to match contract line item numbers from the delivery orders to the EDS contract. o EDS verified that

Distinctive features of "chronotherapeutic" and "pulsatile" drug delivery systems negating the practice of their interchangeable terminology.

PubMed

Ali, Javed; Baboota, Sanjula; Ahuja, Alka; Saigal, Nitin

2010-07-01

The term pulsatile drug delivery has often been used as a synonym to chronotherapeutic drug delivery. This needs to be given a thought as both the drug delivery systems are entirely addressing different needs of the patients as well as the intentions of the formulators being different. Chronotherapeutic systems are based completely on circadian needs and response of the body and the need of the drug to be in its maximum concentrations at a particular time of the day, the fact being supported by endless list of ailments which elicit the related symptoms at a particular time of the day. Considering the formulation approach, one does not find major differences among site-specific chronotherapeutic systems and the basic and more conventional intestinal or colon targeted systems due to the mechanism and the site of landing of drug of both being almost similar even though the intention of the formulator being different. An ideal pulsatile system is the one delivering drug in different pulses with multiple troughs in release profile. The article explores the major differences in between the two systems and highlights the need of using appropriate terminology for these individual and distinct systems catering different needs.

Lipid-associated oral delivery: Mechanisms and analysis of oral absorption enhancement.

PubMed

Rezhdo, Oljora; Speciner, Lauren; Carrier, Rebecca

2016-10-28

The majority of newly discovered oral drugs are poorly water soluble, and co-administration with lipids has proven effective in significantly enhancing bioavailability of some compounds with low aqueous solubility. Yet, lipid-based delivery technologies have not been widely employed in commercial oral products. Lipids can impact drug transport and fate in the gastrointestinal (GI) tract through multiple mechanisms including enhancement of solubility and dissolution kinetics, enhancement of permeation through the intestinal mucosa, and triggering drug precipitation upon lipid emulsion depletion (e.g., by digestion). The effect of lipids on drug absorption is currently not quantitatively predictable, in part due to the multiple complex dynamic processes that can be impacted by lipids. Quantitative mechanistic analysis of the processes significant to lipid system function and overall impact on drug absorption can aid in the understanding of drug-lipid interactions in the GI tract and exploitation of such interactions to achieve optimal lipid-based drug delivery. In this review, we discuss the impact of co-delivered lipids and lipid digestion on drug dissolution, partitioning, and absorption in the context of the experimental tools and associated kinetic expressions used to study and model these processes. The potential benefit of a systems-based consideration of the concurrent multiple dynamic processes occurring upon co-dosing lipids and drugs to predict the impact of lipids on drug absorption and enable rational design of lipid-based delivery systems is presented. Copyright © 2016 Elsevier B.V. All rights reserved.

A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer.

PubMed

Levy, Oren; Brennen, W Nathaniel; Han, Edward; Rosen, David Marc; Musabeyezu, Juliet; Safaee, Helia; Ranganath, Sudhir; Ngai, Jessica; Heinelt, Martina; Milton, Yuka; Wang, Hao; Bhagchandani, Sachin H; Joshi, Nitin; Bhowmick, Neil; Denmeade, Samuel R; Isaacs, John T; Karp, Jeffrey M

2016-06-01

Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. In this proof-of-principle study, human mesenchymal stem cells (MSCs) were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulate the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-particles (∼950 nm in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting PCa cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 PCa xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in-vitro or in-vivo. This study demonstrates a potentially promising approach to assemble a cell-based drug delivery platform, which inhibits cancer growth in-vivo without the need of genetic engineering. We envision that upon achieving efficient homing of systemically infused MSCs to cancer sites, this MSC-based platform may be developed into an effective, systemic 'Trojan Horse' therapy for targeted delivery of therapeutic agents to sites of metastatic PCa. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuropeptide Y Y1 receptors meditate targeted delivery of anticancer drug with encapsulated nanoparticles to breast cancer cells with high selectivity and its potential for breast cancer therapy.

PubMed

Li, Juan; Shen, Zheyu; Ma, Xuehua; Ren, Wenzhi; Xiang, Lingchao; Gong, An; Xia, Tian; Guo, Junming; Wu, Aiguo

2015-03-11

By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.

Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system.

PubMed

Zeniya, Satoshi; Kuwahara, Hiroya; Daizo, Kaiichi; Watari, Akihiro; Kondoh, Masuo; Yoshida-Tanaka, Kie; Kaburagi, Hidetoshi; Asada, Ken; Nagata, Tetsuya; Nagahama, Masahiro; Yagi, Kiyohito; Yokota, Takanori

2018-05-17

Within the field of RNA therapeutics, antisense oligonucleotide-based therapeutics are a potentially powerful means of treating intractable diseases. However, if these therapeutics are used for the treatment of neurological disorders, safe yet efficient methods of delivering antisense oligonucleotides across the blood-brain barrier to the central nervous system must be developed. Here, we examined the use of angubindin-1, a binder to the tricellular tight junction, to modulate paracellular transport between brain microvascular endothelial cells in the blood-brain barrier for the delivery of antisense oligonucleotides to the central nervous system. This proof-of-concept study demonstrated that intravenously injected angubindin-1 increased the permeability of the blood-brain barrier and enabled transient delivery of subsequently administered antisense oligonucleotides into the mouse brain and spinal cord, leading to silencing of a target RNA without any overt adverse effects. We also found that two bicellular tight junction modulators did not produce such a silencing effect, suggesting that the tricellular tight junction is likely a better target for the delivery of antisense oligonucleotides than the bicellular tight junction. Our delivery strategy of modulating the tricellular tight junction in the blood-brain barrier via angubindin-1 provides a novel avenue of research for the development of antisense oligonucleotide-based therapeutics for the treatment of neurological disorders. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study

PubMed Central

LaPelle, Nancy R; Luckmann, Roger; Simpson, E Hatheway; Martin, Elaine R

2006-01-01

Background Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. Methods Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. Results Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. Conclusion Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners. PMID:16597331

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

PubMed

Ge, Yanxiu; Ma, Yakun; Li, Lingbing

2016-10-01

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

Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery.

PubMed

Llinàs, Maria C; Martínez-Edo, Gabriel; Cascante, Anna; Porcar, Irene; Borrós, Salvador; Sánchez-García, David

2018-11-01

A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide-polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy.

Standards for Libraries Within Regional Library Systems in Saskatchewan.

ERIC Educational Resources Information Center

Saskatchewan Library Association, Regina.

These quantitative standards for the delivery of library services to a dispersed population, which were developed by the Saskatchewan Library Association, are based on the decentralized delivery of library services backed up by the centralized provision of technical services, resource people, and special collections in Saskatchewan. The roles of…

Zero-order drug delivery system: theory and preliminary testing.

PubMed

Brooke, D; Washkuhn, R J

1977-02-01

A new approach to zero-order drug delivery that includes geometric factors is described. An experimental device based on the theory was tested by following the release of stearic acid into ethanol. Three separate trials indicated that the solid was released via a zero-order process in a reproducible manner.

Microprocessor Based Temperature Control of Liquid Delivery with Flow Disturbances.

ERIC Educational Resources Information Center

Kaya, Azmi

1982-01-01

Discusses analytical design and experimental verification of a PID control value for a temperature controlled liquid delivery system, demonstrating that the analytical design techniques can be experimentally verified by using digital controls as a tool. Digital control instrumentation and implementation are also demonstrated and documented for…

42 CFR 1003.101 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., such as a prospective payment system; and (b) In the case of a claim based on costs, any entry or...; or (4) Incentives given to individuals to promote the delivery of preventive care services where the delivery of such services is not tied (directly or indirectly) to the provision of other services...

42 CFR 1003.101 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., such as a prospective payment system; and (b) In the case of a claim based on costs, any entry or...; or (4) Incentives given to individuals to promote the delivery of preventive care services where the delivery of such services is not tied (directly or indirectly) to the provision of other services...

Space-Based Solar Power Conversion and Delivery Systems Study. Volume 1: Executive Summary

NASA Technical Reports Server (NTRS)

1977-01-01

The research concerning space-based solar power conversion and delivery systems is summarized. The potential concepts for a photovoltaic satellite solar power system was studied with emphasis on ground output power levels of 5,000 MW and 10,000 MW. A power relay satellite, and certain aspects of the economics of these systems were also studied. A second study phase examined in greater depth the technical and economic aspects of satellite solar power systems. Throughout this study, the focus was on the economics of satellite solar power. The results indicate technical feasibility of the concept, and provide a preliminary economic justification for the first phase of a substantial development program. A development program containing test satellites is recommended. Also, development of alternative solar cell materials (other than silicon) is recommended.

TIL system with nonlinear phase conjugation

NASA Astrophysics Data System (ADS)

Khizhnyak, Anatoliy; Markov, Vladimir

2007-09-01

Efficient laser beam delivery on a distant target remains a key problem for practical implementation of tactical laser systems. Since the conventional target-in-the-loop (TIL) concept is generally not effective in such operational environments, new solutions are needed. In this report we discuss an innovative approach for effective compensation of laser beam aberrations in TIL systems. It is based on a recently devised technique that combines optical phase conjugation (OPC) with a TIL system for effective hot-spot formation. The proposed method should enable delivery of enhanced density laser energy to a target within a finite number of iteration cycles. Using the model based on an analogy between the TIL system and laser resonator, pointing of the laser beam on the target is performed at the image plane, resulting in reduced hot-spot formation time.

Review of Spatial-Database System Usability: Recommendations for the ADDNS Project

DTIC Science & Technology

2007-12-01

basic GIS background information , with a closer look at spatial databases. A GIS is also a computer- based system designed to capture, manage...foundation for deploying enterprise-wide spatial information systems . According to Oracle® [18], it enables accurate delivery of location- based services...Toronto TR 2007-141 Lanter, D.P. (1991). Design of a lineage- based meta-data base for GIS. Cartography and Geographic Information Systems , 18

Increase in facility-based deliveries associated with a maternal health voucher programme in informal settlements in Nairobi, Kenya

PubMed Central

Bellows, Ben; Kyobutungi, Catherine; Mutua, Martin Kavao; Warren, Charlotte; Ezeh, Alex

2013-01-01

Objective To measure whether there was an association between the introduction of an output-based voucher programme and the odds of a facility-based delivery in two Nairobi informal settlements. Data sources Nairobi Urban Health and Demographic Surveillance System (NUHDSS) and two cross-sectional household surveys in Korogocho and Viwandani informal settlements in 2004–05 and 2006–08. Methods Odds of facility-based delivery were estimated before and after introduction of an output-based voucher. Supporting NUHDSS data were used to determine whether any trend in maternal health care was coincident with immunizations, a non-voucher outpatient service. As part of NUHDSS, households in Korogocho and Viwandani reported place of delivery and the presence of a skilled birth attendant (2003–10) and vaccination coverage (2003–09). A detailed maternal and child health (MCH) tool was added to NUHDSS (September 2006–10). Prospective enrolment in NUHDSS-MCH was conditional on having a newborn after September 2006. In addition to recording mother’s place of delivery, NUHDSS-MCH recorded the use of the voucher. Findings There were significantly greater odds of a facility-based delivery among respondents during the voucher programme compared with similar respondents prior to voucher launch. Testing whether unrelated outpatient care also increased, a falsification exercise found no significant increase in immunizations for children 12–23 months of age in the same period. Although the proportion completing any antenatal care (ANC) visit remained above 95% of all reported pregnancies and there was a significant increase in facility-based deliveries, the proportion of women completing 4+ ANC visits was significantly lower during the voucher programme. Conclusions A positive association was observed between vouchers and facility-based deliveries in Nairobi. Although there is a need for higher quality evidence and validation in future studies, this statistically significant and policy relevant finding suggests that increases in facility-based deliveries can be achieved through output-based finance models that target subsidies to underserved populations. PMID:22437506

A space transportation system operations model

NASA Technical Reports Server (NTRS)

Morris, W. Douglas; White, Nancy H.

1987-01-01

Presented is a description of a computer program which permits assessment of the operational support requirements of space transportation systems functioning in both a ground- and space-based environment. The scenario depicted provides for the delivery of payloads from Earth to a space station and beyond using upper stages based at the station. Model results are scenario dependent and rely on the input definitions of delivery requirements, task times, and available resources. Output is in terms of flight rate capabilities, resource requirements, and facility utilization. A general program description, program listing, input requirements, and sample output are included.

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

PubMed

Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

2016-01-01

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

Designing liposomal adjuvants for the next generation of vaccines.

PubMed

Perrie, Yvonne; Crofts, Fraser; Devitt, Andrew; Griffiths, Helen R; Kastner, Elisabeth; Nadella, Vinod

2016-04-01

Liposomes not only offer the ability to enhance drug delivery, but can effectively act as vaccine delivery systems and adjuvants. Their flexibility in size, charge, bilayer rigidity and composition allow for targeted antigen delivery via a range of administration routes. In the development of liposomal adjuvants, the type of immune response promoted has been linked to their physico-chemical characteristics, with the size and charge of the liposomal particles impacting on liposome biodistribution, exposure in the lymph nodes and recruitment of the innate immune system. The addition of immunostimulatory agents can further potentiate their immunogenic properties. Here, we outline the attributes that should be considered in the design and manufacture of liposomal adjuvants for the delivery of sub-unit and nucleic acid based vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

Magnetic nanoparticle drug delivery systems for targeting tumor

NASA Astrophysics Data System (ADS)

Mody, Vicky V.; Cox, Arthur; Shah, Samit; Singh, Ajay; Bevins, Wesley; Parihar, Harish

2014-04-01

Tumor hypoxia, or low oxygen concentration, is a result of disordered vasculature that lead to distinctive hypoxic microenvironments not found in normal tissues. Many traditional anti-cancer agents are not able to penetrate into these hypoxic zones, whereas, conventional cancer therapies that work by blocking cell division are not effective to treat tumors within hypoxic zones. Under these circumstances the use of magnetic nanoparticles as a drug delivering agent system under the influence of external magnetic field has received much attention, based on their simplicity, ease of preparation, and ability to tailor their properties for specific biological applications. Hence in this review article we have reviewed current magnetic drug delivery systems, along with their application and clinical status in the field of magnetic drug delivery.

Improving Health-care Delivery for Post-Traumatic Stress Disorder: An Interrelated Approach Leveraging Systems Engineering and Optimization

DTIC Science & Technology

2011-09-01

AND EXPERIMENTAL DESIGN ..........................................................................................................31   1...PRIMARY RESERCH QUESTION ............................................................41   C.   OBJECTIVE ACHIEVEMENT...Based Outpatient Clinic CPT Cognitive Processing Therapy DISE Distributed Information Systems Experimentation EBT Evidence-Based Treatment GMC

Recent advances in mechanism-based chemotherapy drug-siRNA pairs in co-delivery systems for cancer: A review.

PubMed

Wang, Mingfang; Wang, Jinyu; Li, Bingcheng; Meng, Lingxin; Tian, Zhaoxing

2017-09-01

Co-delivery of chemotherapy drugs and siRNA for cancer therapy has achieved remarkable results according to synergistic/combined antitumor effects, and is recognized as a promising therapeutic modality. However, little attention has been paid to the extremely complex mechanisms of chemotherapy drug-siRNA pairs during co-delivery process. Proper selection of chemotherapy drug-siRNA pairs is beneficial for achieving desirable cancer therapeutic effects. Exploring the inherent principles during chemotherapy drug-siRNA pair selection for co-delivery would greatly enhanced therapeutic efficiency. To achieve ideal results, this article will systematically review current different mechanism-based chemotherapy drug-siRNA pairs for co-delivery in cancer treatment. Large-scale library screening of recent different chemotherapy drug-siRNA pairs for co-delivery would help to establish the chemotherapy drug-siRNA pair selection principle, which could pave the way for co-delivery of chemotherapy drugs and siRNA for cancer treatment in clinic. Following the inherent principle of chemotherapy drug-siRNA pair, more effective co-delivery vectors can be designed in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy.

PubMed

Mou, Quanbing; Ma, Yuan; Zhu, Xinyuan; Yan, Deyue

2016-05-28

Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

PubMed Central

Fan, Yuchen; Moon, James J.

2016-01-01

Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen-based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co-delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens. PMID:27038091

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.

Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies.

PubMed

Estracanholli, Eder André; Praça, Fabíola Silva Garcia; Cintra, Ana Beatriz; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

2014-12-01

Liquid crystalline systems of monoolein/water could be a promising approach for the delivery of celecoxib (CXB) to the skin because these systems can sustain drug release, improve drug penetration into the skin layers and minimize side effects. This study evaluated the potential of these systems for the delivery of CXB into the skin based on in vitro drug release and skin permeation studies. The amount of CXB that permeated into and/or was retained in the skin was assayed using an HPLC method. Polarizing light microscopy studies showed that liquid crystalline systems of monoolein/water were formed in the presence of CXB, without any changes in the mesophases. The liquid crystalline systems decreased drug release when compared to control solution. Drug release was independent of the initial water content of the systems and CXB was released from cubic phase systems, irrespective of the initial water content. The systems released the CXB following zero-order release kinetics. In vitro drug permeation studies showed that cubic phase systems allowed drug permeation and retention in the skin layers. Cubic phase systems of monoolein/water may be promising vehicles for the delivery of CXB in/through the skin because it improved CXB skin permeation compared with the control solution.

Application of Various Types of Liposomes in Drug Delivery Systems

PubMed Central

Alavi, Mehran; Karimi, Naser; Safaei, Mohsen

2017-01-01

Liposomes, due to their various forms, require further exploration. These structures can deliver both hydrophilic and hydrophobic drugs for cancer, antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines, enzymes and genetic elements. Preparation of liposomes results in different properties for these systems. In addition, based on preparation methods, liposomes types can be unilamellar, multilamellar and giant unilamellar; however, there are many factors and difficulties that affect the development of liposome drug delivery structure. In the present review, we discuss some problems that impact drug delivery by liposomes. In addition, we discuss a new generation of liposomes, which is utilized for decreasing the limitation of the conventional liposomes. PMID:28507932

Viruses, Artificial Viruses and Virus-Based Structures for Biomedical Applications.

PubMed

van Rijn, Patrick; Schirhagl, Romana

2016-06-01

Nanobiomaterials such as virus particles and artificial virus particles offer tremendous opportunities to develop new biomedical applications such as drug- or gene-delivery, imaging and sensing but also improve understanding of biological mechanisms. Recent advances within the field of virus-based systems give insights in how to mimic viral structures and virus assembly processes as well as understanding biodistribution, cell/tissue targeting, controlled and triggered disassembly or release and circulation times. All these factors are of high importance for virus-based functional systems. This review illustrates advances in mimicking and enhancing or controlling these aspects to a high degree toward delivery and imaging applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging

PubMed Central

Li, Yunkun; Li, Yachao; Zhang, Xiao; Xu, Xianghui; Zhang, Zhijun; Hu, Cheng; He, Yiyan; Gu, Zhongwei

2016-01-01

Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum-based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms. PMID:27375780

Fabrication Methods and Performance of Low-Permeability Microfluidic Components for a Miniaturized Wearable Drug Delivery System

PubMed Central

Mescher, Mark J.; Swan, Erin E. Leary; Fiering, Jason; Holmboe, Maria E.; Sewell, William F.; Kujawa, Sharon G.; McKenna, Michael J.; Borenstein, Jeffrey T.

2010-01-01

In this paper, we describe low-permeability components of a microfluidic drug delivery system fabricated with versatile micromilling and lamination techniques. The fabrication process uses laminate sheets which are machined using XY milling tables commonly used in the printed-circuit industry. This adaptable platform for polymer microfluidics readily accommodates integration with silicon-based sensors, printed-circuit, and surface-mount technologies. We have used these methods to build components used in a wearable liquid-drug delivery system for in vivo studies. The design, fabrication, and performance of membrane-based fluidic capacitors and manual screw valves provide detailed examples of the capability and limitations of the fabrication method. We demonstrate fluidic capacitances ranging from 0.015 to 0.15 μL/kPa, screw valves with on/off flow ratios greater than 38 000, and a 45× reduction in the aqueous fluid loss rate to the ambient due to permeation through a silicone diaphragm layer. PMID:20852729

Cell Membrane-formed Nanovesicles for Disease-Targeted Delivery

PubMed Central

Gao, Jin; Chu, Dafeng; Wang, Zhenjia

2016-01-01

Vascular inflammation is underlying components of most diseases. To target inflamed vasculature, nanoparticles are commonly engineered by conjugating antibody to the nanoparticle surface, but this bottom-up approach could affect nanoparticle targeting and therapeutic efficacy in complex, physiologically related systems. During vascular inflammation endothelium via the NF-κB pathway instantly upregulates intercellular adhesion molecule 1 (ICAM-1) which binds integrin β2 on neutrophil membrane. Inspired by this interaction, we created a nanovesicle-based drug delivery system using nitrogen cavitation which rapidly disrupts activated neutrophils to make cell membrane nanovesicles. Studies using intravital microscopy of live mouse cremaster venules showed that these vesicles can selectively bind inflamed vasculature because they possess intact targeting molecules of integrin β2. Administering of nanovesicles loaded with TPCA-1 (a NF-κB inhibitor) markedly mitigated mouse acute lung inflammation. Our studies reveal a new top-down strategy for directly employing a diseased tissue to produce biofunctional nanovesicle-based drug delivery systems potentially applied to treat various diseases. PMID:26778696

Novel vaginal drug delivery system: deformable propylene glycol liposomes-in-hydrogel.

PubMed

Vanić, Željka; Hurler, Julia; Ferderber, Kristina; Golja Gašparović, Petra; Škalko-Basnet, Nataša; Filipović-Grčić, Jelena

2014-03-01

Deformable propylene glycol-containing liposomes (DPGLs) incorporating metronidazole or clotrimazole were prepared and evaluated as an efficient drug delivery system to improve the treatment of vaginal microbial infections. The liposome formulations were optimized based on sufficient trapping efficiencies for both drugs and membrane elasticity as a prerequisite for successful permeability and therapy. An appropriate viscosity for vaginal administration was achieved by incorporating the liposomes into Carbopol hydrogel. DPGLs were able to penetrate through the hydrogel network more rapidly than conventional liposomes. In vitro studies of drug release from the liposomal hydrogel under conditions simulating human treatment confirmed sustained and diffusion-based drug release. Characterization of the rheological and textural properties of the DPGL-containing liposomal hydrogels demonstrated that the incorporation of DPGLs alone had no significant influence on mechanical properties of hydrogels compared to controls. These results support the great potential of DPGL-in-hydrogel as an efficient delivery system for the controlled and sustained release of antimicrobial drugs in the vagina.

Stories and Music for Adolescent/Young Adult Resilience During Transplant Partnerships: Strategies to Support Academic-Clinical Nurse Collaborations in Behavioral Intervention Studies.

PubMed

Hendricks-Ferguson, Verna L; Barnes, Yvonne J; Cherven, Brooke; Stegenga, Kristin; Roll, Lona; Docherty, Sharon L; Haase, Joan E

Evidence-based nursing is in the forefront of healthcare delivery systems. Federal and state agencies, academic institutions, and healthcare delivery systems recognize the importance of nursing research. This article describes the mechanisms that facilitate nursing partnerships yielding high-level research outcomes in a clinical setting. A phase-II multicenter behavioral intervention study with pediatric stem cell transplant patients was the context of this academic/clinical research partnership. Strategies to develop and maintain this partnership involved a thorough understanding of each nurse's focus and barriers. A variety of communication plans and training events maximized preexisting professional networks. Academic/clinical nurses' discussions identified barriers to the research process, the most significant being role conflict. Communication and validation of benefits to each individual and institution facilitated the research process during challenging times. Establishing strong academic/clinical partnerships should lead to evidence-based research outcomes for the nursing profession, healthcare delivery systems, and patients and families.

Development of a health care systems curriculum.

PubMed

Pruitt, Zachary; Mhaskar, Rahul; Kane, Bryan G; Barraco, Robert D; DeWaay, Deborah J; Rosenau, Alex M; Bresnan, Kristin A; Greenberg, Marna Rayl

2017-01-01

There is currently no gold standard for delivery of systems-based practice in medical education, and it is challenging to incorporate into medical education. Health systems competence requires physicians to understand patient care within the broader health care system and is vital to improving the quality of care clinicians provide. We describe a health systems curriculum that utilizes problem-based learning across 4 years of systems-based practice medical education at a single institution. This case study describes the application of a problem-based learning approach to system-based practice medical education. A series of behavioral statements, called entrustable professional activities, was created to assess student health system competence. Student evaluation of course curriculum design, delivery, and assessment was provided through web-based surveys. To meet competency standards for system-based practice, a health systems curriculum was developed and delivered across 4 years of medical school training. Each of the health system lectures and problem-based learning activities are described herein. The majority of first and second year medical students stated they gained working knowledge of health systems by engaging in these sessions. The majority of the 2016 graduating students (88.24%) felt that the course content, overall, prepared them for their career. A health systems curriculum in undergraduate medical education using a problem-based learning approach is feasible. The majority of students learning health systems curriculum through this format reported being prepared to improve individual patient care and optimize the health system's value (better care and health for lower cost).

Recent advances in Optical Computed Tomography (OCT) imaging system for three dimensional (3D) radiotherapy dosimetry

NASA Astrophysics Data System (ADS)

Rahman, Ahmad Taufek Abdul; Farah Rosli, Nurul; Zain, Shafirah Mohd; Zin, Hafiz M.

2018-01-01

Radiotherapy delivery techniques for cancer treatment are becoming more complex and highly focused, to enable accurate radiation dose delivery to the cancerous tissue and minimum dose to the healthy tissue adjacent to tumour. Instrument to verify the complex dose delivery in radiotherapy such as optical computed tomography (OCT) measures the dose from a three-dimensional (3D) radiochromic dosimeter to ensure the accuracy of the radiotherapy beam delivery to the patient. OCT measures the optical density in radiochromic material that changes predictably upon exposure to radiotherapy beams. OCT systems have been developed using a photodiode and charged coupled device (CCD) as the detector. The existing OCT imaging systems have limitation in terms of the accuracy and the speed of the measurement. Advances in on-pixel intelligence CMOS image sensor (CIS) will be exploited in this work to replace current detector in OCT imaging systems. CIS is capable of on-pixel signal processing at a very fast imaging speed (over several hundred images per second) that will allow improvement in the 3D measurement of the optical density. The paper will review 3D radiochromic dosimeters and OCT systems developed and discuss how CMOS based OCT imaging will provide accurate and fast optical density measurements in 3D. The paper will also discuss the configuration of the CMOS based OCT developed in this work and how it may improve the existing OCT system.

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

PubMed

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

2016-02-01

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

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

PubMed

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

2018-02-05

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

Development of a new LDL-based transport system for hydrophobic/amphiphilic drug delivery to cancer cells.

PubMed

Huntosova, Veronika; Buzova, Diana; Petrovajova, Dana; Kasak, Peter; Nadova, Zuzana; Jancura, Daniel; Sureau, Franck; Miskovsky, Pavol

2012-10-15

Low-density lipoproteins (LDL), a natural in vivo carrier of cholesterol in the vascular system, play a key role in the delivery of hydrophobic/amphiphilic photosensitizers to tumor cells in photodynamic therapy of cancer. To make this delivery system even more efficient, we have constructed a nano-delivery system by coating of LDL surface by dextran. Fluorescence spectroscopy, confocal fluorescence imaging, stopped-flow experiments and flow-cytometry were used to characterize redistribution of hypericin (Hyp), a natural occurring potent photosensitizer, loaded in LDL/dextran complex to free LDL molecules as well as to monitor cellular uptake of Hyp by U87-MG cells. It is shown that the redistribution process of Hyp between LDL molecules is significantly suppressed by dextran coating of LDL surface. The modification of LDL molecules by dextran does not inhibit their recognition by cellular LDL receptors and U-87 MG cellular uptake of Hyp loaded in LDL/dextran complex appears to be similar to that one observed for Hyp transported by unmodified LDL particles. Thus, it is proposed that dextran modified LDL molecules could be used as a basis for construction of a drug transport system for targeted delivery of hydrophobic/amphiphilic drugs to cancer cells expressing high level of LDL receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Water-soluble polymers bearing phosphorylcholine group and other zwitterionic groups for carrying DNA derivatives.

PubMed

Lin, Xiaojie; Ishihara, Kazuhiko

2014-01-01

Water-soluble polymers with equal positive and negative charges in the same monomer unit, such as the phosphorylcholine group and other zwitterionic groups, exhibit promising potential in gene delivery with appreciable transfection efficiency, compared with the traditional poly(ethylene glycol)-based polycation-gene complexes. These zwitterionic polymers with various architectural structures and properties have been synthesized by various polymerization methods, such as conventional radical polymerization, atom-transfer radical-polymerization, reversible addition-fragmentation chain-transfer polymerization, and nitroxide-mediated radical polymerization. These techniques have been used to efficiently facilitate gene therapy by fabrication of non-viral vectors with high cytocompatibility, large gene-carrying capacity, effective cell-membrane permeability, and in vivo gene-loading/releasing functionality. Zwitterionic polymer-based gene delivery vectors systems can be categorized into soluble-polymer/gene mixing, molecular self-assembly, and polymer-gene conjugation systems. This review describes the preparation and characterization of various zwitterionic polymer-based gene delivery vectors, specifically water-soluble phospholipid polymers for carrying gene derivatives.

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.

Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus

PubMed Central

Park, Joo Youn; Moon, Bo Youn; Park, Juw Won; Thornton, Justin A.; Park, Yong Ho; Seo, Keun Seok

2017-01-01

Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of virulence genes by generalized transduction. In this study, we demonstrate genetic engineering strategies to overcome these shortcomings by integrating CRISPR/Cas9 system into a temperate phage genome, removing major virulence genes from the host chromosome, and expanding host specificity of the phage by complementing tail fiber protein. This significantly improved the efficacy and safety of CRISPR/Cas9 antimicrobials to therapeutic levels in both in vitro and in vivo assays. The genetic engineering tools and resources established in this study are expected to provide an efficacious and safe CRISPR/Cas9 antimicrobial, broadly applicable to Staphylococcus aureus. PMID:28322317

Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus.

PubMed

Park, Joo Youn; Moon, Bo Youn; Park, Juw Won; Thornton, Justin A; Park, Yong Ho; Seo, Keun Seok

2017-03-21

Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of virulence genes by generalized transduction. In this study, we demonstrate genetic engineering strategies to overcome these shortcomings by integrating CRISPR/Cas9 system into a temperate phage genome, removing major virulence genes from the host chromosome, and expanding host specificity of the phage by complementing tail fiber protein. This significantly improved the efficacy and safety of CRISPR/Cas9 antimicrobials to therapeutic levels in both in vitro and in vivo assays. The genetic engineering tools and resources established in this study are expected to provide an efficacious and safe CRISPR/Cas9 antimicrobial, broadly applicable to Staphylococcus aureus.

Structurally flexible triethanolamine-core poly(amidoamine) dendrimers as effective nanovectors to deliver RNAi-based therapeutics.

PubMed

Liu, Xiaoxuan; Liu, Cheng; Catapano, Carlo V; Peng, Ling; Zhou, Jiehua; Rocchi, Palma

2014-01-01

RNAi-based nucleic acid molecules have attracted considerable attention as compelling therapeutics providing safe and competent delivery systems are available. Dendrimers are emerging as appealing nanocarriers for nucleic acid delivery thanks to their unique well-defined architecture and the resulting cooperativity and multivalency confined within a nanostructure. The present review offers a brief overview of the structurally flexible triethanolamine-core poly(amidoamine) (PAMAM) dendrimers developed in our group as nanovectors for the delivery of RNAi therapeutics. Their excellent activity for delivering different RNAi therapeutics in various disease models in vitro and in vivo will be highlighted here. © 2013.

Pectin-based oral drug delivery to the colon.

PubMed

Sande, Sverre Arne

2005-05-01

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.

Hydroxyapatite-magnetite-MWCNT nanocomposite as a biocompatible multifunctional drug delivery system for bone tissue engineering.

PubMed

Pistone, Alessandro; Iannazzo, Daniela; Panseri, Silvia; Montesi, Monica; Tampieri, Anna; Galvagno, Signorino

2014-10-24

New magnetic hydroxyapatite-based nanomaterials as bone-specific systems for controlled drug delivery have been synthesized. The synthesized hydroxyapatite, HA, decorated with magnetite nanoparticles by a deposition method (HA/Fe3O4) and the nanocomposite system obtained using magnetic multi-walled carbon nanotubes (HA/MWCNT/Fe3O4) as a filler for HA have been characterized by chemical and morphological analyses, and their biological behavior was investigated. The systems have also been doped with clodronate in order to combine the effect of bone biomineralization induced by hydroxyapatite-based composites with the decrease of osteoclast formation induced by the drug. An analysis of the preosteoclastic RAW264.7 cell proliferation by MTT assay confirmed the high biocompatibility of the three systems. TRAP staining of RAW 264.7 conditioned with sRAKL to induce osteoclastogenesis, cultured in the presence of the systems doped and undoped with clodronate, showed the inhibitory effect of clodronate after we counted the MNC TRAP(+)cells but only in the osteoclast formation; in particular, the system HA/Fe3O4-Clo exerted a high inhibitory effect compared to the drug alone. These results demonstrate that the synthesized nanocomposites are a biocompatible magnetic drug delivery system and can represent a useful multimodal platform for applications in bone tissue engineering.

Drug Delivery in Cancer Therapy, Quo Vadis?

PubMed

Lu, Zheng-Rong; Qiao, Peter

2018-03-22

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

Implementation of wireless power transfer and communications for an implantable ocular drug delivery system.

PubMed

Tang, T B; Smith, S; Flynn, B W; Stevenson, J T M; Gundlach, A M; Reekie, H M; Murray, A F; Renshaw, D; Dhillon, B; Ohtori, A; Inoue, Y; Terry, J G; Walton, A J

2008-09-01

A wireless power transfer and communication system based on near-field inductive coupling has been designed and implemented. The feasibility of using such a system to remotely control drug release from an implantable drug delivery system is addressed. The architecture of the wireless system is described and the signal attenuation over distance in both water and phosphate buffered saline is studied. Additionally, the health risk due to exposure to radio frequency (RF) radiation is examined using a biological model. The experimental results demonstrate that the system can trigger the release of drug within 5 s, and that such short exposure to RF radiation does not produce any significant (

Interactions of sugar-based bolaamphiphiles with biomimetic systems of plasma membranes.

PubMed

Nasir, Mehmet Nail; Crowet, Jean-Marc; Lins, Laurence; Obounou Akong, Firmin; Haudrechy, Arnaud; Bouquillon, Sandrine; Deleu, Magali

2016-11-01

Glycolipids constitute a class of molecules with various biological activities. Among them, sugar-based bolaamphiphiles characterized by their biocompatibility, biodegradability and lower toxicity, became interesting for the development of efficient and low cost lipid-based drug delivery systems. Their activity seems to be closely related to their interactions with the lipid components of the plasma membrane of target cells. Despite many works devoted to the chemical synthesis and characterization of sugar-based bolaamphiphiles, their interactions with plasma membrane have not been completely elucidated. In this work, two sugar-based bolaamphiphiles differing only at the level of their sugar residues were chemically synthetized. Their interactions with membranes have been investigated using model membranes containing or not sterol and with in silico approaches. Our findings indicate that the nature of sugar residues has no significant influence for their membrane interacting properties, while the presence of sterol attenuates the interactions of both bolaamphiphiles with the membrane systems. The understanding of this distinct behavior of bolaamphiphiles towards sterol-containing membrane systems could be useful for their applications as drug delivery systems. Copyright © 2016. Published by Elsevier B.V.

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.

Ultraviolet, visible, and infrared laser delivery using laser-to-fiber coupling via a grazing-incidence-based hollow taper

NASA Astrophysics Data System (ADS)

Ilev, Ilko K.; Waynant, Ronald W.

2001-01-01

We present a novel all-optical-waveguide method for ultraviolet (UV), visible (VIS) and infrared (IR) laser delivery including a lens-free method of laser-to-fiber coupling using a simple uncoated glass hollow taper. Based on the grazing incidence effect, the hollow taper provides a way of direct launching, without any intermediate focusing elements, high power laser radiation into delivery fibers. Because of the mutual action of the nearly parallel laser excitation, the mode coupling process, and mode filtering effect, the hollow taper serves as a mode converter that transforms the highly multimode profile of the input laser emission into a high-quality Gaussian-shaped profile at the taper output. When the grazing incidence effect of the taper is applied to laser delivery, the maintenance of high reflectance coefficients in a wide spectral region allows to utilize the same uncoated hollow taper for laser radiation in the UV, VIS and IR ranges. Applying the experimental hollow-taper based delivery systems, we obtain high laser- to-taper and taper-to-fiber coupling efficiencies.

Solid Footing.

ERIC Educational Resources Information Center

Franzen, Mark; Gorrell, Kyle

2002-01-01

Based on one school district's experience, discusses raised access flooring systems for schools. Addresses the nuts and bolts of such flooring systems, integrating an air delivery system below the flooring, advantages of floor-level air supply, and design issues. (EV)

Perceptions of International Students on Service Quality Delivery in a Malaysian Public University

ERIC Educational Resources Information Center

Njie, Baboucarr; Asimiran, Soaib; Baki, Roselan

2012-01-01

Purpose: The purpose of this study is to explore the perceptions of international students of service quality delivery (SQD) in a Malaysian public university. Design/methodology/approach: The study was limited to the University's immediate physical environment and its associated human and systems-based services. The physical environment in this…

TOC/DOC: "It Has Changed the Way I Do Science".

ERIC Educational Resources Information Center

Douglas, Kimberly; Roth, Dana L.

1997-01-01

Describes a user-based automated service developed at the California Institute of Technology that combines access to journal article databases with an in-house document delivery system. TOC/DOC (Tables of Contents/Document Delivery) has undergone a conceptual change from a catalog of locally-held journal articles to a broader, more retrospective…