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Sample records for acid delivery system

  1. Advancing polymeric delivery systems amidst a nucleic acid therapy renaissance

    PubMed Central

    Burke, Paul A.; Pun, Suzie H.; Reineke, Theresa M.

    2013-01-01

    Nucleic acid therapeutics are attracting renewed interest due to recent clinical advances and product approvals. Most leading programs use chemical conjugates, or viral vectors in the case of gene therapy, while several use no delivery system at all. Polymer systems, which have been at the periphery of this renaissance, often involve greater molecular complexity than competing approaches, which must be justified by their advantages. Advanced analytical methods, along with biological tools for characterizing biotransformation and intracellular trafficking, are increasingly being applied to nucleic acid delivery systems including those based on polymers. These frontiers of investigation create the opportunity for an era where highly defined polymer compositions are optimized based on mechanistic insights in a way that has not been previously possible, offering the prospect of greater differentiation from alternatives. This will require integrated collaboration between polymer scientists and those from other disciplines. PMID:24683504

  2. Skin delivery of ferulic acid from different vesicular systems.

    PubMed

    Chen, Ming; Liu, Xiangli; Fahr, Alfred

    2010-10-01

    The aim of the present research is to evaluate the skin delivery capabilities of different vesicular systems, including conventional liposomes (CL), Tween 80-based deformable liposomes (DL), invasomes (INS) and ethosomes bearing ferulic acid (FA) being an antioxidant exhibiting a wide range of therapeutic effects against various diseases. All of the test formulations were characterized for particle size distribution, zeta-potential, vesicular shape and surface morphology, in vitro human skin permeation and skin deposition. Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) defined that all of liposomal vesicles were almost spherical, displaying unilamellar structures with low polydispersity (PDI < 0.2) and nanometric size range (z-average no more than 150 nm). In addition, all the vesicular systems except conventional liposomes were negatively charged to a certain extent. In vitro skin permeation and skin deposition experiments demonstrated that the permeation profile of ferulic acid through human stratum corneum epidermis membrane (SCE) and the drug deposition in skin were both improved significantly using these vesicular liposomal systems. Permeation and skin deposition enhancing effect was highlighted by the ethosomal system containing 18.0 mg/ml of ferulic acid with an significantly (P < 0.01) enhanced skin flux (267.8 +/- 16.77 microg/cm2/h) and skin drug deposition (51.67 +/- 1.94 microg/cm2), which was 75 times and 7.3 times higher than those of ferulic acid from saturated PBS (pH 7.4) solution, respectively. This study demonstrated that ethosomes are promising vesicular carriers for delivering ferulic acid into or across the skin.

  3. Drug delivery systems based on nucleic acid nanostructures.

    PubMed

    de Vries, Jan Willem; Zhang, Feng; Herrmann, Andreas

    2013-12-10

    The field of DNA nanotechnology has progressed rapidly in recent years and hence a large variety of 1D-, 2D- and 3D DNA nanostructures with various sizes, geometries and shapes is readily accessible. DNA-based nanoobjects are fabricated by straight forward design and self-assembly processes allowing the exact positioning of functional moieties and the integration of other materials. At the same time some of these nanosystems are characterized by a low toxicity profile. As a consequence, the use of these architectures in a biomedical context has been explored. In this review the progress and possibilities of pristine nucleic acid nanostructures and DNA hybrid materials for drug delivery will be discussed. For the latter class of structures, a distinction is made between carriers with an inorganic core composed of gold or silica and amphiphilic DNA block copolymers that exhibit a soft hydrophobic interior.

  4. Solid lipid nanoparticles as nucleic acid delivery system: properties and molecular mechanisms.

    PubMed

    de Jesus, Marcelo B; Zuhorn, Inge S

    2015-03-10

    Solid lipid nanoparticles (SLNs) have been proposed in the 1990s as appropriate drug delivery systems, and ever since they have been applied in a wide variety of cosmetic and pharmaceutical applications. In addition, SLNs are considered suitable alternatives as carriers in gene delivery. Although important advances have been made in this particular field, fundamental knowledge of the underlying mechanisms of SLN-mediated gene delivery is conspicuously lacking, an imperative requirement in efforts aimed at further improving their efficiency. Here, we address recent advances in the use of SLNs as platform for delivery of nucleic acids as therapeutic agents. In addition, we will discuss available technology for conveniently producing SLNs. In particular, we will focus on underlying molecular mechanisms by which SLNs and nucleic acids assemble into complexes and how the nucleic acid cargo may be released intracellularly. In discussing underlying mechanisms, we will, when appropriate, refer to analogous studies carried out with systems based on cationic lipids and polymers, that have proven useful in the assessment of structure-function relationships. Finally, we will give suggestions for improving SLN-based gene delivery systems, by pointing to alternative methods for SLNplex assembly, focusing on the realization of a sustained nucleic acid release.

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

    PubMed Central

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

    2016-01-01

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

  6. Comparative analysis of ascorbic acid in human milk and infant formula using varied milk delivery systems

    PubMed Central

    Francis, Jimi; Rogers, Kristy; Brewer, Paul; Dickton, Darby; Pardini, Ron

    2008-01-01

    Background The expression of human milk for later use is on the rise. Bottle systems are used to deliver the expressed milk. Research has shown that storage of both human milk and artificial baby milk, or infant formula, leads to a loss of ascorbic acid (commonly called Vitamin C). As milk is removed from the bottle during feeding and replaced by ambient air, it is unknown if loss of ascorbic acid occurs during the course of a feeding. The purpose of this study is to investigate the effect of the milk delivery system on levels of ascorbic acid in human milk and infant formula. The objectives are to 1) determine changes in ascorbic acid concentration during a 20 minute "feed," 2) determine if there is a difference in ascorbic acid concentration between delivery systems, and 3) evaluate if any differences are of clinical importance. Methods Commonly available bottles were used for comparison of bottle delivery systems. Mature human milk was standardized to 42 mg/L of ascorbic acid. Infant formula with iron and infant formula with docosahexanoic acid were used for the formula samples. Each sample was analyzed for ascorbic acid concentration at baseline (0), 5, 10, 15, and 20 minutes. Each collection of samples was completed in triplicate. Samples were analyzed for ascorbic acid using normal-phase high performance liquid chromatography. Results Ascorbic acid concentration declined in all bottle systems during testing, Differences between the bottle systems were noted. Ascorbic acid concentrations declined to less than 40% of recommended daily intake for infants in 4 of the bottles systems at the 20 minute sampling. Conclusion The bottle systems used in this study had measurable decreases in the mean concentration of ascorbic acid. More research is needed to determine if the observed decreases are related to lower plasma ascorbic acid concentration in infants exclusively bottle fed. The decrease of ascorbic acid concentration observed in both human milk and infant

  7. 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

    2017-02-06

    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.

  8. Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

    PubMed Central

    Gonçalez, M. L.; Corrêa, M. A.; Chorilli, M.

    2013-01-01

    The aging process causes a number of changes in the skin, including oxidative stress and dyschromia. The kojic acid (KA) is iron chelator employed in treatment of skin aging, and inhibits tyrosinase, promotes depigmentation. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation through the skin and improve the drug activity. This study is aimed at structurally developing and characterizing a kojic acid-loaded LCS, consists of water (W), cetostearyl isononanoate (oil—O) and PPG-5-CETETH-20 (surfactant-S) and evaluating its in vitro skin permeation and retention. Three regions of the diagram were selected for characterization: A (35% O, 50% S, 15% W), B (30% O, 50% S, 20% W) and C (20% O, 50% S, 30% W), to which 2% KA was added. The formulations were subjected to polarized light microscopy, which indicated the presence of a hexagonal mesophase. Texture and bioadhesion assay showed that formulation B is suitable for topical application. According to the results from the in vitro permeation and retention of KA, the formulations developed can modulate the permeation of KA in the skin. The in vitro cytotoxic assays showed that KA-unloaded LCS and KA-loaded LCS didn't present cytotoxicity. PPG-5-CETETH-20-based systems may be a promising platform for KA skin delivery. PMID:24369010

  9. Progress in nanoparticulate systems for peptide, proteins and nucleic acid drug delivery.

    PubMed

    Slomkowski, Stanislaw; Gosecki, Mateusz

    2011-11-01

    Progress in many therapies, in particular in the therapies based on peptides, proteins and nucleic acids used as bioactive compounds, strongly depends on development of appropriate carriers which would be suitable for controlled delivery of the intact abovementioned compounds to required tissues, cells and intracellular compartments. This review presents last ten years' achievements and problems in development and application of synthetic polymer nanoparticulate carriers for oral, pulmonary and nasal delivery routes of oligopeptides and proteins. Whereas some traditional synthetic polymer carriers are only briefly recalled the main attention is concentrated on nanoparticles produced from functional copolymers mostly with hydroxyl, carboxyl and amino groups, suitable for immobilization of targeting moieties and for assuring prolonged circulation of nanoparticles in blood. Formulations of various nanoparticulate systems are described, including solid particles, polymer micelles, nanovesicles and nanogels, especially systems allowing drug release induced by external stimuli. Discussed are properties of these species, in particular stability in buffers and models of body fluids, loading with drugs and with drug models, drug release processes and results of biological studies. There are also discussed systems for gene delivery with special attention devoted to polymers suitable for compacting nucleic acids into nanoparticles as well as the relations between chemical structure of polymer carriers and ability of the latter for crossing cell membranes and for endosomal escape.

  10. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    NASA Astrophysics Data System (ADS)

    Andhariya, Nidhi; Upadhyay, Ramesh; Mehta, Rasbindu; Chudasama, Bhupendra

    2013-01-01

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  11. Large amino acid transporter 1 (LAT1) prodrugs of valproic acid: new prodrug design ideas for central nervous system delivery.

    PubMed

    Peura, Lauri; Malmioja, Kalle; Laine, Krista; Leppänen, Jukka; Gynther, Mikko; Isotalo, Antti; Rautio, Jarkko

    2011-10-03

    Central nervous system (CNS) drug delivery is a major challenge in drug development because the blood-brain barrier (BBB) efficiently restricts the entry of drug molecules into the CNS at sufficient amounts. The brain uptake of poorly penetrating drugs could be improved by utilizing the transporters at the BBB with a prodrug approach. In this study, we designed four phenylalanine derivatives of valproic acid and studied their ability to utilize a large amino acid transporter 1 (LAT1) in CNS delivery with an aim to show that the meta-substituted phenylalanine prodrugs bind to LAT1 with a higher affinity compared with the affinity of the para-substituted derivatives. All of the prodrugs crossed the BBB carrier mediatedly via LAT1 in in situ rat brain perfusion. For the first time, we introduced a novel meta-substituted phenylalanine analogue promoiety which improved the LAT1 affinity 10-fold and more importantly the rat brain uptake of the prodrug 2-fold compared with those of the para-substituted derivatives. Therefore, we have characterized a new prodrug design idea for CNS drug delivery utilizing a transporter-mediated prodrug approach.

  12. A Review of Nanoliposomal Delivery System for Stabilization of Bioactive Omega-3 Fatty Acids

    PubMed Central

    Hadian, Zahra

    2016-01-01

    Currently, bioactive compounds are required in the design and production of functional foods, with the aim of improving the health status of consumers all around the world. Various epidemiological and clinical studies have demonstrated the salutary role of eicosapentaenoic acid (EPA, 22:6 n−3) and docosahexaenoic acid (DHA, 22:5 n−3) in preventing diseases and reducing mortality from cardiovascular diseases. The unsaturated nature of bioactive lipids leads to susceptibility to oxidation under environmental conditions. Oxidative deterioration of omega-3 fatty acids can cause the reduction in their nutritional quality and sensory properties. Encapsulation of these fatty acids could create a barrier against reaction with harmful environmental factors. Currently, fortification of foods containing bioactive omega-3 fatty acids has found great application in the food industries of different countries. Previous studies have suggested that nano-encapsulation has significant effects on the stability of physical and chemical properties of bioactive compounds. Considering the functional role of omega-3 fatty acids, this study has provided a literature review on applications of nanoliposomal delivery systems for encapsulation of these bioactive compounds. PMID:26955449

  13. A Review of Nanoliposomal Delivery System for Stabilization of Bioactive Omega-3 Fatty Acids.

    PubMed

    Hadian, Zahra

    2016-01-01

    Currently, bioactive compounds are required in the design and production of functional foods, with the aim of improving the health status of consumers all around the world. Various epidemiological and clinical studies have demonstrated the salutary role of eicosapentaenoic acid (EPA, 22:6 n-3) and docosahexaenoic acid (DHA, 22:5 n-3) in preventing diseases and reducing mortality from cardiovascular diseases. The unsaturated nature of bioactive lipids leads to susceptibility to oxidation under environmental conditions. Oxidative deterioration of omega-3 fatty acids can cause the reduction in their nutritional quality and sensory properties. Encapsulation of these fatty acids could create a barrier against reaction with harmful environmental factors. Currently, fortification of foods containing bioactive omega-3 fatty acids has found great application in the food industries of different countries. Previous studies have suggested that nano-encapsulation has significant effects on the stability of physical and chemical properties of bioactive compounds. Considering the functional role of omega-3 fatty acids, this study has provided a literature review on applications of nanoliposomal delivery systems for encapsulation of these bioactive compounds.

  14. Effect of ca2+ to salicylic acid release in pectin based controlled drug delivery system

    NASA Astrophysics Data System (ADS)

    Kistriyani, L.; Wirawan, S. K.; Sediawan, W. B.

    2016-01-01

    Wastes from orange peel are potentially be utilized to produce pectin, which are currently an import commodity. Pectin can be used in making edible film. Edible films are potentially used as a drug delivery system membrane after a tooth extraction. Drug which is used in the drug delivery system is salicylic acid. It is an antiseptic. In order to control the drug release rate, crosslinking process is added in the manufacturing of membrane with CaCl2.2H2O as crosslinker. Pectin was diluted in water and mixed with a plasticizer and CaCl2.2H2O solution at 66°C to make edible film. Then the mixture was dried in an oven at 50 °C. After edible film was formed, it was coated using plasticizer and CaCl2.2H2O solution with various concentration 0, 0.015, 0.03 and 0.05g/mL. This study showed that the more concentration of crosslinker added, the slower release of salicylic acid would be. This was indicated by the value of diffusivites were getting smaller respectively. The addition of crosslinker also caused smaller gels swelling value,which made the membrane is mechanically stronger

  15. Dendrimers as Nanovectors for Nucleic Acid Delivery

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoxuan; Wang, Qi; Peng, Ling

    2013-09-01

    Nucleic acid based gene therapy holds great promise in the treatment of various diseases. However, the success of both DNA- and siRNAbased gene therapies depends critically on safe and efficient nucleic acid delivery systems. Owing to their well-defined structure and multivalent cooperativity, dendrimers have attracted particular attention as ideal nanocarriers for nucleic acid delivery. The present chapter highlights the current status of dendrimers as non-viral nanovectors for both DNA and siRNA delivery, focusing on the different dendrimers investigated for their delivery efficiency with respect to structural alterations in the view to developing safe and efficient nanovectors for gene therapy application.

  16. Development of stable flaxseed oil emulsions as a potential delivery system of ω-3 fatty acids.

    PubMed

    Goyal, Ankit; Sharma, Vivek; Upadhyay, Neelam; Singh, A K; Arora, Sumit; Lal, Darshan; Sabikhi, Latha

    2015-07-01

    The objective of the present study was to develop a stable flaxseed oil emulsion for the delivery of omega-3 (ω-3) fatty acids through food fortification. Oil-in-water emulsions containing 12.5 % flaxseed oil, 10 % lactose and whey protein concentrate (WPC)-80 ranging from 5 to 12.5 % were prepared at 1,500, 3,000 and 4,500 psi homogenization pressure. Flaxseed oil emulsions were studied for its physical stability, oxidative stability (peroxide value), particle size distribution, zeta (ζ)-potential and rheological properties. Emulsions homogenized at 1,500 and 4,500 psi pressure showed oil separation and curdling of WPC, respectively, during preparation or storage. All the combinations of emulsions (homogenized at 3,000 psi) were physically stable for 28 days at 4-7 ºC temperature and did not show separation of phases. Emulsion with 7.5 % WPC showed the narrowest particle size distribution (190 to 615 nm) and maximum zeta (ζ)-potential (-33.5 mV). There was a slight increase in peroxide value (~20.98 %) of all the emulsions (except 5 % WPC emulsion), as compared to that of free flaxseed oil (~44.26 %) after 4 weeks of storage. Emulsions showed flow behavior index (n) in the range of 0.206 to 0.591, indicating higher shear thinning behavior, which is a characteristic of food emulsions. Results indicated that the most stable emulsion of flaxseed oil (12.5 %) can be formulated with 7.5 % WPC-80 and 10 % lactose (filler), homogenized at 3,000 psi pressure. The formulated emulsion can be used as potential omega-3 (ω-3) fatty acids delivery system in developing functional foods such as pastry, ice-creams, curd, milk, yogurt, cakes, etc.

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

    PubMed Central

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

    2016-01-01

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

  18. Nucleic acid delivery with microbubbles and ultrasound

    PubMed Central

    Rychak, Joshua J.; Klibanov, Alexander L.

    2014-01-01

    Nucleic acid-based therapy is a growing field of drug delivery research. Although ultrasound has been suggested to enhance transfection decades ago, it took a combination of ultrasound with nucleic acid carrier systems (microbubbles, liposomes, polyplexes, viral carriers) to achieve reasonable nucleic acid delivery efficacy. Microbubbles serve as foci for local deposition of ultrasound energy near the target cell, and greatly enhance sonoporation. Major advantage of this approach is in the minimal transfection in the non-insonated non-target tissues. Microbubbles can be simply co-administered with the nucleic acid carrier or can be modified to carry nucleic acid themselves. Liposomes with embedded gas or gas precursor particles can also be used to carry nucleic acid, release and deliver it by the ultrasound trigger. Successful testing in a wide variety of animal models (myocardium, solid tumors, skeletal muscle, pancreas) proves the potential usefulness of this technique for nucleic acid drug delivery. PMID:24486388

  19. Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine

    PubMed Central

    Abdelkader, Hamdy; Longman, Michael R; Alany, Raid G; Pierscionek, Barbara

    2016-01-01

    This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L-carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380–450 nm, polydispersity index of 0.12–0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes. PMID:27366062

  20. Mucoadhesive drug delivery systems

    PubMed Central

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

    2011-01-01

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

  1. 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.

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

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

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

  3. A bioabsorbable delivery system for antibiotic treatment of osteomyelitis. The use of lactic acid oligomer as a carrier.

    PubMed

    Wei, G; Kotoura, Y; Oka, M; Yamamuro, T; Wada, R; Hyon, S H; Ikada, Y

    1991-03-01

    We prepared a composite of D,L-lactic acid oligomer and dideoxykanamycin B for use as a biodegradable antibiotic delivery system with sustained effect. The composite was implanted in the distal portion of the rabbit femur, and the effective concentration of the antibiotic was measured in the cortex, the cancellous bone, and the bone marrow. In all bone tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for six weeks. Most of the implant material had been absorbed and the bone marrow had been repaired to a nearly normal state within nine weeks of implantation. The implant caused no systemic side effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.

  4. Omega-3 fatty acids incorporated colloidal systems for the delivery of Angelica gigas Nakai extract.

    PubMed

    Lee, Jeong-Jun; Park, Ju-Hwan; Lee, Jae-Young; Jeong, Jae Young; Lee, Song Yi; Yoon, In-Soo; Kang, Wie-Soo; Kim, Dae-Duk; Cho, Hyun-Jong

    2016-04-01

    Omega-3 (ω-3) fish oil-enriched colloidal systems were developed for the oral delivery of Angelica gigas Nakai (AGN) extract (ext). By constructing a pseudo-ternary phase diagram, the composition of oil-in-water (o/w) microemulsion (ME) systems based on ω-3 (oil), Labrasol (surfactant), and water was determined. AGN ext was dissolved into the ME system and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was added to the ME formulation in order to enhance the mucosal absorption of the pharmacologically active ingredients in the AGN ext. The droplet size of AGN-loaded MEs was 205-277 nm and their morphology was spherical. The release of major components of AGN, decursin (D) and decursinol angelate (DA), from ME formulations in pH 1.2 and 6.8 buffers was significantly greater (P<0.05) than that from the AGN suspension group. The pharmacokinetic properties of AGN-loaded MEs in rats were evaluated by measuring decursinol (DOH) concentrations in plasma after oral administration. TPGS-included ME (F2) resulted in significantly greater (P<0.05) systemic exposure of DOH than that with ME without TPGS (F1), AGN ext+TPGS, and AGN in suspension. Severe toxicity of F1 and F2 on the intestinal epithelium was not observed by histological staining. The colloidal carriers described herein are promising delivery systems for oral administration of AGN ext.

  5. Drug delivery systems using sandwich configurations of electrospun poly(lactic acid) nanofiber membranes and ibuprofen.

    PubMed

    Immich, Ana Paula Serafini; Arias, Manuel Lis; Carreras, Núria; Boemo, Rafael Luís; Tornero, José Antonio

    2013-10-01

    The primary advantages of electrospun membranes include the ability to obtain very thin fibers that are on the order of magnitude of several nanometers with a considerable superficial area and the possibility for these membranes to be manipulated and processed for many different applications. The purpose of this study is to evaluate and quantify the transport mechanisms that control the release of drugs from polymer-based sandwich membranes produced using the electrospinning processes. These electrospun membranes were composed of poly(lactic acid) (PLA) because it is one of the most promising biodegradable polymers due to its mechanical properties, thermoplastic processability and biological properties, such as its biocompatibility and biodegradability. The transport mechanism that controls the drug delivery was evaluated via the release kinetics of a bioactive agent in physiological serum, which was used as a corporal fluid simulation. To describe the delivery process, mathematical models, such as the Power Law, the classical Higuchi equation and an approach to Fick's Second Law were used. Using the applied mathematical models, it is possible to conclude that control over the release of the drug is significantly dependent on the thickness of the membrane rather than the concentration of the drug.

  6. Zein nanoparticles as delivery systems for covalently linked and physically entrapped folic acid

    NASA Astrophysics Data System (ADS)

    Chuacharoen, Thanida; Sabliov, Cristina M.

    2017-02-01

    Zein nanoparticles covalently linked to folic acid were hypothesized to sustain the release of the folic acid in addition to targeting cancer cells overexpressing folate-binding receptors, whereas zein nanoparticles with physically entrapped folic acid would only be able to control the release of the bioactive without targeting of cancer cells. The two types of particles, folic acid covalently linked zein nanoparticles (ZN-FA nps) and zein nanoparticles with entrapped folic acid (ZN(FA) nps), were synthesized and the covalent link between folic acid and zein was assessed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (1H NMR). Their size, polydispersity index, zeta potential, morphology, and loading capacity were evaluated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometric technique. The release studies of the folic acid preformed in phosphate-buffered saline (PBS) at 37 °C for 7 days concluded that the release of the loaded folic acid was sustained over 7 days for both systems. The cytotoxicity was investigated using a methyl thiazolyl tetrazolium (MTT) assay, and the results showed that zein nanoparticles were biocompatible to HeLa (an overexpressing folate receptor cells) and A549 (a deficient folate receptor cells) cells, which have different levels of folate receptors on surface and both folic acid nanoparticle systems were able to diminish the adverse toxic effect of folic acid to cells. The increased uptake of ZN-FA nps relative to ZN(FA) nps supported the use of ZN-FA nps as targeting nanoagents to cells overexpressing folate receptors.

  7. Carbohydrate Polymers for Nonviral Nucleic Acid Delivery

    PubMed Central

    Sizovs, Antons; McLendon, Patrick M.; Srinivasachari, Sathya

    2014-01-01

    Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific delivery is also briefly reviewed. We contend that carbohydrates have contributed significantly to progress in the field of non-viral DNA delivery, and these new discoveries are impactful for developing new vehicles and materials for treatment of human disease. PMID:21504102

  8. Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis.

    PubMed

    Deshpande, Dipti; Kethireddy, Sravani; Janero, David R; Amiji, Mansoor M

    2016-01-01

    Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE)-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs) with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/-) mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease.

  9. Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis

    PubMed Central

    Deshpande, Dipti; Kethireddy, Sravani; Janero, David R.; Amiji, Mansoor M.

    2016-01-01

    Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE)-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs) with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/-) mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease. PMID:26840601

  10. Injectable dopamine-modified poly(α,β-aspartic acid) nanocomposite hydrogel as bioadhesive drug delivery system.

    PubMed

    Gong, Chu; Lu, Caicai; Li, Bingqiang; Shan, Meng; Wu, Guolin

    2017-04-01

    Hydrogel systems based on cross-linked polymeric materials with adhesive properties in wet environments have been considered as promising candidates for tissue adhesives. The 3,4-dihydroxyphenylalanine (DOPA) is believed to be responsible for the water-resistant adhesive characteristics of mussel adhesive proteins. Under the inspiration of DOPA containing adhesive proteins, a dopamine-modified poly(α,β-aspartic acid) derivative (PDAEA) was successfully synthesized by successive ring-opening reactions of polysuccinimide (PSI) with dopamine and ethanolamine, and an injectable bioadhesive hydrogel was prepared via simply mixing PDAEA and FeCl3 solutions. The formation mechanism of the hydrogel was investigated by ultraviolet-visible (UV-vis) spectroscopic, Fourier transformation infrared (FT-IR) spectroscopic, visual colorimetric measurements and EDTA immersion methods. The study demonstrated that the PDAEA-Fe(3+) hydrogel is a dual cross-linking system composed of covalent and coordination crosslinks. The PDAEA-Fe(3+) hydrogel is suitable to serve as a bioadhesive agent according to the rheological behaviors and the observed significant shear adhesive strength. The slow and sustained release of the model drug curcumin from the hydrogel in vitro demonstrated the hydrogel could also be potentially used for drug delivery. Moreover, the cytotoxicity tests in vitro suggested the prepared polymer and hydrogel possessed excellent cytocompatibility. All the results indicated that the dopamine modified poly(α,β-aspartic acid) derivative based hydrogel was a promising candidate for bioadhesive drug delivery system. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1000-1008, 2017.

  11. Development of pH-sensitive self-nanoemulsifying drug delivery systems for acid-labile lipophilic drugs.

    PubMed

    Zhao, Tianjing; Maniglio, Devid; Chen, Jie; Chen, Bin; Migliaresi, Claudio

    2016-03-01

    Oral administration is the most convenient way of all the drug delivery routes. Orally administered bioactive compounds must resist the harsh acidic fluids or enzyme digestion in stomach, to reach their absorbed destination in small intestine. This is the case for silibinin, a drug used to protect liver cells against toxins that has also been demonstrated in vitro to possess anti-cancer effects. However, as many other drugs, silibinin can degrade in the stomach due to the action of the gastric fluid. The use of pH-sensitive self-nanoemulsifying drug delivery systems (pH-SNEDDS) could overcome the drawback due to degradation of the drug in the stomach while enhancing its solubility and dissolution rate. In this paper we have investigated pH-sensitive self-nanoemulsifying formulations containing silibinin as model drug. Pseudo-ternary phase diagrams have been constructed in order to identify the self-emulsification regions under different pH. Solubility of silibinin in selected formulations has been assessed and stability of the pure drug and of the silibinin loaded pH-SNEDDS formulations in simulated gastric fluid had been compared. Droplet size of the optimized pH-SNEDDS has been correlated to pH, volume of dilution medium and silibinin loading amount. TEM (transmission electron microscopy) studies have shown that emulsion droplets had spherical shape and narrow size distribution. In vitro drug release studies of the optimal pH-SNEDDS indicated substantial increase of the drug release and release rate in comparison to pure silibinin and to the commercial silibinin tablet. The results indicated that pH-SNEDDS have potential to improve the biopharmaceutics properties of acid-labile lipophilic drugs.

  12. Educational Telecommunications Delivery Systems.

    ERIC Educational Resources Information Center

    Curtis, John A., Ed.; Biedenbach, Joseph M., Ed.

    This monograph is a single volume reference manual providing an overall review of the current status and likely near future application of six major educational telecommunications delivery technologies. The introduction provides an overview to the usage and potential for these systems in the context of the major educational issues involved. Each…

  13. Comparison of simple, double and gelled double emulsions as hydroxytyrosol and n-3 fatty acid delivery systems.

    PubMed

    Flaiz, Linda; Freire, María; Cofrades, Susana; Mateos, Raquel; Weiss, Jochen; Jiménez-Colmenero, Francisco; Bou, Ricard

    2016-12-15

    The purpose of this study was to compare three different emulsion-based systems, namely simple emulsion, double emulsion and gelled double emulsion, for delivery of n-3 fatty acids (perilla oil at 300g/kg) and hydroxytyrosol (300mg/kg). Considering that their structural differences may affect their physical and oxidative stability, this was studied by storing them at 4°C for 22days in the dark. The results showed that the oxidative status was maintained in all systems by the addition of hydroxytyrosol. However, there was some loss of hydroxytyrosol, mainly during sample storage and during preparation of the gelled double emulsion. Moreover, the antioxidant loss was more pronounced in more compartmentalized systems, which was attributed to their increased surface area. However, the double emulsion was found to be less stable than the gelled emulsion. Overall, the encapsulation of labile compounds in more complex systems needs to be carefully studied and adapted to specific technological and/or nutritional requirements.

  14. Hyaluronic acid based hydrogel system for soft tissue regeneration and drug delivery

    NASA Astrophysics Data System (ADS)

    Jha, Amit Kumar

    We have developed hyaluronic acid (HA)-based, biomimetic hydrogel matrices that are hierarchically structured, mechanically robust and biologically active. Specifically, HA-based hydrogel particles (HGPs) with controlled sizes, defined porosity, and improved stability were synthesized using different inverse emulsion systems and crosslinking chemistries. The resultant particles either contained residual functional groups or were rendered reactive by subsequent chemical modifications. HA-based doubly crosslinked networks (DXNs) were synthesized via covalent crosslinking of HA HGPs with soluble HA macromers carrying mutually reactive functional groups. These hybrid matrices are hierarchical in nature, consisting of densely crosslinked HGPs integrated in a loosely connected secondary matrix. Their mechanical properties and degradation kinetics can be readily tuned by varying the particle size, functional group density, intra- and interparticle crosslinking. To improve the biological functions of HA HGPs, perlecan domain I (PlnDI), a basement membrane proteoglycan that has strong affinity for various heparin binding growth factors (HBGFs), was successfully conjugated to the particles through the core protein via a flexible poly(ethylene glycol) (PEG) linker. The immobilized PlnDI maintains its ability to bind bone morphogenetic proteins (BMP-2) and modulates its in vitro release. A similar, sustained release of BMP-2 was achieved by encapsulating BMP-2-loaded HGPs within a photocrosslinked HA matrix. When encapsulated in HA DXNs, primary bovine chondrocytes were able to maintain their phenotype, proliferate readily and produce abundant glycosaminoglycan. Finally, cell-adhesive HA DXNs were fabricated by encapsulating gelatin-decorated HA HGPs in a secondary HA matrix. Human MSCs were shown to adhere to the composite matrix through the focal adhesion sites clustered on particle surface. The cell-adhesive composite matrices supported hMSC proliferation and migration into

  15. Colloidal drug delivery systems in vaccine delivery.

    PubMed

    Beg, Sarwar; Samad, Abdus; Nazish, Iram; Sultana, Ruksar; Rahman, Mahfoozur; Ahmad, Md Zaki; Akbar, Md

    2013-01-01

    Vaccines play a vital role in the field of community medicine to combat against several diseases of human existence. Vaccines primarily trigger the acquired immune system to develop long-lasting immunity against pathogens. Conventional approaches for vaccine delivery lacks potential to target a particular antigen to develop acquired immunity by specific antibodies. Recent advancements in vaccine delivery showed that inclusion of adjuvants in vaccine formulations or delivery of them in a carrier helps in achieving desired targeting ability, reducing the immunogenicity and significant augmentation in the immune response. Colloidal carriers (liposomes, niosomes, microspheres, proteosomes, virosomes and virus like particles (VLPs), antigen cochleates, dendrimers and carbon nanotubes) have been widely explored for vaccine delivery. Further, surface engineering of these carriers with ligands, functional moieties and monoclonal antibodies tend to enhance the immune recognition potential of vaccines by differentiation of antigen specific memory T-cells. The current review, therefore, provides an updated account on the recent advancements in various colloidal delivery systems in vaccine delivery, outlining the mechanism of immune response initiated by them along with potential applications and marketed instances in an explicit manner.

  16. Preparation and characterization of polyelectrolyte complex nanoparticles based on poly (malic acid), chitosan. A pH-dependent delivery system.

    PubMed

    Arif, Muhammad; Raja, Mazhar Ali; Zeenat, Shah; Chi, Zhe; Liu, Chenguang

    2017-01-01

    The main objective of this work was to develop polyelectrolyte complex (PEC) nanoparticles based on poly (malic acid), chitosan (PMLA/CS) as pH-dependent delivery systems. The results indicated that the PMLA/CS Nps were successfully prepared. The prepared PMLA/CS Nps showed spherical morphology with a mean diameter of 212.81 nm and negative surface charge of -24.60 mV, and revealing significant pH-sensitive properties as the mass ratio of PMLA to CS was 5:5. The prepared PMLA/CS Nps were characterized by FT-IR, TEM and DLS. The prepared PMLA/CS Nps remained stable over a temperature range of 4-53 °C. Doxorubicin (Dox) as a model drug was loaded on the nanoparticles through the physical adsorption method. The high drug loading efficiency (16.9%) and the sustained release patterns in acidic media were observed, and the release accelerated in alkaline solutions. MTT based cytotoxic analysis also depicted the non-toxic nature of PMLA/CS Nps, while Dox-PMLA/CS Nps showed dose-dependent cytotoxicity towards MDA-MB-231 cells. Hence, the nanoparticles could be potentially applied as pH sensitive drug vehicles for controlled release.

  17. Modified MCM-41 as a drug delivery system for acetylsalicylic acid

    NASA Astrophysics Data System (ADS)

    Vyskočilová, Eliška; Luštická, Ivana; Paterová, Iva; Machová, Libuše; Červený, Libor

    2014-12-01

    The modification of prepared MCM-41 by different groups (amino, chloro and oxo) was studied. Prepared materials were treated by acetylsalicylic acid and hybrid materials were characterized, compared from the point of view of immobilized amount of active substance. The highest amount of acetylsalicylic acid was detected using methyl-tert- butyl ether as a solvent and MCM-41 without modification after 1 h (0.35 g per 1 g of the support) or MCM modified by amino group after 5 h (0.37 g per 1 g of the support) as a support. Using amino modified MCM, the longer treatment by acetylsalicylic acid converged to the equilibrium and after 24 h the immobilized amount was 0.3 g per 1 g. A dissolution in vitro study was carried out, comparing the stability of formed interactions. The slowest dissolution was detected using non-modified MCM-41 and oxo modified material.

  18. Enhanced anticancer potency using an acid-responsive ZnO-incorporated liposomal drug-delivery system

    NASA Astrophysics Data System (ADS)

    Tripathy, Nirmalya; Ahmad, Rafiq; Ko, Hyun Ah; Khang, Gilson; Hahn, Yoon-Bong

    2015-02-01

    The development of stimuli-responsive nanocarriers is becoming important in chemotherapy. Liposomes, with an appropriate triggering mechanism, can efficiently deliver their encapsulated cargo in a controlled manner. We explored the use of acid-sensitive zinc oxide nanoparticles (ZNPs) as modulators of the responsive properties of liposomes. Nanocomplexes formed by the incorporation of ZNPs in liposomes (ZNP-liposomes) were designed to demonstrate the pH-responsive release of a drug (daunorubicin) without premature drug leakage and with the maintenance of the relevant therapeutic concentrations. The nanocomplexes were spherical in shape with a narrow size distribution and showed a high drug-encapsulating efficiency. Under acidic conditions, the ZNP-liposome nanocomplexes released the loaded drug more rapidly than bare liposomes. Using flow cytometry, confocal microscopy and an MTT assay, we demonstrated that these nanocomplexes were readily taken up by cancer cells, resulting in significantly enhanced cytotoxicity. On exposure to the acidic conditions inside cancer cells, the ZNPs rapidly decomposed, releasing the entrapped drug molecules from the ZNP-liposome nanocomplexes, producing widespread cytotoxic effects. The incorporated ZNPs were multimodal in that they not only resulted in a pH-responsive drug-delivery system, but they also had a synergistic chemo-photodynamic anticancer action. This design provides a significant step towards the development of multimodal liposome structures.The development of stimuli-responsive nanocarriers is becoming important in chemotherapy. Liposomes, with an appropriate triggering mechanism, can efficiently deliver their encapsulated cargo in a controlled manner. We explored the use of acid-sensitive zinc oxide nanoparticles (ZNPs) as modulators of the responsive properties of liposomes. Nanocomplexes formed by the incorporation of ZNPs in liposomes (ZNP-liposomes) were designed to demonstrate the pH-responsive release of a drug

  19. [Site-specific drug delivery systems. I. Colon targeted delivery].

    PubMed

    Szente, Virág; Zelkó, Romána

    2007-01-01

    Colon specific drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Chron's disease, ulcerative colitis, irritable bowel syndrome, cancer or infections, but also for the potential it holds for the systemic delivery of proteins (e.g. insulin) and therapeutic peptides. These systems enable the protection of healthy tissues from the side effects of drugs and the drug intake of targeted cells, as well. The formulation of colon specific drug delivery systems is of great impact in the case of diseases having circadian rhythm (midnight gerd). Such circadian rhythm release drug delivery systems are designed to provide a plasma concentration--time profile, which varies according to physiological need at different times during the dosing period, i.e., mimicking the circadian rhythm and severity/manifestation of gastric acid secretion (and/or midnight gerd). In general four primary approaches have been proposed for colon targeted delivery namely pH-dependent systems, time dependent systems, colonic microflora activated systems and prodrugs.

  20. A protein delivery system: biodegradable alginate-chitosan-poly(lactic-co-glycolic acid) composite microspheres.

    PubMed

    Zheng, Cai-Hong; Gao, Jian-Qing; Zhang, Ye-Ping; Liang, Wen-Quan

    2004-10-29

    In the present study we developed alginate-chitosan-poly(lactic-co-glycolic acid) (PLGA) composite microspheres to elevate protein entrapment efficiency and decrease its burst release. Bovine serum albumin (BSA), which used as the model protein, was entrapped into the alginate microcapsules by a modified emulsification method in an isopropyl alcohol-washed way. The rapid drug releases were sustained by chitosan coating. To obtain the desired release properties, the alginate-chitosan microcapsules were further incorporated in the PLGA to form the composite microspheres. The average diameter of the composite microcapsules was 31+/-9microm and the encapsulation efficiency was 81-87%, while that of conventional PLGA microspheres was just 61-65%. Furthermore, the burst releases at 1h of BSA entrapped in composite microspheres which containing PLGA (50:50) and PLGA (70:30) decreased to 24% and 8% in PBS, and further decreased to 5% and 2% in saline. On the contrary, the burst releases of conventional PLGA microspheres were 48% and 52% in PBS, respectively. Moreover, the release profiles could be manipulated by regulating the ratios of poly(lactic acid) to poly(glycolic acid) in the composite microspheres.

  1. Lipid and polymeric carrier-mediated nucleic acid delivery

    PubMed Central

    Zhu, Lin; Mahato, Ram I

    2010-01-01

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

  2. Mucoadhesive vaginal drug delivery systems.

    PubMed

    Acartürk, Füsun

    2009-11-01

    Vaginal delivery is an important route of drug administration for both local and systemic diseases. The vaginal route has some advantages due to its large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to many drugs and self-insertion. The traditional commercial preparations, such as creams, foams, gels, irrigations and tablets, are known to reside in the vaginal cavity for a relatively short period of time owing to the self-cleaning action of the vaginal tract, and often require multiple daily doses to ensure the desired therapeutic effect. The vaginal route appears to be highly appropriate for bioadhesive drug delivery systems in order to retain drugs for treating largely local conditions, or for use in contraception. In particular, protection against sexually-transmitted diseases is critical. To prolong the residence time in the vaginal cavity, bioadhesive therapeutic systems have been developed in the form of semi-solid and solid dosage forms. The most commonly used mucoadhesive polymers that are capable of forming hydrogels are synthetic polyacrylates, polycarbophil, chitosan, cellulose derivatives (hydroxyethycellulose, hydroxy-propylcellulose and hydroxypropylmethylcellulose), hyaluronic acid derivatives, pectin, tragacanth, carrageenan and sodium alginate. The present article is a comprehensive review of the patents related to mucoadhesive vaginal drug delivery systems.

  3. Nanovehicular Intracellular Delivery Systems

    PubMed Central

    PROKOP, ALES; DAVIDSON, JEFFREY M.

    2013-01-01

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

  4. Delivery systems for brachytherapy.

    PubMed

    de la Puente, Pilar; Azab, Abdel Kareem

    2014-10-28

    Brachytherapy is described as the short distance treatment of cancer with a radioactive isotope placed on, in, or near the lesions or tumor to be treated. The main advantage of brachytherapy compared with external beam radiation (EBR) is the improved localized delivery of dose to the target volume of interest, thus normal tissue irradiation is reduced. The precise and targeted nature of brachytherapy provides a number of key benefits for the effective treatment of cancer such as efficacy, minimized risk of side effects, short treatment times, and cost-effectiveness. Brachytherapy devices have yielded promising results in preclinical and clinical studies. However, brachytherapy can only be used in localized and relatively small tumors. Although the introduction of new delivery devices allows the treatment of more complex tumor sites, with wider range of dose rate for improving treatment efficacy and reduction of side effects, a better understanding about the safety, efficacy, and accuracy of these systems is required, and further development of new techniques is warranted. Therefore, this review focuses on the delivery devices for brachytherapy and their application in prostate, breast, brain, and other tumor sites.

  5. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the “E2 scaffold” of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  6. Secondary fuel delivery system

    DOEpatents

    Parker, David M.; Cai, Weidong; Garan, Daniel W.; Harris, Arthur J.

    2010-02-23

    A secondary fuel delivery system for delivering a secondary stream of fuel and/or diluent to a secondary combustion zone located in the transition piece of a combustion engine, downstream of the engine primary combustion region is disclosed. The system includes a manifold formed integral to, and surrounding a portion of, the transition piece, a manifold inlet port, and a collection of injection nozzles. A flowsleeve augments fuel/diluent flow velocity and improves the system cooling effectiveness. Passive cooling elements, including effusion cooling holes located within the transition boundary and thermal-stress-dissipating gaps that resist thermal stress accumulation, provide supplemental heat dissipation in key areas. The system delivers a secondary fuel/diluent mixture to a secondary combustion zone located along the length of the transition piece, while reducing the impact of elevated vibration levels found within the transition piece and avoiding the heat dissipation difficulties often associated with traditional vibration reduction methods.

  7. History of Polymeric Gene Delivery Systems.

    PubMed

    Zhang, Peng; Wagner, Ernst

    2017-04-01

    As an option for genetic disease treatment and an alternative for traditional cancer chemotherapy, gene therapy achieves significant attention. Nucleic acid delivery, however, remains a main challenge in human gene therapy. Polymer-based delivery systems offer a safer and promising route for therapeutic gene delivery. Over the past five decades, various cationic polymers have been optimized for increasingly effective nucleic acid transfer. This resulted in a chemical evolution of cationic polymers from the first-generation polycations towards bioinspired multifunctional sequence-defined polymers and nanocomposites. With the increasing of knowledge in molecular biological processes and rapid progress of macromolecular chemistry, further improvement of polymeric nucleic acid delivery systems will provide effective tool for gene-based therapy in the near future.

  8. Tumor-targeted Chlorotoxin-coupled Nanoparticles for Nucleic Acid Delivery to Glioblastoma Cells: A Promising System for Glioblastoma Treatment

    PubMed Central

    Costa, Pedro M; Cardoso, Ana L; Mendonça, Liliana S; Serani, Angelo; Custódia, Carlos; Conceição, Mariana; Simões, Sérgio; Moreira, João N; Pereira de Almeida, Luís; Pedroso de Lima, Maria C

    2013-01-01

    The present work aimed at the development and application of a lipid-based nanocarrier for targeted delivery of nucleic acids to glioblastoma (GBM). For this purpose, chlorotoxin (CTX), a peptide reported to bind selectively to glioma cells while showing no affinity for non-neoplastic cells, was covalently coupled to liposomes encapsulating antisense oligonucleotides (asOs) or small interfering RNAs (siRNAs). The resulting targeted nanoparticles, designated CTX-coupled stable nucleic acid lipid particles (SNALPs), exhibited excellent features for in vivo application, namely small size (<180 nm) and neutral surface charge. Cellular association and internalization studies revealed that attachment of CTX onto the liposomal surface enhanced particle internalization into glioma cells, whereas no significant internalization was observed in noncancer cells. Moreover, nanoparticle-mediated miR-21 silencing in U87 human GBM and GL261 mouse glioma cells resulted in increased levels of the tumor suppressors PTEN and PDCD4, caspase 3/7 activation and decreased tumor cell proliferation. Preliminary in vivo studies revealed that CTX enhances particle internalization into established intracranial tumors. Overall, our results indicate that the developed targeted nanoparticles represent a valuable tool for targeted nucleic acid delivery to cancer cells. Combined with a drug-based therapy, nanoparticle-mediated miR-21 silencing constitutes a promising multimodal therapeutic approach towards GBM. PMID:23778499

  9. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  10. Electronic Nicotine Delivery Systems.

    PubMed

    Walley, Susan C; Jenssen, Brian P

    2015-11-01

    Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control.

  11. 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, LD50 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.

  12. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  13. 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.

  14. Fluid delivery control system

    SciTech Connect

    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.

  15. 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

  16. Liposomes as Advanced Delivery Systems for Nutraceuticals

    PubMed Central

    Shade, Christopher W.

    2016-01-01

    Liposomes are delivery vehicles for transporting substances into the body effectively via facilitating absorption directly in the mouth or by preventing breakdown by stomach acid. Since the 1970s, liposomes have been investigated as potential drug delivery systems because of their biocompatibility and ability to incorporate both hydrophilic and hydrophobic therapeutic agents. Despite early promise, it was decades later, in the late 1990s to the present, that liposome technologies could create successful commercial products. Oral deliveries are recently emerging as availability of quality phospholipids and reliable homogenization and sizing equipment have become routinely available. Nutritional industry use of liposomes will grow rapidly in the next 5–10 y. High-quality products with more complex mixtures of pure compounds and complex botanical mixtures will offer clinicians less-invasive options for dosing and delivery of these actives. PMID:27053934

  17. 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.

  18. Characterization and evaluation of a folic acid receptor-targeted cyclodextrin complex as an anticancer drug delivery system.

    PubMed

    Xu, Jiaojiao; Xu, Beihua; Shou, Dan; Qin, Fuhua; Xu, Yong; Hu, Ying

    2016-02-15

    -targeting efficacy and diminished systemic side effects. These results suggest that the novel FR-targeted cyclodextrin complex is a promising alternative as an anticancer drug delivery system.

  19. Synthesis of zinc-crosslinked thiolated alginic acid beads and their in vitro evaluation as potential enteric delivery system with folic acid as model drug.

    PubMed

    Taha, M O; Aiedeh, K M; Al-Hiari, Y; Al-Khatib, H

    2005-10-01

    The aim of this study is to explore the potential of synthetic modifications of alginic acid as a method to enhance the stability of its complexes with divalent cations under physiological conditions. A fraction of algin's carboxylic acid moieties was substituted with thiol groups to different substitution degrees through conjugating alginate to cysteine to produce alginate-cysteine (AC) conjugates. Infrared spectrophotometry and iodometry were used to characterize the resulting polymeric conjugates in terms of structure and degree of substitution. Moreover, zinc ions were used to crosslink the resulting AC polymers. Folic acid loaded beads were prepared from Zinc-crosslinked AC polymers (AC-Zn) of different cysteine substitution degrees. The generated beads were then investigated in vitro for their capacity to modify folic acid release. AC-Zn polymeric beads resisted drug release under acidic conditions (pH 1.0). However, upon transfer to a phosphate buffer solution (pH 7.0) they released most of their contents almost immediately. This change in drug release behavior is most probably due to the sequestering of zinc cations by phosphate ions within the buffer solution to form insoluble chelates and, to a lesser extent, the ionization of the carboxylic acid and thiol moieties. Removal of zinc ions from the polymeric matrix seems to promote polymeric disintegration and subsequent drug release. A similar behavior is expected in vivo due to the presence of natural zinc sequestering agents in the intestinal fluids. AC-Zn polymers provided a novel approach for enteric drug delivery as drug release from these matrices complied with the USP specifications for enteric dosage forms.

  20. Chitosan-coated poly(lactic-co-glycolic) acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine.

    PubMed

    Zhao, Kai; Zhang, Yang; Zhang, Xiaoyan; Shi, Ci; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Cui, Shangjin

    2014-01-01

    We determined the efficacy and safety of chitosan (CS)-coated poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) as a delivery system for a vaccine to protect chickens against Newcastle disease virus (NDV). The newly constructed vaccine contained DNA (the F gene) of NDV. The Newcastle disease virus (NDV) F gene deoxyribonucleic acid (DNA) plasmid (pFDNA)-CS/PLGA-NPs were spherical (diameter =699.1 ± 5.21 nm [mean ± standard deviation]) and smooth, with an encapsulation efficiency of 98.1% and a Zeta potential of +6.35 mV. An in vitro release assay indicated that CS controlled the burst release of plasmid DNA, such that up to 67.4% of the entire quantity of plasmid DNA was steadily released from the pFDNA-CS/PLGA-NPs. An in vitro expression assay indicated that the expression of nanoparticles (NPs) was maintained in the NPs. In an immunization test with specific pathogen-free chickens, the pFDNA-CS/PLGA-NPs induced stronger cellular, humoral, and mucosal immune responses than the plasmid DNA vaccine alone. The pFDNA-CS/PLGA-NPs did not harm 293T cells in an in vitro assay and did not harm chickens in an in vivo assay. Overall, the results indicated that CS-coated PLGA NPs can serve as an efficient and safe mucosal immune delivery system for NDV DNA vaccine.

  1. A surface-mediated siRNA delivery system developed with chitosan/hyaluronic acid-siRNA multilayer films through layer-by-layer self-assembly

    NASA Astrophysics Data System (ADS)

    Wu, Lijuan; Wu, Changlin; Liu, Guangwan; Liao, Nannan; Zhao, Fang; Yang, Xuxia; Qu, Hongyuan; Peng, Bo; Chen, Li; Yang, Guang

    2016-12-01

    siRNA delivery remains highly challenging because of its hydrophilic and anionic nature and its sensitivity to nuclease degradation. Effective siRNA loading and improved transfection efficiency into cells represents a key problem. In our study, we prepared Chitosan/Hyaluronic acid-siRNA multilayer films through layer-by-layer self-assembly, in which siRNAs can be effectively loaded and protected. The construction process was characterized by FTIR, 13C NMR (CP/MAS), UV-vis spectroscopy, and atomic force microscopy (AFM). We presented the controlled-release performance of the films during incubation in 1 M NaCl solution for several days through UV-vis spectroscopy and polyacrylamide gel electrophoresis (PAGE). Additionally, we verified the stability and integrity of the siRNA loaded on multilayer films. Finally, the biological efficacy of the siRNA delivery system was evaluated via cells adhesion and gene silencing analyses in eGFP-HEK 293T cells. This new type of surface-mediated non-viral multilayer films may have considerable potential in the localized and controlled-release delivery of siRNA in mucosal tissues, and tissue engineering application.

  2. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  3. Preactivated hyaluronic acid: A potential mucoadhesive polymer for vaginal delivery.

    PubMed

    Nowak, Jessika; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2015-01-15

    The objective of this study was to develop mucoadhesive polymeric excipients for vaginal drug delivery systems. Hyaluronic acid was thiolated and subsequently preactivated with 6-mercaptonicotinamide (HA-CYS-MNA) to enhance stability and mucoadhesive properties on vaginal mucosa. After determination of the thiol group content, disintegration studies and in vitro mucoadhesion studies (rotating cylinder and tensile) were performed. Furthermore, swelling behavior and cytotoxicity studies were performed in comparison with corresponding polymers. Both, disintegration and in vitro mucoadhesive studies revealed that modifying HA-CYS with MNA resulted in higher stability (3.6-fold prolonged disintegration time compared to unmodified hyaluronic acid) and prolonged mucoadhesion time. MTT assay and LDH revealed no toxicity for the polymeric excipients and safe for their use. Disintegration and swelling results conducted more pronounced stability of the preactivated thiomers compared to corresponding unmodified ones. According to these results preactivated hyaluronic acid might be a useful tool for vaginal delivery systems.

  4. Stimuli-responsive biodegradable poly(methacrylic acid) based nanocapsules for ultrasound traced and triggered drug delivery system.

    PubMed

    Yang, Peng; Li, Dian; Jin, Sha; Ding, Jing; Guo, Jia; Shi, Weibin; Wang, Changchun

    2014-02-01

    Ultrasound contrast agents (UCAs) have been investigated for echogenic intravenous drug delivery system. Due to the traditional UCAs with overlarge size (micro-scale), their reluctant accumulation in target organs and the instability have presented severe obstacles to the accurate response to the ultrasound and severely limited their further clinical application. Furthermore, elimination of drug carriers from the biologic system after their carrying out the diagnostic or therapeutic functions is one important aspect to be considered. The drug carriers with large sizes, avoiding renal filtration, will lead to increasing toxicity. In this present paper, we design and develop a new type of triple-stimuli responsive (ultrasound/pH/GSH) biodegradable nanocapsules, in which fill up with perfluorohexane, and the DOX-loaded PMAA with disulfide crosslinking forms the wall. These soft nanocapsules with uniform size of 300 nm can easily enter the tumor tissues via EPR effects. The PMAA shell has high DOX-loading content (36 wt%) and great drug loading efficiency (93.5%), the PFH filled can effectively enhance US imaging signal through acoustic droplet vaporization (ADV), ensuring diagnostic and image-guided therapeutic applications. What is more, the disulfide-crosslinked PMAA shell is biodegradable and thus safe for normal organisms. These merits enabled us optimize the balance of diagnostic, therapeutic and biodegradable functionalities in a multifunctional theranostic nanoplatform.

  5. Delivery System, 2003-2004.

    ERIC Educational Resources Information Center

    Office of Federal Student Aid (ED), Washington, DC.

    This workshop guide for financial aid administrators provides training in the federal student financial aid delivery system. An introduction enables the participant to share some information about his or her responsibilities and to reflect on the relevance of the training to the job. Session 1, "Application Systems," identifies methods of applying…

  6. N-Succinyl-chitosan systems for 5-aminosalicylic acid colon delivery: in vivo study with TNBS-induced colitis model in rats.

    PubMed

    Mura, C; Nácher, A; Merino, V; Merino-Sanjuan, M; Carda, C; Ruiz, A; Manconi, M; Loy, G; Fadda, A M; Diez-Sales, O

    2011-09-15

    5-Aminosalicylic acid (5-ASA) loaded N-Succinyl-chitosan (SucCH) microparticle and freeze-dried system were prepared as potential delivery systems to the colon. Physicochemical characterization and in vitro release and swelling studies were previously assessed and showed that the two formulations appeared to be good candidates to deliver the drug to the colon. In this work the effectiveness of these two systems in the treatment of inflammatory bowel disease was evaluated. In vitro mucoadhesive studies showed excellent mucoadhesive properties of both the systems to the inflamed colonic mucosa. Experimental colitis was induced by rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into male Wistar rats. Colon/body weight ratio, clinical activity score system, myeloperoxidase activity and histological evaluation were determined as inflammatory indices. The two formulations were compared with drug suspension and SucCH suspension. The results showed that the loading of 5-ASA into SucCH polymer markedly improved efficacy in the healing of induced colitis in rats.

  7. Microphase Separation and Gelation of Methylcellulose in the Presence of Gallic Acid and NaCl as an In Situ Gel-Forming Drug Delivery System.

    PubMed

    Sangfai, Tanatchaporn; Tantishaiyakul, Vimon; Hirun, Namon; Li, Lin

    2016-05-11

    Novel hydrogels of methylcellulose (MC) with gallic acid (GA) and NaCl were developed for an in situ gel-forming delivery system. Plain MC and GA/NaCl/MC were characterized using micro-differential scanning calorimetry (micro-DSC), rheological and turbidity methods. The gelation temperatures of MC were reduced to body temperature with adding GA/NaCl. GA and NaCl caused slightly different effects on the gelation/degelation temperatures during heating/cooling, respectively, based on the different sensitivities of these three techniques. The gelation mechanism was investigated by UV spectrophotometry, and the hydrophobic interaction between the aromatic ring of GA and MC was verified. The NaCl/MC hydrogel had smaller micropores than GA/MC and MC, indicating a greater cross-linked density. Doxycycline (DX) was loaded into the systems and demonstrated a synergistic effect of DX/GA. Both GA and DX exhibited a sustained release. The hydrogel of GA/4NaCl/MC could be potentially used for the in situ delivery of DX for deep wound healing.

  8. Physicochemical properties of pH-sensitive hydrogels based on hydroxyethyl cellulose-hyaluronic acid and for applications as transdermal delivery systems for skin lesions.

    PubMed

    Kwon, Soon Sik; Kong, Bong Ju; Park, Soo Nam

    2015-05-01

    We investigated the physicochemical properties of pH-sensitive hydroxyethyl cellulose (HEC)/hyaluronic acid (HA) complex hydrogels containing isoliquiritigenin (ILTG), and discussed potential applications as transdermal delivery systems for the treatment of skin lesions caused by pH imbalance. HA has skin compatibility and pH functional groups and HEC serves as scaffold to build hydrogels with varied HCE:HA mass ratio. Hydrogels were synthesized via chemical cross-linking, and three-dimensional network structures were characterized via scanning electron microscopy (SEM). The swelling properties and polymer ratios of the hydrogels were investigated at pH values in the range 1-13. HECHA13 (i.e., an HEC:HA mass ratio of 1:3) was found to have optimal rheological and adhesive properties, and was used to investigate the drug release efficiency as a function of pH; the efficiency was greater than 70% at pH 7. Antimicrobial activity assays against Propionibacterium acnes were conducted to take advantage of the pH-sensitive properties of HECHA13. At pH 7, we found that HECHA13, which contained ILTG, inhibited the growth of P. acnes. Furthermore, HECHA13 was found to exhibit excellent permeability into the skin, which penetrated mostly via the hair follicle. These results indicate that this pH-sensitive hydrogel is effective as a transdermal delivery system for antimicrobial therapeutics, with potential applications in the treatment of acne.

  9. Software Build and Delivery Systems

    SciTech Connect

    Robey, Robert W.

    2016-07-10

    This presentation deals with the hierarchy of software build and delivery systems. One of the goals is to maximize the success rate of new users and developers when first trying your software. First impressions are important. Early successes are important. This also reduces critical documentation costs. This is a presentation focused on computer science and goes into detail about code documentation.

  10. Poly(lactic acid) for delivery of bioactive macromolecules.

    PubMed

    James, Roshan; Manoukian, Ohan S; Kumbar, Sangamesh G

    2016-12-15

    Therapeutic biomolecules often require frequent administration and supramolecular dosing to achieve therapeutic efficiencies and direct infusion into treatment or defect sites results in inadequate physiological response and at times severe side effects or mis-targeting. Delivery systems serve several purposes such as increased circulatory time, increased biomolecule half-life, and incorporation of new innovations can enable highly specific cell targeting and improved cell and nucleus permeability. Poly(lactic acid) (PLA) has become a "material of choice" due to wide availability, reproducible synthetic route, customization, versatility, biodegradability and biocompatibility. Furthermore, PLA is amenable to a variety of fabrication methodologies and chemistries allowing an expansive library correlating physio-chemical properties, characteristics, and applications. This article discusses challenges to biomolecule delivery, and classical approaches of PLA based biomolecule delivery and targeting strategies under development and in trials.

  11. Optimizing Consulting Delivery Systems.

    ERIC Educational Resources Information Center

    Spottswood, Curran

    1980-01-01

    Summarizes a study of several types of consulting groups in the Bell System and describes characteristics which are associated with high-impact consulting. A strategy which is designed for internal consulting organizations to maximize the likelihood of both initial success and long-term survival of the group is proposed. (Author/MER)

  12. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

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

  13. Insulin Delivery System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    When Programmable Implantable Medication System (PIMS) is implanted in human body, it delivers precise programmed amounts of insulin over long periods of time. Mini-Med Technologies has been refining the Technologies since initial development at APL. The size of a hockey puck, and encased in titanium shell, PIMS holds about 2 1/2 teaspoons of insulin at a programmed basal rate. If a change in measured blood sugar level dictates a different dose, the patient can vary the amount of insulin delivered by holding a small radio transceiver over the implanted system and dialing in a specific program held in the PIMS computer memory. Insulin refills are accomplished approximately 4 times a year by hypodermic needle.

  14. Pharmacokinetics of formulated tenoxicam transdermal delivery systems.

    PubMed

    Kim, Taekyung; Kang, Eunyoung; Chun, Inkoo; Gwak, Hyesun

    2008-01-01

    To investigate the feasibility of developing a new tenoxicam transdermal delivery system (TDS), the pharmacokinetics of tenoxicam from various formulated TDS were evaluated and compared with values following oral administration of tenoxicam and with application of a piroxicam plaster (Trast) marketed in Korea. Based on previous in-vitro study results, a mixture of diethylene glycol monoethyl ether (DGME) and propylene glycol monolaurate (PGML) (40:60) was used as a vehicle, and caprylic acid, capric acid, lauric acid, oleic acid or linoleic acid (each at 3%) was added as an enhancer. Triethanolamine (5%) was used as a solubilizer, and Duro-Tak 87-2510 as a pressure-sensitive adhesive. Among these fatty acids used for the formulation of tenoxicam TDS, caprylic acid showed the greatest enhancing effect; the area under the plasma concentration-time profile (AUC) decreased in the order of caprylic acid>linoleic acid>or=oleic acid>lauric acid>capric acid. Compared with oral administration, maximum plasma concentration (Cmax) was significantly lower, and time to reach Cmax (Tmax) delayed with all formulated tenoxicam TDS. All formulated TDS resulted in a lower AUC than with the oral formulation, except for TDS containing caprylic acid, although the difference was statistically significant only with capric acid. The AUC for all the formulated tenoxicam TDS was significantly higher than that of the piroxicam plaster; TDS with caprylic acid increased AUC 8.53-fold compared with the piroxicam plaster. Even though the Tmax of tenoxicam TDS was not significantly different from that of the piroxicam plaster, Cmax was higher; formulations containing caprylic acid and linoleic acid increased Cmax by 7.39- and 8.76-fold, respectively. In conclusion, a formulation containing 1.5 mL DGME-PGML (40:60) with 3% caprylic acid and 5% triethanolamine mixed with 6 g Duro-Tak 87-2510 could be a good candidate for developing a new tenoxicam TDS to maintain a comparable extent of absorption

  15. Cyclodextrins in delivery systems: Applications

    PubMed Central

    Tiwari, Gaurav; Tiwari, Ruchi; Rai, Awani K.

    2010-01-01

    Cyclodextrins (CDs) are a family of cyclic oligosaccharides with a hydrophilic outer surface and a lipophilic central cavity. CD molecules are relatively large with a number of hydrogen donors and acceptors and, thus in general, they do not permeate lipophilic membranes. In the pharmaceutical industry, CDs have mainly been used as complexing agents to increase aqueous solubility of poorly soluble drugs and to increase their bioavailability and stability. CDs are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current CD-based therapeutics is described and possible future applications are discussed. CD-containing polymers are reviewed and their use in drug delivery is presented. Of specific interest is the use of CD-containing polymers to provide unique capabilities for the delivery of nucleic acids. Studies in both humans and animals have shown that CDs can be used to improve drug delivery from almost any type of drug formulation. Currently, there are approximately 30 different pharmaceutical products worldwide containing drug/CD complexes in the market. PMID:21814436

  16. Hyaluronic acid for anticancer drug and nucleic acid delivery.

    PubMed

    Dosio, Franco; Arpicco, Silvia; Stella, Barbara; Fattal, Elias

    2016-02-01

    Hyaluronic acid (HA) is widely used in anticancer drug delivery, since it is biocompatible, biodegradable, non-toxic, and non-immunogenic; moreover, HA receptors are overexpressed on many tumor cells. Exploiting this ligand-receptor interaction, the use of HA is now a rapidly-growing platform for targeting CD44-overexpressing cells, to improve anticancer therapies. The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed. Comprehensive descriptions are given of HA-based drug conjugates, particulate carriers (micelles, liposomes, nanoparticles, microparticles), inorganic nanostructures, and hydrogels, with particular emphasis on reports of preclinical/clinical results.

  17. Biopolymers as transdermal drug delivery systems in dermatology therapy.

    PubMed

    Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

    2010-01-01

    The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

  18. Micro injector sample delivery system for charged molecules

    DOEpatents

    Davidson, James C.; Balch, Joseph W.

    1999-11-09

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

  19. Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo.

    PubMed

    Luo, Yuling; Liu, Zhongbing; Zhang, Xiaoqin; Huang, Juan; Yu, Xin; Li, Jinwei; Xiong, Dan; Sun, Xiaoduan; Zhong, Zhirong

    2016-01-01

    The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA) to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs) were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 μm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger-Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy.

  20. Encapsulation of ω-3 fatty acids in nanoemulsion-based delivery systems fabricated from natural emulsifiers: Sunflower phospholipids.

    PubMed

    Komaiko, Jennifer; Sastrosubroto, Ashtri; McClements, David Julian

    2016-07-15

    Nanoemulsions have considerable potential for encapsulating and delivering ω-3 fatty acids, but they are typically fabricated from synthetic surfactants. This study shows that fish oil-in-water nanoemulsions can be formed from sunflower phospholipids, which have advantages for food applications because they have low allergenicity and do not come from genetically modified organisms. Nanoemulsions containing small droplets (d<150 nm) could be produced using microfluidization, by optimizing phospholipid type and concentration, with the smallest droplets being formed at high phosphatidylcholine levels and at surfactant-to-oil ratios exceeding unity. The physical stability of the nanoemulsions was mainly attributed to electrostatic repulsion, with droplet aggregation occurring at low pH values (low charge magnitude) and at high ionic strengths (electrostatic screening). These results suggest that sunflower phospholipids may be a viable natural emulsifier to deliver ω-3 fatty acids into food and beverage products.

  1. Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Wang, Lei; Hao, Yongwei; Li, Haixia; Zhao, Yalin; Meng, Dehui; Li, Dong; Shi, Jinjin; Zhang, Hongling; Zhang, Zhenzhong; Zhang, Yun

    2015-01-01

    It is very challenging to treat brain cancer because of the blood-brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.

  2. Insulin-loaded alginic acid nanoparticles for sublingual delivery.

    PubMed

    Patil, Nilam H; Devarajan, Padma V

    2016-01-01

    Alginic acid nanoparticles (NPs) containing insulin, with nicotinamide as permeation enhancer were developed for sublingual delivery. The lower concentration of proteolytic enzymes, lower thickness and enhanced retention due to bioadhesive property, were relied on for enhanced insulin absorption. Insulin-loaded NPs were prepared by mild and aqueous based nanoprecipitation process. NPs were negatively charged and had a mean size of ∼200 nm with low dispersity index. Insulin loading capacities of >95% suggested a high association of insulin with alginic acid. Fourier Transform Infra-Red Spectroscopy (FTIR) spectra and DSC (Differential Scanning Calorimetry) thermogram of insulin-loaded NPs revealed the association of insulin with alginic acid. Circular dichroism (CD) spectra confirmed conformational stability, while HPLC analysis confirmed chemical stability of insulin in the NPs. Sublingually delivered NPs with nicotinamide exhibited high pharmacological availability (>100%) and bioavailability (>80%) at a dose of 5 IU/kg. The high absolute pharmacological availability of 20.2% and bioavailability of 24.1% in comparison with subcutaneous injection at 1 IU/kg, in the streptozotocin-induced diabetic rat model, suggest the insulin-loaded alginic acid NPs as a promising sublingual delivery system of insulin.

  3. Implantable drug-delivery systems.

    PubMed

    Blackshear, P J

    1979-12-01

    Implantable drug-delivery systems are being developed to release drugs to the bloodstream continuously as well as free patients from being hospitalized to receive intravenous infusions or frequent injections. One technique is implantation of a pellet in the subcutaneous tissue so the pellet may be released by erosion. Drugs are also diffused through silicone rubber capsules but only polyacrylamide is able to release large molecules. Contraceptive rings containing progesterone and placed in the uterus or vagina and implanted silicone-rubber capsules use these principles. Disadvantages to the subcutaneous delivery of drugs include: 1) release of the drug in subcutaneous tissue rather than in the bloodstream directly; 2) entry into the circulatory system is controlled by surrounding blood supplies which vary with fat; 3) diffusion may be difficult due to dense layers of fibrous tissue; and 4) drug amounts cannot be readily regulated. The Ommaya reservoir uses a container with a self-sealing membrane implanted in the scalp and connected to a cerebral ventricle to treat forms of leukemia and fungal meningitis. Another development is an implantable disk-shaped infusion pump with 2 compartments, the outer one containing a propellant and the inner chamber containing the drug, holds 45 milliliters and releases about 1 milliliter/day. In the future these systems may release drugs in response to biochemical feedback or deliver a drug to 1 specific area.

  4. Sustained release of anticancer agent phytic acid from its chitosan-coated magnetic nanoparticles for drug-delivery system

    PubMed Central

    Barahuie, Farahnaz; Dorniani, Dena; Saifullah, Bullo; Gothai, Sivapragasam; Hussein, Mohd Zobir; Pandurangan, Ashok Kumar; Arulselvan, Palanisamy; Norhaizan, Mohd Esa

    2017-01-01

    Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell. PMID:28392693

  5. Application of living free radical polymerization for nucleic acid delivery.

    PubMed

    Chu, David S H; Schellinger, Joan G; Shi, Julie; Convertine, Anthony J; Stayton, Patrick S; Pun, Suzie H

    2012-07-17

    Therapeutic gene delivery can alter protein function either through the replacement of nonfunctional genes to restore cellular health or through RNA interference (RNAi) to mask mutated and harmful genes. Researchers have investigated a range of nucleic acid-based therapeutics as potential treatments for hereditary, acquired, and infectious diseases. Candidate drugs include plasmids that induce gene expression and small, interfering RNAs (siRNAs) that silence target genes. Because of their self-assembly with nucleic acids into virus-sized nanoparticles and high transfection efficiency in vitro, cationic polymers have been extensively studied for nucleic acid delivery applications, but toxicity and particle stability have limited the clinical applications of these systems. The advent of living free radical polymerization has improved the quality, control, and reproducibility of these synthesized materials. This process yields well-defined, narrowly disperse materials with designed architectures and molecular weights. As a result, researchers can study the effects of polymer architecture and molecular weight on transfection efficiency and cytotoxicity, which will improve the design of next-generation vectors. In this Account, we review findings from structure-function studies that have elucidated key design motifs necessary for the development of effective nucleic acid vectors. Researchers have used robust methods such as atom transfer radical polymerization (ATRP), reverse addition-fragmentation chain transfer polymerization (RAFT), and ring-opening metastasis polymerization (ROMP) to engineer materials that enhance extracellular stability and cellular specificity and decrease toxicity. In addition, we discuss polymers that are biodegradable, form supramolecular structures, target specific cells, or facilitate endosomal release. Finally, we describe promising materials with a range of in vivo applications from pulmonary gene delivery to DNA vaccines.

  6. In Situ Forming Polymeric Drug Delivery Systems

    PubMed Central

    Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J. A.

    2009-01-01

    In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel. The formation of gels depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. Various polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly(DL-lactic acid), poly(DL-lactide-co-glycolide) and poly-caprolactone. The choice of solvents like water, dimethylsulphoxide, N-methyl pyrrolidone, triacetin and 2-pyrrolidone for these formulations depends on the solubility of polymer used. Mainly in situ gels are administered by oral, ocular, rectal, vaginal, injectable and intraperitoneal routes. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. The article presents a detailed review of these types of polymeric systems, their evaluation, advancements and their commercial formulations. From a manufacturing point of view, the production of such devices is less complex and thus lowers the investment and manufacturing cost. PMID:20490289

  7. Porous calcium phosphate-poly (lactic-co-glycolic) acid composite bone cement: A viable tunable drug delivery system.

    PubMed

    Roy, Abhijit; Jhunjhunwala, Siddharth; Bayer, Emily; Fedorchak, Morgan; Little, Steve R; Kumta, Prashant N

    2016-02-01

    Calcium phosphate based cements (CPCs) are frequently used as bone void fillers for non-load bearing segmental bone defects due to their clinically relevant handling characteristics and ability to promote natural bone growth. Macroporous CPC scaffolds with interconnected pores are preferred for their ability to degrade faster and enable accelerated bone regeneration. Herein, a composite CPC scaffold is developed using newly developed resorbable calcium phosphate cement (ReCaPP) formulation containing degradable microspheres of bio-compatible poly (lactic-co-glycolic acid) (PLGA) serving as porogen. The present study is aimed at characterizing the effect of in-vitro degradation of PLGA microspheres on the physical, chemical and structural characteristics of the composite cements. The porosity measurements results reveal the formation of highly interconnected macroporous scaffolds after degradation of PLGA microspheres. The in-vitro characterizations also suggest that the degradation by products of PLGA reduces the pH of the local environment thereby increasing the dissolution rate of the cement. In addition, the in-vitro vancomycin release from the composite CPC scaffold suggests that the drug association with the composite scaffolds can be tuned to achieve control release kinetics. Further, the study demonstrates control release lasting for longer than 10weeks from the composite cements in which vancomycin is encapsulated in PLGA microspheres.

  8. Delivery systems and adjuvants for oral vaccines.

    PubMed

    Lavelle, Ed C; O'Hagan, D T

    2006-11-01

    The oral route is the ideal means of delivering prophylactic and therapeutic vaccines, offering significant advantages over systemic delivery. Most notably, oral delivery is associated with simple administration and improved safety. In addition, unlike systemic immunisation, oral delivery can induce mucosal immune responses. However, the oral route of vaccine delivery is the most difficult because of the numerous barriers posed by the gastrointestinal tract. To facilitate effective immunisation with peptide and protein vaccines, antigens must be protected, uptake enhanced and the innate immune response activated. Numerous delivery systems and adjuvants have been evaluated for oral vaccine delivery, including live vectors, inert particles and bacterial toxins. Although developments in oral vaccines have been disappointing so far, in terms of the generation of products, the availability of a range of novel delivery systems offers much greater hope for the future development of improved oral vaccines.

  9. Nanotechnology for delivery of peptide nucleic acids (PNAs).

    PubMed

    Gupta, Anisha; Bahal, Raman; Gupta, Meera; Glazer, Peter M; Saltzman, W Mark

    2016-10-28

    Over the past three decades, peptide nucleic acids have been employed in numerous chemical and biological applications. Peptide nucleic acids possess enormous potential because of their superior biophysical properties, compared to other oligonucleotide chemistries. However, for therapeutic applications, intracellular delivery of peptide nucleic acids remains a challenge. In this review, we summarize the progress that has been made in delivering peptide nucleic acids to intracellular targets. In addition, we emphasize recent nanoparticle-based strategies for efficient delivery of conventional and chemically-modified peptides nucleic acids.

  10. 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…

  11. Rapid Data Delivery System (RDDS)

    USGS Publications Warehouse

    Cress, Jill J.; Goplen, Susan E.

    2007-01-01

    Since the start of the active 2000 summer fire season, the U. S. Geological Survey (USGS) Rocky Mountain Geographic Science Center (RMGSC) has been actively engaged in providing crucial and timely support to Federal, State, and local natural hazards monitoring, analysis, response, and recovery activities. As part of this support, RMGSC has developed the Rapid Data Delivery System (RDDS) to provide emergency and incident response teams with timely access to geospatial data. The RDDS meets these needs by combining a simple web-enabled data viewer for the selection and preview of vector and raster geospatial data with an easy to use data ordering form. The RDDS viewer also incorporates geospatial locations for current natural hazard incidents, including wildfires, earthquakes, hurricanes, and volcanoes, allowing incident responders to quickly focus on their area of interest for data selection.

  12. Microfabricated injectable drug delivery system

    DOEpatents

    Krulevitch, Peter A.; Wang, Amy W.

    2002-01-01

    A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

  13. pH-Responsive Polyethylene Glycol Monomethyl Ether-ε-Polylysine-G-Poly (Lactic Acid)-Based Nanoparticles as Protein Delivery Systems

    PubMed Central

    Liu, Huiqin; Li, Yijia; Yang, Rui; Gao, Xiujun; Ying, Guoguang

    2016-01-01

    The application of poly(lactic acid) for sustained protein delivery is restricted by the harsh pH inside carriers. In this study, we synthesized a pH-responsive comb-shaped block copolymer, polyethylene glycol monomethyl ether-ε-polylysine-g-poly (lactic acid) (PEP)to deliver protein (bovine serum albumin (BSA)). The PEP nanoparticles could automatically adjust the internal pH to a milder level, as shown by the quantitative ratio metric results. The circular dichroism spectra showed that proteins from the PEP nanoparticles were more stable than those from poly(lactic acid) nanoparticles. PEP nanoparticles could achieve sustained BSA release in both in vitro and in vivo experiments. Cytotoxicity results in HL-7702 cells suggested good cell compatibility of PEP carriers. Acute toxicity results showed that the PEP nanoparticles induced no toxic response in Kunming mice. Thus, PEP nanoparticles hold potential as efficient carriers for sustained protein release. PMID:27467072

  14. pH-Responsive Polyethylene Glycol Monomethyl Ether-ε-Polylysine-G-Poly (Lactic Acid)-Based Nanoparticles as Protein Delivery Systems.

    PubMed

    Liu, Huiqin; Li, Yijia; Yang, Rui; Gao, Xiujun; Ying, Guoguang

    2016-01-01

    The application of poly(lactic acid) for sustained protein delivery is restricted by the harsh pH inside carriers. In this study, we synthesized a pH-responsive comb-shaped block copolymer, polyethylene glycol monomethyl ether-ε-polylysine-g-poly (lactic acid) (PEP)to deliver protein (bovine serum albumin (BSA)). The PEP nanoparticles could automatically adjust the internal pH to a milder level, as shown by the quantitative ratio metric results. The circular dichroism spectra showed that proteins from the PEP nanoparticles were more stable than those from poly(lactic acid) nanoparticles. PEP nanoparticles could achieve sustained BSA release in both in vitro and in vivo experiments. Cytotoxicity results in HL-7702 cells suggested good cell compatibility of PEP carriers. Acute toxicity results showed that the PEP nanoparticles induced no toxic response in Kunming mice. Thus, PEP nanoparticles hold potential as efficient carriers for sustained protein release.

  15. Synthesis and characterization of poly(lactic-co-glycolic) acid nanoparticles-loaded chitosan/bioactive glass scaffolds as a localized delivery system in the bone defects.

    PubMed

    Nazemi, K; Moztarzadeh, F; Jalali, N; Asgari, S; Mozafari, M

    2014-01-01

    The functionality of tissue engineering scaffolds can be enhanced by localized delivery of appropriate biological macromolecules incorporated within biodegradable nanoparticles. In this research, chitosan/58 S-bioactive glass (58 S-BG) containing poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been prepared and then characterized. The effects of further addition of 58 S-BG on the structure of scaffolds have been investigated to optimize the characteristics of the scaffolds for bone tissue engineering applications. The results showed that the scaffolds had high porosity with open pores. It was also shown that the porosity decreased with increasing 58 S-BG content. Furthermore, the PLGA nanoparticles were homogenously distributed within the scaffolds. According to the obtained results, the nanocomposites could be considered as highly bioactive bone tissue engineering scaffolds with the potential of localized delivery of biological macromolecules.

  16. Electronic Delivery Systems: A Selection Model.

    ERIC Educational Resources Information Center

    Pallesen, Peter J.; Haley, Paul; Jones, Edward S.; Moore, Bobbie; Widlake, Dina E.; Medsker, Karen L.

    1999-01-01

    Discussion of electronic learning delivery systems focuses on a delivery system selection model that is designed for use by performance improvement professionals who are choosing between satellite networks, teleconferencing, Internet/Intranet networks, desktop multimedia, electronic performance support systems, transportable audio/video, and the…

  17. Intelligent hydrogels for drug delivery system.

    PubMed

    He, Liumin; Zuo, Qinhua; Xie, Shasha; Huang, Yuexin; Xue, Wei

    2011-09-01

    Intelligent hydrogel, also known as smart hydrogels, are materials with great potential for development in drug delivery system. Intelligent hydrogel also has the ability to perceive as a signal structure change and stimulation. The review introduces the temperature-, pH-, electric signal-, biochemical molecule-, light- and pressure- sensitive hydrogels. Finally, we described the application of intelligent hydrogel in drug delivery system and the recent patents involved for hydrogel in drug delivery.

  18. Fiber coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan

    2008-08-12

    A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

  19. Enterprise networks. Strategies for integrated delivery systems.

    PubMed

    Siwicki, B

    1997-02-01

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

  20. Development of the Choctaw Health Delivery System.

    ERIC Educational Resources Information Center

    Nguyen, Binh N.

    The Choctaw Tribe is the first and only tribe to develop a health delivery system to take over an existing Indian Health Service inpatient facility. The takeover was accomplished in January 1984 under the Indian Self-Determination Act through a contract with the Indian Health Service. The Choctaw Health Delivery System includes a 35-bed general…

  1. Viral and nonviral delivery systems for gene delivery

    PubMed Central

    Nayerossadat, Nouri; Maedeh, Talebi; Ali, Palizban Abas

    2012-01-01

    Gene therapy is the process of introducing foreign genomic materials into host cells to elicit a therapeutic benefit. Although initially the main focus of gene therapy was on special genetic disorders, now diverse diseases with different patterns of inheritance and acquired diseases are targets of gene therapy. There are 2 major categories of gene therapy, including germline gene therapy and somatic gene therapy. Although germline gene therapy may have great potential, because it is currently ethically forbidden, it cannot be used; however, to date human gene therapy has been limited to somatic cells. Although numerous viral and nonviral gene delivery systems have been developed in the last 3 decades, no delivery system has been designed that can be applied in gene therapy of all kinds of cell types in vitro and in vivo with no limitation and side effects. In this review we explain about the history of gene therapy, all types of gene delivery systems for germline (nuclei, egg cells, embryonic stem cells, pronuclear, microinjection, sperm cells) and somatic cells by viral [retroviral, adenoviral, adeno association, helper-dependent adenoviral systems, hybrid adenoviral systems, herpes simplex, pox virus, lentivirus, Epstein–Barr virus)] and nonviral systems (physical: Naked DNA, DNA bombardant, electroporation, hydrodynamic, ultrasound, magnetofection) and (chemical: Cationic lipids, different cationic polymers, lipid polymers). In addition to the above-mentioned, advantages, disadvantages, and practical use of each system are discussed. PMID:23210086

  2. Drug delivery systems: An updated review

    PubMed Central

    Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K

    2012-01-01

    Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time. PMID:23071954

  3. Starch Applications for Delivery Systems

    NASA Astrophysics Data System (ADS)

    Li, Jason

    2013-03-01

    Starch is one of the most abundant and economical renewable biopolymers in nature. Starch molecules are high molecular weight polymers of D-glucose linked by α-(1,4) and α-(1,6) glycosidic bonds, forming linear (amylose) and branched (amylopectin) structures. Octenyl succinic anhydride modified starches (OSA-starch) are designed by carefully choosing a proper starch source, path and degree of modification. This enables emulsion and micro-encapsulation delivery systems for oil based flavors, micronutrients, fragrance, and pharmaceutical actives. A large percentage of flavors are encapsulated by spray drying in today's industry due to its high throughput. However, spray drying encapsulation faces constant challenges with retention of volatile compounds, oxidation of sensitive compound, and manufacturing yield. Specialty OSA-starches were developed suitable for the complex dynamics in spray drying and to provide high encapsulation efficiency and high microcapsule quality. The OSA starch surface activity, low viscosity and film forming capability contribute to high volatile retention and low active oxidation. OSA starches exhibit superior performance, especially in high solids and high oil load encapsulations compared with other hydrocolloids. The submission is based on research and development of Ingredion

  4. 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

  5. Nonviral Approaches for Neuronal Delivery of Nucleic Acids

    PubMed Central

    Bergen, Jamie M.; Park, In-Kyu; Horner, Philip J.

    2007-01-01

    The delivery of therapeutic nucleic acids to neurons has the potential to treat neurological disease and spinal cord injury. While select viral vectors have shown promise as gene carriers to neurons, their potential as therapeutic agents is limited by their toxicity and immunogenicity, their broad tropism, and the cost of large-scale formulation. Nonviral vectors are an attractive alternative in that they offer improved safety profiles compared to viruses, are less expensive to produce, and can be targeted to specific neuronal subpopulations. However, most nonviral vectors suffer from significantly lower transfection efficiencies than neurotropic viruses, severely limiting their utility in neuron-targeted delivery applications. To realize the potential of nonviral delivery technology in neurons, vectors must be designed to overcome a series of extra- and intracellular barriers. In this article, we describe the challenges preventing successful nonviral delivery of nucleic acids to neurons and review strategies aimed at overcoming these challenges. PMID:17932730

  6. Fiber laser coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan; Joshi, Sachin; Reynolds, Adam

    2008-03-04

    A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

  7. Multi-channel gas-delivery system

    SciTech Connect

    Rozenzon, Yan; Trujillo, Robert T.; Beese, Steven C.

    2016-09-13

    One embodiment of the present invention provides a gas-delivery system for delivering reaction gas to a reactor chamber. The gas-delivery system includes a main gas-inlet port for receiving reaction gases and a gas-delivery plate that includes a plurality of gas channels. A gas channel includes a plurality of gas holes for allowing the reaction gases to enter the reactor chamber from the gas channel. The gas-delivery system further includes a plurality of sub-gas lines coupling together the main gas-inlet port and the gas-delivery plate, and a respective sub-gas line is configured to deliver a portion of the received reaction gases to a corresponding gas channel.

  8. Organized Athletics as a Leisure Delivery System.

    ERIC Educational Resources Information Center

    Kidd, Thomas R.; Mendell, Ron

    1980-01-01

    Athletic programs are leisure time delivery systems for the athletes, spectators, and the local community as long as scholarships and extensive media coverage are not involved. College administration should make sure that sports and athletics do not become a delivery sytem for public relations and finance. (CJ)

  9. New delivery systems and propellants.

    PubMed

    Dolovich, M

    1999-01-01

    The removal of chlorofluorocarbon (CFC) propellants from industrial and household products has been agreed to by over 165 countries of which more than 135 are developing countries. The timetable for this process is outlined in the Montreal Protocol on Substances that Deplete the Ozone Layer document and in several subsequent amendments. Pressured metered dose inhalers (pMDIs) for medical use have been granted temporary exemptions until replacement formulations, providing the same medication via the same route, and with the same efficacy and safety profiles, are approved for human use. Hydrofluoroalkanes (HFAs) are the alternative propellants for CFCs-12 and -114. Their potential for damage to the ozone layer is nonexistent, and while they are greenhouse gases, their global warming potential is a fraction (one-tenth) of that of CFCs. Replacement formulations for almost all inhalant respiratory medications have been or are being produced and tested; in Canada, it is anticipated that the transition to these HFA or CFC-free pMDIs will be complete by the year 2005. Initially, an HFA pMDI was to be equivalent to the CFC pMDI being replaced, in terms of aerosol properties and effective clinical dose. However, this will not necessarily be the situation, particularly for some corticosteroid products. Currently, only one CFC-free formulation is available in Canada - Airomir, a HFA salbutamol pMDI. This paper discusses the in vitro aerosol characteristics, in vivo deposition and clinical data for several HFA pMDIs for which there are data available in the literature. Alternative delivery systems to the pMDI, namely, dry powder inhalers and nebulizers, are briefly reviewed.

  10. Drug delivery systems from nose to brain.

    PubMed

    Misra, Ambikanandan; Kher, Gitanjali

    2012-09-01

    The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drug delivery systems, the various intranasal drug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed.

  11. Hybrid polymeric hydrogels for ocular drug delivery: nanoparticulate systems from copolymers of acrylic acid-functionalized chitosan and N-isopropylacrylamide or 2-hydroxyethyl methacrylate.

    PubMed

    Barbu, Eugen; Verestiuc, Liliana; Iancu, Mihaela; Jatariu, Anca; Lungu, Adriana; Tsibouklis, John

    2009-06-03

    Nanoparticulate hybrid polymeric hydrogels (10-70 nm) have been obtained via the radical-induced co-polymerization of acrylic acid-functionalized chitosan with either N-isopropylacrylamide or 2-hydroxyethyl methacrylate, and the materials have been investigated for their ability to act as controlled release vehicles in ophthalmic drug delivery. Studies on the effects of network structure upon swelling properties, adhesiveness to substrates that mimic mucosal surfaces and biodegradability, coupled with in vitro drug release investigations employing ophthalmic drugs with differing aqueous solubilities, have identified nanoparticle compositions for each of the candidate drug molecules. The hybrid nanoparticles combine the temperature sensitivity of N-isopropylacrylamide or the good swelling characteristics of 2-hydroxyethyl methacrylate with the susceptibility of chitosan to lysozyme-induced biodegradation.

  12. Hybrid polymeric hydrogels for ocular drug delivery: nanoparticulate systems from copolymers of acrylic acid-functionalized chitosan and N-isopropylacrylamide or 2-hydroxyethyl methacrylate

    NASA Astrophysics Data System (ADS)

    Barbu, Eugen; Verestiuc, Liliana; Iancu, Mihaela; Jatariu, Anca; Lungu, Adriana; Tsibouklis, John

    2009-06-01

    Nanoparticulate hybrid polymeric hydrogels (10-70 nm) have been obtained via the radical-induced co-polymerization of acrylic acid-functionalized chitosan with either N-isopropylacrylamide or 2-hydroxyethyl methacrylate, and the materials have been investigated for their ability to act as controlled release vehicles in ophthalmic drug delivery. Studies on the effects of network structure upon swelling properties, adhesiveness to substrates that mimic mucosal surfaces and biodegradability, coupled with in vitro drug release investigations employing ophthalmic drugs with differing aqueous solubilities, have identified nanoparticle compositions for each of the candidate drug molecules. The hybrid nanoparticles combine the temperature sensitivity of N-isopropylacrylamide or the good swelling characteristics of 2-hydroxyethyl methacrylate with the susceptibility of chitosan to lysozyme-induced biodegradation.

  13. Alternative delivery systems in rural areas.

    PubMed Central

    Christianson, J B

    1989-01-01

    Alternative delivery systems, such as HMOs, PPOs, and primary care case-management programs, have a long history in rural America despite significant impediments to their development. However, little is known about the effect of these systems on rural communities and their medical care delivery systems. Existing studies, which focus on rural HMOs, are qualitative in nature and generally are directed at identifying factors that facilitate or retard HMO development. Despite their limitations, the studies do raise a variety of issues deserving of quantitative analysis. Research is now needed that (1) investigates the effect of rural alternative delivery systems on the cost and quality of care received by rural residents, (2) assesses the effectiveness of different mechanisms used by these systems to contain costs, (3) estimates the effect of alternative delivery systems on rural providers, (4) determines the extent to which the presence or absence of alternative delivery systems influences physician decisions to locate in rural areas, (5) identifies factors that are important in consumer decisions to enroll or not enroll in a rural alternative delivery system, and (6) analyzes the diffusion patterns of these systems in rural areas. PMID:2645250

  14. Radiation sterilization of new drug delivery systems.

    PubMed

    Abuhanoğlu, Gürhan; Ozer, A Yekta

    2014-06-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation.

  15. Hydrogen storage and delivery system development

    SciTech Connect

    Handrock, J.L.; Wally, K.; Raber, T.N.

    1995-09-01

    Hydrogen storage and delivery is an important element in effective hydrogen utilization for energy applications and is an important part of the FY1994-1998 Hydrogen Program Implementation Plan. The purpose of this project is to develop a platform for the engineering evaluation of hydrogen storage and delivery systems with an added focus on lightweight hydride utilization. Hybrid vehicles represent the primary application area of interest, with secondary interests including such items as existing vehicles and stationary uses. The near term goal is the demonstration of an internal combustion engine/storage/delivery subsystem. The long term goal is optimization of storage technologies for both vehicular and industrial stationary uses. In this project an integrated approach is being used to couple system operating characteristics to hardware development. A model has been developed which integrates engine and storage material characteristics into the design of hydride storage and delivery systems. By specifying engine operating parameters, as well as a variety of storage/delivery design features, hydride bed sizing calculations are completed. The model allows engineering trade-off studies to be completed on various hydride material/delivery system configurations. A more generalized model is also being developed to allow the performance characteristics of various hydrogen storage and delivery systems to be compared (liquid, activated carbon, etc.). Many of the features of the hydride storage model are applicable to the development of this more generalized model.

  16. Designing Bioactive Delivery Systems for Tissue Regeneration

    PubMed Central

    Davis, Hillary E.

    2010-01-01

    The direct infusion of macromolecules into defect sites generally does not impart adequate physiological responses. Without the protection of delivery systems, inductive molecules may likely redistribute away from their desired locale and are vulnerable to degradation. In order to achieve efficacy, large doses supplied at interval time periods are necessary, often at great expense and ensuing detrimental side effects. The selection of a delivery system plays an important role in the rate of re-growth and functionality of regenerating tissue: not only do the release kinetics of inductive molecules and their consequent bioactivities need to be considered, but also how the delivery system interacts and integrates with its surrounding host environment. In the current review, we describe the means of release of macromolecules from hydrogels, polymeric microspheres, and porous scaffolds along with the selection and utilization of bioactive delivery systems in a variety of tissue-engineering strategies. PMID:20676773

  17. WEDDS: The WITS Encrypted Data Delivery System

    NASA Technical Reports Server (NTRS)

    Norris, J.; Backes, P.

    1999-01-01

    WEDDS, the WITS Encrypted Data Delivery System, is a framework for supporting distributed mission operations by automatically transferring sensitive mission data in a secure and efficient manner to and from remote mission participants over the internet.

  18. Coacervate delivery systems for proteins and small molecule drugs

    PubMed Central

    Johnson, Noah R; Wang, Yadong

    2015-01-01

    Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including Elastin-like peptides for delivery of anti-cancer therapeutics,Heparin-based coacervates with synthetic polycations for controlled growth factor delivery,Carboxymethyl chitosan aggregates for oral drug delivery,Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future. PMID:25138695

  19. Water-compatible silica sol-gel molecularly imprinted polymer as a potential delivery system for the controlled release of salicylic acid.

    PubMed

    Li, Bin; Xu, Jingjing; Hall, Andrew J; Haupt, Karsten; Tse Sum Bui, Bernadette

    2014-09-01

    Molecularly imprinted polymers (MIPs) for salicylic acid were synthesized and evaluated in aqueous environments in the aim to apply them as drug delivery carriers. One organic MIP and one inorganic MIP based on the sol-gel process were synthesized. The organic MIP was prepared by radical polymerization using the stoichiometric functional monomer, 1-(4-vinylphenyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea, which can establish strong electrostatic interactions with the -COOH of salicylic acid. The sol-gel MIP was prepared with 3-(aminopropyl)triethoxysilane and trimethoxyphenylsilane, as functional monomers and tetraethyl orthosilicate as the crosslinker. While the organic MIPs bound the target specifically in acetonitrile, they exhibited lower binding in the presence of water, although the imprinting factor increased under these conditions, due to reduced non-specific binding. The sol-gel MIP has a high specificity and capacity for the drug in ethanol, a solvent compatible with drug formulation and biomedical applications. In vitro release profiles of the polymers in water were evaluated, and the results were modelled by Fick's law of diffusion and the power law. Analysis shows that the release mechanism was predominantly diffusion-controlled.

  20. Planetary Regolith Delivery Systems for ISRU

    NASA Technical Reports Server (NTRS)

    Mantovani, James G.; Townsend, Ivan I., III

    2012-01-01

    The challenges associated with collecting regolith on a planetary surface and delivering it to an in-situ resource utilization system differ significantly from similar activities conducted on Earth. Since system maintenance on a planetary body can be difficult or impossible to do, high reliability and service life are expected of a regolith delivery system. Mission costs impose upper limits on power and mass. The regolith delivery system must provide a leak-tight interface between the near-vacuum planetary surface and the pressurized ISRU system. Regolith delivery in amounts ranging from a few grams to tens of kilograms may be required. Finally, the spent regolith must be removed from the ISRU chamber and returned to the planetary environment via dust tolerant valves capable of operating and sealing over a large temperature range. This paper will describe pneumatic and auger regolith transfer systems that have already been field tested for ISRU, and discuss other systems that await future field testing.

  1. Glycosylated carriers for cell-selective and nuclear delivery of nucleic acids.

    PubMed

    Wijagkanalan, Wassana; Kawakami, Shigeru; Hashida, Mitsuru

    2011-06-01

    Targeted gene delivery via selective cellular receptors has been realized as a crucial strategy for successful gene therapy by maximizing therapeutic efficiency in target cells and minimizing systemic toxicity. The membrane carbohydrate-binding proteins (membrane lectins) with different carbohydrate specificities are differentially expressed on the cellular and intracellular membranes of a number of cells. Their multiplicity, high affinity, and effective endocytosis after receptor binding as well as the biocompatibility of carbohydrate ligands endow them as potential ligands for glycosylated carriers in cell-selective delivery of nucleic acids. To achieve the in vivo application, glycosylated carriers/nucleic acid complexes have to fulfill certain conditions, including having a suitable size, minimal nonspecific interactions, low immunogenicity, and high uptake in target cells. Accordingly, the effective nuclear delivery of nucleic acids is the paramount important step for efficient gene transfer. This review summarizes the recent progress regarding application of glycosylated carriers for cell-selective and nuclear delivery of nucleic acids and their critical factors for efficient gene transfer. In addition, the development of new materials, such as carbon nanotubes, carbon nanospheres, and gold nanoparticles, as innovative carriers will be discussed with regards to glycosylation-mediated delivery of nucleic acids.

  2. Goals for Postsecondary Instructional Delivery Systems.

    ERIC Educational Resources Information Center

    Knapp, Stuart E.; Valentine, Carol A.

    Extrapolating from the trends in postsecondary instructional delivery systems identified by Brown, Lewis and Harcleroad, this report attempts to identify how these trends might be implemented in Oregon. Separating the systems into technology-centered and people-centered, the report proposes future applications of dial access systems, self learning…

  3. Bacterial-Derived Polymer Poly-γ-Glutamic Acid (γ-PGA)-Based Micro/Nanoparticles as a Delivery System for Antimicrobials and Other Biomedical Applications

    PubMed Central

    Khalil, Ibrahim R.; Burns, Alan T. H.; Radecka, Iza; Kowalczuk, Marek; Khalaf, Tamara; Adamus, Grazyna; Johnston, Brian; Khechara, Martin P.

    2017-01-01

    In the past decade, poly-γ-glutamic acid (γ-PGA)-based micro/nanoparticles have garnered remarkable attention as antimicrobial agents and for drug delivery, owing to their controlled and sustained-release properties, low toxicity, as well as biocompatibility with tissue and cells. γ-PGA is a naturally occurring biopolymer produced by several gram-positive bacteria that, due to its biodegradable, non-toxic and non-immunogenic properties, has been used successfully in the medical, food and wastewater industries. Moreover, its carboxylic group on the side chains can offer an attachment point to conjugate antimicrobial and various therapeutic agents, or to chemically modify the solubility of the biopolymer. The unique characteristics of γ-PGA have a promising future for medical and pharmaceutical applications. In the present review, the structure, properties and micro/nanoparticle preparation methods of γ-PGA and its derivatives are covered. Also, we have highlighted the impact of micro/nanoencapsulation or immobilisation of antimicrobial agents and various disease-related drugs on biodegradable γ-PGA micro/nanoparticles. PMID:28157175

  4. Advances in polymeric and inorganic vectors for nonviral nucleic acid delivery

    PubMed Central

    Sunshine, Joel C; Bishop, Corey J; Green, Jordan J

    2014-01-01

    Nonviral systems for nucleic acid delivery offer a host of potential advantages compared with viruses, including reduced toxicity and immunogenicity, increased ease of production and less stringent vector size limitations, but remain far less efficient than their viral counterparts. In this article we review recent advances in the delivery of nucleic acids using polymeric and inorganic vectors. We discuss the wide range of materials being designed and evaluated for these purposes while considering the physical requirements and barriers to entry that these agents face and reviewing recent novel approaches towards improving delivery with respect to each of these barriers. Furthermore, we provide a brief overview of past and ongoing nonviral gene therapy clinical trials. We conclude with a discussion of multifunctional nucleic acid carriers and future directions. PMID:22826857

  5. Intelligent, self-powered, drug delivery systems.

    PubMed

    Patra, Debabrata; Sengupta, Samudra; Duan, Wentao; Zhang, Hua; Pavlick, Ryan; Sen, Ayusman

    2013-02-21

    Self-propelled nano/micromotors and pumps are considered to be next generation drug delivery systems since the carriers can either propel themselves ("motor"-based drug delivery) or be delivered ("pump"-based drug delivery) to the target in response to specific biomarkers. Recently, there has been significant advancement towards developing nano/microtransporters into proof-of-concept tools for biomedical applications. This review encompasses the progress made to date on the design of synthetic nano/micromotors and pumps with respect to transportation and delivery of cargo at specific locations. Looking ahead, it is possible to imagine a day when intelligent machines navigate through the human body and perform challenging tasks.

  6. Polylactic acid (PLA) controlled delivery carriers for biomedical applications.

    PubMed

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

    2016-12-15

    Polylactic acid (PLA) and its copolymers have a long history of safety in humans and an extensive range of applications. PLA is biocompatible, biodegradable by hydrolysis and enzymatic activity, has a large range of mechanical and physical properties that can be engineered appropriately to suit multiple applications, and has low immunogenicity. Formulations containing PLA have also been Food and Drug Administration (FDA)-approved for multiple applications making PLA suitable for expedited clinical translatability. These biomaterials can be fashioned into sutures, scaffolds, cell carriers, drug delivery systems, and a myriad of fabrications. PLA has been the focus of a multitude of preclinical and clinical testing. Three-dimensional printing has expanded the possibilities of biomedical engineering and has enabled the fabrication of a myriad of platforms for an extensive variety of applications. PLA has been widely used as temporary extracellular matrices in tissue engineering. At the other end of the spectrum, PLA's application as drug-loaded nanoparticle drug carriers, such as liposomes, polymeric nanoparticles, dendrimers, and micelles, can encapsulate otherwise toxic hydrophobic anti-tumor drugs and evade systemic toxicities. The clinical translation of these technologies from preclinical experimental settings is an ever-evolving field with incremental advancements. In this review, some of the biomedical applications of PLA and its copolymers are highlighted and briefly summarized.

  7. Main chain acid-degradable polymers for the delivery of bioactive materials

    DOEpatents

    Frechet, Jean M. J. [Oakland, CA; Standley, Stephany M [Evanston, IL; Jain, Rachna [Milpitas, CA; Lee, Cameron C [Cambridge, MA

    2012-03-20

    Novel main chain acid degradable polymer backbones and drug delivery systems comprised of materials capable of delivering bioactive materials to cells for use as vaccines or other therapeutic agents are described. The polymers are synthesized using monomers that contain acid-degradable linkages cleavable under mild acidic conditions. The main chain of the resulting polymers readily degrade into many small molecules at low pH, but remain relatively stable and intact at physiological pH. The new materials have the common characteristic of being able to degrade by acid hydrolysis under conditions commonly found within the endosomal or lysosomal compartments of cells thereby releasing their payload within the cell. The materials can also be used for the delivery of therapeutics to the acidic regions of tumors and other sites of inflammation.

  8. Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

    PubMed

    Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

    Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery

  9. Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement

    PubMed Central

    Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

    2016-01-01

    Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery

  10. Educational Power Tools: New Instructional Delivery Systems.

    ERIC Educational Resources Information Center

    Van Horn, Royal

    1991-01-01

    New instructional delivery systems are needed to individualize instruction, relieve the teacher's burden as sole information provider, and meet the challenge of student diversity. Microcomputers, optical memory devices, videodiscs, and hypermedia programs are being combined to create integrated learning systems, multimedia work stations, and other…

  11. Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery

    PubMed Central

    Woo, J. O.; Misran, M.; Lee, P. F.; Tan, L. P.

    2014-01-01

    Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release. PMID:24578624

  12. Bioplex technology: novel synthetic gene delivery pharmaceutical based on peptides anchored to nucleic acids.

    PubMed

    Simonson, Oscar E; Svahn, Mathias G; Törnquist, Elisabeth; Lundin, Karin E; Smith, C I E

    2005-01-01

    Non-viral gene delivery is an important approach in order to establish safe in vivo gene therapy in the clinic. Although viral vectors currently exhibit superior gene transfer efficacy, the safety aspect of viral gene delivery is a concern. In order to improve non-viral in vivo gene delivery we have designed a pharmaceutical platform called Bioplex (biological complex). The concept of Bioplex is to link functional entities via hybridising anchors, such as Peptide Nucleic Acids (PNA), directly to naked DNA. In order to promote delivery functional entities consisting of biologically active peptides or carbohydrates, are linked to the PNA anchor. The PNA acts as genetic glue and hybridises with DNA in a sequence specific manner. By using functional entities, which elicit receptor-mediated endocytosis, improved endosomal escape and enhance nuclear entry we wish to improve the transfer of genetic material into the cell. An important aspect is that the functional entities should also have tissue-targeting properties in vivo. Examples of functional entities investigated to date are the Simian virus 40 nuclear localisation signal to improve nuclear uptake and different carbohydrate ligands in order to achieve receptor specific uptake. The delivery system is also endowed with regulatory capability, since the release of functional entities can be controlled. The aim is to create a safe, pharmaceutically defined and stable delivery system for nucleic acids with enhanced transfection properties that can be used in the clinic.

  13. Renewable energy delivery systems and methods

    DOEpatents

    Walker, Howard Andrew

    2013-12-10

    A system, method and/or apparatus for the delivery of energy at a site, at least a portion of the energy being delivered by at least one or more of a plurality of renewable energy technologies, the system and method including calculating the load required by the site for the period; calculating the amount of renewable energy for the period, including obtaining a capacity and a percentage of the period for the renewable energy to be delivered; comparing the total load to the renewable energy available; and, implementing one or both of additional and alternative renewable energy sources for delivery of energy to the site.

  14. Hydrazone linkages in pH responsive drug delivery systems.

    PubMed

    Sonawane, Sandeep J; Kalhapure, Rahul S; Govender, Thirumala

    2017-03-01

    Stimuli-responsive polymeric drug delivery systems using various triggers to release the drug at the sites have become a major focus area. Among various stimuli-responsive materials, pH-responsiveness has been studied extensively. The materials used for fabricating pH-responsive drug delivery systems include a specific chemical functionality in their structure that can respond to changes in the pH of the surrounding environment. Various chemical functionalities, for example, acetal, amine, ortho ester, amine and hydrazone, have been used to design materials that are capable of releasing their payload at the acidic pH conditions of the tumor or infection sites. Hydrazone linkages are significant synthons for numerous transformations and have gained importance in pharmaceutical sciences due to their various biological and clinical applications. These linkages have been employed in various drug delivery vehicles, such as linear polymers, star shaped polymers, dendrimers, micelles, liposomes and inorganic nanoparticles, for pH-responsive drug delivery. This review paper focuses on the synthesis and characterization methods of hydrazone bond containing materials and their applications in pH-responsive drug delivery systems. It provides detailed suggestions as guidelines to materials and formulation scientists for designing biocompatible pH-responsive materials with hydrazone linkages and identifying future studies.

  15. Liposomal drug delivery systems: from concept to clinical applications.

    PubMed

    Allen, Theresa M; Cullis, Pieter R

    2013-01-01

    The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future.

  16. Deep Space Systems Technology Program Future Deliveries

    NASA Technical Reports Server (NTRS)

    Salvo, Christopher G.; Keuneke, Matthew S.

    2000-01-01

    NASA is in a period of frequent launches of low cost deep space missions with challenging performance needs. The modest budgets of these missions make it impossible for each to develop its own technology, therefore, efficient and effective development and insertion of technology for these missions must be approached at a higher level than has been done in the past. The Deep Space Systems Technology Program (DSST), often referred to as X2000, has been formed to address this need. The program is divided into a series of "Deliveries" that develop and demonstrate a set of spacecraft system capabilities with broad applicability for use by multiple missions. The First Delivery Project, to be completed in 2001, will provide a one MRAD-tolerant flight computer, power switching electronics, efficient radioisotope power source, and a transponder with services at 8.4 GHz and 32 GHz bands. Plans call for a Second Delivery in late 2003 to enable complete deep space systems in the 10 to 50 kg class, and a Third Delivery built around Systems on a Chip (extreme levels of electronic and microsystems integration) around 2006. Formulation of Future Deliveries (past the First Delivery) is ongoing and includes plans for such developments as highly miniaturized digital/analog/power electronics, optical communications, multifunctional structures, miniature lightweight propulsion, advanced thermal control techniques, highly efficient radioisotope power sources, and a unified flight ground software architecture to support the needs of future highly intelligent space systems. All developments are targeted at broad applicability and reuse, and will be commercialized within the US.

  17. Brain drug delivery systems for neurodegenerative disorders.

    PubMed

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2012-09-01

    Neurodegenerative disorders (NDs) are rapidly increasing as population ages. However, successful treatments for NDs have so far been limited and drug delivery to the brain remains one of the major challenges to overcome. There has recently been growing interest in the development of drug delivery systems (DDS) for local or systemic brain administration. DDS are able to improve the pharmacological and therapeutic properties of conventional drugs and reduce their side effects. The present review provides a concise overview of the recent advances made in the field of brain drug delivery for treating neurodegenerative disorders. Examples include polymeric micro and nanoparticles, lipidic nanoparticles, pegylated liposomes, microemulsions and nanogels that have been tested in experimental models of Parkinson's, Alzheimer's and Huntington's disease. Overall, the results reviewed here show that DDS have great potential for NDs treatment.

  18. Exploring the role of polymer structure on intracellular nucleic acid delivery via polymeric nanoparticles.

    PubMed

    Bishop, Corey J; Kozielski, Kristen L; Green, Jordan J

    2015-12-10

    Intracellular nucleic acid delivery has the potential to treat many genetically-based diseases, however, gene delivery safety and efficacy remains a challenging obstacle. One promising approach is the use of polymers to form polymeric nanoparticles with nucleic acids that have led to exciting advances in non-viral gene delivery. Understanding the successes and failures of gene delivery polymers and structures is the key to engineering optimal polymers for gene delivery in the future. This article discusses the polymer structural features that enable effective intracellular delivery of DNA and RNA, including protection of nucleic acid cargo, cellular uptake, endosomal escape, vector unpacking, and delivery to the intracellular site of activity. The chemical properties that aid in each step of intracellular nucleic acid delivery are described and specific structures of note are highlighted. Understanding the chemical design parameters of polymeric nucleic acid delivery nanoparticles is important to achieving the goal of safe and effective non-viral genetic nanomedicine.

  19. Biomimetic high density lipoprotein nanoparticles for nucleic acid delivery.

    PubMed

    McMahon, Kaylin M; Mutharasan, R Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K; Luthi, Andrea J; Helfand, Brian T; Ardehali, Hossein; Mirkin, Chad A; Volpert, Olga; Thaxton, C Shad

    2011-03-09

    We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy that combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy, and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery.

  20. Surface-Mediated Nucleic Acid Delivery by Lipoplexes Prepared in Microwell Arrays

    PubMed Central

    Wu, Yun; Terp, Megan Cavanaugh; Kwak, Kwang Joo; Gallego-Perez, Daniel; Nana-Sinkam, Serge P.; Lee, L. James

    2014-01-01

    Many delivery methods have been developed to improve the therapeutic efficacy and facilitate the clinical translation of nucleic acid-based therapeutics. A facile surface-mediated nucleic acid delivery by lipoplexes is prepared in a microwell array, which combines the advantages of lipoplexes as an efficient carrier system, surface-mediated delivery, and the control of surface topography. Uniform disc-like lipoplexes containing nucleic acids are formed in the microwell array with a diameter of ~ 818 nm and thickness of ~ 195 nm. The microwell array-mediated delivery of lipoplexes containing FAM-oligodeoxynucleotides is ~ 18.6 and ~ 10.6 times more efficient than the conventional transfection method in an adherent cell line (A549 non-small cell lung cancer cells) and a suspension cell line (KG-1a acute myelogenous leukemia cells), respectively. MicroRNA-29b is then used as a model nucleic acid to investigate the therapeutic efficacy of lipoplexes delivered by the microwell array. Compared to conventional transfection methods, the effective therapeutic dosage of microRNA-29b is reduced from the microgram level to the nanogram level by lipoplexes prepared in the microwell array. The microwell array is also a very flexible platform. Both nucleic acid therapeutics and imaging reagents are incorporated in lipoplexes and successfully delivered to A549 cells, demonstrating its potential applications in theranostic medicine. PMID:23471869

  1. Brain-specific delivery of naproxen using different carrier systems.

    PubMed

    Mahmoud, Sheha; Mohammad, Alhawi

    2010-11-01

    Naproxen is one of the most potent NSAIDs and plays an important role in the treatment of neurodegenerative diseases. Poor brain delivery of naproxen at therapeutic doses, in addition to its serious gastrointestinal side effects, has prompted research into the development of a specific carrier system that is capable of delivering naproxen to the brain at smaller doses. The purpose of this study was to evaluate two brain-specific carrier systems of naproxen. The first was the dihydropyridine/pyridinium redox system that utilized a lipophilic chemical delivery system coupled to the carboxylic acid group of naproxen through an ethanolamine linker. Secondly, an ascorbic acid system, which has reducing properties and acts as a biological carrier through sodium-dependent vitamin-C transporter, was used for brain-specific delivery of naproxen. The prepared prodrugs were stable in aqueous buffers (pH 1.2 and 7.4) and rapidly hydrolyzed in biological fluids. Bioavailability studies revealed that both prodrugs 10 and 17 were rapidly cleared from blood with half lives of about 1 h, which will likely decrease systemic adverse effects. The rapid clearance from the blood was accompanied by an increase in the prodrug concentration in the brain, which occurred as a result of the prodrug being more locked in compared to the parent drug naproxen.

  2. Waste Feed Delivery Transfer System Analysis

    SciTech Connect

    JULYK, L.J.

    2000-05-05

    This document provides a documented basis for the required design pressure rating and pump pressure capacity of the Hanford Site waste-transfer system in support of the waste feed delivery to the privatization contractor for vitrification. The scope of the analysis includes the 200 East Area double-shell tank waste transfer pipeline system and the associated transfer system pumps for a11 Phase 1B and Phase 2 waste transfers from AN, AP, AW, AY, and A2 Tank Farms.

  3. Investigation of microemulsion microstructure and its impact on skin delivery of flufenamic acid.

    PubMed

    Mahrhauser, Denise-Silvia; Kählig, Hanspeter; Partyka-Jankowska, Ewa; Peterlik, Herwig; Binder, Lisa; Kwizda, Kristina; Valenta, Claudia

    2015-07-25

    Microemulsions are well known penetration enhancing delivery systems. Several properties are described that influence the transdermal delivery of active components. Therefore, this study aimed to characterize fluorosurfactant-based microemulsions and to assess the impact of formulation variables on the transdermal delivery of incorporated flufenamic acid. The microemulsion systems prepared in this study consisted of bistilled water, oleic acid, isopropanol as co-solvent, flufenamic acid as active ingredient and either Hexafor(TM)670 (Hex) or Chemguard S-550-100 (Sin) as fluorosurfactant. Characterization was performed by a combination of techniques including electrical conductivity measurements, small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) self-diffusion experiments. In vitro skin permeation experiments were performed with each prepared microemulsion using Franz type diffusion cells to correlate their present microstructure with their drug delivery to skin. Electrical conductivity increased with added water content. Consequently, the absence of a conductivity maximum as well as the NMR and SAXS data rather suggest O/W type microemulsions with spherical or rod-like microstructures. Skin permeation data revealed enhanced diffusion for Hex- and Sin-microemulsions if the shape of the structures was rather elongated than spherical implying that the shape of droplets had an essential impact on the skin permeation of flufenamic acid.

  4. Targeted drug delivery to bone: pharmacokinetic and pharmacological properties of acidic oligopeptide-tagged drugs.

    PubMed

    Takahashi-Nishioka, Tatsuo; Yokogawa, Koichi; Tomatsu, Shunji; Nomura, Masaaki; Kobayashi, Shinjiro; Miyamoto, Ken-Ichi

    2008-03-01

    Site-specific drug delivery to bone is considered to be achievable by utilizing acidic amino acid homopeptides. We found that fluorescence-labeled acidic amino acid (L-Asp or L-Glu) homopeptides containing six or more residues bound strongly to hydroxyapatite, which is a major component of bone, and were selectively delivered to and retained in bone after systemic administration. We explored the applicability of this result for drug delivery by conjugation of estradiol and levofloxacin with an L-Asp hexapeptide. We also similarly tagged an enzyme, tissue-nonspecific alkaline phosphatase, to see whether this would improve the efficacy of enzyme replacement therapy. The L-Asp hexapeptide-tagged drugs, including the enzyme, were selectively delivered to bone in comparison with the untagged drugs. It was expected that the ester linkage to the hexapeptide would be susceptible to hydrolysis in situ, releasing the drug or enzyme from the acidic oligopeptide. An in vivo experiment confirmed the efficacy of L-Asp hexapeptide-tagged estradiol and levofloxacin, although there was some loss of bioactivity of estradiol and levofloxacin in vitro, suggesting that the acidic hexapeptide was partly removed by hydrolysis in the body after delivery to bone. The adverse effect of estradiol on the uterus was greatly reduced by conjugation to the hexapeptide. These results support the usefulness of acidic oligopeptides as bone-targeting carriers for therapeutic agents. We present some pharmacokinetic and pharmacological properties of the L-Asp hexapeptide-tagged drugs and enzyme.

  5. Lipid-Based Drug Delivery Systems

    PubMed Central

    Shrestha, Hina; Bala, Rajni; Arora, Sandeep

    2014-01-01

    The principle objective of formulation of lipid-based drugs is to enhance their bioavailability. The use of lipids in drug delivery is no more a new trend now but is still the promising concept. Lipid-based drug delivery systems (LBDDS) are one of the emerging technologies designed to address challenges like the solubility and bioavailability of poorly water-soluble drugs. Lipid-based formulations can be tailored to meet a wide range of product requirements dictated by disease indication, route of administration, cost consideration, product stability, toxicity, and efficacy. These formulations are also a commercially viable strategy to formulate pharmaceuticals, for topical, oral, pulmonary, or parenteral delivery. In addition, lipid-based formulations have been shown to reduce the toxicity of various drugs by changing the biodistribution of the drug away from sensitive organs. However, the number of applications for lipid-based formulations has expanded as the nature and type of active drugs under investigation have become more varied. This paper mainly focuses on novel lipid-based formulations, namely, emulsions, vesicular systems, and lipid particulate systems and their subcategories as well as on their prominent applications in pharmaceutical drug delivery. PMID:26556202

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

    PubMed

    2005-03-01

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

  7. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

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

  8. Calibrator for microflow delivery systems

    NASA Astrophysics Data System (ADS)

    Marinozzi, Franco; Bini, Fabiano; Cappa, Paolo

    2005-01-01

    An apparatus for calibrating the fluid flow rate down to 3×10-2ml/h is proposed, based on the volumetric pump working principle. Constant flow rate is assured by means of the constant speed at which the plunger of a laboratory syringe is moved. To test effectiveness of the system, a flow sensor, composed by a differential pressure transducer and a needle was calibrated and afterward utilized for characterizing a clinical drug infusion device. The proposed apparatus showed a full scale (FS) uncertainty approximately equal to 3.5% over a range of 6 ml/h. The calibration range starts at 3×10-2ml/h with a 1 ml syringe and at 3×10-3ml/h with a 0.1 ml syringe. The minimum detectable signal (evaluated at 6 dB SNR) was equal to about 1.4×10-2ml/h by using a syringe of 1 ml. The outcomes of the adopted procedure allowed a characterization of the performance of an infusion pump, without the need of the usual but somewhat cumbersome gravimetric calibration standard. Moreover, some issues about the expected resolution and uncertainty, depending on the characteristics of the system, is also reported.

  9. Biomaterials for Nanoparticle Vaccine Delivery Systems

    PubMed Central

    Sahdev, Preety; Ochyl, Lukasz J.; Moon, James J.

    2014-01-01

    Subunit vaccination benefits from improved safety over attenuated or inactivated vaccines, but their limited capability to elicit long-lasting, concerted cellular and humoral immune responses is a major challenge. Recent studies have demonstrated that antigen delivery via nanoparticle formulations significantly improve immunogenicity of vaccines due to either intrinsic immunostimulatory properties of the materials or by co-entrapment of molecular adjuvants such as Toll-like receptor agonists. These studies have collectively shown that nanoparticles designed to mimic biophysical and biochemical cues of pathogens offer new exciting opportunities to enhance activation of innate immunity and elicit potent cellular and humoral immunity with minimal cytotoxicity. In this review, we present key research advances that were made within the last 5 years in the field of nanoparticle vaccine delivery systems. In particular, we focus on the impact of biomaterials composition, size, and surface charge of nanoparticles on modulation of particle biodistribution, delivery of antigens and immunostimulatory molecules, trafficking and targeting of antigen presenting cells, and overall immune responses in systemic and mucosal tissues. This review describes recent progresses in the design of nanoparticle vaccine delivery carriers, including liposomes, lipid-based particles, micelles and nanostructures composed of natural or synthetic polymers, and lipid-polymer hybrid nanoparticles. PMID:24848341

  10. Liposomal drug delivery systems--clinical applications.

    PubMed

    Goyal, Parveen; Goyal, Kumud; Vijaya Kumar, Sengodan Gurusamy; Singh, Ajit; Katare, Om Prakash; Mishra, Dina Nath

    2005-03-01

    Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made, thus making this technology potentially useful for the treatment of certain diseases in the clinics. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. The current pharmaceutical preparations of liposome-based therapeutic systems mainly result from our understanding of lipid-drug interactions and liposome disposition mechanisms. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes that can be targeted on tissues, cells or intracellular compartments with or without expression of target recognition molecules on liposome membranes. This review is mainly focused on the diseases that have attracted most attention with respect to liposomal drug delivery and have therefore yielded most progress, namely cancer, antibacterial and antifungal disorders. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.

  11. Recent Advances in Nucleic Acid-Based Delivery: From Bench to Clinical Trials in Genetic Diseases.

    PubMed

    Oliveira, Cláudia; Ribeiro, António J; Veiga, Francisco; Silveira, Isabel

    2016-05-01

    Delivery of nucleic acids is the most promising therapy for many diseases that remain untreatable. Therefore, many research efforts have been put on finding a safe and efficient delivery system able to provide a sustained response. Viral vectors have proved to be the most efficient for delivery of nucleic acids and, thus, stand as the foremost vector used in current clinical trials. However, safety issues arise as a main concern and mitigate their use, impelling the improvement of non-viral alternatives. This review focuses on the recent advances in pre-clinical development of non-viral polyplexes and lipoplexes for nucleic acid-based delivery, in contrast with vectors being used in present clinical trials. Nucleic acid vectors for neurodegenerative ataxias, Parkinson's disease, retinitis pigmentosa, cystic fibrosis, hemophilia, pancreatic and lung cancer, and rheumatoid arthritis are discussed to illustrate current state of pre-clinical and clinical studies. Thereby, denoting the prospects for treatment of genetic diseases and elucidating the trend in non-viral vector development and improvement which is expected to significantly increase disease rescue exceeding the modest clinical successes observed so far.

  12. Hyaluronic acid enhances gene delivery into the cochlea.

    PubMed

    Shibata, Seiji B; Cortez, Sarah R; Wiler, James A; Swiderski, Donald L; Raphael, Yehoash

    2012-03-01

    Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application.

  13. Hydrogen storage and delivery system development: Fabrication

    SciTech Connect

    Handrock, J.L.; Malinowski, M.E.; Wally, K.

    1996-10-01

    Hydrogen storage and delivery is an important element in effective hydrogen utilization for energy applications and is an important part of the FY1994-1998 Hydrogen Program Implementation Plan. This project is part of the Field Work Proposal entitled Hydrogen Utilization in Internal Combustion Engines (ICE). The goal of the Hydrogen Storage and Delivery System Development Project is to expand the state-of-the-art of hydrogen storage and delivery system design and development. At the foundation of this activity is the development of both analytical and experimental evaluation platforms. These tools provide the basis for an integrated approach for coupling hydrogen storage and delivery technology to the operating characteristics of potential hydrogen energy use applications. Analytical models have been developed for internal combustion engine (ICE) hybrid and fuel cell driven vehicles. The dependence of hydride storage system weight and energy use efficiency on engine brake efficiency and exhaust temperature for ICE hybrid vehicle applications is examined. Results show that while storage system weight decreases with increasing engine brake efficiency energy use efficiency remains relatively unchanged. The development, capability, and use of a newly developed fuel cell vehicle hydride storage system model will also be discussed. As an example of model use power distribution and control for a simulated driving cycle is presented. An experimental test facility, the Hydride Bed Testing Laboratory (HBTL) has been designed and fabricated. The development of this facility and its use in storage system development will be reviewed. These two capabilities (analytical and experimental) form the basis of an integrated approach to storage system design and development. The initial focus of these activities has been on hydride utilization for vehicular applications.

  14. Topical Delivery of Hyaluronic Acid into Skin using SPACE-peptide Carriers

    PubMed Central

    Chen, Ming; Gupta, Vivek; Anselmo, Aaron C.; Muraski, John A.; Mitragotri, Samir

    2014-01-01

    Topical penetration of macromolecules into skin is limited by their low permeability. Here, we report the use of a skin penetrating peptide, SPACE peptide, to enhance topical delivery of a macromolecule, hyaluronic acid (HA, MW: 200–325 kDa). The peptide was conjugated to phospholipids and used to prepare an ethosomal carrier system (~110 nm diameter), encapsulating HA. The SPACE-ethosomal system (SES) enhanced HA penetration into porcine skin in vitro by 7.8+/−1.1-fold compared to PBS. The system also enhanced penetration of HA in human skin in vitro, penetrating deep into the epidermis and dermis in skin of both species. In vivo experiments performed using SKH1 hairless mice also confirmed increased dermal penetration of HA using the delivery system; a 5-fold enhancement in penetration was found compared to PBS control. Concentrations of HA in skin were about 1000-fold higher than those in blood; confirming the localized nature of HA delivery into skin. The SPACE-ethosomal delivery system provides a formulation for topical delivery of macromolecules that are otherwise difficult to deliver into skin. PMID:24129342

  15. Tumor acidity-sensitive linkage-bridged block copolymer for therapeutic siRNA delivery.

    PubMed

    Xu, Cong-Fei; Zhang, Hou-Bing; Sun, Chun-Yang; Liu, Yang; Shen, Song; Yang, Xian-Zhu; Zhu, Yan-Hua; Wang, Jun

    2016-05-01

    The design of ideal nanoparticle delivery systems should be capable of meeting the requirements of several stages of drug delivery, including prolonged circulation, enhanced accumulation and penetration in the tumor, facilitated cellular internalization and rapid release of the active drug in the tumor cells. However, among the current design strategies, meeting the requirements of one stage often conflicts with the other. Herein, a tumor pH-labile linkage-bridged block copolymer of poly(ethylene glycol) with poly(lacide-co-glycolide) (PEG-Dlinkm-PLGA) was used for siRNA delivery to fulfill all aforementioned requirements of these delivery stages. The obtained siRNA-encapsulating PEG-Dlinkm-PLGA nanoparticle gained efficiently prolonged circulation in the blood and preferential accumulation in tumor sites via the PEGylation. Furthermore, the PEG surface layer was detached in response to the tumor acidic microenvironment to facilitate cellular uptake, and the siRNA was rapidly released within tumor cells due to the hydrophobic PLGA layer. Hence, PEG-Dlinkm-PLGA nanoparticles met the requirements of several stages of drug delivery, and resulted in the enhanced therapeutic effect of the nanoparticular delivery systems.

  16. Active targeting co-delivery system based on pH-sensitive methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K for enhanced cancer therapy.

    PubMed

    Li, Nuannuan; Huang, Chunzhi; Luan, Yuxia; Song, Aixin; Song, Yunmei; Garg, Sanjay

    2016-06-15

    In this paper, we successfully synthesized folate-modified pH-sensitive copolymer methoxy-poly(ethylene glycol)2K-poly(ε-caprolactone)4K-poly(glutamic acid)1K (mPEG2K-PCL4K-PGA1K-FA), which could form the polymeric assembly in an aqueous solution, for co-delivering hydrophilic drugs doxorubicin hydrochloride (DOX) and verapamil hydrochloride (VER) (FA-poly(DOX+VER)). Since VER was an effective P-glycoprotein inhibitor, the combination of DOX and VER could reverse the multidrug resistance efficiently and enhance the therapeutic effect. Therefore, the inhibition ratios of MCF-7/ADR resistant cancer cell treated by FA-poly (DOX+VER) were almost more than 30% higher than those of FA-polyDOX after 48h and 72h. Furthermore, the conjugation of FA could lead the co-delivery systems actively targeting into the FA receptor over-expressing cancer cells in addition to the passive accumulation of the assembly in tumor tissues. Importantly, the prepared mPEG2K-PCL4K-PGA1K-FA assembly showed high pH-sensitive property, which made the drugs mostly released in tumor tissue (acid environment) than in physiological environment (neutral environment). In summary, the as-prepared co-delivery system FA-poly(DOX+VER) demonstrated a high efficiency in reversing the multidrug resistance and targeting FA receptor to improve the anticancer effect of DOX in MCF-7/ADR resistant cells.

  17. Hydrogen storage and delivery system development: Analysis

    SciTech Connect

    Handrock, J.L.

    1996-10-01

    Hydrogen storage and delivery is an important element in effective hydrogen utilization for energy applications and is an important part of the FY1994-1998 Hydrogen Program Implementation Plan. This project is part of the Field Work Proposal entitled Hydrogen Utilization in Internal Combustion Engines (ICE). The goal of the Hydrogen Storage and Delivery System Development Project is to expand the state-of-the-art of hydrogen storage and delivery system design and development. At the foundation of this activity is the development of both analytical and experimental evaluation platforms. These tools provide the basis for an integrated approach for coupling hydrogen storage and delivery technology to the operating characteristics of potential hydrogen energy use applications. Results of the analytical model development portion of this project will be discussed. Analytical models have been developed for internal combustion engine (ICE) hybrid and fuel cell driven vehicles. The dependence of hydride storage system weight and energy use efficiency on engine brake efficiency and exhaust temperature for ICE hybrid vehicle applications is examined. Results show that while storage system weight decreases with increasing engine brake efficiency energy use efficiency remains relatively unchanged. The development, capability, and use of a recently developed fuel cell vehicle storage system model will also be discussed. As an example of model use, power distribution and control for a simulated driving cycle is presented. Model calibration results of fuel cell fluid inlet and exit temperatures at various fuel cell idle speeds, assumed fuel cell heat capacities, and ambient temperatures are presented. The model predicts general increases in temperature with fuel cell power and differences between inlet and exit temperatures, but under predicts absolute temperature values, especially at higher power levels.

  18. Chitosan magnetic nanoparticles for drug delivery systems.

    PubMed

    Assa, Farnaz; Jafarizadeh-Malmiri, Hoda; Ajamein, Hossein; Vaghari, Hamideh; Anarjan, Navideh; Ahmadi, Omid; Berenjian, Aydin

    2016-06-01

    The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

  19. Transdermal testosterone delivery: comparison between scrotal and nonscrotal delivery systems.

    PubMed

    Lin, S; Xing, Q F; Chien, Y W

    1999-08-01

    The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs). Testoderm, designed to deliver testosterone through scrotal skin, and Androderm, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is approximately 13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg/day), maximum concentration (Cmax) (54.2 versus 218.0 ng/dl), and area under concentration-time curve (AUC0-28)[665 versus 3208 (ng/dl) x hr] between these T-TDSs. However, there is no difference in time to reach Cmax mean residence time, and daily-delivered-dose-normalized Cmax and AUC0-28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (approximately 13-fold) between the nonscrotal and scrotal T-TDSs.

  20. Magnetic nanoparticles as targeted delivery systems in oncology

    PubMed Central

    Prijic, Sara; Sersa, Gregor

    2011-01-01

    Background Many different types of nanoparticles, magnetic nanoparticles being just a category among them, offer exciting opportunities for technologies at the interfaces between chemistry, physics and biology. Some magnetic nanoparticles have already been utilized in clinical practice as contrast enhancing agents for magnetic resonance imaging (MRI). However, their physicochemical properties are constantly being improved upon also for other biological applications, such as magnetically-guided delivery systems for different therapeutics. By exposure of magnetic nanoparticles with attached therapeutics to an external magnetic field with appropriate characteristics, they are concentrated and retained at the preferred site which enables the targeted delivery of therapeutics to the desired spot. Conclusions The idea of binding chemotherapeutics to magnetic nanoparticles has been around for 30 years, however, no magnetic nanoparticles as delivery systems have yet been approved for clinical practice. Recently, binding of nucleic acids to magnetic nanoparticles has been demonstrated as a successful non-viral transfection method of different cell lines in vitro. With the optimization of this method called magnetofection, it will hopefully become another form of gene delivery for the treatment of cancer. PMID:22933928

  1. Exosome mimetics: a novel class of drug delivery systems.

    PubMed

    Kooijmans, Sander A A; Vader, Pieter; van Dommelen, Susan M; van Solinge, Wouter W; Schiffelers, Raymond M

    2012-01-01

    The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics.

  2. Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs

    PubMed Central

    Ezzati Nazhad Dolatabadi, Jafar; Valizadeh, Hadi; Hamishehkar, Hamed

    2015-01-01

    In recent years, nanomaterials have been widely applied as advanced drug and gene delivery nanosystems. Among them, solid lipid nanoparticles (SLNs) have attracted great attention as colloidal drug delivery systems for incorporating hydrophilic or lipophilic drugs and various macromolecules as well as proteins and nucleic acids. Therefore, SLNs offer great promise for controlled and site specific drug and gene delivery. This article includes general information about SLN structures and properties, production procedures, characterization. In addition, recent progress on development of drug and gene delivery systems using SLNs was reviewed. PMID:26236652

  3. Drug delivery system and breast cancer cells

    NASA Astrophysics Data System (ADS)

    Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.

  4. Systemic delivery to central nervous system by engineered PLGA nanoparticles

    PubMed Central

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  5. 42 CFR 457.490 - Delivery and utilization control systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Delivery and utilization control systems. 457.490... State Plan Requirements: Coverage and Benefits § 457.490 Delivery and utilization control systems. A... control systems. A State must— (a) Describe the methods of delivery of child health assistance...

  6. 42 CFR 457.490 - Delivery and utilization control systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Delivery and utilization control systems. 457.490... State Plan Requirements: Coverage and Benefits § 457.490 Delivery and utilization control systems. A... control systems. A State must— (a) Describe the methods of delivery of child health assistance...

  7. Applications of polymers in intraocular drug delivery systems

    PubMed Central

    Alhalafi, Ali Mohammed

    2017-01-01

    We are entering a new era of ophthalmic pharmacology where new drugs are rapidly being developed for the treatment of anterior and posterior segment of the eye disease. The pharmacokinetics of drug delivery to the eye remains a very active area of ophthalmic research. Intraocular drug delivery systems allow the release of the drug, bypassing the blood-ocular barrier. The main advantage of these preparations is that they can release the drug over a long time with one single administration. These pharmaceutical systems are of great important in the treatment of the posterior segment diseases, and they can be prepared from biodegradable or nonbiodegradable polymers. Biodegradable polymers have the advantage of disappearing from the site of action after releasing the drug. The majority of intraocular devices are prepared from nonbiodegradable polymers, and they can release controlled amounts of drugs for months. Nonbiodegradable polymers include silicone, polyvinyl alcohol, and ethylene-vinyl acetate. The polymers usually employed to prepare nanoparticles for the topical ophthalmic route are poly (acrylic acid) derivatives (polyalquilcyanocrylates), albumin, poly-ε-caprolactone, and chitosan. Dendrimers are a recent class of polymeric materials with unique nanostructure which has been studied to discover their role in the delivery of therapeutics and imaging agents. Hydrogels are polymers that can swell in aqueous solvent system, and they hold the solvents in a swollen cross-linked gel for delivery. This review exhibits the current literature regarding applications of polymers in ophthalmic drug delivery systems including pharmacokinetics, advantages, disadvantages, and indications aimed to obtain successful eye therapy. Method of Literature Search: A systematic literature review was performed using PubMed databases into two steps. The first step was oriented to classification of intraocular polymers implants focusing on their advantages and disadvantages. The second

  8. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    PubMed Central

    Lee, Sang-Soo; George Priya Doss, C.; Yagihara, Shin; Kim, Do-Young

    2014-01-01

    Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD) blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole. PMID:25250340

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  11. pH-responsive drug delivery system based on luminescent CaF(2):Ce(3+)/Tb(3+)-poly(acrylic acid) hybrid microspheres.

    PubMed

    Dai, Yunlu; Zhang, Cuimiao; Cheng, Ziyong; Ma, Ping'an; Li, Chunxia; Kang, Xiaojiao; Yang, Dongmei; Lin, Jun

    2012-03-01

    In this study, we design a controlled release system based on CaF(2):Ce(3+)/Tb(3+)-poly(acrylic acid) (PAA) composite microspheres, which were fabricated by filling the pH-responsive PAA inside CaF(2):Ce(3+)/Tb(3+) hollow spheres via photopolymerization route. The CaF(2):Ce(3+)/Tb(3+) hollow spheres prepared by hydrothermal route possess mesoporous structure and show strong green fluorescence from Tb(3+) under UV excitation. Doxorubicin hydrochloride (DOX), a widely used anti-cancer drug, was used as a model drug to evaluate the loading and controlled release behaviors of the composite microspheres due to the good biocompatibility of the samples using MTT assay. The composite carriers provide a strongly pH-dependent drug release behavior owing to the intrinsic property of PAA and its interactions with DOX. The endocytosis process of drug-loaded microspheres was observed using confocal laser scanning microscopy (CLSM) and the in vitro cytotoxic effect against SKOV3 ovarian cancer cells of the DOX-loaded carriers was investigated. In addition, the extent of drug release could be monitored by the altering of photoluminescence (PL) intensity of CaF(2):Ce(3+)/Tb(3+). Considering the good biocompatibility, high drug loading content and pH-dependent drug release of the materials, these hybrid luminescent microspheres have potential applications in drug controlled release and disease therapy.

  12. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

    A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative.

  13. Application of proteins in burst delivery systems

    NASA Astrophysics Data System (ADS)

    Freeman, E.; Weiland, L. M.; Meng, W. S.

    2010-09-01

    Biological proteins embedded in either a biological or an engineered membrane will actively maintain electrochemical balance across that membrane. In this study two applications will be examined. First a system of governing equations will be calibrated for a biological endosome. The endocytosis predictions presented then serve to validate the model. In addition, these predictions introduce new insights into endosome burst, which is of interest for advancing DNA vaccine delivery. The calibrated model is subsequently adapted to an analogous engineering scenario for targeted payload delivery. In the presence of a specific external stimulus, burst release of an arbitrary payload encased in a vesicle akin to an endosome is explored. Control of the process through manipulation of vesicle size, stimulus, and transporters is presented. A case is made for application of proteins as building blocks in the design of targeted response materials.

  14. Sequence-defined shuttles for targeted nucleic acid and protein delivery.

    PubMed

    Röder, Ruth; Wagner, Ernst

    2014-01-01

    Molecular medicine opens into a space of novel specific therapeutic agents: intracellularly active drugs such as peptides, proteins or nucleic acids, which are not able to cross cell membranes and enter the intracellular space on their own. Through the development of cell-targeted shuttles for specific delivery, this restriction in delivery has the potential to be converted into an advantage. On the one hand, due to the multiple extra- and intracellular barriers, such carrier systems need to be multifunctional. On the other hand, they must be precise and reproducibly manufactured due to pharmaceutical reasons. Here we review the design of precise sequence-defined delivery carriers, including solid-phase synthesized peptides and nonpeptidic oligomers, or nucleotide-based carriers such as aptamers and origami nanoboxes.

  15. Acid-Degradable Cationic Dextran Particles for the Delivery of siRNA Therapeutics

    PubMed Central

    Cohen, Jessica L.; Schubert, Stephanie; Wich, Peter R.; Cui, Lina; Cohen, Joel A.; Mynar, Justin L.; Fréchet, Jean M. J.

    2011-01-01

    We report a new acid-sensitive, biocompatible and biodegradable microparticulate delivery system, spermine modified acetalated-dextran (Spermine-Ac-DEX), which can be used to efficiently encapsulate siRNA. These particles demonstrated efficient gene knockdown in HeLa-luc cells with minimal toxicity. This knockdown was comparable to that obtained using Lipofectamine, a commercially available transfection reagent generally limited to in vitro use due to its high toxicity. PMID:21539393

  16. Fatty acid vesicles acting as expanding horizon for transdermal delivery.

    PubMed

    Kumar, Lalit; Verma, Shivani; Kumar, Sanjeev; Prasad, Deo Nandan; Jain, Amit Kumar

    2017-03-01

    The body is protected against the external environment by the skin due to its physical barrier nature. Stratum corneum composed of corneocytes surrounded by lipid region performs a major barrier function as it lies in the uppermost area of skin. Alteration in barrier function, increase in permeability, and disorganization of stratum corneum represent diseased skin. Drugs applied to the diseased skin should induce a local effect at the site of application or area close to it along with cutaneous absorption rather than percutaneous absorption. Conventional formulations like ointments, gels, and creams suffer from the drawback of limited local activity. For the enhancement of drug penetration and localization of the drug at the site of action approaches explored are liposomes, niosomes, ethosomes microparticles, and solid lipid nanoparticles. Vesicles composed of fatty acids like oleic acid and linoleic acid represent the new approach used for transdermal penetration and localization. In this review article, our major aim was to explore the applications of fatty acid vesicles for transdermal delivery of various bioactives.

  17. Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides.

    PubMed

    Han, Su-Eun; Kang, Hyungu; Shim, Ga Yong; Kim, Sun Jae; Choi, Han-Gon; Kim, Jiseok; Hahn, Sei Kwang; Oh, Yu-Kyoung

    2009-02-01

    In this study, we tested the use of cationic polymer derivatives of biocompatible hyaluronic acid (HA) as a delivery system of siRNA and antisense oligonucleotides. HA was modified with cationic polymer polyethylenimine (PEI). When compared with PEI alone, cationic PEI derivatives of HA (HA-PEI) provided increased cellular delivery of Small interfering RNA (siRNA) in B16F1, A549, HeLa, and Hep3B tumor cells. Indeed, more than 95% of the cells were positive for siRNA following its delivery with HA-PEI. A survivin-specific siRNA that was delivered using HA-PEI potently reduced the mRNA expression levels of the target gene in all of the cell lines. By contrast, survivin-specific siRNA delivered by PEI alone did not induce a significant reduction in mRNA levels. In green fluorescent protein (GFP)-expressing 293 T cells, a loss of GFP expression was evident in the cells that had been treated with GFP-specific siRNA and HA-PEI complex. The inhibition of target gene expression by antisense oligonucleotide G3139 was also enhanced after delivery with HA-PEI. Moreover, HA-PEI displayed lower cytotoxicity than PEI alone. These results suggest that HA-PEI could be further developed as biocompatible delivery systems of siRNA and antisense oligonucleotides for enhanced cellular uptake and inhibition of target gene expression.

  18. Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

    PubMed

    Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-07-30

    Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

  19. pH-responsive biocompatible fluorescent polymer nanoparticles based on phenylboronic acid for intracellular imaging and drug delivery

    NASA Astrophysics Data System (ADS)

    Li, Shengliang; Hu, Kelei; Cao, Weipeng; Sun, Yun; Sheng, Wang; Li, Feng; Wu, Yan; Liang, Xing-Jie

    2014-10-01

    To address current medical challenges, there is an urgent need to develop drug delivery systems with multiple functions, such as simultaneous stimuli-responsive drug release and real-time imaging. Biocompatible polymers have great potential for constructing smart multifunctional drug-delivery systems through grafting with other functional ligands. More importantly, novel biocompatible polymers with intrinsic fluorescence emission can work as theranostic nanomedicines for real-time imaging and drug delivery. Herein, we developed a highly fluorescent nanoparticle based on a phenylboronic acid-modified poly(lactic acid)-poly(ethyleneimine)(PLA-PEI) copolymer loaded with doxorubicin (Dox) for intracellular imaging and pH-responsive drug delivery. The nanoparticles exhibited superior fluorescence properties, such as fluorescence stability, no blinking and excitation-dependent fluorescence behavior. The Dox-loaded fluorescent nanoparticles showed pH-responsive drug release and were more effective in suppressing the proliferation of MCF-7 cells. In addition, the biocompatible fluorescent nanoparticles could be used as a tool for intracellular imaging and drug delivery, and the process of endosomal escape was traced by real-time imaging. These pH-responsive and biocompatible fluorescent polymer nanoparticles, based on phenylboronic acid, are promising tools for intracellular imaging and drug delivery.To address current medical challenges, there is an urgent need to develop drug delivery systems with multiple functions, such as simultaneous stimuli-responsive drug release and real-time imaging. Biocompatible polymers have great potential for constructing smart multifunctional drug-delivery systems through grafting with other functional ligands. More importantly, novel biocompatible polymers with intrinsic fluorescence emission can work as theranostic nanomedicines for real-time imaging and drug delivery. Herein, we developed a highly fluorescent nanoparticle based on a

  20. 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.

  1. Drug Delivery Systems for Platinum Drugs

    NASA Astrophysics Data System (ADS)

    Huynh, Vien T.; Scarano, Wei; Stenzel, Martina H.

    2013-09-01

    Since the discovery of cisplatin, drugs based on platinum, have made a significant impact on the treatment of various cancers. The administration of platinum drugs is however accompanied by significant side effects. This chapter discusses the types of drug delivery systems that have been developed in order to enable the targeted delivery while maintaining controlled temporal supply of the drug. The sizes of carriers range from nanometer to micrometer sized particles. The most common types of drug carriers are micelles, liposomes, nanoparticles, and dendrimers, but also a few microspheres have been developed. Most striking aspect of the delivery of platinum drugs is the possibility of physical encapsulation but also the binding of the drug to the polymer carrier coordinate covalent bond. Since platinum drugs have typically two permanent and two leaving ligands, the polymer can be part of either ligand. As the leaving ligand, the platinum drug is released often as cisplatin. If the polymer provides the functionality for the permanent ligand, a new macromolecular drug has been formed. In addition to the attachment of pt(II) drugs, recent offorts are devoted to the conjugation via the Pt((IV) prodrug.

  2. 42 CFR 457.490 - Delivery and utilization control systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... State Plan Requirements: Coverage and Benefits § 457.490 Delivery and utilization control systems. A... 42 Public Health 4 2013-10-01 2013-10-01 false Delivery and utilization control systems. 457.490... targeted low-income children, including a description of the proposed methods of delivery and...

  3. 42 CFR 457.490 - Delivery and utilization control systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... State Plan Requirements: Coverage and Benefits § 457.490 Delivery and utilization control systems. A... 42 Public Health 4 2014-10-01 2014-10-01 false Delivery and utilization control systems. 457.490... targeted low-income children, including a description of the proposed methods of delivery and...

  4. 42 CFR 457.490 - Delivery and utilization control systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... State Plan Requirements: Coverage and Benefits § 457.490 Delivery and utilization control systems. A... 42 Public Health 4 2012-10-01 2012-10-01 false Delivery and utilization control systems. 457.490... targeted low-income children, including a description of the proposed methods of delivery and...

  5. Modeling the Delivery Physiology of Distributed Learning Systems.

    ERIC Educational Resources Information Center

    Paquette, Gilbert; Rosca, Ioan

    2003-01-01

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

  6. The use of gelatin in a multiple drug delivery system

    NASA Astrophysics Data System (ADS)

    Morgan, Abby W.

    The use of gelatin for growth factor delivery was investigated. Protein-gelatin interactions were characterized using the Biomolecular Interaction Detection (BIND) system. Acidic gelatin sheets and basic gelatin microspheres were fabricated and optimized for delivering transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2. The two delivery vehicles were then combined to produce two distinct release sequences and the effect of sequence on bone healing was determined. Using the BIND system, TGF-beta1 was found to interact more strongly with acidic gelatin than basic gelatin whereas BMP-2 only slightly favors basic gelatin over acidic gelatin. Acidic gelatin sheets were fabricated by a casting technique. These sheets successfully delivered TGF-beta1 to a rabbit ulna defect to encourage new bone formation. Basic gelatin microspheres were fabricated by the precision particle fabrication (PPF) method. Uniform drug distribution within the microspheres lead to controlled release of BMP-2 that induced bone formation within the thigh muscle of mice. The sheets and microspheres were combined to deliver both drugs either simultaneously or with a four-day delay to a rabbit calvarial defect. Both sequences encouraged more bone regeneration than empty defects by 8 weeks. Protein-gelatin interactions improved protein stability and lead to release through enzymatic degradation of the gelatin. Growth factors released either singly or in a dual system from gelatin successfully produced bone in vivo. However, single release systems require higher dosages to achieve similar healing results as observed in the dual release systems. No difference was observed between the dual release systems investigated.

  7. Biodegradable block copolymers as injectable drug-delivery systems

    NASA Astrophysics Data System (ADS)

    Jeong, Byeongmoon; Bae, You Han; Lee, Doo Sung; Kim, Sung Wan

    1997-08-01

    Polymers that display a physicochemical response to stimuli are widely explored as potential drug-delivery systems. Stimuli studied to date include chemical substances and changes in temperature, pH and electric field. Homopolymers or copolymers of N-isopropylacrylamide, and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (known as poloxamers) are typical examples of thermosensitive polymers, but their use in drug delivery is problematic because they are toxic and non-biodegradable. Biodegradable polymers used for drug delivery to date have mostly been in the form of injectable microspheres or implant systems, which require complicated fabrication processes using organic solvents. Such systems have the disadvantage that the use of organic solvents can cause denaturation when protein drugs are to be encapsulated. Furthermore, the solid form requires surgical insertion, which often results in tissue irritation and damage. Here we report the synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid). Aqueous solutions of these copolymers exhibit temperature-dependent reversible gel-sol transitions. The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45 °C), where they form a sol. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act as a sustained-release matrix for drugs.

  8. Liposomes as delivery systems for antineoplastic drugs

    NASA Astrophysics Data System (ADS)

    Medina, Luis Alberto

    2014-11-01

    Liposome drug formulations are defined as pharmaceutical products containing active drug substances encapsulated within the lipid bilayer or in the interior aqueous space of the liposomes. The main importance of this drug delivery system is based on its drastic reduction in systemic dose and concomitant systemic toxicity that in comparison with the free drug, results in an improvement of patient compliance and in a more effective treatment. There are several therapeutic drugs that are potential candidates to be encapsulated into liposomes; particular interest has been focused in therapeutic and antineoplastic drugs, which are characterized for its low therapeutic index and high systemic toxicity. The use of liposomes as drug carriers has been extensively justified and the importance of the development of different formulations or techniques to encapsulate therapeutic drugs has an enormous value in benefit of patients affected by neoplastic diseases.

  9. RALA-mediated delivery of FKBPL nucleic acid therapeutics

    PubMed Central

    Bennett, Rachel; Yakkundi, Anita; McKeen, Hayley D; McClements, Lana; McKeogh, Thomas J; McCrudden, Cian M; Arthur, Kenneth; Robson, Tracy; McCarthy, Helen O

    2015-01-01

    Aims: RALA is a novel 30 mer bioinspired amphipathic peptide that is showing promise for gene delivery. Here, we used RALA to deliver the FK506-binding protein like – FKBPL gene (pFKBPL) – a novel member of the immunophilin protein family. FKBPL is a secreted protein, with overexpression shown to inhibit angiogenesis, tumor growth and stemness, through a variety of intra- and extracellular signaling mechanisms. We also elucidated proangiogenic activity and stemness after utilizing RALA to deliver siRNA (siFKBPL). Materials & methods: The RALA/pFKBPL and RALA/siFKBPL nanoparticles were characterized in terms of size, charge, stability and toxicity. Overexpression and knockdown of FKBPL was assessed in vitro and in vivo. Results: RALA delivered both pFKBPL and siFKBPL with less cytotoxicity than commercially available counterparts. In vivo, RALA/pFKBPL delivery retarded tumor growth, and prolonged survival with an associated decrease in angiogenesis, while RALA/siFKBPL had no effect on tumor growth rate or survival, but resulted in an increase in angiogenesis and stemness. Conclusion: RALA is an effective delivery system for both FKBPL DNA and RNAi and highlights an alternative therapeutic approach to harnessing FKBPL's antiangiogenic and antistemness activity. PMID:26419658

  10. Fuel delivery system including heat exchanger means

    NASA Technical Reports Server (NTRS)

    Coffinberry, G. A. (Inventor)

    1978-01-01

    A fuel delivery system is presented wherein first and second heat exchanger means are each adapted to provide the transfer of heat between the fuel and a second fluid such as lubricating oil associated with the gas turbine engine. Valve means are included which are operative in a first mode to provide for flow of the second fluid through both first and second heat exchange means and further operative in a second mode for bypassing the second fluid around the second heat exchanger means.

  11. Mucoadhesive drug delivery system: An overview

    PubMed Central

    Boddupalli, Bindu M.; Mohammed, Zulkar N. K.; Nath, Ravinder A.; Banji, David

    2010-01-01

    Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity. In this regard, this review covers the areas of mechanisms and theories of mucoadhesion, factors influencing the mucoadhesive devices and also various mucoadhesive dosage forms. PMID:22247877

  12. Folic acid-conjugated amphiphilic alternating copolymer as a new active tumor targeting drug delivery platform

    PubMed Central

    Li, Xia; Szewczuk, Myron R; Malardier-Jugroot, Cecile

    2016-01-01

    Targeted drug delivery using polymeric nanostructures is an emerging cancer research area, engineered for safer, more efficient, and effective use of chemotherapeutic drugs. A pH-responsive, active targeting delivery system was designed using folic acid functionalized amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA). The polymeric template is pH responsive, forming amphiphilic nanostructures at pH 7, allowing the encapsulation of hydrophobic drugs on its interior. Moreover, the structure is stable only at neutral pH and collapses in the acidic tumor microenvironment, releasing drugs on-site from its core. The delivery vehicle is investigated using human pancreatic PANC-1 cancer cells and RAW-Blue™ mouse macrophage reporter cell line, both of which have overly expression of folic acid receptors. To trace the cellular uptake by both cell lines, curcumin was selected as a dye and drug mimic owing to its fluorescence nature and hydrophobic properties. Fluorescent microscopy of FA-DABA-SMA loaded with curcumin revealed a significant internalization of the dye by human pancreatic PANC-1 cancer cells compared to those with unfunctionalized polymers (SMA). Moreover, the FA-DABA-SMA polymers exhibit rodlike association specific to the cells. Both empty SMA and FA-DABA-SMA show little toxicity to PANC-1 cells as characterized by WST-1 cell proliferation assay. These results clearly indicate that FA-DABA-SMA polymers show potential as an active tumor targeting drug delivery system with the ability to internalize hydrophobic chemotherapeutics after they specifically attach to cancer cells. PMID:28008233

  13. Soy protein/soy polysaccharide complex nanogels: folic acid loading, protection, and controlled delivery.

    PubMed

    Ding, Xuzhe; Yao, Ping

    2013-07-09

    In this study, we developed a facile approach to produce nanogels via self-assembly of folic acid, soy protein, and soy polysaccharide. High-pressure homogenization was introduced to break down the original aggregates of soy protein, which benefits the binding of soy protein with soy polysaccharide and folic acid at pH 4.0. After a heat treatment that causes the soy protein denaturation and gelation, folic acid-loaded soy protein/soy polysaccharide complex nanogels were fabricated. The nanogels have a polysaccharide surface that makes the nanogels dispersible in acidic conditions where folic acid is insoluble and soy protein forms precipitates after heating. More importantly, the protein and polysaccharide can inhibit the reactions between dissolved oxygen and folic acid during UV irradiation. After the preparation and storage of the nanogels in the presence of heat, oxygen, and light in acidic conditions, most of the folic acid molecules in the nanogels remain in their natural structure and can be released rapidly at neutral pH, that is, in the intestine. Because most food and beverages are acidic, the nanogels are a suitable delivery system of folic acid in food and beverages.

  14. [Studies on transdermal delivery of ferulic acid through rat skin treated by microneedle arrays].

    PubMed

    Yang, Bing; Du, Shou-ying; Bai, Jie; Shang, Ke-xin; Lu, Yang; Li, Peng-yue

    2014-12-01

    In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P <0.01). The accumulation of FA increased with the enhancement of insertion force as to as the increase of retention time. Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.

  15. Online Mapping Systems for Climate Data Delivery

    NASA Astrophysics Data System (ADS)

    Gray, S. T.; Nicholson, C. M.; Bergantino, A. R.

    2009-12-01

    Online, map-based applications have experienced an explosion in popularity over the past decade. The success of these systems is largely due to their ability to provide a spatial framework data exploration, and for the visual context (e.g., satellite images) they offer. Here we detail the development of a new online mapping system for Wyoming that will serve as a portal for the delivery of weather, climate, and water-related data for users across the state. While capitalizing on the success of previous online mapping efforts, this new system also highlights the potential for additional applications and functionality. Known as the Wyoming Internet Map Server (WyoIMS), the system brings together real-time observations and summary products from multiple federal agencies (NOAA-NWS, NRCS, USGS) to provide “one-stop-shopping” for key climatic datasets. Likewise this system is providing a platform for data delivery, archiving, and QC/QA as part of a new statewide hydroclimatic monitoring network. Moving beyond the simple transfer of data, this system also allows users to access information from resources that include state libraries and various databases that contain information related to climate and water resources. Users can, for example, select individual counties, watersheds, irrigation districts, or municipalities and download a wide range of documents and reports specific to those locations. On the whole, WyoIMS has become a catalyst for the development of new climate-related products, and a foundation for decision support with applications in water resources, wildlife management, and agriculture.

  16. Stimulus-responsive "smart" hydrogels as novel drug delivery systems.

    PubMed

    Soppimath, K S; Aminabhavi, T M; Dave, A M; Kumbar, S G; Rudzinski, W E

    2002-09-01

    Recently, there has been a great deal of research activity in the development of stimulus-responsive polymeric hydrogels. These hydrogels are responsive to external or internal stimuli and the response can be observed through abrupt changes in the physical nature of the network. This property can be favorable in many drug delivery applications. The external stimuli can be temperature, pH, ionic strength, ultrasonic sound, electric current, etc. A majority of the literature related to the development of stimulus-responsive drug delivery systems deals with temperature-sensitive poly(N-isopropyl acrylamide) (pNIPAAm) and its various derivatives. However, acrylic-based pH-sensitive systems with weakly acidic/basic functional groups have also been widely studied. Quite recently, glucose-sensitive hydrogels that are responsive to glucose concentration have been developed to monitor the release of insulin. The present article provides a brief introduction and recent developments in the area of stimulus-responsive hydrogels, particularly those that respond to temperature and pH, and their applications in drug delivery.

  17. In Vitro Sustained Release Study of Gallic Acid Coated with Magnetite-PEG and Magnetite-PVA for Drug Delivery System

    PubMed Central

    Kura, Aminu Umar; Hussein-Al-Ali, Samer Hasan; Bin Hussein, Mohd Zobir; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

    2014-01-01

    The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG. PMID:24737969

  18. Silk Electrogel Based Gastroretentive Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Wang, Qianrui

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

  19. Delivery of dietary triglycerides to Caenorhabditis elegans using lipid nanoparticles: Nanoemulsion-based delivery systems.

    PubMed

    Colmenares, Daniel; Sun, Quancai; Shen, Peiyi; Yue, Yiren; McClements, D Julian; Park, Yeonhwa

    2016-07-01

    The nematode Caenorhabditis elegans is a powerful tool for studying food bioactives on specific biochemical pathways. However, many food bioactives are highly hydrophobic with extremely low water-solubilities, thereby making them difficult to study using C. elegans. The purpose of this study was to develop nanoemulsion-based systems to deliver hydrophobic molecules in a form that could be ingested by C. elegans. Optical microscopy showed that oil-in-water nanoemulsions with a range of particle diameters (40-500nm) could be ingested by C. elegans. The amount of lipid ingested depended on the size and concentration of the nanoparticles. Fatty acid analysis showed incorporation of conjugated linoleic acid and there was a significant reduction in the fat levels of C. elegans when they were incubated with nanoemulsions containing conjugated linoleic acid, which suggested that this hydrophobic lipid was successfully delivered to the nematodes. The incorporation of hydrophobic molecules into nanoemulsion based-delivery systems may therefore enable their activities to be studied using C. elegans.

  20. Development of phenylboronic acid-functionalized nanoparticles for emodin delivery

    PubMed Central

    Wang, Bo; Chen, Limin; Sun, Yingjuan; Zhu, Youliang; Sun, Zhaoyan; An, Tiezhu; Li, Yuhua; Lin, Yuan; Fan, Daping; Wang, Qian

    2015-01-01

    Stable and monodisperse phenylboronic acid-functionalized nanoparticles (PBA-NPs) were fabricated using 3-((acrylamido)methyl)phenylboronic acid homopolymer (PBAH) via solvent displacement technique. The effect of operating parameters, including stirring time, initial polymer concentration and the proportion of methanol on the self-assembly process were systematically investigated. The diameters of the PBA-NPs were increased as increasing the initial PBAH concentration and the proportion of methanol. Likewise, there was a linear dependence between the size of self-assembled nanoparticles and the polymer concentration. Moreover, the dissipative particle dynamics (DPD) simulation technique was used to investigate the mechanism of self-assembly behavior of PBAH, which indicated that the interior of PBA-NPs was hydrophobic and compact, and the boronic acid groups were displayed on both the outermost and interior of PBA-NPs. The resulting PBA-NPs could successfully encapsulate emodin through PBA-diol interaction and the encapsulation efficiency (EE%) and drug loading content (DLC%) of drug-loaded PBA-NPs were 78% and 2.1%, respectively. Owing to the acid-labile feature of the boronate linkage, a reduction in environmental pH from pH 7.4 to 5.0 could trigger the disassociation of the boronate ester bonds, which could accelerate the drug release from PBA-Emodin-NPs. Besides, PBA-Emodin-NPs showed a much higher cytotoxicity to HepG2 cells (cancer cells) than that to MC-3T3-E1 cells (normal cells). These results imply that PBA-NPs would be a promising scaffold for the delivery of polyphenolic drugs. PMID:25960874

  1. Responsive Boronic Acid-Decorated (Co)polymers: From Glucose Sensors to Autonomous Drug Delivery

    PubMed Central

    Vancoillie, Gertjan; Hoogenboom, Richard

    2016-01-01

    Boronic acid-containing (co)polymers have fascinated researchers for decades, garnering attention for their unique responsiveness toward 1,2- and 1,3-diols, including saccharides and nucleotides. The applications of materials that exert this property are manifold including sensing, but also self-regulated drug delivery systems through responsive membranes or micelles. In this review, some of the main applications of boronic acid containing (co)polymers are discussed focusing on the role of the boronic acid group in the response mechanism. We hope that this summary, which highlights the importance and potential of boronic acid-decorated polymeric materials, will inspire further research within this interesting field of responsive polymers and polymeric materials. PMID:27775572

  2. [Studies on market of drug delivery system product and drug delivery system of compound Chinese medicine].

    PubMed

    Feng, Yi; Xu, De-Sheng; Hong, Yan-Long; Zhang, Ning; Ma, Yue-Ming

    2006-10-01

    Based on the progress in the world market of drug delivery system (DDS) product and the research profile of DDS of compound Chinese Medicine, The article puts forward a new method of studies on DDS of compound Chinese Medicine. It is expected that the theory of compatibility of compound Chinese Medicine can be shown and its role can be exerted to the largest extent with the application of pharmaceutics technology to change the mode of drug delivery of activated components of compound Chinese Medicine.

  3. Turbomachine injection nozzle including a coolant delivery system

    DOEpatents

    Zuo, Baifang [Simpsonville, SC

    2012-02-14

    An injection nozzle for a turbomachine includes a main body having a first end portion that extends to a second end portion defining an exterior wall having an outer surface. A plurality of fluid delivery tubes extend through the main body. Each of the plurality of fluid delivery tubes includes a first fluid inlet for receiving a first fluid, a second fluid inlet for receiving a second fluid and an outlet. The injection nozzle further includes a coolant delivery system arranged within the main body. The coolant delivery system guides a coolant along at least one of a portion of the exterior wall and around the plurality of fluid delivery tubes.

  4. Fluid Delivery System For Capillary Electrophoretic Applications.

    SciTech Connect

    Li, Qingbo; Liu, Changsheng; Kane, Thomas E.; Kernan, John R.; Sonnenschein, Bernard; Sharer, Michael V.

    2002-04-23

    An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths. An off-line capillary reconditioner thoroughly cleans a capillary cartridge to enable simultaneous execution of electrophoresis with another capillary cartridge. The streamlined nature of the off-line capillary reconditioner offers the advantage of increased system throughput with a minimal increase in system cost.

  5. 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.

  6. Light-sensitive intelligent drug delivery systems.

    PubMed

    Alvarez-Lorenzo, Carmen; Bromberg, Lev; Concheiro, Angel

    2009-01-01

    Drug delivery systems (DDS) capable of releasing an active molecule at the appropriate site and at a rate that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism are particularly appealing. Biocompatible materials sensitive to certain physiological variables or external physicochemical stimuli (intelligent materials) can be used for achieving this aim. Light-responsiveness is receiving increasing attention owing to the possibility of developing materials sensitive to innocuous electromagnetic radiation (mainly in the UV, visible and near-infrared range), which can be applied on demand at well delimited sites of the body. Some light-responsive DDS are of a single use (i.e. the light triggers an irreversible structural change that provokes the delivery of the entire dose) while others able to undergo reversible structural changes when cycles of light/dark are applied, behave as multi-switchable carriers (releasing the drug in a pulsatile manner). In this review, the mechanisms used to develop polymeric micelles, gels, liposomes and nanocomposites with light-sensitiveness are analyzed. Examples of the capability of some polymeric, lipidic and inorganic structures to regulate the release of small solutes and biomacromolecules are presented and the potential of light-sensitive carriers as functional components of intelligent DDS is discussed.

  7. Phospholipid nanodisc engineering for drug delivery systems.

    PubMed

    Murakami, Tatsuya

    2012-06-01

    Biocompatible mesoscale nanoparticles (5-100 nm in diameter) are attractive tools for drug delivery. Among them are several types of liposomes and polymer micelles already in clinical trial or use. Generally, biocompatibility of such particles is achieved by coating them with polyethylene glycol (PEG). Without PEG coating, particles are quickly trapped in the reticuloendothelial system when intravenously administered. However, recent studies have revealed several potential problems with PEG coating, including antigenicity and restriction of cellular uptake. This has motivated the development of alternative drug and gene delivery vehicles, including chemically and genetically engineered high-density lipoprotein (HDL)-like nanodiscs or "bicelles". HDL is a naturally occurring mesoscale nanoparticle that normally ferries cholesterol around in the body. Its initial "nascent" form is thought to be a simple 10 nm disc of phospholipids in a bilayer, and can be easily synthesized in vitro by mixing recombinant apoA-I proteins with various phospholipids. In this review, the use of synthetic HDL-like phospholipid nanodiscs as biocompatible drug carriers is summarized, focussing on manufacturing, size-control, drug loading and cell targeting.

  8. Electronic nicotine delivery systems: a research agenda.

    PubMed

    Etter, Jean-François; Bullen, Chris; Flouris, Andreas D; Laugesen, Murray; Eissenberg, Thomas

    2011-05-01

    Electronic nicotine delivery systems (ENDS, also called electronic cigarettes or e-cigarettes) are marketed to deliver nicotine and sometimes other substances by inhalation. Some tobacco smokers report that they used ENDS as a smoking cessation aid. Whether sold as tobacco products or drug delivery devices, these products need to be regulated, and thus far, across countries and states, there has been a wide range of regulatory responses ranging from no regulation to complete bans. The empirical basis for these regulatory decisions is uncertain, and more research on ENDS must be conducted in order to ensure that the decisions of regulators, health care providers and consumers are based on science. However, there is a dearth of scientific research on these products, including safety, abuse liability and efficacy for smoking cessation. The authors, who cover a broad range of scientific expertise, from basic science to public health, suggest research priorities for non-clinical, clinical and public health studies. They conclude that the first priority is to characterize the safety profile of these products, including in long-term users. If these products are demonstrated to be safe, their efficacy as smoking cessation aids should then be tested in appropriately designed trials. Until these studies are conducted, continued marketing constitutes an uncontrolled experiment and the primary outcome measure, poorly assessed, is user health. Potentially, this research effort, contributing to the safety and efficacy of new smoking cessation devices and to the withdrawal of dangerous products, could save many lives.

  9. Electronic nicotine delivery systems: a research agenda

    PubMed Central

    Etter, Jean-François; Bullen, Chris; Flouris, Andreas D; Laugesen, Murray; Eissenberg, Thomas

    2011-01-01

    Electronic nicotine delivery systems (ENDS, also called electronic cigarettes or e-cigarettes) are marketed to deliver nicotine and sometimes other substances by inhalation. Some tobacco smokers report that they used ENDS as a smoking cessation aid. Whether sold as tobacco products or drug delivery devices, these products need to be regulated, and thus far, across countries and states, there has been a wide range of regulatory responses ranging from no regulation to complete bans. The empirical basis for these regulatory decisions is uncertain, and more research on ENDS must be conducted in order to ensure that the decisions of regulators, health care providers and consumers are based on science. However, there is a dearth of scientific research on these products, including safety, abuse liability and efficacy for smoking cessation. The authors, who cover a broad range of scientific expertise, from basic science to public health, suggest research priorities for non-clinical, clinical and public health studies. They conclude that the first priority is to characterize the safety profile of these products, including in long-term users. If these products are demonstrated to be safe, their efficacy as smoking cessation aids should then be tested in appropriately designed trials. Until these studies are conducted, continued marketing constitutes an uncontrolled experiment and the primary outcome measure, poorly assessed, is user health. Potentially, this research effort, contributing to the safety and efficacy of new smoking cessation devices and to the withdrawal of dangerous products, could save many lives. PMID:21415064

  10. Chitinosans as tableting excipients for modified release delivery systems.

    PubMed

    Rege, P R; Shukla, D J; Block, L H

    1999-04-20

    The term 'chitinosans' embraces the spectrum of acetylated poly(N-glucosamines) ranging from chitin to chitosan. Chitinosans (I), at acidic pH, have protonated amines which can interact with oppositely charged drug ions and, thereby, modify drug release from drug delivery systems. Tablets were compressed from a physical mixture containing salicylic acid (II) as the model drug, I, and magnesium stearate. Five commercial I compounds, varying in degree of deacetylation and molecular weight, were selected. Tablets were compressed at 5000, 10 000, and 15 000 psig using a Carver and a single punch tablet press. The differential scanning calorimetry thermograms provided evidence of I-II interaction in the powder blend. Analysis of variance (ANOVA) indicated that the compression pressure did not significantly affect the crushing strength (CS) or the release profile of II from the I-matrix tablets (P?0.05). Furthermore, the ANOVA also indicated that the tablet press used during manufacture did not affect the above properties (P?0.05); however, the chitinosans significantly affected the CS as well as the release profile of II from I-matrix tablets (P<0.05). This study provides further evidence for the use of commercial I compounds as excipients for use in modified release drug delivery systems.

  11. Pulsatile Release of Parathyroid Hormone from an Implantable Delivery System

    PubMed Central

    Liu, Xiaohua; Pettway, Glenda J.; McCauley, Laurie K.; Ma, Peter X.

    2007-01-01

    Intermittent (pulsatile) administration of parathyroid hormone (PTH) is known to improve bone micro-architecture, mineral density and strength. Therefore, daily injection of PTH has been clinically used for the treatment of osteoporosis. However, this regimen of administration is not convenient and is not a favorable choice of patients. In this study, an implantable delivery system has been developed to achieve pulsatile release of PTH. A well-defined cylindrical device was first fabricated with a biodegradable polymer, poly(lactic acid) (PLLA), using a reverse solid free form fabrication technique. Three-component polyanhydrides composed of sebacic acid, 1,3-bis(p-carboxyphenoxy) propane and poly(ethylene glycol) were synthesized and used as isolation layers. The polyanhydride isolation layers and PTH-loaded alginate layers were then stacked alternately within the delivery device. The gap between the stacked PTH-releasing core and the device frame was filled with PLLA to seal. Multi-pulse PTH release was achieved using the implantable device. The lag time between two adjacent pulses were modulated by the composition and the film thickness of the polyanhydride. The released PTH was demonstrated to be biologically active using an in vitro assay. Timed sequential release of multiple drugs has also been demonstrated. The implantable device holds promise for both systemic and local therapies. PMID:17576005

  12. Leadership Dynamics Promoting Systemic Reform for Inclusive Service Delivery

    ERIC Educational Resources Information Center

    Scanlan, Martin

    2009-01-01

    This article presents a multicase study of two systems of schools striving to reform service delivery systems for students with special needs. Considering these systems as institutional actors, the study examines what promotes the understanding and implementation of special education service delivery within a system of schools in a manner that…

  13. Oral Dispersible System: A New Approach in Drug Delivery System

    PubMed Central

    Hannan, P. A.; Khan, J. A.; Khan, A.; Safiullah, S.

    2016-01-01

    Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day's more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form. PMID:27168675

  14. New serine-derived gemini surfactants as gene delivery systems.

    PubMed

    Cardoso, Ana M; Morais, Catarina M; Cruz, A Rita; Silva, Sandra G; do Vale, M Luísa; Marques, Eduardo F; de Lima, Maria C Pedroso; Jurado, Amália S

    2015-01-01

    Gemini surfactants have been extensively used for in vitro gene delivery. Amino acid-derived gemini surfactants combine the special aggregation properties characteristic of the gemini surfactants with high biocompatibility and biodegradability. In this work, novel serine-derived gemini surfactants, differing in alkyl chain lengths and in the linker group bridging the spacer to the headgroups (amine, amide and ester), were evaluated for their ability to mediate gene delivery either per se or in combination with helper lipids. Gemini surfactant-based DNA complexes were characterized in terms of hydrodynamic diameter, surface charge, stability in aqueous buffer and ability to protect DNA. Efficient formulations, able to transfect up to 50% of the cells without causing toxicity, were found at very low surfactant/DNA charge ratios (1/1-2/1). The most efficient complexes presented sizes suitable for intravenous administration and negative surface charge, a feature known to preclude potentially adverse interactions with serum components. This work brings forward a new family of gemini surfactants with great potential as gene delivery systems.

  15. Preparation, characterization and drug delivery study of a novel nanobiopolymeric multidrug delivery system.

    PubMed

    Dadkhah Tehrani, Abbas; Parsamanesh, Masoumeh

    2017-04-01

    New nanocarrier for codelivery of curcumin and doxorubicin as the anticancer drugs was synthesized using biocompatible and biodegradable materials. Firstly, an inclusion complex of amylose (Am) and curcumin (CUR) was formed through entrapment of curcumin into the amylose helices. Then the surface of amylose-curcumin (Am-CUR) complex was modified by polycaprolactone (PCL) via esterification reaction between hydroxyl functional groups of amylose and carbonyl groups of PCL. Finally, poly citric acid (PCA) reacted with terminal hydroxyl groups of PCL by esterification reaction. Then, doxorubicin (DOX) reacted with the surface carboxylic acid functional groups of Am-CUR-PCL-PCA through noncovalent interactions to form Am-CUR-PCL-PCA-DOX as a multidrug delivery system. These new synthesized nanomaterials were characterized by spectroscopic measurement methods such as IR spectroscopy, UV-vis spectroscopy, NMR spectroscopy, and scanning electron microscopy. FE-SEM analyses and DLS measurements showed that the hydrodynamic dimensions of Am-Cur-PCL-PCA were about 50nm. Due to the presence of ester bonds, the synthesized nanomaterials are pH sensitive. Furthermore, the resulting copolymer was completely water soluble because of the hydrophilic nature of poly citric acid part of copolymer and therefore successfully can be utilized in biomedical applications.

  16. In vitro digestion testing of lipid-based delivery systems: calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products.

    PubMed

    Devraj, Ravi; Williams, Hywel D; Warren, Dallas B; Mullertz, Anette; Porter, Christopher J H; Pouton, Colin W

    2013-01-30

    In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces the availability of liberated fatty acids to form mixed micelles and vesicles, thereby reducing drug solubilization. The use of high calcium concentrations does indeed force in vitro digestion of LCTs but may overestimate the extent of drug precipitation that occurs within the intestinal lumen.

  17. Biomedical microelectromechanical systems (BioMEMS): Revolution in drug delivery and analytical techniques

    PubMed Central

    Jivani, Rishad R.; Lakhtaria, Gaurang J.; Patadiya, Dhaval D.; Patel, Laxman D.; Jivani, Nurrudin P.; Jhala, Bhagyesh P.

    2013-01-01

    Advancement in microelectromechanical system has facilitated the microfabrication of polymeric substrates and the development of the novel class of controlled drug delivery devices. These vehicles have specifically tailored three dimensional physical and chemical features which together, provide the capacity to target cell, stimulate unidirectional controlled release of therapeutics and augment permeation across the barriers. Apart from drug delivery devices microfabrication technology’s offer exciting prospects to generate biomimetic gastrointestinal tract models. BioMEMS are capable of analysing biochemical liquid sample like solution of metabolites, macromolecules, proteins, nucleic acid, cells and viruses. This review summarized multidisciplinary application of biomedical microelectromechanical systems in drug delivery and its potential in analytical procedures. PMID:26903763

  18. Biomedical Imaging in Implantable Drug Delivery Systems

    PubMed Central

    Zhou, Haoyan; Hernandez, Christopher; Goss, Monika; Gawlik, Anna; Exner, Agata A.

    2015-01-01

    Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant-body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS. PMID:25418857

  19. Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin.

    PubMed

    Mano, Francisca; Martins, Marta; Sá-Nogueira, Isabel; Barreiros, Susana; Borges, João Paulo; Reis, Rui L; Duarte, Ana Rita C; Paiva, Alexandre

    2017-02-24

    Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30% w/v) with 2% (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.

  20. Herbal Excipients in Novel Drug Delivery Systems

    PubMed Central

    Shirwaikar, A.; Shirwaikar, Annie; Prabu, S. Lakshmana; Kumar, G. Aravind

    2008-01-01

    The use of natural excipients to deliver the bioactive agents has been hampered by the synthetic materials. However advantages offered by these natural excipients are their being non-toxic, less expensive and freely available. The performance of the excipients partly determines the quality of the medicines. The traditional concept of the excipients as any component other than the active substance has undergone a substantial evolution from an inert and cheap vehicle to an essential constituent of the formulation. Excipients are any component other than the active substance(s) intentionally added to formulation of a dosage form. This article gives an overview of herbal excipients which are used in conventional dosage forms as well as novel drug delivery systems. PMID:20046764

  1. A multiportal compensator system for IMRT delivery.

    PubMed

    Yoda, Kiyoshi; Aoki, Yukimasa

    2003-05-01

    We have developed a multiportal compensator system for IMRT delivery, comprising a rotational compensator mount for a linac head, cylindrical compensator enclosures positioned in the mount, a vacuum-formed thermoplastic sheet with heavy alloy granules inside the enclosure, and a vacuum thermoforming device. The mount rotates like a revolver by a stepping motor, thus allowing automatic multiportal IMRT without exchanging compensators by human operators during treatment. The thermoforming device has servo-motor-driven 10 x 10 metal rod elements to actualize an arbitrary intensity profile. The thermoplastic sheet is preheated by a built-in biplanar heater and then it is placed over the rod elements. Subsequently, vacuum forming is performed through corner cutouts of the rod elements. After forced cooling down, the heavy alloy granules are fed into the formed sheet. Preliminary experiment using solid water phantoms and an x-ray film has shown that the intensity profile on the film agrees reasonably well with the desired profile.

  2. LNG delivery system for gas powered vehicles

    SciTech Connect

    Nesser, T.A.; Hedegard, K.W.

    1992-07-07

    This patent describes a natural gas delivery system. It comprises a first vehicle mounted tank for storing liquid natural gas and natural gas vapor; a second vehicle mounted tank for storing liquid natural gas and natural gas vapor; a use line connected to the first and second tanks for receiving natural gas from the first and second tanks and delivering natural gas vapor to the use device on the vehicle and means for pressurizing the natural gas in the use line; means for selecting one of the first or second tanks to deliver natural gas to the use line; and means for overriding the selecting means to deliver natural gas vapor to the use line from either of the tanks in response to detecting a pressure rise therein which exceeds a preselected maximum.

  3. Implantable microchip: the futuristic controlled drug delivery system.

    PubMed

    Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta

    2016-01-01

    There is no doubt that controlled and pulsatile drug delivery system is an important challenge in medicine over the conventional drug delivery system in case of therapeutic efficacy. However, the conventional drug delivery systems often offer a limited by their inability to drug delivery which consists of systemic toxicity, narrow therapeutic window, complex dosing schedule for long term treatment etc. Therefore, there has been a search for the drug delivery system that exhibit broad enhancing activity for more drugs with less complication. More recently, some elegant study has noted that, a new type of micro-electrochemical system or MEMS-based drug delivery systems called microchip has been improved to overcome the problems related to conventional drug delivery. Moreover, micro-fabrication technology has enabled to develop the implantable controlled released microchip devices with improved drug administration and patient compliance. In this article, we have presented an overview of the investigations on the feasibility and application of microchip as an advanced drug delivery system. Commercial manufacturing materials and methods, related other research works and current advancement of the microchips for controlled drug delivery have also been summarized.

  4. Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: Role of docosahexaenoic acid.

    PubMed

    Shinde, Rajshree L; Bharkad, Gopal P; Devarajan, Padma V

    2015-10-01

    Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection are reported. MEs prepared by simple solution exhibited a globule size <20nm, negative zeta potential and good stability. The docosahexaenoic acid (DHA) ME revealed high and rapid ex vivo permeation of drugs through sheep nasal mucosa. Intranasal DHA ME resulted in high brain concentrations and 10.76 (ABZ-SO) and 3.24 (CUR) fold enhancement in brain area-under-the-curve (AUC) compared to intravenous DHA MEs at the same dose. Direct nose to brain transport (DTP) of >95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (P<0.05) suggested the role of DHA in aiding nose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10ng/mL) DHA ME in vitro on Taenia solium cysts was confirmed by complete ALP inhibition and disintegration of cysts at 96h. Considering that the brain concentration at 24h was 1400±160.1ng/g (ABZ-SO) and 120±35.2ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery.

  5. Extracellular vesicles for nucleic acid delivery: progress and prospects for safe RNA-based gene therapy.

    PubMed

    Jiang, L; Vader, P; Schiffelers, R M

    2017-03-01

    Nucleic acid-based drugs offer a potentially effective tool for treatment of a variety of diseases, including cancer, cardiovascular diseases, neurological disorders and infectious diseases. However, clinical applications are hindered by instability of RNA molecules in the circulation and lack of efficient vectors that can deliver RNAs to target tissues and into diseased target cells. Synthetic polymer and lipids as well as virus-based vectors are among the most widely explored vehicles for RNA delivery, but clinical progress has been limited as a result of issues related to toxicity, immunogenicity and low efficiency. Most recently, the discovery that extracellular vesicles (EVs) are endogenous RNA carriers, which may display better biocompatibility and higher delivery efficiency as compared with the synthetic systems, has provided a ray of hope in coping with the delivery dilemma, and EV-based gene therapy has already sparked general interest both in academia and industry. In this review, the current knowledge on EV biology and their role in cell-cell communication will be summarized. Promises of EVs as drug carriers and recent technologies on tailoring EVs' biological attributes will be included, and preclinical studies in which EVs have shown promise for therapeutic RNA delivery will be discussed.

  6. Ocular drug delivery systems: An overview

    PubMed Central

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

    2014-01-01

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

  7. ICS-283: a system for targeted intravenous delivery of siRNA.

    PubMed

    Schiffelers, Raymond M; Storm, Gert

    2006-05-01

    ICS-283 was developed within Intradigm Corporation as a system that is designed for the systemic delivery of therapeutic small interfering (siRNA) to sites of pathological angiogenesis. The non-viral siRNA delivery system is based on synthetic nanoparticles, known as Targe (Intradigm Corporation), which functions as a broad-platform technology to deliver siRNA to specific target cells in diseased tissues. The system is constructed to incorporate different functionalities that address critical needs for successful nucleic acid delivery. The TargeTran synthetic vector is a self-assembling, layered nanoparticle that protects and targets siRNA to specific cell types in pathological tissues. At present, ICS-283 is the only antiangiogenic siRNA delivery system that is designed for intravenous administration to treat angiogenesis-driven diseases.

  8. Acid-responsive PEGylated doxorubicin prodrug nanoparticles for neuropilin-1 receptor-mediated targeted drug delivery.

    PubMed

    Song, Huijuan; Zhang, Ju; Wang, Weiwei; Huang, Pingsheng; Zhang, Yumin; Liu, Jianfeng; Li, Chen; Kong, Deling

    2015-12-01

    Self-assembled prodrug nanoparticles have demonstrated great promise in cancer chemotherapy. In the present study, we developed a new kind of prodrug nanoparticles for targeted drug delivery. PEGylated doxorubicin conjugate with an acid-cleavable cis-aconityl spacer was prepared. Then it was functionalized with a tumor-penetrating peptide, Cys-Arg-Gly-Asp-Lys (CRGDK), providing the prodrug nanoparticles with the specific binding ability to neurophilin-1 receptor. In acid mediums, doxorubicin could be released from the prodrug nanoparticles with an accumulative release around 60% through the acid-triggered hydrolysis of cis-aconityl bond and nanoparticle disassembly. Whereas, drug release was slow under a neutral pH and the accumulative drug release was less than 16%. In the cell culture tests, our prodrug nanoparticles showed enhanced endocytosis and cytotoxicity in cancer cells including HepG2, MCF-7 and MDA-MB-231 cells, but lower cytotoxicity in human cardiomyocyte H2C9. In the animal experiments, the prodrug nanoparticles were intravenously injected into Balb/c nude mice bearing MDA-MB-231 tumors. Enhanced drug penetration and accumulation in tumors, accompanying with a rapid early tumor-binding behavior, was observed after intravenous injection of the peptide modified prodrug nanoparticles. These data suggests that the acid-sensitive and tumor-targeting PEGylated doxorubicin prodrug nanoparticle may be an efficient drug delivery system for cancer chemotherapy.

  9. Influence of the composition of monoacyl phosphatidylcholine based microemulsions on the dermal delivery of flufenamic acid.

    PubMed

    Hoppel, Magdalena; Ettl, Hanna; Holper, Evelyn; Valenta, Claudia

    2014-11-20

    Although microemulsions are one of the most promising dermal carrier systems, their clinical use is limited due to their skin irritation potential. Therefore, microemulsions based on naturally derived monoacyl phosphatidylcholine (MAPL) were developed. The influence of the water, oil and surfactant content on dermal delivery of flufenamic acid was systematically investigated for the first time. A water-rich microemulsion led to significantly higher in vitro skin penetration of flufenamic acid compared to other microemulsions. The superiority of the water-rich microemulsion over a marketed flufenamic acid containing formulation was additionally confirmed. Differences in drug delivery could be explained by alterations of the microemulsions after application. Evaporation of isopropanol led to crystal-like structures of MAPL on the skin surface from the surfactant- or oleic acid-rich microemulsions. In contrast, the formation of this additional barrier was hindered in case of the water-rich microemulsion. The skin penetration of MAPL was additionally analyzed by combined ATR-FTIR and tape stripping experiments, where MAPL itself penetrated only into the initial layers of the stratum corneum, independent of the microemulsion composition. Since a surfactant must penetrate the skin to cause irritation, MAPL can be presumed as a skin-friendly emulsifier with the ability to stabilize pharmaceutically acceptable microemulsions.

  10. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

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

    2012-01-01

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

  11. New Delivery Systems for the 21st Century.

    ERIC Educational Resources Information Center

    Van Patten, James J.

    This paper presents an historical perspective on the development of educational delivery systems, and then turns to the challenges of the information age and the issues of developing new delivery systems in this challenging environment. The paper discusses the fragility of power sources and of the networked world; technological weaknesses; freedom…

  12. Guidelines for Psychological Practice in Health Care Delivery Systems

    ERIC Educational Resources Information Center

    American Psychologist, 2013

    2013-01-01

    Psychologists practice in an increasingly diverse range of health care delivery systems. The following guidelines are intended to assist psychologists, other health care providers, administrators in health care delivery systems, and the public to conceptualize the roles and responsibilities of psychologists in these diverse contexts. These…

  13. Vesicular system: Versatile carrier for transdermal delivery of bioactives.

    PubMed

    Singh, Deependra; Pradhan, Madhulika; Nag, Mukesh; Singh, Manju Rawat

    2015-01-01

    The transdermal route of drug delivery has gained immense interest for pharmaceutical researchers. The major hurdle for diffusion of drugs and bioactives through transdermal route is the stratum corneum, the outermost layer of the skin. Currently, various approaches such as physical approach, chemical approach, and delivery carriers have been used to augment the transdermal delivery of bioactives. This review provides a brief overview of mechanism of drug transport across skin, different lipid vesicular systems, with special emphasis on lipid vesicular systems including transfersomes, liposomes, niosomes, ethosomes, virosomes, and pharmacosomes and their application for the delivery of different bioactives.

  14. Spatiotemporal drug delivery using laser-generated-focused ultrasound system

    PubMed Central

    Di, Jin; Kim, Jinwook; Hu, Quanyin; Jiang, Xiaoning; Gu, Zhen

    2016-01-01

    Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation. PMID:26299506

  15. Gastroretentive drug delivery systems for therapeutic management of peptic ulcer.

    PubMed

    Garg, Tarun; Kumar, Animesh; Rath, Goutam; Goyal, Amit K

    2014-01-01

    A peptic ulcer, stomach ulcer, or gastric ulcer, also known as peptic ulcer disease (PUD), is a very common chronic disorder of the stomach which is mainly caused by damage or impairment of the stomach lining. Various factors such as pepsin, gastric acid, H. pylori, NSAIDs, prostaglandins, mucus, bicarbonate, and blood flow to mucosa play an important role in causing peptic ulcers. In this review article, our main focus is on some important gastroretentive drug delivery systems (GRDDS) (floating, bioadhesive, high density, swellable, raft forming, superporous hydrogel, and magnetic systems) which will be helpful in gastroretention of different dosage forms for treatment of peptic ulcer. GRDDS provides a mean for controlled release of compounds that are absorbed by active transport in the upper intestine. It also enables controlled delivery for paracellularly absorbed drugs without a decrease in bioavailability. The above approaches are specific for targeting and leading to a marked improvement in the quality of life for a large number of patients. In the future, it is expected that they will become of growing significance, finally leading to improved efficiencies of various types of pharmacotherapies.

  16. Microparticulate based topical delivery system of clobetasol propionate.

    PubMed

    Badıllı, Ulya; Sen, Tangül; Tarımcı, Nilüfer

    2011-09-01

    Psoriasis is a chronic, autoimmune skin disease affecting approximately 2% of the world's population. Clobetasol propionate which is a superpotent topical corticosteroid is widely used for topical treatment of psoriasis. Conventional dosage forms like creams and ointments are commonly prefered for the therapy. The purpose of this study was to develop a new topical delivery system in order to provide the prolonged release of clobetasol propionate and to reduce systemic absorption and side effects of the drug. Clobetasol propionate loaded-poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by oil-in-water emulsion-solvent evaporation technique. Particle size analysis, morphological characterization, DSC and XRD analyses and in vitro drug release studies were performed on the microparticle formulations. Emulgel formulations were prepared as an alternative for topical delivery of clobetasol propionate. In vitro drug release studies were carried out from the emulgel formulations containing pure drug and drug-loaded microspheres. In addition, the same studies were performed to determine the drug release from the commercial cream product of clobetasol propionate. The release of clobetasol propionate from the emulgel formulations was significantly higher than the commercial product. In addition, the encapsulation of clobetasol propionate in the PLGA microspheres significantly delayed the drug release from the emulgel formulation. As a result, the decrease in the side effects of clobetasol propionate by the formulation containing PLGA microspheres is expected.

  17. Superparamagnetic Iron Oxide Nanoparticle-Based Delivery Systems for Biotherapeutics

    PubMed Central

    Mok, Hyejung; Zhang, Miqin

    2014-01-01

    Introduction Superparamagnetic iron oxide nanoparticle (SPION)-based carrier systems have many advantages over other nanoparticle-based systems. They are biocompatible, biodegradable, facilely tunable, and superparamagnetic and thus controllable by an external magnetic field. These attributes enable their broad biomedical applications. In particular, magnetically-driven carriers are drawing considerable interest as an emerging therapeutic delivery system because of their superior delivery efficiency. Area covered This article reviews the recent advances in use of SPION-based carrier systems to improve the delivery efficiency and target specificity of biotherapeutics. We examine various formulations of SPION-based delivery systems, including SPION micelles, clusters, hydrogels, liposomes, and micro/nanospheres, as well as their specific applications in delivery of biotherapeutics. Expert opinion Recently, biotherapeutics including therapeutic cells, proteins and genes have been studied as alternative treatments to various diseases. Despite the advantages of high target specificity and low adverse effects, clinical translation of biotherapeutics has been hindered by the poor stability and low delivery efficiency compared to chemical drugs. Accordingly, biotherapeutic delivery systems that can overcome these limitations are actively pursued. SPION-based materials can be ideal candidates for developing such delivery systems because of their excellent biocompatibility and superparamagnetism that enables long-term accumulation/retention at target sites by utilization of a suitable magnet. In addition, synthesis technologies for production of finely-tuned, homogeneous SPIONs have been well developed, which may promise their rapid clinical translation. PMID:23199200

  18. Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs

    PubMed Central

    2015-01-01

    Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells. PMID:24779637

  19. CLIPS: An expert system tool for delivery and training

    NASA Technical Reports Server (NTRS)

    Riley, Gary; Culbert, Chris; Savely, Robert T.; Lopez, Frank

    1987-01-01

    The C Language Integrated Production System (CLIPS) is a forward chaining rule-based language. The requirements necessary for an expert system tool which is used for development, delivery, and training are examined. Because of its high portability, low cost, and ease of integration with external systems, CLIPS has great potential as an expert system tool for delivery and training. In addition, its representation flexibility, debugging aids, and performance, along with its other strengths, make it a viable alternative for expert system development.

  20. Chitosan-thioglycolic acid conjugate: an alternative carrier for oral nonviral gene delivery?

    PubMed

    Martien, Ronny; Loretz, Brigitta; Thaler, Marlene; Majzoob, Sayeh; Bernkop-Schnürch, Andreas

    2007-07-01

    Regarding safety concerns, nonviral gene delivery vehicles that have the required efficiency and safety for use in human gene therapy are being widely investigated. The aim of this study was to synthesize and evaluate a thiolated chitosan to improve the efficacy of oral gene delivery systems. Thiolated chitosan was synthesized by introducing thioglycolic acid (TGA) to chitosan via amide bond formation mediated by a carbodiimide. Based on this conjugate, nanoparticles with pDNA were generated at pH 4.0 and 5.0. Cytotoxicity of the thiolated chitosan/pDNA nanoparticles on Caco-2 cells was evaluated. The diameter of thiolated chitosan/pDNA nanoparticles was in the range of 100-200 nm. The zeta potential was determined to be 5-6 mV. Due to stability toward nucleases, the transfection rate of thiolated chitosan/pDNA nanoparticles was fivefold higher than that of unmodified chitosan/pDNA nanoparticles. Lactate dehydrogenase tests for thiolated chitosan/pDNA (pH 4.0 and 5.0) showed that (3.79 +/- 0.23)% and (2.9 +/- 0.13)% cell damage. According to these results, thiolated chitosan represents promising excipients for preparation DNA nanoparticles in nonviral gene delivery system.

  1. Marine Origin Polysaccharides in Drug Delivery Systems

    PubMed Central

    Cardoso, Matias J.; Costa, Rui R.; Mano, João F.

    2016-01-01

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID:26861358

  2. Marine Origin Polysaccharides in Drug Delivery Systems.

    PubMed

    Cardoso, Matias J; Costa, Rui R; Mano, João F

    2016-02-05

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

  3. Recent advancements in erythrocytes, platelets, and albumin as delivery systems

    PubMed Central

    Xu, Peipei; Wang, Ruju; Wang, Xiaohui; Ouyang, Jian

    2016-01-01

    In the past few years, nanomaterial-based drug delivery systems have been applied to enhance the efficacy of therapeutics and to alleviate negative effects through the controlled delivery of targeting and releasing agents. However, few drug carriers can achieve high targeting efficacy, even when targeting modalities and surface markers are introduced. Immunological problems have also limited their wide applications. Biological drug delivery systems, such as erythrocytes, platelets, and albumin, have been extensively investigated because of their unique properties. In this review, erythrocytes, platelets, and albumin are described as efficient drug delivery systems. Their properties, applications, advantages, and limitations in disease treatment are explained. This review confirms that these systems can be used to facilitate a specific, biocompatible, and smart drug delivery. PMID:27274282

  4. Characterization of Release Mechanism in Polymeric Drug Delivery Systems

    NASA Astrophysics Data System (ADS)

    Laplante, Arthur James; Plachy, Robin Marie; Aou, Kaoru; Ferguson, Jake; Hsu, Shaw Ling

    2006-03-01

    Our polymeric drug delivery system is based on our understanding of phase behavior of polymers [e.g poly(lactic acid)], low molecular drugs and various solvents used in processing. Clearly the different morphologies achieved, based on different phase separation kinetics, can affect drug release rates. Release of drugs, in most cases, involves the exchange between the extraction media and drug. We have characterized the transport behavior using a number of unique techniques. Reflectance infrared spectroscopy has given us a detailed description of the release rate of drugs into the extraction media. Surface plasmon resonance has shown the overall mass loss. UV-visible spectroscopy has yielded the concentration of drug in the solution. These measurements are compared to the release mechanism based on Fickian diffusion. The two step release rates observed can only be explained by taking into account differences in the morphological features of the phase separated films.

  5. Formulation and Application of Biodegradable Nanoparticles Based Biopharmaceutical Delivery - An Efficient Delivery System.

    PubMed

    Bhattacharjee, Surajit; Sarkar, Biplab; Sharma, Ashish Ranjan; Gupta, Priya; Sharma, Garima; Lee, Sang-Soo; Chakraborty, Chiranjib

    2016-01-01

    Biodegradable polymer based drug delivery has emerged as a promising and successful clinical tool for specific targeting and controlled drug release delivery system. Various other unique advantages associated with this delivery system include prolonged circulation, biocompatibility, degradation in nontoxic by-products etc. Till date, various biopharmaceutical agents have been successfully encapsulated within biodegradable polymers and used in clinics. However, before the clinical implementation of such nanocarriers different parameters have to be considered which influence the success of these nanocarriers such as drug release profile, size of nanocarrier, degradation mechanism, toxicity profile, type of polymer used, appropriate synthesis method, selection of mode of delivery etc. The following review focuses on such considerations to explore the area of designing and development of biodegradable polymeric nanosystems which when encapsulated with biopharmaceutical agents can be efficient for clinical application.

  6. Self-assembled polymeric nanocarriers for the targeted delivery of retinoic acid to the hair follicle

    NASA Astrophysics Data System (ADS)

    Lapteva, Maria; Möller, Michael; Gurny, Robert; Kalia, Yogeshvar N.

    2015-11-01

    Acne vulgaris is a highly prevalent dermatological disease of the pilosebaceous unit (PSU). An inability to target drug delivery to the PSU results in poor treatment efficacy and the incidence of local side-effects. Cutaneous application of nanoparticulate systems is reported to induce preferential accumulation in appendageal structures. The aim of this work was to prepare stable polymeric micelles containing retinoic acid (RA) using a biodegradable and biocompatible diblock methoxy-poly(ethylene glycol)-poly(hexylsubstituted lactic acid) copolymer (MPEG-dihexPLA) and to evaluate their ability to deliver RA to skin. An innovative punch biopsy sample preparation method was developed to selectively quantify follicular delivery; the amounts of RA present were compared to those in bulk skin, (i.e. without PSU), which served as the control. RA was successfully incorporated into micelle nanocarriers and protected from photoisomerization by inclusion of Quinoline Yellow. Incorporation into the spherical, homogeneous and nanometer-scale micelles (dn < 20 nm) increased the aqueous solubility of RA by >400-fold. Drug delivery experiments in vitro showed that micelles were able to deliver RA to porcine and human skins more efficiently than Retin-A® Micro (0.04%), a marketed gel containing RA loaded microspheres, (7.1 +/- 1.1% vs. 0.4 +/- 0.1% and 7.5 +/- 0.8% vs. 0.8 +/- 0.1% of the applied dose, respectively). In contrast to a non-colloidal RA solution, Effederm® (0.05%), both the RA loaded MPEG-dihexPLA polymeric micelles (0.005%) and Retin-A® Micro (0.04%) displayed selectivity for delivery to the PSU with 2-fold higher delivery to PSU containing samples than to control samples. Moreover, the micelle formulation outperformed Retin-A® Micro in terms of delivery efficiency to PSU presenting human skin (10.4 +/- 3.2% vs. 0.6 +/- 0.2%, respectively). The results indicate that the polymeric micelle formulation enabled an increased and targeted delivery of RA to the PSU

  7. A new approach in gastroretentive drug delivery system using cholestyramine.

    PubMed

    Umamaheshwari, R B; Jain, Subheet; Jain, N K

    2003-01-01

    We prepared cellulose acetate butyrate (CAB)-coated cholestyramine microcapsules as a intragastric floating drug delivery system endowed with floating ability due to the carbon dioxide generation when exposed to the gastric fluid. The microcapsules also have a mucoadhesive property. Ion-exchange resin particles can be loaded with bicarbonate followed by acetohydroxamic acid (AHA) and coated with CAB by emulsion solvent evaporation method. The drug concentration was monitored to maintain the floating property and minimum effective concentration. The effect of CAB: drug-resin ratio (2:1, 4:1, 6:1 w/w) on the particle size, floating time, and drug release was determined. Cholestyramine microcapsules were characterized for shape, surface characteristics, and size distribution; cholestyramine/acetohydroxamic acid interactions inside microcapsules were investigated by X-ray diffractometry. The buoyancy time of CAB-coated formulations was better than that of uncoated resin particles. Also, a longer floating time was observed with a higher polymer:drug resin complex ratio (6:1). With increasing coating thickness the particle size was increased but drug release rate was decreased. The drug release rate was higher in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF). The in vivo mucoadhesion studies were performed with rhodamine-isothiocyanate (RITC) by fluorescent probe method. The amount of CAB-coated cholestyramine microcapsules that remained in the stomach was slightly lower than that of uncoated resin particles. Cholestyramine microcapsules were distributed throughout the stomach and exhibited prolonged gastric residence via mucoadhesion. These results suggest that CAB-coated microcapsules could be a floating as well as a mucoadhesive drug delivery system. Thus, it has promise in the treatment of Helicobacter pylori.

  8. The LITA Drill and Sample Delivery System

    NASA Astrophysics Data System (ADS)

    Paulsen, G.; Yoon, S.; Zacny, K.; Wettergreeng, D.; Cabrol, N. A.

    2013-12-01

    The Life in the Atacama (LITA) project has a goal of demonstrating autonomous roving, sample acquisition, delivery and analysis operations in Atacama, Chile. To enable the sample handling requirement, Honeybee Robotics developed a rover-deployed, rotary-percussive, autonomous drill, called the LITA Drill, capable of penetrating to ~80 cm in various formations, capturing and delivering subsurface samples to a 20 cup carousel. The carousel has a built-in capability to press the samples within each cup, and position target cups underneath instruments for analysis. The drill and sample delivery system had to have mass and power requirements consistent with a flight system. The drill weighs 12 kg and uses less than 100 watt of power to penetrate ~80 cm. The LITA Drill auger has been designed with two distinct stages. The lower part has deep and gently sloping flutes for retaining powdered sample, while the upper section has shallow and steep flutes for preventing borehole collapse and for efficient movement of cuttings and fall back material out of the hole. The drill uses the so called 'bite-sampling' approach that is samples are taken in short, 5-10 cm bites. To take the first bite, the drill is lowered onto the ground and upon drilling of the first bite it is then retracted into an auger tube. The auger with the auger tube are then lifted off the ground and positioned next to the carousel. To deposit the sample, the auger is rotated and retracted above the auger tube. The cuttings retained on the flutes are either gravity fed or are brushed off by a passive side brush into the cup. After the sample from the first bite has been deposited, the drill is lowered back into the same hole to take the next bite. This process is repeated until a target depth is reached. The bite sampling is analogous to peck drilling in the machining process where a bit is periodically retracted to clear chips. If there is some fall back into the hole once the auger has cleared the hole, this

  9. 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.

  10. Systemic Delivery of Blood-Brain Barrier Targeted Polymeric Nanoparticles Enhances Delivery to Brain Tissue

    PubMed Central

    Saucier-Sawyer, Jennifer K.; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J.; Zhang, Junwei; Quijano, Elias; Saltzman, W. Mark

    2016-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer nanoparticle systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All nanoparticle preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One nanoparticle produced significantly higher brain uptake (~0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad nanoparticles provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing nanoparticle transport across the BBB does not necessarily yield proportional pharmacological effects. PMID:26453169

  11. Optical diagnostics integrated with laser spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan; Joshi, Sachin; Reynolds, Adam

    2008-09-02

    A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

  12. Potential of nanoparticulate drug delivery systems by intranasal administration.

    PubMed

    Ali, Javed; Ali, Mushir; Baboota, Sanjula; Sahani, Jasjeet Kaur; Ramassamy, Charles; Dao, Lé; Bhavna

    2010-05-01

    Due to number of problems related with oral, parenteral, rectal and other routes of drug administration, the interest of pharmaceutical scientists has increased towards exploring the possibilities of intranasal delivery of various drugs. Nasal drug delivery system is commonly known for the treatment of local ailments like cold, cough, rhinitis, etc. Efforts have been made to deliver various drugs, especially peptides and proteins, through nasal route for systemic use; utilizing the principles and concepts of various nanoparticulate drug delivery systems using various polymers and absorption promoters. The incorporation of drugs into nanoparticles might be a promising approach, since colloidal formulations have been shown to protect them from the degrading milieu in the nasal cavity and facilitate their transport across the mucosal barriers. The use of nanoparticles for vaccine delivery provides beneficial effect, by achieving good immune responses. This could be due to the fact that small particles can be transported preferentially by the lymphoid tissue of the nasal cavity (NALT). The brain gets benefited through the intranasal delivery as direct olfactory transport bypasses the blood brain barrier and nanoparticles are taken up and conveyed along cell processes of olfactory neurons through the cribriform plate to synaptic junctions with neurons of the olfactory bulb. The intranasal delivery is aimed at optimizing drug bioavailability for systemic drugs, as absorption decreases with increasing molecular weight, and for drugs, which are susceptible to enzymatic degradation such as proteins and polypeptides. This review discusses the potential benefits of using nanoparticles for nasal delivery of drugs and vaccines for brain, systemic and topical delivery. The article aims at giving an insight into nasal cavity, consideration of factors affecting and strategies to improve drug absorption through nasal route, pharmaceutical dosage forms and delivery systems with

  13. Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    NASA Astrophysics Data System (ADS)

    Yu, Meihua; Jambhrunkar, Siddharth; Thorn, Peter; Chen, Jiezhong; Gu, Wenyi; Yu, Chengzhong

    2012-12-01

    In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.

  14. A Molecular Communication System Model for Particulate Drug Delivery Systems.

    PubMed

    Chahibi, Youssef; Pierobon, Massimiliano; Song, Sang Ok; Akyildiz, Ian F

    2013-12-01

    The goal of a drug delivery system (DDS) is to convey a drug where the medication is needed, while, at the same time, preventing the drug from affecting other healthy parts of the body. Drugs composed of micro- or nano-sized particles (particulate DDS) that are able to cross barriers which prevent large particles from escaping the bloodstream are used in the most advanced solutions. Molecular communication (MC) is used as an abstraction of the propagation of drug particles in the body. MC is a new paradigm in communication research where the exchange of information is achieved through the propagation of molecules. Here, the transmitter is the drug injection, the receiver is the drug delivery, and the channel is realized by the transport of drug particles, thus enabling the analysis and design of a particulate DDS using communication tools. This is achieved by modeling the MC channel as two separate contributions, namely, the cardiovascular network model and the drug propagation network. The cardiovascular network model allows to analytically compute the blood velocity profile in every location of the cardiovascular system given the flow input by the heart. The drug propagation network model allows the analytical expression of the drug delivery rate at the targeted site given the drug injection rate. Numerical results are also presented to assess the flexibility and accuracy of the developed model. The study of novel optimization techniques for a more effective and less invasive drug delivery will be aided by this model, while paving the way for novel communication techniques for Intrabody communication networks.

  15. 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.

  16. Thiolated polymers as mucoadhesive drug delivery systems.

    PubMed

    Duggan, Sarah; Cummins, Wayne; O' Donovan, Orla; Hughes, Helen; Owens, Eleanor

    2017-03-30

    Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices.

  17. Freeze dried chitosan/ poly-(glutamic acid) microparticles for intestinal delivery of lansoprazole.

    PubMed

    Singh, Mangla Nand; Yadav, Hemant K S; Ram, Munshi; Shivakumar, H G

    2012-01-01

    Lansoprazole sodium is a proton pump inhibitor used in treating gastroesophageal reflux disease (GERD). It is highly acid-labile and presents many formulation challenges. Therefore, this drug needs to be protected from the harsh environment in the stomach. In order to achieve this, a pH-sensitive microparticle system composed of chitosan and γ- poly-(glutamic acid) was prepared and loaded with Lansoprazole. The prepared microparticles were not stable in gastric pH. To overcome this problem microparticles were freez-dried and filled in an enteric-coated capsule. Upon oral administration, the enteric-coated capsule remained intact in the acidic environment of the stomach, but dissolved rapidly in the distal segment of the GIT. Consequently, all the microparticles loaded in the capsule were brought into the intestine, thus enhancing the intestinal absorption of drug. Drug encapsulation efficiency of formulation F3 was found to be 82.82 % and in vitro release of prepared formulation F3 was found to be 94% after 8 h of dissolution in 7.4 pH phosphate buffer. FTIR and DSC studies showed no interaction between the drug and polymer. The formulation showed good swelling property. SEM photographs showed that microparticles are spherical and lies in size range of 300-400 μm. From the above, it can be concluded that the prepared chitosan/ γ-poly-(glutamic acid) microparticles can be used as carriers for the intestinal delivery of acid liable drugs such as lansoprazole.

  18. Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems.

    PubMed

    Guan, S; Rosenecker, J

    2017-02-02

    Because of its safe and effective protein expression profile, in vitro transcribed messenger RNA (IVT-mRNA) represents a promising candidate in the development of novel therapeutics for genetic diseases, vaccines or gene editing strategies, especially when its inherent shortcomings (for example, instability and immunogenicity) have been partially addressed via structural modifications. However, numerous unsolved technical difficulties in successful in vivo delivery of IVT-mRNA have greatly hindered the applications of IVT-mRNA in clinical development. Recent advances in nanotechnology and material science have yielded many promising nonviral delivery systems, some of which were able to efficiently facilitate targeted in vivo delivery of IVT-mRNA in safe and noninvasive manners. The diversity and flexibility of these delivery systems highlight the recent progress of IVT-mRNA-based therapy using nonviral vectors. In this review, we summarize recent advances of existing and emerging nonviral vector-based nanotechnologies for IVT-mRNA delivery and briefly summarize the interesting but rarely discussed applications on simultaneous delivery of IVT-mRNA with DNA.Gene Therapy advance online publication, 2 February 2017; doi:10.1038/gt.2017.5.

  19. Delivery system for molten salt oxidation of solid waste

    DOEpatents

    Brummond, William A.; Squire, Dwight V.; Robinson, Jeffrey A.; House, Palmer A.

    2002-01-01

    The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a temperature below incineration temperature while entering the molten salt reactor.

  20. Convection-enhanced delivery to the central nervous system.

    PubMed

    Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

    2015-03-01

    Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

  1. Biomimetics in drug delivery systems: A critical review.

    PubMed

    Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

    2017-03-18

    Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems.

  2. Intracellular delivery of peptide nucleic acid and organic molecules using zeolite-L nanocrystals.

    PubMed

    Bertucci, Alessandro; Lülf, Henning; Septiadi, Dedy; Manicardi, Alex; Corradini, Roberto; De Cola, Luisa

    2014-11-01

    The design and synthesis of smart nanomaterials can provide interesting potential applications for biomedical purposes from bioimaging to drug delivery. Manufacturing multifunctional systems in a way to carry bioactive molecules, like peptide nucleic acids able to recognize specific targets in living cells, represents an achievement towards the development of highly selective tools for both diagnosis and therapeutics. This work describes a very first example of the use of zeolite nanocrystals as multifunctional nanocarriers to deliver simultaneously PNA and organic molecules into living cells. Zeolite-L nanocrystals are functionalized by covalently attaching the PNA probes onto the surface, while the channel system is filled with fluorescent guest molecules. The cellular uptake of the PNA/Zeolite-L hybrid material is then significantly increased by coating the whole system with a thin layer of biodegradable poly-L-lysine. The delivery of DAPI as a model drug molecule, inserted into the zeolite pores, is also demonstrated to occur in the cells, proving the multifunctional ability of the system. Using this zeolite nanosystem carrying PNA probes designed to target specific RNA sequences of interest in living cells could open new possibilities for theranostic and gene therapy applications.

  3. Poly(lactic acid) and poly(lactic-co-glycolic acid) particles as versatile carrier platforms for vaccine delivery.

    PubMed

    Pavot, Vincent; Berthet, Morgane; Rességuier, Julien; Legaz, Sophie; Handké, Nadège; Gilbert, Sarah C; Paul, Stéphane; Verrier, Bernard

    2014-12-01

    The development of safe and effective vaccines for cancer and infectious diseases remains a major goal in public health. Over the last two decades, controlled release of vaccine antigens and immunostimulant molecules has been achieved using nanometer or micron-sized delivery vehicles synthesized using biodegradable polymers. In addition to achieving a depot effect, enhanced vaccine efficacy using such delivery vehicles has been attributed to efficient targeting of antigen presenting cells such as dendritic cells. Biodegradable and biocompatible poly(lactic acid) and poly(lactic-co-glycolic acid) polymers belong to one such family of polymers that have been a popular choice of material used in the design of these delivery vehicles. This review summarizes research findings from ourselves and others highlighting the promise of poly(lactic acid)- and poly(lactic-co-glycolic acid)-based vaccine carriers in enhancing immune responses.

  4. Drug delivery systems for brain tumor therapy.

    PubMed

    Rautioa, Jarkko; Chikhale, Prashant J

    2004-01-01

    Brain tumors are one of the most lethal forms of cancer. They are extremely difficult to treat. Although, the rate of brain tumor incidence is relatively low, the field clearly lacks therapeutic strategies capable of overcoming barriers for effective delivery of drugs to brain tumors. Clinical failure of many potentially effective therapeutics for the treatment of brain tumors is usually not due to a lack of drug potency, but rather can be attributed to shortcomings in the methods by which a drug is delivered to the brain and into brain tumors. In response to the lack of efficacy of conventional drug delivery methods, extensive efforts have been made to develop novel strategies to overcome the obstacles for brain tumor drug delivery. The challenge is to design therapeutic strategies that deliver drugs to brain tumors in a safe and effective manner. This review provides some insight into several potential techniques that have been developed to improve drug delivery to brain tumors, and it should be helpful to clinicians and research scientists as well.

  5. CHAPTER 11. DELIVERY AND DISTRIBUTION SYSTEMS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water delivery through canals or pipelines usually implies that several farms must somehow share access to the water in terms of flow rate, duration of access, and the return time to access the flow again, called an irrigation schedule, which can be rigid or flexible regarding the rate, duration and...

  6. Information Delivery Systems: The Future Is Here.

    ERIC Educational Resources Information Center

    O'Malley, Penelope Grenoble

    1993-01-01

    Looks at developments in information delivery (including new interactive media formats, vastly increased channel capacity for standard cable television, and the development of wireless cable and other distribution technologies) that are revolutionizing the communications industry. Raises questions about the role technical communicators are being…

  7. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    PubMed Central

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

  8. Perspectives on Dual Targeting Delivery Systems for Brain Tumors.

    PubMed

    Gao, Huile

    2017-03-01

    Brain tumor remains one of the most serious threats to human beings. Different from peripheral tumors, drug delivery to brain tumor is largely restricted by the blood brain barrier (BBB). To fully conquer this barrier and specifically deliver drugs to brain tumor, dual targeting delivery systems were explored, which are functionalized with two active targeting ligands: one to the BBB and the other to the brain tumor. The development of dual targeting delivery system is still in its early stage, and attentions need to be paid to issues and concerns that remain unresolved in future studies.

  9. Design and Biological Evaluation of Delivery Systems Containing Bisphosphonates

    PubMed Central

    Aderibigbe, Blessing; Aderibigbe, Isiaka; Popoola, Patricia

    2016-01-01

    Bisphosphonates have found application in the treatment of reoccurrence of bone diseases, breast cancer, etc. They have also been found to exhibit antimicrobial, anticancer and antimalarial activities. However, they suffer from pharmacological deficiencies such as toxicity, poor bioavailability and low intestinal adsorption. These shortcomings have resulted in several researchers developing delivery systems that can enhance their overall therapeutic effectiveness. This review provides a detailed overview of the published studies on delivery systems designed for the delivery of bisphosphonates and the corresponding in vitro/in vivo results. PMID:28035945

  10. Poly(alkylene oxide) Copolymers for Nucleic Acid Delivery

    DTIC Science & Technology

    2012-07-17

    biofilm infection treatments, pain control and cancer chemotherapy. Charles M. Roth is an Associate Professor in the Department of Chemical and...technology and engineering approaches to cancer . REFERENCES 1. Aigner A. Nonviral in vivo delivery of therapeutic small interfering RNAs. Curr Opin Mol Ther

  11. Bionanocomposites based on layered double hydroxides as drug delivery systems

    NASA Astrophysics Data System (ADS)

    Aranda, Pilar; Alcântara, Ana C. S.; Ribeiro, Ligia N. M.; Darder, Margarita; Ruiz-Hitzky, Eduardo

    2012-10-01

    The present work introduces new biohybrid materials involving layered double hydroxides (LDH) and biopolymers to produce bionanocomposites, able to act as effective drug delivery systems (DDS). Ibuprofen (IBU) and 5-aminosalicylic acid (5-ASA) have been chosen as model drugs, being intercalated in a Mg-Al LDH matrix. On the one side, the LDHIBU intercalation compound prepared by ion-exchange reaction was blended with the biopolymers zein, a highly hydrophobic protein, and alginate, a polysaccharide widely applied for encapsulating drugs. On the other side, the LDH- 5-ASA intercalation compound prepared by co-precipitation was assembled to the polysaccharides chitosan and pectin, which show mucoadhesive properties and resistance to acid pH values, respectively. Characterization of the intercalation compounds and the resulting bionanocomposites was carried out by means of different experimental techniques: X-ray diffraction, infrared spectroscopy, chemical and thermal analysis, as well as optical and scanning electron microscopies. Data on the swelling behavior and drug release under different pH conditions are also reported.

  12. Inspection program improves bulk cement system delivery

    SciTech Connect

    O'Bannion, T. ); Guidroz, B.; Morris, G. )

    1993-12-20

    A recently implemented survey of pneumatically operated bulk cement-handling equipment offshore has improved bulk cement deliverability on several Gulf of Mexico rigs. The 30-point survey helps ensure an adequate rate of bulk cement delivery throughout the cement job. The inspection survey was developed because the source of many cement job failures was a lack of adequate, steady delivery of bulk cement to the cementing unit during the job. The job failures caused by flow interruptions, plugging of tools by chunks of set cement, and erratic flow resulted in poor primary cement jobs, many of which required remedial cementing jobs. A better-controlled flow of cement may help prevent these types of failure, thereby reducing the number of remedial cement operations. The paper describes the inspection procedures.

  13. Chitosan-based nanoparticles for rosmarinic acid ocular delivery--In vitro tests.

    PubMed

    da Silva, Sara Baptista; Ferreira, Domingos; Pintado, Manuela; Sarmento, Bruno

    2016-03-01

    In this study, chitosan nanoparticles were used to encapsulate antioxidant rosmarinic acid, Salvia officinalis (sage) and Satureja montana (savory) extracts as rosmarinic acid natural vehicles. The nanoparticles were prepared by ionic gelation using chitosan and sodium tripolyphosphate (TPP) in a mass ratio of 7:1, at pH 5.8. Particle size distribution analysis and transmission electron microscopy (TEM) confirmed the size ranging from 200 to 300 nm, while surface charge of nanoparticles ranged from 20 to 30 mV. Nanoparticles demonstrate to be safe without relevant cytotoxicity against retina pigment epithelium (ARPE-19) and human cornea cell line (HCE-T). The permeability study in HCE monolayer cell line showed an apparent permeability coefficient Papp of 3.41±0.99×10(-5) and 3.24±0.79×10(-5) cm/s for rosmarinic acid loaded chitosan nanoparticles and free in solution, respectively. In ARPE-19 monolayer cell line the Papp was 3.39±0.18×10(-5) and 3.60±0.05×10(-5) cm/s for rosmarinic acid loaded chitosan nanoparticles and free in solution, respectively. Considering the mucin interaction method, nanoparticles indicate mucoadhesive proprieties suggesting an increased retention time over the ocular mucosa after instillation. These nanoparticles may be promising drug delivery systems for ocular application in oxidative eye conditions.

  14. Hydrogen storage and delivery: the carbon dioxide - formic acid couple.

    PubMed

    Laurenczy, Gábor

    2011-01-01

    Carbon dioxide and the carbonates, the available natural C1 sources, can be easily hydrogenated into formic acid and formates in water; the rate of this reduction strongly depends on the pH of the solution. This reaction is catalysed by ruthenium(II) pre-catalyst complexes with a large variety of water-soluble phosphine ligands; high conversions and turnover numbers have been realised. Although ruthenium(II) is predominant in these reactions, the iron(II) - tris[(2-diphenylphosphino)-ethyl]phosphine (PP3) complex is also active, showing a new perspective to use abundant and inexpensive iron-based compounds in the CO2 reduction. In the catalytic hydrogenation cycles the in situ formed metal hydride complexes play a key role, their structures with several other intermediates have been proven by multinuclear NMR spectroscopy. In the other hand safe and convenient hydrogen storage and supply is the fundamental question for the further development of the hydrogen economy; and carbon dioxide has been recognised to be a viable H2 vector. Formic acid--containing 4.4 weight % of H2, that is 53 g hydrogen per litre--is suitable for H2 storage; we have shown that in aqueous solutions it can be selectively decomposed into CO-free (CO < 10 ppm) CO2 and H2. The reaction takes place under mild experimental conditions and it is able to generate high pressure H2 (up to 600 bar). The cleavage of HCOOH is catalysed by several hydrophilic Ru(II) phosphine complexes (meta-trisulfonated triphenylphosphine, mTPPTS, being the most efficient one), either in homogeneous systems or as immobilised catalysts. We have also shown that the iron(II)--hydrido tris[(2-diphenylphosphino)ethyl]phosphine complex catalyses with an exceptionally high rate and efficiency (turnover frequency, TOF = 9425 h(-1)mol(-1); turnover number, TON = 92400) the formic acid cleavage, in environmentally friendly propylene carbonate solution, opening the way to use cheap, non-noble metal based catalysts for this

  15. Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery

    NASA Astrophysics Data System (ADS)

    Hayward, Stephen L.; Francis, David M.; Sis, Matthew J.; Kidambi, Srivatsan

    2015-10-01

    The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) “(PLL/SPS)4.5” followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited HALNP monolayer further facilitated complete nanoparticle immobilization, cell adhesion, and provided nanoparticle confinement for controlled linear release profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the first study to demonstrate the successful embedment of a translatable lipid based nanocarrier into a substrate that allows for temporal and spatial release of both hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we believe the development of our HALNP embedded PEM system is significant and will catalyze the usage of substrate mediated delivery platforms in biomedical applications.

  16. Poly(L-lactic acid) membranes: absence of genotoxic hazard and potential for drug delivery.

    PubMed

    Uzun, Nelson; Martins, Thomás Duzzi; Teixeira, Gabriella Machado; Cunha, Nayanne Larissa; Oliveira, Rogério Belle; Nassar, Eduardo José; Dos Santos, Raquel Alves

    2015-01-22

    The use of poly(L-lactic acid) (PLA) has been considered an important alternative for medical devices once this polyester presents biomechanical, optical and biodegradable properties. Moreover, the use of PLA results in less inflammatory reactions and more recently it has been proposed its application in drug delivery systems. Genotoxicological evaluations are considered part of the battery assays in toxicological analysis. Considering the wide applications of PLA, the present work evaluated the potential cytotoxic and genotoxic effects of PLA in CHO-K1 cells, as well as its physicochemical properties. No cytotoxic effects of PLA were detected by colorimetric tetrazolium assay (XTT) analysis, and the clonogenic survival assay showed that PLA did not disrupt the replicative cell homeostasis, neither exhibited genotoxic effects as evidenced by comet and micronucleus assays. Thermogravimetric properties of PLA were not altered after contact with cells and this film exhibited ability in absorb and release Europium(III) complex. All these data suggest genotoxicological safety of PLA for further applications in drug delivery systems.

  17. Tumour microenvironment-responsive lipoic acid nanoparticles for targeted delivery of docetaxel to lung cancer

    PubMed Central

    Gu, Fenfen; Hu, Chuling; Tai, Zhongguang; Yao, Chong; Tian, Jing; Zhang, Lijuan; Xia, Qingming; Gong, Chunai; Gao, Yuan; Gao, Shen

    2016-01-01

    In the present study, we developed a novel type of reduction-sensitive nanoparticles (NPs) for docetaxel (DTX) delivery based on cross-linked lipoic acid NPs (LANPs). The physicochemical properties, cellular uptake and in vitro cytotoxicity of DTX loaded LANPs (DTX-LANPs) on A549 cells were investigated. Furthermore, the in vivo distribution and in vivo efficacy of DTX-LANPs was evaluated. The results showed that DTX-LANPs had a particle size of 110 nm and a negative zeta potential of −35 mv with excellent colloidal stability. LANPs efficiently encapsulated DTX with a high drug loading of 4.51% ± 0.49% and showed remarkable reduction-sensitive drug release in vitro. Cellular uptake experiments demonstrated that LANPs significantly increased intracellular DTX uptake by about 10 fold as compared with free DTX. The cytotoxicity of DTX-LANPs showed significantly higher potency in inhibiting A549 cell growth than free DTX, while blank LANPs had a good biocompatibility. In addition, in vivo experiments demonstrated that DTX-LANPs could enhance tumour targeting and anti-tumour efficacy with low systemic toxicity. In conclusion, LANPs may prove to be a potential tumour microenvironment-responsive delivery system for cancer treatment, with the potential for commercialization due to the simple component, controllable synthesis, stability and economy. PMID:27805051

  18. Micromachined therapeutic delivery systems: from concept to clinic

    NASA Astrophysics Data System (ADS)

    Desai, Tejal A.

    2001-05-01

    Microfabrication techniques which permit the creation of therapeutic delivery systems that possess a combination of structural, mechanical, and perhaps electronic features may surmount challenges associated with conventional delivery of therapy. In this review, delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells--as a possible treatment for diabetes--and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug- loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs.

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

    PubMed

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

    2013-12-10

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

  20. Promoting Quality of Program Delivery via an Internet Message Delivery System

    ERIC Educational Resources Information Center

    Bishop, Dana C.; Dusenbury, Linda; Pankratz, Melinda M.; Hansen, William B.

    2013-01-01

    This article presents results from a study that evaluated an online message system designed to improve the delivery of prevention programs. We conducted a quasi-experimental study with 32 agencies and schools that implemented substance use prevention programs and examined differences between the comparison and intervention groups. We also examined…

  1. In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin

    PubMed Central

    Alvarez-Berríos, Merlis P; Vivero-Escoto, Juan L

    2016-01-01

    The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction. To prove this hypothesis, internalization and localization studies in HeLa cancer cells were performed using flow cytometry and confocal microscopy. The ability of MSNs to escape from the endolysosomal compartments, the formation of DNA adducts, and the cytotoxic effects of the MSNs were also evaluated. Our results confirmed that this MSN-based delivery platform was capable of delivering cisplatin into the cytosol of HeLa cells, inducing DNA adducts and subsequent cell death. PMID:27920531

  2. In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin.

    PubMed

    Alvarez-Berríos, Merlis P; Vivero-Escoto, Juan L

    The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction. To prove this hypothesis, internalization and localization studies in HeLa cancer cells were performed using flow cytometry and confocal microscopy. The ability of MSNs to escape from the endolysosomal compartments, the formation of DNA adducts, and the cytotoxic effects of the MSNs were also evaluated. Our results confirmed that this MSN-based delivery platform was capable of delivering cisplatin into the cytosol of HeLa cells, inducing DNA adducts and subsequent cell death.

  3. Targeted Delivery Systems for Molecular Therapy in Skeletal Disorders

    PubMed Central

    Dang, Lei; Liu, Jin; Li, Fangfei; Wang, Luyao; Li, Defang; Guo, Baosheng; He, Xiaojuan; Jiang, Feng; Liang, Chao; Liu, Biao; Badshah, Shaikh Atik; He, Bing; Lu, Jun; Lu, Cheng; Lu, Aiping; Zhang, Ge

    2016-01-01

    Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk of toxic effects in non-skeletal tissues, which remain clinical challenges in the treatment of skeletal disorders. Thus, targeted delivery systems are urgently needed to achieve higher drug delivery efficiency, improve therapeutic efficacy in the targeted cells/tissues, and minimize toxicities in non-targeted cells/tissues. In this review, we summarize recent progress in the application of different targeting moieties and nanoparticles for targeted drug delivery in skeletal disorders, and also discuss the advantages, challenges and perspectives in their clinical translation. PMID:27011176

  4. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

    PubMed Central

    Madry, Henning

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair. PMID:27642587

  5. Drug delivery system based on chronobiology--A review.

    PubMed

    Mandal, Asim Sattwa; Biswas, Nikhil; Karim, Kazi Masud; Guha, Arijit; Chatterjee, Sugata; Behera, Mamata; Kuotsu, Ketousetuo

    2010-11-01

    With the advancement in the field of chronobiology, modern drug delivery approaches have been elevated to a new concept of chronopharmacology i.e. the ability to deliver the therapeutic agent to a patient in a staggered profile. However the major drawback in the development of such delivery system that matches the circadian rhythm requires the availability of precise technology (pulsatile drug delivery). The increasing research interest surrounding this delivery system has widened the areas of pharmaceutics in particular with many more sub-disciplines expected to coexist in the near future. This review on chronopharmaceutics gives a comprehensive emphasis on potential disease targets, revisits the existing technologies in hand and also addresses the theoretical approaches to emerging discipline such as genetic engineering and target based specific molecules. With the biological prospective approaches in delivering drugs it is well understood that safer and more realistic approaches in the therapy of diseases will be achieved in the days to come.

  6. Inulin Derivatives Obtained Via Enhanced Microwave Synthesis for Nucleic Acid Based Drug Delivery.

    PubMed

    Sardo, Carla; Craparo, Emanuela Fabiola; Fiorica, Calogero; Giammona, Gaetano; Cavallaro, Gennara

    2015-01-01

    A new class of therapeutic agents with a high potential for the treatment of different socially relevant human diseases is represented by Nucleic Acid Based Drugs (NABD), including small interfering RNAs (siRNA), decoy oligodeoxynucleotides (decoy ODN) and antisense oligonucleotides (ASOs). Although NABD can be engineered to be specifically directed against virtually any target, their susceptibility to nuclease degradation and the difficulty of delivery into target tissues severely limit their use in clinical practice and require the development of an appropriate nanostructured delivery system. For delivery of NABD, Inulin (Inu), a natural, water soluble and biocompatible polysaccharide, was derivatized by Spermine (Spm), a flexible molecule with four amine groups that, having pKa values in the range between 8-11, is mainly in the protonated form at pH 7.4. The synthesis of related copolymers (Inu-Spm) was performed by a two step reaction, using a method termed Enhanced Microwave Synthesis (EMS) which has the advantage, compared to conventional microwave reaction, that high amount of energy can be applied to the reaction system, by administering microwave irradiation and simultaneously controlling the temperature in the reaction vessel with cooled air. The synthesized inulin derivatives were characterized by FT-IR spectra and (1)H-NMR. INU-Spm derivatives with a degree of derivatization of about 14 % mol/mol were obtained. These polycations were tested to evaluate their ability to form non covalent complexes with genetic material (polyplexes). Agarose gel retardation assays showed that the obtained copolymers are able to electrostatically interact with DNA duplex to form polyplexes at different c/p weight ratios. Moreover, light scattering studies, performed to analyze size and z-potential of polyplexes, evidenced that copolymers are able to interact with genetic material leading to the formation of nanoscaled systems. In addition, biocompatibility of polyplexes

  7. 'Smart' non-viral delivery systems for targeted delivery of RNAi to the lungs.

    PubMed

    Ramsey, Joanne M; Hibbitts, Alan; Barlow, James; Kelly, Ciara; Sivadas, Neeraj; Cryan, Sally-Ann

    2013-01-01

    The emergence of RNAi offers a potentially exciting new therapeutic paradigm for respiratory diseases. However, effective delivery remains a key requirement for their translation into the clinic and has been a major factor in the limited clinical success seen to date. Inhalation offers tissue-specific targeting of the RNAi to treat respiratory diseases and a diminished risk of off-target effects. In order to deliver RNAi directly to the respiratory tract via inhalation, 'smart' non-viral carriers are required to protect the RNAi during delivery/aerosolization and enhance cell-specific uptake to target cells. Here, we review the state-of-the-art in therapeutic aerosol bioengineering, and specifically non-viral siRNA delivery platforms, for delivery via inhalation. This includes developments in inhaler device engineering and particle engineering, including manufacturing methods and excipients used in therapeutic aerosol bioengineering that underpin the development of smart, cell type-specific delivery systems to target siRNA to respiratory epithelial cells and/or alveolar macrophages.

  8. Vinylpyrrolidone-co-(meth)acrylic acid inserts for ocular drug delivery: synthesis and evaluation.

    PubMed

    Barbu, Eugen; Sarvaiya, Indrajeetsinh; Green, Keith L; Nevell, Thomas G; Tsibouklis, John

    2005-09-15

    Copolymeric hydrogels constituting of vinylpyrrolidone and methacrylic or acrylic acid repeat units have been prepared and investigated for their ability to act as controlled release vehicles in ophthalmic drug delivery. The materials were synthesized by radical-induced polymerization in the presence of N,N'-methylenebisacrylamide crosslinker, and the influences of network composition and drug solubility upon the swelling properties, adhesion behavior, and drug release characteristics were studied. In vitro release experiments showed that some of these materials could be useful vehicles for the delivery of drugs such as pilocarpine or chloramphenicol, while in vivo studies, using the rabbit model, confirmed their high potential for the controlled ocular delivery of pilocarpine hydrochloride.

  9. Enterotoxin Vaccine Delivery System With Bioadherence. Phase 1.

    DTIC Science & Technology

    1995-12-05

    Microencapsulation 33 Bioadhesive Biodegradable 16. PRICE CODE Perorally Controlled Delivery 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19. SECURITY...this magnitude requires a delivery system configured with a bioadhesive polymer that integrates the surface of the microcapsules and the mucosa. SBIR...integrates the surface of the microcapsules and the mucosa. SBIR Phase I Program efforts focused on the development of the most feasible method(s) for

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

    PubMed

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

    2014-07-28

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

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

    PubMed Central

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

    2014-01-01

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

  12. [Treatment of rheumatic diseases with intraarticular drug delivery systems].

    PubMed

    Szabó, Andrea; Zelkó, Romána; Antal, István

    2011-01-01

    Present work provides an overall study about the types and the medicinal treatment of the rheumatic diseases especially the intraarticular formulations. Due to the localized nature of the joint, intraarticular injections are very favourable drug delivery systems. It has a big advantage over the oral medication; the systemic side effects are kept away. The review shows two types of the rheumatic diseases on the example of the healthy joint: the joint damage (osteoarthritis) and the inflamed joint (rheumatoid arthritis). There are many active ingredients for the treatment of the rheumatic diseases but the number of the intraarticular products is limited. At present are only formulations with hyaluronic acid or glucocorticoid on the market. Several physiological and biopharmaceutical aspects must be considered for the design of intraarticular injections. During and after the production many quality requirements have to be complied. On the market the formulations in solution or in suspension are available, which provide a short-term effect. The aim of the developments is to achieve long-term effect based on nano- or microparticles.

  13. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

    There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations.

  14. The Impact of Virginia's Career Information Delivery System.

    ERIC Educational Resources Information Center

    Snipes, Juanita K.; McDaniels, Carl

    1984-01-01

    Reported the impact of Virginia's Vital Information for Education and Work (VIEW) System, which is modeled on the Michigan Occupational Information System (MOIS). Suggested that a statewide career information delivery system could serve as an impetus for generating excitement and new activities in local guidance programs. (LLL)

  15. The Benefits and Challenges Associated with the Use of Drug Delivery Systems in Cancer Therapy

    PubMed Central

    Cukierman, Edna; Khan, David R.

    2010-01-01

    The use of Drug Delivery Systems as nanocarriers for chemotherapeutic agents can improve the pharmacological properties of drugs by altering drug pharmacokinetics and biodistribution. Among the many drug delivery systems available, both micelles and liposomes have gained the most attention in recent years due to their clinical success. There are several formulations of these nanocarrier systems in various stages of clinical trials, as well as currently clinically approved liposomal-based drugs. In this review, we discuss these drug carrier systems, as well as current efforts that are being made in order to further improve their delivery efficacy through the incorporation of targeting ligands. In addition, this review discusses aspects of drug resistance attributed to the remodeling of the extracellular matrix that occurs during tumor development and progression, as well as to the acidic, hypoxic, and glucose deprived tumor microenvironment. Finally, we address future prospective approaches to overcoming drug resistance by further modifications made to these drug delivery systems, as well as the possibility of coencapsulation/coadministration of various drugs aimed to surmount some of these microenvironmental-influenced obstacles for efficacious drug delivery in chemotherapy. PMID:20417189

  16. Oligomeric bile acid-mediated oral delivery of low molecular weight heparin.

    PubMed

    Al-Hilal, Taslim A; Park, Jooho; Alam, Farzana; Chung, Seung Woo; Park, Jin Woo; Kim, Kwangmeyung; Kwon, Ick Chan; Kim, In-San; Kim, Sang Yoon; Byun, Youngro

    2014-02-10

    Intestinal transporters are limited to the transport of small molecular substrates. Here, we describe the development of apical sodium-dependent bile acid transporter (ASBT)-targeted high-affinity oligomeric bile acid substrates that mediate the transmembrane transport of low molecular weight heparin (LMWH). Several oligomers of deoxycholic acid (oligoDOCA) were synthesized to investigate the substrate specificity of ASBT. To see the binding of oligoDOCA on the substrate-binding pocket of ASBT, molecular docking was used and the dissociation rate constants (KD) were measured using surface plasmon resonance. The KD for tetrameric DOCA (tetraDOCA) was 50-fold lower than that for monomeric DOCA, because tetraDOCA interacted with several hydrophobic grooves in the substrate-binding pocket of ASBT. The synthesized oligoDOCA compounds were subsequently chemically conjugated to macromolecular LMWH. In vitro, tetraDOCA-conjugated LMWH (LHe-tetraD) had highest selectivity for ASBT during its transport. Orally administered LHe-tetraD showed remarkable systemic anticoagulation activity and high oral bioavailability of 33.5±3.2% and 19.9±2.5% in rats and monkeys, respectively. Notably, LHe-tetraD successfully prevented thrombosis in a rat model of deep vein thrombosis. These results represent a major advancement in ASBT-mediated LMWH delivery and may facilitate administration of many important therapeutic macromolecules through a non-invasive oral route.

  17. Cell Penetrating Peptide Conjugated Chitosan for Enhanced Delivery of Nucleic Acid

    PubMed Central

    Layek, Buddhadev; Lipp, Lindsey; Singh, Jagdish

    2015-01-01

    Gene therapy is an emerging therapeutic strategy for the cure or treatment of a spectrum of genetic disorders. Nevertheless, advances in gene therapy are immensely reliant upon design of an efficient gene carrier that can deliver genetic cargoes into the desired cell populations. Among various nonviral gene delivery systems, chitosan-based carriers have gained increasing attention because of their high cationic charge density, excellent biocompatibility, nearly nonexistent cytotoxicity, negligible immune response, and ideal ability to undergo chemical conjugation. However, a major shortcoming of chitosan-based carriers is their poor cellular uptake, leading to inadequate transfection efficiency. The intrinsic feature of cell penetrating peptides (CPPs) for transporting diverse cargoes into multiple cell and tissue types in a safe manner suggests that they can be conjugated to chitosan for improving its transfection efficiency. In this review, we briefly discuss CPPs and their classification, and also the major mechanisms contributing to the cellular uptake of CPPs and cargo conjugates. We also discuss immense improvements for the delivery of nucleic acids using CPP-conjugated chitosan-based carriers with special emphasis on plasmid DNA and small interfering RNA. PMID:26690119

  18. Sustained Small Molecule Delivery from Injectable Hyaluronic Acid Hydrogels through Host-Guest Mediated Retention

    PubMed Central

    Mealy, Joshua E.; Rodell, Christopher B.; Burdick, Jason A.

    2015-01-01

    Self-assembled and injectable hydrogels have many beneficial properties for the local delivery of therapeutics; however, challenges still exist in the sustained release of small molecules from these highly hydrated networks. Host-guest chemistry between cyclodextrin and adamantane has been used to create supramolecular hydrogels from modified polymers. Beyond assembly, this chemistry may also provide increased drug retention and sustained release through the formation of inclusion complexes between drugs and cyclodextrin. Here, we engineered a two-component system from adamantane-modified and β-cyclodextrin (CD)-modified hyaluronic acid (HA), a natural component of the extracellular matrix, to produce hydrogels that are both injectable and able to sustain the release of small molecules. The conjugation of cyclodextrin to HA dramatically altered its affinity for hydrophobic small molecules, such as tryptophan. This interaction led to lower molecule diffusivity and the release of small molecules for up to 21 days with release profiles dependent on CD concentration and drug-CD affinity. There was significant attenuation of release from the supramolecular hydrogels (~20% release in 24h) when compared to hydrogels without CD (~90% release in 24h). The loading of small molecules also had no effect on hydrogel mechanics or self-assembly properties. Finally, to illustrate this controlled delivery approach with clinically used small molecule pharmaceuticals, we sustained the release of two widely used drugs (i.e., doxycycline and doxorubicin) from these hydrogels. PMID:26693019

  19. Poly(lactic-co-glycolic) Acid/Solutol HS15-Based Nanoparticles for Docetaxel Delivery.

    PubMed

    Cho, Hyun-Jong; Park, Ju-Hwan; Kim, Dae-Duk; Yoon, In-Soo

    2016-02-01

    Docetaxel (DCT) is one of anti-mitotic chemotherapeutic agents and has been used for the treatment of gastric cancer as well as head and neck cancer, breast cancer and prostate cancer. Poly(lactic- co-glycolic) acid (PLGA) is one of representative biocompatible and biodegradable polymers, and polyoxyl 15 hydroxystearate (Solutol HS15) is a nonionic solubilizer and emulsifying agent. In this investigation, PLGA/Solutol HS15-based nanoparticles (NPs) for DCT delivery were fabricated by a modified emulsification-solvent evaporation method. PLGA/Solutol HS15/DCT NPs with about 169 nm of mean diameter, narrow size distribution, negative zeta potential, and spherical morphology were prepared. The results of solid-state studies revealed the successful dispersion of DCT in PLGA matrix and its amorphization during the preparation process of NPs. According to the result of in vitro release test, emulsifying property of Solutol HS15 seemed to contribute to the enhanced drug release from NPs at physiological pH. All these findings imply that developed PLGA/Solutol HS15-based NP can be a promising local anticancer drug delivery system for cancer therapy.

  20. MAST Propellant and Delivery System Design Methods

    NASA Technical Reports Server (NTRS)

    Nadeem, Uzair; Mc Cleskey, Carey M.

    2015-01-01

    A Mars Aerospace Taxi (MAST) concept and propellant storage and delivery case study is undergoing investigation by NASA's Element Design and Architectural Impact (EDAI) design and analysis forum. The MAST lander concept envisions landing with its ascent propellant storage tanks empty and supplying these reusable Mars landers with propellant that is generated and transferred while on the Mars surface. The report provides an overview of the data derived from modeling between different methods of propellant line routing (or "lining") and differentiate the resulting design and operations complexity of fluid and gaseous paths based on a given set of fluid sources and destinations. The EDAI team desires a rough-order-magnitude algorithm for estimating the lining characteristics (i.e., the plumbing mass and complexity) associated different numbers of vehicle propellant sources and destinations. This paper explored the feasibility of preparing a mathematically sound algorithm for this purpose, and offers a method for the EDAI team to implement.

  1. Supramolecular hydrogels as drug delivery systems.

    PubMed

    Saboktakin, Mohammad Reza; Tabatabaei, Roya Mahdavi

    2015-04-01

    Drug delivery from a hydrogel carrier implanted under the kidney capsule is an innovative way to induce kidney tissue regeneration and/or prevent kidney inflammation or fibrosis. We report here on the development of supramolecular hydrogels for this application. Chain-extended hydrogelators containing hydrogen bonding units in the main chain, and bifunctional hydrogelators end-functionalized with hydrogen bonding moieties, were made. The influence of these hydrogels on the renal cortex when implanted under the kidney capsule was studied. The overall tissue response to these hydrogels was found to be mild, and minimal damage to the cortex was observed, using the infiltration of macrophages, formation of myofibroblasts, and the deposition of collagen III as relevant read-out parameters. Differences in tissue response to these hydrogels could be related to the different physico-chemical properties of the three hydrogels.

  2. Technology for an Efficient Delivery System.

    DTIC Science & Technology

    1979-06-01

    Delivery Sytm ial e 06 ;Jul 787- May A979 191 nI VWM A WMM.. 1V~W dB E R 7. A 8. CONTRACT OR GRANT NUMBER(s) w.~ in DU KribsN130, rAiO OF 9. PERFORMING...digital storage, development of high-resolution 1,000 scan-line discs which could store approximately 15,000 typed 81" x 11" documents, and develop...reversed to approximate the layout of a typical 81" x 11" typed page. Phil ps personnel have discussed experimentation with a 1,200 line format, which

  3. Hydrocolloid-based nutraceutical delivery systems

    SciTech Connect

    Janaswamy, Srinivas; Youngren, Susanne R.

    2012-07-11

    Nutraceuticals are important due to their inherent health benefits. However, utilization and consumption are limited by their poor water solubility and instability at normal processing and storage conditions. Herein, we propose an elegant and novel approach for the delivery of nutraceuticals in their active form using hydrocolloid matrices that are inexpensive and non-toxic with generally recognized as safe (GRAS) status. Iota-carrageenan and curcumin have been chosen as models of hydrocolloid and nutraceutical compounds, respectively. The iota-carrageenan network maintains a stable organization after encapsulating curcumin molecules, protects them from melting and then releases them in a sustained manner. These findings lay a strong foundation for developing value-added functional and medicinal foods.

  4. Recent advances of cocktail chemotherapy by combination drug delivery systems.

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease

    PubMed Central

    Gunay, Mine Silindir; Ozer, A. Yekta; Chalon, Sylvie

    2016-01-01

    Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. Methods: This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. Results: It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson’s disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α-synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Conclusion: Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson’s disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson’s Disease therapy and reduce its side effects. PMID:26714584

  7. Non-covalent complexes of folic acid and oleic acid conjugated polyethylenimine: An efficient vehicle for antisense oligonucleotide delivery

    PubMed Central

    Yang, Shuang; Yang, Xuewei; Liu, Yan; Zheng, Bin; Meng, Lingjun; Lee, Robert J.; Xie, Jing; Teng, Lesheng

    2016-01-01

    Polyethylenimine (PEI) was conjugated to oleic acid (PEI-OA) and evaluated as a delivery agent for LOR-2501, an antisense oligonucleotide against ribonucleotide reductase R1 subunit. PEI-OA/LOR-2501 complexes were further coated with folic acid (FA/PEI-OA/LOR-2501) and evaluated in tumor cells. The level of cellular uptake of FA/PEI-OA/LOR-2501 was more than double that of PEI/LOR-2501 complexes, and was not affected by the expression level of folate receptor (FR) on the cell surface. Efficient delivery was seen in several cell lines. Furthermore, pathway specific cellular internalization inhibitors and markers were used to reveal the principal mechanism of cellular uptake. FA/PEI-OA/LOR-2501 significantly induced the downregulation of R1 mRNA and R1 protein. This novel formulation of FA/PEI-OA provides a reliable and highly efficient method for delivery of oligonucleotide and warrants further investigation. PMID:26263216

  8. Dendrimeric Systems and Their Applications in Ocular Drug Delivery

    PubMed Central

    Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2013-01-01

    Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

  9. Nucleic Acid Delivery for Endothelial Dysfunction in Cardiovascular Diseases

    PubMed Central

    Deshpande, Dipti; Janero, David R.; Segura-Ibarra, Victor; Blanco, Elvin; Amiji, Mansoor M.

    2016-01-01

    Endothelial dysfunction has been implicated in the pathophysiology of multiple cardiovascular diseases and involves components of both innate and acquired immune mechanisms. Identifying signature patterns and targets associated with endothelial dysfunction can help in the development of novel nanotherapeutic platforms for treatment of vascular diseases. This review discusses nucleic acid-based regulation of endothelial function and the different nucleic acid-based nanotherapeutic approaches designed to target endothelial dysfunction in cardiovascular disorders. PMID:27826366

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

    PubMed Central

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

    2008-01-01

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

  11. Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome.

    PubMed

    Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

    2016-01-01

    Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a

  12. Nanoscaled boron-containing delivery systems and therapeutic agents for cancer treatment.

    PubMed

    Wang, Jing; Wu, Wei; Jiang, Xiqun

    2015-01-01

    Significant efforts have recently been made to develop nanoscaled boron-containing delivery systems for improving drug delivery in cancer therapy. On one hand, borate ester chemistry has shown importance in ligand-mediated tumor targeting owing to the recognition ability of boronic acid to polyol residues in cell membranes. In particular, the phenylboronic acid-functionalized nanocarriers for specific targeting to sialic acid groups which are overexpressed on tumor cells have made great achievements. On the other hand, nanoscaled boron neutron capture therapy agents show growing potential in efficiently transporting boron to tumor. The current review outlines the recent developments in the application of borate ester chemistry in tumor targeting by nanoparticles, then summarizes recent work on the development of boron-based nanomaterials as boron neutron capture therapy agents.

  13. Self-assembled nanoparticles based on chondroitin sulfate-deoxycholic acid conjugates for docetaxel delivery: Effect of degree of substitution of deoxycholic acid.

    PubMed

    Liu, Mengrui; Du, Hongliang; Zhai, Guangxi

    2016-10-01

    Hydrophobically-modified polymers based on chondroitin sulfate with different degree of substitution (DS) of deoxycholic acid (DOCA) were developed for docetaxel delivery. Chondroitin sulfate-deoxycholic acid (CSAD) bioconjugates were synthesized via the linker of adipic dihydrazide by amide bond. They were characterized with spherical shape, mean diameter of around 165.2nm and negative zeta potential (-14.87 to -20.53mV). An increase of DOCA DS reduced size of nanoparticles, while increasing drug loading efficiency. Drug release in vitro showed a triphasic sustained pattern and higher accumulative drug release percentage was observed with increased DS of DOCA on polymer. Self-assemblies with higher DS also had enhanced internalization of nanoparticles and stronger cytotoxicity at the cellular level. The self-assemble nanoparticles demonstrate to be excellent targeting drug delivery systems and the desired therapeutics can be achieved via the alteration of DS.

  14. Niosomes: a controlled and novel drug delivery system.

    PubMed

    Rajera, Rampal; Nagpal, Kalpana; Singh, Shailendra Kumar; Mishra, Dina Nath

    2011-01-01

    During the past decade formulation of vesicles as a tool to improve drug delivery, has created a lot of interest amongst the scientist working in the area of drug delivery systems. Vesicular system such as liposomes, niosomes, transferosomes, pharmacosomes and ethosomes provide an alternative to improve the drug delivery. Niosomes play an important role owing to their nonionic properties, in such drug delivery system. Design and development of novel drug delivery system (NDDS) has two prerequisites. First, it should deliver the drug in accordance with a predetermined rate and second it should release therapeutically effective amount of drug at the site of action. Conventional dosage forms are unable to meet these requisites. Niosomes are essentially non-ionic surfactant based multilamellar or unilamellar vesicles in which an aqueous solution of solute is entirely enclosed by a membrane resulting from the organization of surfactant macromolecules as bilayer. Niosomes are formed on hydration of non-ionic surfactant film which eventually hydrates imbibing or encapsulating the hydrating aqueous solution. The main aim of development of niosomes is to control the release of drug in a sustained way, modification of distribution profile of drug and for targeting the drug to the specific body site. This paper deals with composition, characterization/evaluation, merits, demerits and applications of niosomes.

  15. Improving oral healthcare delivery systems through workforce innovations: an introduction.

    PubMed

    Mertz, Elizabeth A; Finocchio, Len

    2010-06-01

    The objective of this paper is to describe the purpose, rationale and key elements of the special issue, Improving Oral Healthcare Delivery Systems through Workforce Innovations. The purpose of the special issue is to further develop ideas presented at the 2009 Institute of Medicine (IOM) workshop, Sufficiency of the U.S. Oral Health Workforce in the Coming Decade. Using the IOM discussions as their starting point, the authors evaluate oral health care delivery system performance for specific populations' needs and explore the roles that the workforce can play in improving the care delivery model. The contributing articles provide a broad framework for stimulating and evaluating innovation and change in the oral health care delivery system. The articles in this special issue point to many deficits in the current oral health care delivery system and provide compelling arguments and proposals for improvements. The issues presented and solutions recommended are not entirely new, but add to a growing body of work that is of critical importance given the context of wider health care reform.

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

    NASA Astrophysics Data System (ADS)

    Pezzoli, Daniele; Candiani, Gabriele

    2013-03-01

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

  17. Polysaccharides-based polyelectrolyte nanoparticles as protein drugs delivery system

    NASA Astrophysics Data System (ADS)

    Shu, Shujun; Sun, Lei; Zhang, Xinge; Wu, Zhongming; Wang, Zhen; Li, Chaoxing

    2011-09-01

    Polysaccharides-based nanoparticles were prepared by synthesized quaternized chitosan and dextran sulfate through simple ionic-gelation self-assembled method. Introduction of quaternized groups was intended to increase water solubility of chitosan and make the nanoparticles have broader pH sensitive range which can remain more stable in physiological pH and decrease the loss of protein drugs caused by the gastric cavity. The load of BSA was affected by molecular parameter, i.e., degree of substitution, and average molecular weight of quaternized chitosan, as well as concentration of BSA. Fast release occurred in phosphate buffer solution (pH 7.4) while the release was slow in hydrochloric acid (pH 1.4). The drug release mechanism is Fickian diffusion through release kinetics analysis. Cell uptake demonstrated nanoparicles can internalize into Caco-2 cells, which suggested that nanoparticles had good biocompatibility. No significant conformation change was noted for the released BSA in comparison with native BSA using circular dichroism spectroscopy. This kind of novel composite nanoparticles may be a promising delivery system for oral protein and peptide drugs.

  18. From Print to Nonprint Materials: Library Information Delivery Systems.

    ERIC Educational Resources Information Center

    Drake, Miriam A.

    1988-01-01

    Discussion of advanced technology and its effects on libraries and information delivery systems describes online information systems and CD-ROMs at the Georgia Institute of Technology Library; explains the changes in information services from supply-oriented to demand-driven, and considers nonprint materials and their effect on the publishing…

  19. 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…

  20. 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

  1. Futures of Service Delivery Systems for Handicapped Individuals. No. 12.

    ERIC Educational Resources Information Center

    Stedman, Donald J.; Wiegerink, Ronald

    Seventeen issues relating to service delivery systems for the handicapped are discussed, including the following: integration of human service systems; meshinq of planning, service, research, and training; installing a monitoring, evaluation, and feedback activity into the planning process; evaluating public education programs; coordinating…

  2. Preparation of drug delivery systems using supercritical fluid technology.

    PubMed

    Kompella, U B; Koushik, K

    2001-01-01

    Small changes in temperature and pressure near the critical region induce dramatic changes in the density and solubility of supercritical fluids, thereby facilitating the use of environmentally benign agents such as CO2 for their solvent and antisolvent properties in processing a wide variety of materials. While supercritical fluid technologies have been in commercial use in the food and chromatography industries for several years, only recently has this technology made inroads in the formulation of drug delivery systems. This review summarizes some of the recent applications of supercritical fluid technology in the preparation of drug delivery systems. Drugs containing polymeric particles, plain drug particles, solute-containing liposomes, and inclusion complexes of drug and carrier have been formulated using this technology. Also, polymer separation using this technology is enabling the selection of a pure fraction of a polymer, thereby allowing a more precise control of drug release from polymeric delivery systems.

  3. The influence of microwave radiation on transdermal delivery systems.

    PubMed

    Moseley, H; Johnston, S; Allen, A

    1990-03-01

    It has been alleged that the exposure of a transdermal delivery system to leakage of microwave radiation from a domestic microwave oven can result in the user receiving a second-degree burn in the area of the patch. Several transdermal delivery systems were exposed to microwave radiation from an Electro Medical Supplies Microtron 200 microwave diathermy unit. Temperature rises of up to 2.2 degrees C were recorded at a maximum power density of 800 W/m2. These temperature rises were considered insignificant compared to that required to produce a burn. The exposure of transdermal delivery systems to a microwave diathermy field or lower level leakage radiation from a microwave oven is unlikely to cause direct thermal injury to the wearer.

  4. Bioengineered Silk Gene Delivery System for Nuclear Targeting

    PubMed Central

    Yigit, Sezin; Tokareva, Olena; Varone, Antonio; Georgakoudi, Irene

    2015-01-01

    Gene delivery research has gained momentum with the use of lipophilic vectors that mimic viral systems to increase transfection efficiency. However, maintaining cell viability with these systems remains a major challenge. Therefore biocompatible and nontoxic biopolymers that are designed by combining non-immunological viral mimicking components with suitable carriers have been explored to address these limitations. In the present study recombinant DNA technology was used to design a multi-functional gene delivery system for nuclear targeting, while also supporting cell viability. Spider dragline silk recombinant proteins were modified with DNA condensing units and the proton sponge endosomal escape pathway was utilized for enhanced delivery. Short-term transfection efficiency in a COS-7 cell line (adherent kidney cells isolated from African green monkey) was enhanced compared to lipofectamine and polyethyleneimine (PEI), as was cell viability with these recombinant bio-polyplexes. Endosomal escape and consequent nuclear targeting were shown with fluorescence microscopy. PMID:24889658

  5. Importance of dual delivery systems for bone tissue engineering.

    PubMed

    Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

    2016-03-10

    Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering.

  6. Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System

    NASA Astrophysics Data System (ADS)

    Ouyang, Mengxing; Hill, Winfield; Lee, Jung Hyun; Hur, Soojung Claire

    2017-03-01

    Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages.

  7. A clinical perspective on mucoadhesive buccal drug delivery systems

    PubMed Central

    Gilhotra, Ritu M; Ikram, Mohd; Srivastava, Sunny; Gilhotra, Neeraj

    2014-01-01

    Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems. PMID:24683406

  8. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    PubMed Central

    Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

    2012-01-01

    Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

  9. A block copolymer of zwitterionic polyphosphoester and polylactic acid for drug delivery.

    PubMed

    Sun, Rong; Du, Xiao-Jiao; Sun, Chun-Yang; Shen, Song; Liu, Yang; Yang, Xian-Zhu; Bao, Yan; Zhu, Yan-Hua; Wang, Jun

    2015-07-01

    Polymeric nanoparticles have been widely used as nano-drug delivery systems in preclinical and clinical trials for cancer therapy, and these systems usually need to be sterically stabilized by poly(ethylene glycol) (PEG) to maintain stability and avoid rapid clearance by the immune system. Recently, zwitterionic materials have been demonstrated to be potential alternatives to the classic PEG. Herein, we developed two drug delivery systems stabilized by zwitterionic polyphosphoesters. These nanoparticles showed favourable stability and anti-protein absorption ability in vitro. Meanwhile, as drug carriers, these zwitterionic polyphosphoester-stabilized nanoparticles significantly prolonged drug circulation half-lives and increased drug accumulation in tumors, which was comparable to PEG-stabilized nanoparticles. Systemic delivery of doxorubicin (DOX) by zwitterionic polyphosphoester-stabilized nanoparticles significantly inhibited tumor growth in a MDA-MB-231 tumor model, suggesting the potential of zwitterionic polyphosphoester-based nanoparticles in anticancer drug delivery.

  10. Formulation and Optimization of Mucoadhesive Nanodrug Delivery System of Acyclovir

    PubMed Central

    Bhosale, UV; Kusum, Devi V; Jain, N

    2011-01-01

    Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infections, with an oral bioavailability of only 10–20% [limiting absorption in gastrointestinal tract to duodenum and jejunum] and half-life of about 3 h, and is soluble only at acidic pH (pKa 2.27). Mucoadhesive polymeric nanodrug delivery systems of acyclovir have been designed and optimized using 23 full factorial design. Poly (lactic-co-glycolic acid) (PLGA) (50:50) was used as the polymer along with polycarbophil (Noveon AA-1) as the mucoadhesive polymer and pluronic F68 as the stabilizer. From the preliminary trials, the constraints for independent variables X1 (amount of PLGA), X2 (amount of pluronic F68) and X3 (amount of polycarbophil) have been fixed. The dependent variables that were selected for study were particle size (Y1), % drug entrapment (Y2) and % drug release in 12 h (Y3). The derived polynomial equations were verified by check point formulation. The application of factorial design gave a statistically systematic approach for the formulation and optimization of nanoparticles with the desired particle size, % drug release and high entrapment efficiency. Drug: Polymer ratio and concentration of stabilizer were found to influence the particle size and entrapment efficiency of acyclovir-loaded PLGA nanoparticles. The release was found to follow Fickian as well as non-Fickian diffusion mechanism with zero-order drug release for all batches. In vitro intestinal mucoadhesion of nanoparticles increased with increasing concentration of polycarbophil. These preliminary results indicate that acyclovir-loaded mucoadhesive PLGA nanoparticles could be effective in sustaining drug release for a prolonged period. PMID:22224033

  11. Cell Delivery System for Traumatic Brain Injury

    DTIC Science & Technology

    2008-03-21

    from collagen sponges using the dish test method (Figure 16B). The advantage of the dish test over the diffusion cells test is that samples can be...composite mat with collagen fibers and some chitosan fibers as well as globules but were not able to test for cell response to these matrices...dimensional collagen scaffold. MSCs cultured in monolayer and on a three- dimensional collagen sponge were treated with retinoic acid (RA) for up to

  12. Folic acid-Functionalized Nanoparticles for Enhanced Oral Drug Delivery

    PubMed Central

    Roger, Emilie; Kalscheuer, Stephen; Kirtane, Ameya; Guru, Bharath Raja; Grill, Alex E.; Whittum-Hudson, Judith; Panyam, Jayanth

    2012-01-01

    The oral absorption of drugs that have poor bioavailability can be enhanced by encapsulation in polymeric nanoparticles. Transcellular transport of nanoparticle-encapsulated drug, possibly through transcytosis, is likely the major mechanism through which nanoparticles improve drug absorption. We hypothesized that the cellular uptake and transport of nanoparticles can be further increased by targeting the folate receptors expressed on the intestinal epithelial cells. The objective of this research was to study the effect of folic acid functionalization on transcellular transport of nanoparticle-encapsulated paclitaxel, a chemotherapeutic with poor oral bioavailability. Surface-functionalized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with paclitaxel were prepared by the interfacial activity assisted surface functionalization technique. Transport of paclitaxel-loaded nanoparticles was investigated using Caco-2 cell monolayers as an in vitro model. Caco-2 cells were found to express folate receptor and the drug efflux protein, p-glycoprotein, to high levels. Encapsulation of paclitaxel in PLGA nanoparticles resulted in a 5-fold increase in apparent permeability (Papp) across Caco-2 cells. Functionalization of nanoparticles with folic acid further increased the transport (8-fold higher transport compared to free paclitaxel). Confocal microscopic studies showed that folic acid-functionalized nanoparticles were internalized by the cells and that nanoparticles did not have any gross effects on tight junction integrity. In conclusion, our studies indicate that folic acid functionalized nanoparticles have the potential to enhance the oral absorption of drugs with poor oral bioavailability. PMID:22670575

  13. Programmable nanomedicine: synergistic and sequential drug delivery systems

    NASA Astrophysics Data System (ADS)

    Pacardo, Dennis B.; Ligler, Frances S.; Gu, Zhen

    2015-02-01

    Recent developments in nanomedicine for the cancer therapy have enabled programmable delivery of therapeutics by exploiting the stimuli-responsive properties of nanocarriers. These therapeutic systems were designed with the relevant chemical and physical properties that respond to different triggers for enhanced anticancer efficacy, including the reduced development of drug-resistance, lower therapeutic dose, site-specific transport, and spatiotemporally controlled release. This minireview discusses the current advances in programmable nanocarriers for cancer therapy with particular emphasis on synergistic and sequential drug delivery systems.

  14. 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.

  15. Self-assembled triangular DNA nanoparticles are an efficient system for gene delivery.

    PubMed

    Wang, Yingming; You, Zaichun; Du, Juan; Li, Hongli; Chen, Huaping; Li, Jingtong; Dong, Weijie; He, Binfeng; Mao, Chengde; Wang, Guansong

    2016-07-10

    Developing an advanced nucleic acid drug delivery system is of great significance in order to achieve optimal gene delivery. Self-assembled nucleic acid nanoparticles are an excellent platform for the delivery of nucleic acids and other small molecular drugs. In this study, we developed the efficient, three-stranded, RNA/DNA hybrid triangular self-assembled nanoparticles, namely, mTOR single-stranded siRNA-loaded triangular DNA nanoparticles (ssRNA-TNP). The ssRNA-TNP is formed by the complementary association of the above mentioned three components and is more stable in complete medium than standard duplex siRNA. It could be efficiently transfected into NCI-H292 cells in a dose- and time-dependent manner, resulting in high transfection efficiency. Furthermore, ssRNA-TNP uptake is dependent on macropinocytosis and clathrin-mediated endocytosis pathways. Interestingly, ssRNA-TNP is more efficient to inhibit the expression of mTOR. This ssRNA-TNP has a simpler structure, better stability, and higher transfection efficiency; therefore it may become a novel nonviral nanosystem for gene delivery.

  16. Designing a fiber-optic beam delivery system

    SciTech Connect

    Hunter, B.V. |; Leong, K.H.; Sanders, P.G.

    1997-03-01

    One of the advantages offered by visible and NIR lasers over CO and CO{sub 2} lasers is that they can be delivered through optical fibers. Fiber-optic beam delivery is ideal when the beam must be delivered along a complex path or processing requires complicated manipulation of the beam delivery optics. Harnessing the power of a high-power laser requires that knowledgeable and prudent choices be made when selecting the laser and its beam delivery system. The purpose of this paper is to discuss a variety of issues important when designing a beam delivery system-data obtained with high power Nd:YAG lasers will be used as illustrative examples. (1) Multimode optical fibers are used for high-power applications. The fiber imposes, to varying degrees, a structure on the beam that is different from the laser output. Fibers degrade the beam quality, although the degree of degradation is dependent on the fiber length, diameter and type. Smaller fibers tend to produce less degradation to beam quality, but the minimum usable fiber size is limited by the quality of the laser beam, focusing optic and the numerical aperture of the fiber. (2) The performance of the beam delivery system is ultimately determined by the quality of the optics. Therefore, well-corrected optics are required to realize the best possible performance. Tests with both homogeneous and GRADIUM{trademark} lenses provide insights into evaluating the benefits offered by improvements in the output optics from gradient-index, aspheric and multi-element lens systems. Additionally, these tests illustrate the origins of variable focused spot size and position with increasing laser power. (3) The physical hardware used in the beam delivery system will have several characteristics which enhance its functionality and ease of use, in addition to facilitating the use of advanced diagnostics and monitoring techniques.

  17. Cyclosporine Amicellar delivery system for dry eyes

    PubMed Central

    Kang, Han; Cha, Kwang-Ho; Cho, Wonkyung; Park, Junsung; Park, Hee Jun; Sun, Bo Kyung; Hyun, Sang-Min; Hwang, Sung-Joo

    2016-01-01

    Background The objectives of this study were to develop stable cyclosporine A (CsA) ophthalmic micelle solutions for dry-eye syndrome and evaluate their physicochemical properties and therapeutic efficacy. Materials and methods CsA-micelle solutions (MS-CsA) were created by a simple method with Cremophor EL, ethanol, and phosphate buffer. We investigated the particle size, pH, and osmolarity. In addition, long-term physical and chemical stability for MS-CsA was observed. To confirm the therapeutic efficacy, tear production in dry eye-induced rabbits was evaluated using the Schirmer tear test (STT). When compared to a commercial product, Restasis, MS-CsA demonstrated improvement in goblet-cell density and conjunctival epithelial morphology, as demonstrated in histological hematoxylin and eosin staining. Results MS-CsA had a smaller particle size (average diameter 14–18 nm) and a narrow size distribution. Physicochemical parameters, such as particle size, pH, osmolarity, and remaining CsA concentration were all within the expected range of 60 days. STT scores significantly improved in MS-CsA treated groups (P<0.05) in comparison to those of the Restasis-treated group. The number of goblet cells for rabbit conjunctivas after the administration of MS-CsA was 94.83±8.38, a significantly higher result than the 65.17±11.51 seen with Restasis. The conjunctival epithelial morphology of dry eye-induced rabbits thinned with loss of goblet cells. However, after 5 days of treatment with drug formulations, rabbit conjunctivas recovered epithelia and showed a relative increase in the number of goblet cells. Conclusion The results of this study indicate the potential use of a novel MS for the ophthalmic delivery of CsA in treating dry eyes. PMID:27382280

  18. Development of a polymeric nanoparticulate delivery system for indocyanine green

    NASA Astrophysics Data System (ADS)

    Saxena, Vishal

    Purpose. The objective of this project was to develop an intravenously administrable poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticulate delivery system for Indocyanine Green (ICG), to enhance the potential for ICG use in tumor imaging and therapy. Methods. For this purpose PLGA nanoparticles entrapping ICG were engineered by spontaneous emulsification solvent diffusion method. ICG entrapment in nanoparticles was determined and physicochemical characterization of nanoparticles was performed. The stability of ICG in nanoparticles formulation under various conditions was determined. The intracellular uptake of ICG in nanoparticles by B16-F10 and C-33A cancer cell lines was studied in comparison with the free ICG solution. Anti-proliferation studies against cancer cells were performed to prove the photodynamic activity of ICG in nanoparticles. Biodistribution of ICG when delivered through nanoparticles and solution were evaluated in mice after tail vein injection. Results. PLGA nanoparticles with a mean diameter of 350 nm and 74% ICG entrapment were obtained. The nanoparticles were nearly spherical in shape with zeta potential of -16 mV. The nanoparticles formulation provided overall stability to ICG with degradation half-lives of 2.5--3.5 days as compared to 10--20 hr of free ICG solutions. The intracellular uptake of ICG through nanoparticles was directly proportional to time and extracellular nanoparticle concentration. The intracellular uptake of ICG was enhanced about 100-fold by nanoparticles formulation as compared to the free ICG solution. Nanoparticles formulation showed significant photodynamic effect at nano-molar ICG concentrations and very low light dose (fluence: 0.22 W/cm2 and energy density: 1.1 J/cm2). In-vivo, the blood circulation-time and retention-time of ICG in various organs was enhanced 2--5 times by nanoparticles formulation as compared to the free ICG solution. Conclusions. A PLGA nanoparticlute delivery system was developed for ICG

  19. Drug delivery systems improve pharmaceutical profile and facilitate medication adherence.

    PubMed

    Wertheimer, Albert I; Santella, Thomas M; Finestone, Albert J; Levy, Richard A

    2005-01-01

    Innovations in dosage forms and dose delivery systems across a wide range of medications offer substantial clinical advantages, including reduced dosing frequency and improved patient adherence; minimized fluctuation of drug concentrations and maintenance of blood levels within a desired range; localized drug delivery; and the potential for reduced adverse effects and increased safety. The advent of new large-molecule drugs for previously untreatable or only partially treatable diseases is stimulating the development of suitable delivery systems for these agents. Although advanced formulations may be more expensive than conventional dosage forms, they often have a more favorable pharmacologic profile and can be cost-effective. Inclusion of these dosage forms on drug formulary lists may help patients remain on therapy and reduce the economic and social burden of care.

  20. Micro and Nanoparticle Drug Delivery Systems for Preventing Allotransplant Rejection

    PubMed Central

    Fisher, James D.; Acharya, Abhinav P.; Little, Steven R.

    2015-01-01

    Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation. PMID:25937032

  1. A framework for describing health care delivery organizations and systems.

    PubMed

    Piña, Ileana L; Cohen, Perry D; Larson, David B; Marion, Lucy N; Sills, Marion R; Solberg, Leif I; Zerzan, Judy

    2015-04-01

    Describing, evaluating, and conducting research on the questions raised by comparative effectiveness research and characterizing care delivery organizations of all kinds, from independent individual provider units to large integrated health systems, has become imperative. Recognizing this challenge, the Delivery Systems Committee, a subgroup of the Agency for Healthcare Research and Quality's Effective Health Care Stakeholders Group, which represents a wide diversity of perspectives on health care, created a draft framework with domains and elements that may be useful in characterizing various sizes and types of care delivery organizations and may contribute to key outcomes of interest. The framework may serve as the door to further studies in areas in which clear definitions and descriptions are lacking.

  2. Lipid-based systemic delivery of siRNA

    PubMed Central

    Tseng, Yu-Cheng; Mozumdar, Subho; Huang, Leaf

    2011-01-01

    RNAi technology has brought a new category of treatments for various diseases including genetic diseases, viral diseases, and cancer. Despite the great versatility of RNAi that can down regulate almost any protein in the cells, the delicate and precise machinery used for silencing is the same. The major challenge indeed for RNAi-based therapy is the delivery system. In this review, we start with the uniqueness and mechanism of RNAi machinery and the utility of RNAi in therapeutics. Then we discuss the challenges in systemic siRNA delivery by dividing them into two categories--kinetic and physical barriers. At the end, we discuss different strategies to overcome these barriers, especially focusing on the step of endosome escape. Toxicity issues and current successful examples for lipid-based delivery are also included in the review. PMID:19328215

  3. Porous Inorganic Drug Delivery Systems-a Review.

    PubMed

    Sayed, E; Haj-Ahmad, R; Ruparelia, K; Arshad, M S; Chang, M-W; Ahmad, Z

    2017-02-28

    Innovative methods and materials have been developed to overcome limitations associated with current drug delivery systems. Significant developments have led to the use of a variety of materials (as excipients) such as inorganic and metallic structures, marking a transition from conventional polymers. Inorganic materials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of drugs (antibiotics, anticancer and anti-inflammatories), providing several advantages in formulation and engineering (encapsulation of drug in amorphous form, controlled delivery and improved targeting). This review focuses on key selected developments in porous drug delivery systems. The review provides a short broad overview of porous polymeric materials for drug delivery before focusing on porous inorganic materials (e.g. Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM)) and their utilisation in drug dosage form development. Methods for their preparation and drug loading thereafter are detailed. Several examples of porous inorganic materials, drugs used and outcomes are discussed providing the reader with an understanding of advances in the field and realistic opportunities.

  4. Controlling In Vivo Stability and Biodistribution in Electrostatically Assembled Nanoparticles for Systemic Delivery

    PubMed Central

    Poon, Zhiyong; Lee, Jong Bum; Morton, Stephen W; Hammond, Paula T

    2011-01-01

    This paper demonstrates the generation of systemically deliverable layer-by-layer (LbL) nanoparticles for cancer applications. LbL-based nanoparticles designed to navigate the body and deliver therapeutics in a programmable fashion are promising new and alternative systems for drug delivery; but there have been very few demonstrations of their systemic delivery in vivo due to a lack of knowledge in building LbL nanofilms that mimic traditional nanoparticle design to optimize delivery. The key to the successful application of these nanocarriers in vivo requires a systematic analysis of the influence of film architecture and adsorbed polyelectrolyte outer layer on their pharmacokinetics, which has thus far not been examined for this new approach to nanoparticle delivery. Herein, we have taken the first steps in stabilizing and controlling the systemic distribution of multilayer nanoparticles. Our findings highlight the unique character of LbL systems: the electrostatically assembled nanoparticles gain increased stability in vivo with larger numbers of deposited layers, and the final layer adsorbed generates a critical surface cascade, which dictates the surface chemistry and biological properties of the nanoparticle. This outer polyelectrolyte layer dramatically affects not only the degree of nonspecific particle uptake, but also the nanoparticle biodistribution. For hyaluronic acid (HA) outer layers, a long blood elimination half-life (~9 h) and low accumulation (~ 10–15 % recovered fluorescence/g) in the liver were observed, illustrating that these systems can be designed to be highly appropriate for clinical translation. PMID:21524115

  5. Smart surface-enhanced Raman scattering traceable drug delivery systems

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Tang, Yonghong; Dai, Sheng; Kleitz, Freddy; Qiao, Shi Zhang

    2016-06-01

    A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells.A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03869g

  6. PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity.

    PubMed

    Silva, A L; Soema, P C; Slütter, B; Ossendorp, F; Jiskoot, W

    2016-04-02

    Among the emerging subunit vaccines are recombinant protein- and synthetic peptide-based vaccine formulations. However, proteins and peptides have a low intrinsic immunogenicity. A common strategy to overcome this is to co-deliver (an) antigen(s) with (an) immune modulator(s) by co-encapsulating them in a particulate delivery system, such as poly(lactic-co-glycolic acid) (PLGA) particles. Particulate PLGA formulations offer many advantages for antigen delivery as they are biocompatible and biodegradable; can protect the antigens from degradation and clearance; allow for co-encapsulation of antigens and immune modulators; can be targeted to antigen presenting cells; and their particulate nature can increase uptake and cross-presentation by mimicking the size and shape of an invading pathogen. In this review we discuss the pros and cons of using PLGA particulate formulations for subunit vaccine delivery and provide an overview of formulation parameters that influence their adjuvanticity and the ensuing immune response.

  7. PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity

    PubMed Central

    Silva, A. L.; Soema, P. C.; Slütter, B.; Ossendorp, F.; Jiskoot, W.

    2016-01-01

    ABSTRACT Among the emerging subunit vaccines are recombinant protein- and synthetic peptide-based vaccine formulations. However, proteins and peptides have a low intrinsic immunogenicity. A common strategy to overcome this is to co-deliver (an) antigen(s) with (an) immune modulator(s) by co-encapsulating them in a particulate delivery system, such as poly(lactic-co-glycolic acid) (PLGA) particles. Particulate PLGA formulations offer many advantages for antigen delivery as they are biocompatible and biodegradable; can protect the antigens from degradation and clearance; allow for co-encapsulation of antigens and immune modulators; can be targeted to antigen presenting cells; and their particulate nature can increase uptake and cross-presentation by mimicking the size and shape of an invading pathogen. In this review we discuss the pros and cons of using PLGA particulate formulations for subunit vaccine delivery and provide an overview of formulation parameters that influence their adjuvanticity and the ensuing immune response. PMID:26752261

  8. Nanostructured lipid carriers system: recent advances in drug delivery.

    PubMed

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  9. 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

  10. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

    PubMed Central

    Rajan, Reshmy; Jose, Shoma; Mukund, V. P. Biju; Vasudevan, Deepa T.

    2011-01-01

    Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era. PMID:22171309

  11. Dopamine-conjugated poly(lactic-co-glycolic acid) nanoparticles for protein delivery to macrophages.

    PubMed

    Lee, Song Yi; Cho, Hyun-Jong

    2017-03-15

    Poly(lactic-co-glycolic acid)-dopamine (PLGA-D)-based nanoparticles (NPs) were developed for the delivery of protein to macrophages. PLGA-D was synthesized via amide bond formation between the amine group of D and the carboxylic acid group of PLGA. Bovine serum albumin (BSA, model protein) was encapsulated in PLGA NPs and PLGA-D NPs, which had an approximately 200nm mean diameter, <0.2 polydispersity index, and negative zeta potential value. There was no increment in the mean diameters of BSA-loaded NPs after 24h of incubation in biological fluid-simulated media (i.e., aqueous buffer and serum media). The primary, secondary, and tertiary structures of BSA released from the NPs were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism, and fluorescence spectrophotometry; the structural stability of BSA was preserved during its encapsulation in the NPs and release from the NPs. PLGA/BSA NPs and PLGA-D/BSA NPs did not induce serious cytotoxicity in RAW 264.7 cells (mouse macrophage cell line) in an established concentration range. In RAW 264.7 cells, the intracellular accumulation of PLGA-D NPs was 2-fold higher than that of PLGA NPs. All of these findings indicated that PLGA-D NPs are a promising system for delivering proteins to macrophages.

  12. Hyaluronic acid-modified multiwalled carbon nanotubes for targeted delivery of doxorubicin into cancer cells.

    PubMed

    Cao, Xueyan; Tao, Lei; Wen, Shihui; Hou, Wenxiu; Shi, Xiangyang

    2015-03-20

    Development of novel drug carriers for targeted cancer therapy with high efficiency and specificity is of paramount importance and has been one of the major topics in current nanomedicine. Here we report a general approach to using multifunctional multiwalled carbon nanotubes (MWCNTs) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for targeted cancer therapy. In this approach, polyethyleneimine (PEI)-modified MWCNTs were covalently conjugated with fluorescein isothiocyanate (FI) and hyaluronic acid (HA). The formed MWCNT/PEI-FI-HA conjugates were characterized via different techniques and were used as a new carrier system to encapsulate the anticancer drug doxorubicin for targeted delivery to cancer cells overexpressing CD44 receptors. We show that the formed MWCNT/PEI-FI-HA/DOX complexes with a drug loading percentage of 72% are water soluble and stable. In vitro release studies show that the drug release rate under an acidic condition (pH 5.8, tumor cell microenvironment) is higher than that under physiological condition (pH 7.4). Cell viability assay demonstrates that the carrier material has good biocompatibility in the tested concentration range, and the MWCNT/PEI-FI-HA/DOX complexes can specifically target cancer cells overexpressing CD44 receptors and exert growth inhibition effect to the cancer cells. The developed HA-modified MWCNTs hold a great promise to be used as an efficient anticancer drug carrier for tumor-targeted chemotherapy.

  13. Systemic and Local Drug Delivery for Treating Diseases of the Central Nervous System in Rodent Models

    PubMed Central

    Serwer, Laura; Hashizume, Rintaro; Ozawa, Tomoko; James, C. David

    2010-01-01

    Thorough preclinical testing of central nervous system (CNS) therapeutics includes a consideration of routes of administration and agent biodistribution in assessing therapeutic efficacy. Between the two major classifications of administration, local vs. systemic, systemic delivery approaches are often preferred due to ease of administration. However, systemic delivery may result in suboptimal drug concentration being achieved in the CNS, and lead to erroneous conclusions regarding agent efficacy. Local drug delivery methods are more invasive, but may be necessary to achieve therapeutic CNS drug levels. Here, we demonstrate proper technique for three routes of systemic drug delivery: intravenous injection, intraperitoneal injection, and oral gavage. In addition, we show a method for local delivery to the brain: convection-enhanced delivery (CED). The use of fluorescently-labeled compounds is included for in vivo imaging and verification of proper drug administration. The methods are presented using murine models, but can easily be adapted for use in rats. PMID:20736920

  14. Development of a glucose-sensitive drug delivery device: Microencapsulated liposomes and poly(2-ethylacrylic acid)

    NASA Astrophysics Data System (ADS)

    Kanokpanont, Sorada

    The current study is the development a self-regulated, glucose responsive drug delivery system, using dioleoylphosphatidylcholine (DOPC) liposomes, a pH sensitive polymer, poly (2-ethylacrylic acid)(PEAA), and the feed back reaction of glucose with glucose oxidase enzyme (GO). The thesis investigates the use of PEAR and liposomes to work inside a microcapsule in response to the glucose level of the environment, by following the release of fluorescence probes, 8-aminonapthalene-1,3,6-trisulfonic acid, disodium salt/p-xylene-bis-pyridimuim bromide (ANTS/DPX) and a model protein, myoglobin. The continuing studies of PEAR and liposome interaction indicated an evidence of the previous hypothesis of two-mode release at different pHs. Differential scanning calorimetric studies of DOPC and PEAA complexes revealed the possibility of polymer adsorption to the liposomes in the pH range 5.5--7.0 and insertion in the liposome bilayer at pH < 5.2. The rate and extent of ANTS/DPX release from un-encapsulated liposomes were found to be affected by pH, PEAR concentration, presence of cholesterol in the liposomes, Ca 2+, and the concentration of sodium alginate. We have also shown possibilities of anchoring PEAR on to liposome by covalent conjugation although this led to inactivation of the polymer. It is also possible to entrap small molecular weight PEAA in liposomes. The evidence of the pH-induced protein release by the interaction of PEAA and liposomes was first demonstrated in this thesis. Kinetic parameters of GO were estimated to use as a basis for determination optimal concentration in the capsules. The pH reduction inside the capsule due to GO reaction showed positive results for the use of GO in a non-buffered system. The procedure of liquid-core alginate capsules was modified to facilitate the pH-responsive release of ANTS/DPX and myoglobin. The capsules responded to high blood glucose concentration by releasing myoglobin within 30 minutes. Although more studies are

  15. Formulation and evaluation of nano based drug delivery system for the buccal delivery of acyclovir.

    PubMed

    Al-Dhubiab, Bandar E; Nair, Anroop B; Kumria, Rachna; Attimarad, Mahesh; Harsha, Sree

    2015-12-01

    Oral bioavailability of acyclovir is limited, primarily because of low permeability across the gastrointestinal membrane. The purpose of this study is the prospective evaluation of buccal films impregnated with acyclovir loaded nanospheres as a drug delivery system to improve systemic bioavailability. Acyclovir polymeric nanospheres were prepared by double emulsion solvent evaporation technique. Nanospheres were embedded into buccoadhesive films (A1-A4) comprising of different concentrations of polymers (Eudragit RL 100, HPMC K15 and carbopol 974P). Films were characterized for physico-mechanical properties, mucoadhesive strength, hydration, drug release and ex vivo permeation. In vivo studies were carried out on rabbits to assess the pharmacokinetic profile of buccal film (A3) as compared to oral therapy. The prepared films demonstrated excellent physical properties, adequate hydration and buccoadhesive strength. In vitro drug release data inferred that the drug release was dependent on the composition of film. Ex vivo permeation studies indicated greater flux in film A3. In vivo studies revealed a significant enhancement in absorption of acyclovir (P<0.0001) with Cmax (~3 folds) and AUC0-α (~8 folds, P<0.0001) when compared to oral dosing. Moreover, the extended Tmax value (6h) signifies the potential of the prepared film to prolong acyclovir delivery. Given the promising results, the study concludes that the developed buccal film (A3) impregnated with acyclovir loaded nanospheres could be a promising approach for effective delivery of acyclovir.

  16. Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome

    PubMed Central

    Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

    2016-01-01

    Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a

  17. Evolution of implantable and insertable drug delivery systems.

    PubMed

    Kleiner, Lothar W; Wright, Jeremy C; Wang, Yunbing

    2014-05-10

    The paper describes the development of implantable and insertable drug delivery systems (IDDS) from their early stage in the 1960s until the current stage in the 2010s. It gives a detailed summary of non-degradable and biodegradable systems and their applications in different areas such as vascular disease treatment, birth control, cancer treatment, and eye disease treatment. It also describes the development of various implantable pump systems and some other atypical IDDS, the challenges and the future of IDDS.

  18. Mercury sorbent delivery system for flue gas

    DOEpatents

    Klunder; ,Edgar B.

    2009-02-24

    The invention presents a device for the removal of elemental mercury from flue gas streams utilizing a layer of activated carbon particles contained within the filter fabric of a filter bag for use in a flue gas scrubbing system.

  19. New Concept Firefighting Agent Delivery System

    DTIC Science & Technology

    1992-05-01

    the firing system to operate properly. The actuator cylinder was controlled by a solenoid-operated spread bore poppet valve (Ross Mod. 2773B7001). For...feet. This load and distance represented the limits of the launcher system, and major modifications were undertaken to replace the firing valve , fit...PROTOTYPE DEVELOPM ENT ........................................ 28 A. PULSED-GAS VALVE LAUNCHER................... 28 ix TABLE OF CONTENTS (CONTINUED

  20. Autonomous Aerial Payload Delivery System Blizzard

    DTIC Science & Technology

    2011-05-01

    known systems. Another technique to achieve a high touchdown accuracy is networking, enabling communication between multiple descending ADSs, UAV...Global System for Mobile ( Communications ) MCCC = mission C2 center PATCAD = Precision Airdrop Technology Conference and Demonstration SA = situational... high performance gimbal (seen in Fig.1 and shown in more details in Fig.2) featuring a full 360° un-obstructed field of view, direct drive

  1. Designing polymeric microparticulate drug delivery system for hydrophobic drug quercetin

    PubMed Central

    Hazra, Moumita; Dasgupta Mandal, Dalia; Mandal, Tamal; Bhuniya, Saikat; Ghosh, Mallika

    2015-01-01

    The aim of this study was to investigate pharmaceutical potentialities of a polymeric microparticulate drug delivery system for modulating the drug profile of poorly water-soluble quercetin. In this research work two cost effective polymers sodium alginate and chitosan were used for entrapping the model drug quercetin through ionic cross linking method. In vitro drug release, swelling index, drug entrapment efficiency, Fourier Transforms Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Differential Scanning Calorimetric (DSC) studies were also done for physicochemical characterization of the formulations. Swelling index and drug release study were done at a pH of 1.2, 6.8 and 7.4 to evaluate the GI mimetic action which entails that the swelling and release of the all the Formulation1 (F1), Formulation2 (F2) and Formulation3 (F3) at pH 1.2 were minimal confirming the prevention of drug release in the acidic environment of stomach. Comparatively more sustained release was seen from the formulations F2 & F3 at pH 6.8 and pH 7.4 after 7 h of drug release profiling. Drug entrapment efficiency of the formulations shows in F1 (D:C:A = 2:5:30) was approximately 70% whereas the increase in chitosan concentration in F2 (D:C:A = 2:10:30) has shown an entrapment efficiency of 81%. But the comparative further increase of chitosan concentration in F3 (D:C:A = 2:15:30) has shown a entrapment of 80% which is not having any remarkable difference from F2. The FTIR analysis of drug, polymers and the formulations indicated the compatibility of the drug with the polymers. The smoothness of microspheres in F2 & F3 was confirmed by Scanning Electron Microscopy (SEM). However F1 microsphere has shown more irregular shape comparatively. The DSC studies indicated the absence of drug-polymer interaction in the microspheres. Our XRD studies have revealed that when pure drug exhibits crystalline structure with less dissolution profile

  2. NimbleTools: A Universally Designed Test Delivery System

    ERIC Educational Resources Information Center

    Russell, Michael; Hoffmann, Thomas; Higgins, Jennifer

    2009-01-01

    Students with disabilities and special needs have faced challenges in accessing educational content, and in taking traditional pen-and-paper tests. How might technology improve the process, while making statewide tests truly accessible to all students? NimbleTools is the first computer-based test delivery system that incorporates principles of…

  3. Current HPLC Methods for Assay of Nano Drug Delivery Systems.

    PubMed

    Tekkeli, Serife Evrim Kepekci; Kiziltas, Mustafa Volkan

    2016-12-22

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

  4. A Study of Alternative Delivery Systems for Audio Instruction.

    ERIC Educational Resources Information Center

    Conner, Pat A.

    The Newark Audio Instruction Project determined and evaluated the cost benefits and efficiency factors in using FM main channel and subchannel, the school intercom system, and audio cassettes for delivery of instructional programming for grades K-9, and developed a master plan for integrating radio/audio instruction into the curriculum. A…

  5. Second-generation legal issues in integrated delivery systems.

    PubMed

    Teske, J M

    1995-01-01

    The formation and operation of integrated healthcare delivery systems raise significant legal issues. Some of these issues, such as antitrust, tax-exempt status, and fraud and abuse, have been discussed extensively. However, other legal issues, such as those involving management of business risk, use of systemwide information management, and securing of tax-exempt financing, have not received much attention.

  6. Noncontact laser fiber delivery system for endoscopic medical applications

    NASA Astrophysics Data System (ADS)

    Denisov, Nikolay A.; Griffin, Stephen E.

    1999-02-01

    The objective of the study was to design and to investigate laser fiber delivery system for treatment of obstructed human internal tubular organs using endoscopic techniques. This system eliminates the main disadvantages of both applied contact and non-contact probes, namely surface contamination with concomitant hydrothermal probe deterioration and large beam divergence with poor energy density, respectively. Proposed silica or sapphire probes produce quasi-collimated beam with specific outside diameter and power distribution. To provide comparative analysis of laser delivery systems' optical properties with non-contact endoscopic probes 'steady beam distance' (SBD) and 'steady beam ratio' (SBR) coefficients are proposed. The calculation results are presented in the form of the plots of the SBR - coefficients and SBDs for a 2.0 mm specific outside beam diameter versus laser wavelength, delivery fiber core diameter and its numerical aperture for both probe material. Additionally, the cross power distributions along the SBD were studied. Results obtained could provide a useful tool to designers of non-contact fiber delivery systems intended for a variety of medical applications, including endoscopic surgery with cw or pulse laser tissue irradiation, skin de-epithelialization, laser-induced fluorescence and photodynamic therapy.

  7. The 2006 ACTER Presidential Address: The Premier Educational Delivery System

    ERIC Educational Resources Information Center

    Elliot, Jack

    2007-01-01

    In this address, ACTER President Jack Elliot states that Career and Technical Education (CTE) is the premier educational delivery system in the world. It addresses all learning styles by employing pedagogical strategies that embrace all of the multiple intelligence areas and incorporate the current knowledge in brain-based research. He discusses…

  8. Construction of a controlled-release delivery system for pesticides using biodegradable PLA-based microcapsules.

    PubMed

    Liu, Baoxia; Wang, Yan; Yang, Fei; Wang, Xing; Shen, Hong; Cui, Haixin; Wu, Decheng

    2016-08-01

    Conventional pesticides usually need to be used in more than recommended dosages due to their loss and degradation, which results in a large waste of resources and serious environmental pollution. Encapsulation of pesticides in biodegradable carriers is a feasible approach to develop environment-friendly and efficient controlled-release delivery system. In this work, we fabricated three kinds of polylactic acid (PLA) carriers including microspheres, microcapsules, and porous microcapsules for controlled delivery of Lambda-Cyhalothrin (LC) via premix membrane emulsification (PME). The microcapsule delivery system had better water dispersion than the other two systems. Various microcapsules with a high LC contents as much as 40% and tunable sizes from 0.68 to 4.6μm were constructed by manipulating the process parameters. Compared with LC technical and commercial microcapsule formulation, the microcapsule systems showed a significantly sustained release of LC for a longer period. The LC release triggered by LC diffusion and matrix degradation could be optimally regulated by tuning LC contents and particle sizes of the microcapsules. This multi-regulated release capability is of great significance to achieve the precisely controlled release of pesticides. A preliminary bioassay against plutella xylostella revealed that 0.68μm LC-loaded microcapsules with good UV and thermal stability exhibited an activity similar to a commercial microcapsule formulation. These results demonstrated such an aqueous microcapsule delivery system had a great potential to be further explored for developing an effective and environmentally friendly pesticide-release formulation.

  9. Gelatin-based nanoparticles as DNA delivery systems: Synthesis, physicochemical and biocompatible characterization.

    PubMed

    Morán, M C; Rosell, N; Ruano, G; Busquets, M A; Vinardell, M P

    2015-10-01

    The rapidly rising demand for therapeutic grade DNA molecules requires associated improvements in encapsulation and delivery technologies. One of the challenges for the efficient intracellular delivery of therapeutic biomolecules after their cell internalization by endocytosis is to manipulate the non-productive trafficking from endosomes to lysosomes, where degradation may occur. The combination of the endosomal acidity with the endosomolytic capability of the nanocarrier can increase the intracellular delivery of many drugs, genes and proteins, which, therefore, might enhance their therapeutic efficacy. Among the suitable compounds, the gelification properties of gelatin as well as the strong dependence of gelatin ionization with pH makes this compound an interesting candidate to be used to the effective intracellular delivery of active biomacromolecules. In the present work, gelatin (either high or low gel strength) and protamine sulfate has been selected to form particles by interaction of oppositely charged compounds. Particles in the absence of DNA (binary system) and in the presence of DNA (ternary system) have been prepared. The physicochemical characterization (particle size, polydispersity index and degree of DNA entrapment) have been evaluated. Cytotoxicity experiments have shown that the isolated systems and the resulting gelatin-based nanoparticles are essentially non-toxic. The pH-dependent hemolysis assay and the response of the nanoparticles co-incubated in buffers at defined pHs that mimic extracellular, early endosomal and late endo-lysosomal environments demonstrated that the nanoparticles tend to destabilize and DNA can be successfully released. It was found that, in addition to the imposed compositions, the gel strength of gelatin is a controlling parameter of the final properties of these nanoparticles. The results indicate that these gelatin-based nanoparticles have excellent properties as highly potent and non-toxic intracellular delivery

  10. Reducible HPMA-co-oligolysine copolymers for nucleic acid delivery

    PubMed Central

    Shi, Julie; Johnson, Russell N.; Schellinger, Joan G.; Carlson, Peter M.

    2011-01-01

    Biodegradability can be incorporated into cationic polymers via use of disulfide linkages that are degraded in the reducing environment of the cell cytosol. In this work, N-(2-hydroxypropyl)methacrylamide (HPMA) and methacrylamido-functionalized oligo-L-lysine peptide monomers with either a non-reducible 6-aminohexanoic acid (AHX) linker or a reducible 3-[(2-aminoethyl)dithiol]propionic acid (AEDP) linker were copolymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Both of the copolymers and a 1:1 (w/w) mixture of copolymers with reducible and non-reducible peptides were complexed with DNA to form polyplexes. The polyplexes were tested for salt stability, transfection efficiency, and cytotoxicity. The HPMA-oligolysine copolymer containing the reducible AEDP linkers was less efficient at transfection than the non-reducible polymer and was prone to flocculation in saline and serum-containing conditions, but was also not cytotoxic at charge ratios tested. Optimal transfection efficiency and toxicity was attained with mixed formulation of copolymers. Flow cytometry uptake studies indicated that blocking extracellular thiols did not restore transfection efficiency and that the decreased transfection of the reducible polyplex is therefore not primarily caused by extracellular polymer reduction by free thiols. The decrease in transfection efficiency of the reducible polymers could be partially mitigated by the addition of low concentrations of EDTA to prevent metal-catalyzed oxidation of reduced polymers. PMID:21893178

  11. Reducible HPMA-co-oligolysine copolymers for nucleic acid delivery.

    PubMed

    Shi, Julie; Johnson, Russell N; Schellinger, Joan G; Carlson, Peter M; Pun, Suzie H

    2012-05-01

    Biodegradability can be incorporated into cationic polymers via use of disulfide linkages that are degraded in the reducing environment of the cell cytosol. In this work, N-(2-hydroxypropyl)methacrylamide (HPMA) and methacrylamido-functionalized oligo-l-lysine peptide monomers with either a non-reducible 6-aminohexanoic acid (AHX) linker or a reducible 3-[(2-aminoethyl)dithiol] propionic acid (AEDP) linker were copolymerized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Both of the copolymers and a 1:1 (w/w) mixture of copolymers with reducible and non-reducible peptides were complexed with DNA to form polyplexes. The polyplexes were tested for salt stability, transfection efficiency, and cytotoxicity. The HPMA-oligolysine copolymer containing the reducible AEDP linkers was less efficient at transfection than the non-reducible polymer and was prone to flocculation in saline and serum-containing conditions, but was also not cytotoxic at charge ratios tested. Optimal transfection efficiency and toxicity were attained with mixed formulation of copolymers. Flow cytometry uptake studies indicated that blocking extracellular thiols did not restore transfection efficiency and that the decreased transfection of the reducible polyplex is therefore not primarily caused by extracellular polymer reduction by free thiols. The decrease in transfection efficiency of the reducible polymers could be partially mitigated by the addition of low concentrations of EDTA to prevent metal-catalyzed oxidation of reduced polymers.

  12. Brucella spp. lumazine synthase: a novel antigen delivery system.

    PubMed

    Sciutto, Edda; Toledo, Andrea; Cruz, Carmen; Rosas, Gabriela; Meneses, Gabriela; Laplagne, Diego; Ainciart, Natalia; Cervantes, Jacquelynne; Fragoso, Gladis; Goldbaum, Fernando A

    2005-04-15

    Lumazine synthase from Brucella spp. (BLS) was evaluated as a protein carrier to improve antigen delivery of KETc1, one of the peptides of the anti-cysticercosis vaccine. KETc1 becomes antigenic, preserved its immunogenicity and its protective capacity when expressed as a recombinant chimeric protein using Brucella spp. lumazine synthase. KETc1 and BLS-KETc1 were not MHC H-2(d), H-2(k) nor H-2(b) haplotype-restricted albeit KETc1 is preferentially presented in the H-2(b) haplotype. These findings support that BLS is a potent new delivery system for the improvement of subunit vaccines.

  13. Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

    PubMed Central

    Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

    2015-01-01

    Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

  14. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

  15. Biodegradable mesoporous delivery system for biomineralization precursors

    PubMed Central

    Yang, Hong-ye; Niu, Li-na; Sun, Jin-long; Huang, Xue-qing; Pei, Dan-dan; Huang, Cui; Tay, Franklin R

    2017-01-01

    Scaffold supplements such as nanoparticles, components of the extracellular matrix, or growth factors have been incorporated in conventional scaffold materials to produce smart scaffolds for tissue engineering of damaged hard tissues. Due to increasing concerns on the clinical side effects of using large doses of recombinant bone-morphogenetic protein-2 in bone surgery, it is desirable to develop an alternative nanoscale scaffold supplement that is not only osteoinductive, but is also multifunctional in that it can perform other significant bone regenerative roles apart from stimulation of osteogenic differentiation. Because both amorphous calcium phosphate (ACP) and silica are osteoinductive, a biodegradable, nonfunctionalized, expanded-pore mesoporous silica nanoparticle carrier was developed for loading, storage, and sustained release of a novel, biosilicification-inspired, polyamine-stabilized liquid precursor phase of ACP for collagen biomineralization and for release of orthosilicic acid, both of which are conducive to bone growth. Positively charged poly(allylamine)-stabilized ACP (PAH-ACP) could be effectively loaded and released from nonfunctionalized expanded-pore mesoporous silica nanoparticles (pMSN). The PAH-ACP released from loaded pMSN still retained its ability to infiltrate and mineralize collagen fibrils. Complete degradation of pMSN occurred following unloading of their PAH-ACP cargo. Because PAH-ACP loaded pMSN possesses relatively low cytotoxicity to human bone marrow-derived mesenchymal stem cells, these nanoparticles may be blended with any osteoconductive scaffold with macro- and microporosities as a versatile scaffold supplement to enhance bone regeneration. PMID:28182119

  16. Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

    PubMed

    Gao, Yuan; Wang, Jingkang; Wang, Yongli; Yin, Qiuxiang; Glennon, Brian; Zhong, Jian; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun

    2015-01-01

    Low water solubility of drug products causes delivery problems such as low bioavailability. The reduced particle size and increased surface area of nanocrystals lead to the increasing of the dissolution rate. The formulation of drug nanocrystals is a robust approach and has been widely applied to drug delivery system (DDS) due to the significant development of nanoscience and nanotechnology. It can be used to improve drug efficacy, provide targeted delivery and minimize side-effects. Crystallization is the main and efficient unit operation to produce nanocrystals. Both traditional crystallization methods such as reactive crystallization, anti-solvent crystallization and new crystallization methods such as supercritical fluid crystallization, high-gravity controlled precipitation can be used to produce nanocrystals. The current mini-review outlines the main crystallization methods addressed in literature. The advantages and disadvantages of each method were summarized and compared.

  17. Medicated chewing gum, a novel drug delivery system

    PubMed Central

    Aslani, Abolfazl; Rostami, Farnaz

    2015-01-01

    New formulations and technologies have been developed through oral drug delivery systems’ researches. Such researches display significance of oral route amongst patients. We’ve reviewed all the features associated with medicated chewing gum as a modern drug delivery by introducing the history, advantages and disadvantages, methods of manufacturing, composition differences, evaluation tests and examples of varieties of medicated chewing gums. Acceptance of medicated chewing gum has been augmented through years. The advantages and therapeutic benefits of chewing gum support its development as we can see new formulations with new drugs contained have been produced from past and are going to find a place in market by formulation of new medicated chewing gums. Potential applications of medicated chewing gums are highly widespread as they will be recognized in future. Nowadays standards for qualifying chewing gums are the same as tablets. Patient-centered studies include medicated chewing gums as a delivery system too which creates compliance for patients. PMID:26109999

  18. 3-dimensional (3D) fabricated polymer based drug delivery systems.

    PubMed

    Moulton, Simon E; Wallace, Gordon G

    2014-11-10

    Drug delivery from 3-dimensional (3D) structures is a rapidly growing area of research. It is essential to achieve structures wherein drug stability is ensured, the drug loading capacity is appropriate and the desired controlled release profile can be attained. Attention must also be paid to the development of appropriate fabrication machinery that allows 3D drug delivery systems (DDS) to be produced in a simple, reliable and reproducible manner. The range of fabrication methods currently being used to form 3D DDSs include electrospinning (solution and melt), wet-spinning and printing (3-dimensional). The use of these techniques enables production of DDSs from the macro-scale down to the nano-scale. This article reviews progress in these fabrication techniques to form DDSs that possess desirable drug delivery kinetics for a wide range of applications.

  19. Intranasal delivery of biologics to the central nervous system.

    PubMed

    Lochhead, Jeffrey J; Thorne, Robert G

    2012-05-15

    Treatment of central nervous system (CNS) diseases is very difficult due to the blood-brain barrier's (BBB) ability to severely restrict entry of all but small, non-polar compounds. Intranasal administration is a non-invasive method of drug delivery which may bypass the BBB to allow therapeutic substances direct access to the CNS. Intranasal delivery of large molecular weight biologics such as proteins, gene vectors, and stem cells is a potentially useful strategy to treat a variety of diseases/disorders of the CNS including stroke, Parkinson's disease, multiple sclerosis, Alzheimer's disease, epilepsy, and psychiatric disorders. Here we give an overview of relevant nasal anatomy and physiology and discuss the pathways and mechanisms likely involved in drug transport from the nasal epithelium to the CNS. Finally we review both pre-clinical and clinical studies involving intranasal delivery of biologics to the CNS.

  20. Electrohydrodynamics: A facile technique to fabricate drug delivery systems

    PubMed Central

    Chakraborty, Syandan; Liao, I-Chien; Adler, Andrew; Leong, Kam W.

    2009-01-01

    Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nano-structured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial-electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material’s functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nano-fiber/particles as drug delivery devices. PMID:19651167

  1. Biological evaluation of redox-sensitive micelles based on hyaluronic acid-deoxycholic acid conjugates for tumor-specific delivery of paclitaxel.

    PubMed

    Li, Jing; Yin, Tingjie; Wang, Lei; Yin, Lifang; Zhou, Jianping; Huo, Meirong

    2015-04-10

    Tumor-targeted drug delivery and microenvironment-responsive drug release are attractive strategies in cancer treatment. Our previous study demonstrated that redox-sensitive micelles based on hyaluronic acid-deoxycholic acid (HA-ss-DOCA) conjugates exhibited excellent drug-loading capacities (34.1%) for paclitaxel (PTX) and rapid drug release in response to reducing agent, glutathione. In the present study, the physicochemical and biological properties of PTX-loaded HA-ss-DOCA (PTX-HA-ss-DOCA) micelles were investigated further. The micelles have an average size of about 120 nm and a zeta potential of about -36 mV. Transmission electron microscopy and wide-angle X-ray diffraction analysis demonstrated redox-sensitive degradation of micelles in the presence of glutathione. Moreover, the encapsulated payload was effectively released from HA-ss-DOCA micelles into cytoplasm and then rapidly transported into nuclei. In vitro cytotoxicity and cell apoptosis assay further revealed that HA significantly improved the tumor-specific drug delivery of HA-ss-DOCA micelles via receptor-mediated endocytosis, while efficient intracellular drug release and transportation lead to marked inhibition of tumor cell growth, as compared to Taxol(®) and insensitive micelles. More importantly, PTX-HA-ss-DOCA micelles demonstrated superior in vivo antitumor activity compared with Taxol(®) and insensitive control, and decreased systemic toxicity. Herein we present data which provide valuable insight into the design and development of tumor-specific drug delivery systems.

  2. Review of Innovative Sediment Delivery Systems

    DTIC Science & Technology

    2013-04-01

    Alternative conveyor belt systems appear to be available from the growing hydraulic fracturing ( fracking , shale gas recovery) industry, which use...tons of aggregate material (with diameters up to 2 in.) per hour. This equates to roughly 150 cu yd per hr, de- pending on sand density. As fracking

  3. 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.

  4. 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

  5. Self emulsifying drug delivery system (SEDDS) for phytoconstituents: a review.

    PubMed

    Chouhan, Neeraj; Mittal, Vineet; Kaushik, Deepak; Khatkar, Anurag; Raina, Mitali

    2015-01-01

    The self emulsifying drug delivery system (SEDDS) is considered to be the novel technique for the delivery of lipophillic plant actives. The self emulsifying (SE) formulation significantly enhance the solubility and bioavailability of poorly aqueous soluble phytoconstituents. The self emulsifying drug delivery system (SEDDS) can be developed for such plant actives to enhance the oral bioavailability using different excipients (lipid, surfactant, co solvent etc.) and their concentration is selected on the basis of pre formulation studies like phase equilibrium studies, solvent capacity of oil for drug and mutual miscibility of excipients. The present review focuses mainly on the development of SEDDS and effect of excipients on oral bioavailability and aqueous solubility of poorly water soluble phytoconstituents/ derived products. A recent list of patents issued for self emulsifying herbal formulation has also been included. The research data for various self emulsifying herbal formulation and patents issued were reviewed using different databases such as PubMed, Google Scholar, Google patents, Scopus and Web of Science. In a nutshell, we can say that SEDDS was established as a novel drug delivery system for herbals and with the advances in this technique, lots of patents on herbal SEDDS can be translated into the commercial products.

  6. Steerable/distance enhanced penetrometer delivery system

    SciTech Connect

    Amini, A.; Boyd, G.M.

    1996-12-31

    Characterization, monitoring, and remediation of many of the nation`s highly contaminated sites are high priority at DOE. Penetrometers are often used for rapid characterization of underground contamination (plumes). Because of their heavy weight, use of penetrometer trucks over shallow buried storage tanks is restricted and risky. To close this gap, UTD developed a new position location device for penetrometers, called POLO (POsition LOcator), which provides real- time position location without blocking downhole access for environmental sensors. UTD also developed a system to make penetrometers steerable and capable of deeper penetration. Products of this work is a Steerable Vibratory System, which a relatively lightweight rig capable of greater penetration than traditional penetrometers of the same weight.

  7. Direct current power delivery system and method

    DOEpatents

    Zhang, Di; Garces, Luis Jose; Dai, Jian; Lai, Rixin

    2016-09-06

    A power transmission system includes a first unit for carrying out the steps of receiving high voltage direct current (HVDC) power from an HVDC power line, generating an alternating current (AC) component indicative of a status of the first unit, and adding the AC component to the HVDC power line. Further, the power transmission system includes a second unit for carrying out the steps of generating a direct current (DC) voltage to transfer the HVDC power on the HVDC power line, wherein the HVDC power line is coupled between the first unit and the second unit, detecting a presence or an absence of the added AC component in the HVDC power line, and determining the status of the first unit based on the added AC component.

  8. Hyaluronic acid-coated niosomes facilitate tacrolimus ocular delivery: Mucoadhesion, precorneal retention, aqueous humor pharmacokinetics, and transcorneal permeability.

    PubMed

    Zeng, Weidong; Li, Qi; Wan, Tao; Liu, Cui; Pan, Wenhui; Wu, Zushuai; Zhang, Guoguang; Pan, Jingtong; Qin, Mengyao; Lin, Yuanyuan; Wu, Chuanbin; Xu, Yuehong

    2016-05-01

    Tacrolimus (FK506) was used to prevent corneal allograft rejection in patients who were resistant to steroids and cyclosporine. However, the formulation for FK506 ocular delivery remained a challenge due to the drug's high hydrophobicity, high molecular weight, and eye's physiological and anatomical constraints. The aim of this project is to develop an ocular delivery system for FK506 based on a combined strategy of niosomes and mucoadhesive hyaluronic acid (HA), i.e., FK506HA-coated niosomes, which exploits virtues of both niosomes and HA to synergistically improve ophthalmic bioavailability. The FK506HA-coated niosomes were characterized with particle size, zeta potential, and rheology behavior. Mucoadhesion of FK506HA-coated niosomes to mucin was investigated through surface plasmon resonance in comparison with non-coated niosomes and HA solution. The results showed that niosomes possessed adhesion to mucin, and HA coating enhanced the adhesion. The in vivo precorneal retention was evaluated in rabbit, and the results showed that HA-coated niosomes prolonged the residence of FK506 significantly in comparison with non-coated niosomes or suspension. Aqueous humor pharmacokinetics test showed that area under curve of HA-coated niosomes was 2.3-fold and 1.2-fold as that of suspension and non-coated niosomes, respectively. Moreover, the synergetic corneal permeability enhancement of the hybrid delivery system on FK506 was visualized and confirmed by confocal laser scanning microscope. Overall, the results indicated that the hybrid system facilitated FK506 ocular delivery on mucoadhesion, precorneal retention, aqueous humor pharmacokinetics and transcorneal permeability. Therefore, HA-coated niosomes may be a promising approach for ocular targeting delivery of FK506.

  9. Improved oral delivery of resveratrol from N-trimethyl chitosan-g-palmitic acid surface-modified solid lipid nanoparticles.

    PubMed

    Ramalingam, Prakash; Ko, Young Tag

    2016-03-01

    Despite the therapeutic effects of resveratrol, its clinical application is restricted by its poor oral bioavailability, low water solubility, and instability. Solid lipid nanoparticles (SLNs)-based drug delivery systems have been shown to provide excellent support for the delivery of hydrophobic drugs. The poor stability and burst release behavior in stomach acidic pH conditions of SLNs result in increased aggregation of the particles in the gastrointestinal environment, limiting the success of these particles as an oral delivery system for hydrophobic drugs. N-trimethyl chitosan (TMC) graft palmitic acid (PA) (TMC-g-PA) mucoadhesive copolymer was hypothesized to be a promising candidate for the surface modification of PA-decorated resveratrol-loaded SLNs to stabilize SLNs and circumvent all the above mentioned obstacles. TMC and TMC-g-PA copolymers were therefore synthesized and characterized by (1)H-nuclear magnetic resonance ((1)H NMR) and Fourier-transformed infra-red (FT-IR) spectroscopy. Resveratrol-loaded SLNs (SLRNs) that comprised Precirol ATO 5, PA, Gelucire 50/13, Tween 80, and resveratrol as well as TMC-g-PA SLRNs were formulated and characterized in terms of physicochemical properties, stability, cytotoxicity, and in vitro and in vivo effects. The in vitro release studies of TMC-g-PA SLRNs demonstrated negligible release of resveratrol in simulated gastric and sustained release in simulated intestinal conditions and the relative bioavailability of resveratrol was furthermore found to be 3.8-fold higher from TMC-g-PA SLRNs than that from resveratrol suspension. Overall, the findings reported here indicate that TMC-g-PA SLRNs represent a potential oral drug delivery system for resveratrol.

  10. Fluid delivery manifolds and microfluidic systems

    DOEpatents

    Renzi, Ronald F.; Sommer, Gregory J.; Singh, Anup K.; Hatch, Anson V.; Claudnic, Mark R.; Wang, Ying-Chih; Van de Vreugde, James L.

    2017-02-28

    Embodiments of fluid distribution manifolds, cartridges, and microfluidic systems are described herein. Fluid distribution manifolds may include an insert member and a manifold base and may define a substantially closed channel within the manifold when the insert member is press-fit into the base. Cartridges described herein may allow for simultaneous electrical and fluidic interconnection with an electrical multiplex board and may be held in place using magnetic attraction.

  11. Delivery of nucleic acid therapeutics by genetically engineered hematopoietic stem cells

    PubMed Central

    Doering, Christopher B.; Archer, David; Spencer, H. Trent

    2010-01-01

    Several populations of adult human stem cells have been identified, but only a few of these are in routine clinical use. The hematopoietic stem cell (HSC) is arguably the most well characterized and the most routinely transplanted adult stem cell. Although details regarding several aspects of this cell’s phenotype are not well understood, transplant of HSCs has advanced to become the standard of care for the treatment of a range of monogenic diseases and several types of cancer. It has also proven to be an excellent target for genetic manipulation, and clinical trials have already demonstrated the usefulness of targeting this cell as a means of delivering nucleic acid therapeutics for the treatment of several previously incurable diseases. It is anticipated that additional clinical trials will soon follow, such as genetically engineering HSCs with vectors to treat monogenic diseases such as hemophilia A. In addition to the direct targeting of HSCs, induced pluripotent stem (iPS) cells have the potential to replace virtually any engineered stem cell therapeutic, including HSCs. We now know that for the broad use of genetically-modified HSCs for the treatment of non-lethal diseases, e.g. hemophilia A, we must be able to regulate the introduction of nucleic acid sequences into these target cells. We can begin to refine transduction protocols to provide safer approaches to genetically manipulate HSCs and strategies are being developed to improve the overall safety of gene transfer. This review focuses on recent advances in the systemic delivery of nucleic acid therapeutics using genetically-modified stem cells, specifically focusing on i) the use of retroviral vectors to genetically modify HSCs, ii) the expression of fVIII from hematopoietic stem cells for the treatment of hemophilia A, and iii) the use of genetically engineered hematopoietic cells generated from iPS cells as treatment for disorders of hematopoiesis. PMID:20869414

  12. Matrix embedded microspherules containing indomethacin as controlled drug delivery systems.

    PubMed

    Swamy, K M Lokamatha; Satyanath, B; Shantakumar, S M; Manjula, D; Mohammedi, Hafsa; Farhana, Ayesha

    2008-10-01

    This work is focused on the development of controlled drug delivery systems using different wax/fat embedded indomethacin (IM). Discrete wax/fat embedded microspherules containing indomethacin were prepared by using cetostearyl alcohol, paraffin wax and stearic acid by employing emulsification-phase separation method. These matrices have been used as barrier coatings due to their hydrophobic nature. Chemically inert and tasteless nature of wax/fats promotes their use as taste masking agents for bitter drugs. Various waxes and fats are available having different physicochemical properties to suit the needs of formulation. Methyl cellulose (MC) 1% w/v, sodium alginate (SA) 0.5% w/v and Tween-80 (TW) 1% w/v were used as emulgents. The resulting microspherules were discrete, large, spherical and also free flowing. It is revealed from the literature that natures of wax/fat emulgents were found to influence the rate of drug release. In the present work the drug content in all the batches of microspherules were found to be uniform. The rate of drug release corresponded best to first order kinetics, followed by Higuchi and zero-order equations. The release of the model drug from these wax/fat microspherules was prolonged over an extended period of time and the drug release mechanism followed anomalous (non-Fickian) diffusion controlled as well as Super Case II transport. Among the three matrix materials used, paraffin wax retarded the drug release more than the other two. Surface characteristics of microspherules have been studied by Scanning Electron Microscope (SEM). A fair degree rank of correlation was found to exist between the size and release retardation in all the three-wax/fat emulgent combinations.

  13. Systemic oxygen delivery and consumption in dogs with heartworm disease.

    PubMed

    Kitagawa, H; Kitoh, K; Yasuda, K; Sasaki, Y

    1995-02-01

    To investigate systemic oxygen (O2) transport, we calculated the oxygen delivery index (Do2I), oxygen consumption index (Vo2I) and oxygen extraction ratio (ER) in dogs with heartworm (HW) disease. The Do2I was 770 +/- 331 ml/min/kg in dogs mildly affected with pulmonary HW disease showing respiratory signs, mild anemia and mild cardiac insufficiency (n = 34); 238 +/- 155 ml/min/kg in dogs with ascitic pulmonary HW disease (n = 7); and 577 +/- 320 ml/min/kg in dogs with caval syndrome (CS) which survived (n = 15) or died (n = 7) after surgical HW removal. The Do2I was lower (P < 0.01) in all HW-infected groups, especially in ascites and CS-non-surviving dogs, than in HW-free dogs (n = 11, 1041 +/- 264 ml/min/kg). The Vo2I was higher in some mildly affected dogs (161 +/- 88 ml/min/kg), and lower (P < 0.01) in ascitic dogs (45 +/- 53 ml/min/kg) than in HW-free dogs (123 +/- 44 ml/min/kg). The ER was higher (P < 0.01) in all HW-infected groups than in HW-free dogs. The Do2I correlated significantly with Vo2I (r = 0.84, P < 0.01), and the Vo2I correlated significantly with ER (r = 0.48, P < 0.01). The Do2I correlated significantly with arterial O2 tension (r = 0.33), serum LDH (r = -0.46) and CK (r = -0.46) activities, serum urea nitrogen (UN, r = -0.32) and lactic acid (LA, r = -0.39) concentrations and cardiac index (r = 0.64).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Phospholipid conjugate for intracellular delivery of peptide nucleic acids

    PubMed Central

    Shen, Gang; Fang, Huafeng; Song, Yinyin; Bielska, Agata A.; Wang, Zhenghui; Taylor, John-Stephen A.

    2009-01-01

    Peptide nucleic acids (PNAs) have a number of attractive features that have made them an ideal choice for antisense and antigene-based tools, probes and drugs, but their poor membrane permeability has limited their application as therapeutic or diagnostic agents. Herein we report a general method for the synthesis of phospholipid-PNAs (LP-PNAs), and compare the effect of non-cleavable lipids and bioreductively cleavable lipids (L and LSS) and phospholipid (LP) on the splice-correcting bioactivity of a PNA bearing the cell penetrating Arg9 group (PNA-R9). While the three constructs show similar and increasing bioactivity at 1–3 μM, the activity of LP-PNA-R9 continues to increase from 4–6 μM while the activity of L-PNA-R9 remains constant and LSS-PNA-R9 decreases rapidly in parallel with their relative cytotoxicity. The activity of both LP-PNA-R9 and L-PNA-R9 were found to dramatically increase with chloroquine, as expected for an endocytotic entry mechanism. Both constructs were also found to have CMC values of 1.0 and 4.5 μM in 150 mM NaCl, pH 7 water, suggesting that micelle formation may play a hitherto unrecognized role in modulating toxicity and/or facilitating endocytosis. PMID:19678628

  15. Achieving breakthrough performance in an integrated delivery system.

    PubMed

    Kelliher, M

    1995-01-01

    The challenges facing Blue Cross and Blue Shield of Massachusetts were considerable. Its products were largely indemnity-oriented. Its cost structure was high compared to the newer managed care industry. Its service culture was more internally directed than the competition. Its financing and payment systems were not well integrated into the delivery system. The ultimate challenge in the face of an increasingly competitive environment was to reengineer the company.

  16. Miniature Videoprobe Hockey Stick Delivery System

    SciTech Connect

    Hale, Lester R.; McMurry, Kyle M.

    1998-06-18

    The present invention is a miniature videoprobe system having a probe termination box, a strong back, and a videoprobe housing. The videoprobe system is able to obtain images from a restricted space at least as small as 0.125 inches while producing a high quality image. The strong back has a hockey stick shape with the probe termination box connecting to the top of the handle-like portion of the hockey stick and the videoprobe housing attaching to the opposite end or nose of the hockey stick shape. The videoprobe housing has a roughly arrowhead shape with two thin steel plates sandwiching the internal components there between. The internal components are connected in series to allow for a minor dimension of the videoprobe housing of 0.110 inches. The internal components include an optics train, a CCD chip, and an electronics package. An electrical signal is transmitted from the electronics package through wiring within an internal channel of the strong back to the probe termination box. The strong back has milled into it multiple internal channels for facilitating the transfer of information, items, or devices between the probe termination box and the videoprobe housing.

  17. HIV: challenging the health care delivery system.

    PubMed Central

    Levi, J; Kates, J

    2000-01-01

    HIV offers a lens through which the underlying problems of the US health care system can be examined. New treatments offer the potential of prolonged quality of life for people living with HIV if they have adequate access to health care. However, increasing numbers of new cases of HIV occur among individuals with poor access to health care. Restrictions on eligibility for Medicaid (and state-by-state variability) contribute to uneven access to the most important safety net source of HIV care financing, while relatively modest discretionary programs attempt to fill in the gap with an ever-increasing caseload. Many poor people with HIV are going without care, even though aggregate public spending on HIV-related care will total $7.7 billion in fiscal year 2000, an amount sufficient to cover the care costs of one half of those living with HIV. But inefficiencies and inequities in the system (both structural and geographic) require assessment of the steps that can be taken to create a more rational model of care financing for people living with HIV that could become a model for all chronic diseases. PMID:10897178

  18. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.

    PubMed

    Xiao, Bo; Xu, Zhigang; Viennois, Emilie; Zhang, Yuchen; Zhang, Zhan; Zhang, Mingzhen; Han, Moon Kwon; Kang, Yuejun; Merlin, Didier

    2017-01-28

    Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC.

  19. Using DNA nanotechnology to produce a drug delivery system

    NASA Astrophysics Data System (ADS)

    Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang

    2013-03-01

    Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October-2 November, 2012, Ha Long, Vietnam.

  20. 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.

  1. Emulsion forming drug delivery system for lipophilic drugs.

    PubMed

    Wadhwa, Jyoti; Nair, Anroop; Kumria, Rachna

    2012-01-01

    In the recent years, there is a growing interest in the lipid-based formulations for delivery of lipophilic drugs. Due to their potential as therapeutic agents, preferably these lipid soluble drugs are incorporated into inert lipid carriers such as oils, surfactant dispersions, emulsions, liposomes etc. Among them, emulsion forming drug delivery systems appear to be a unique and industrially feasible approach to overcome the problem of low oral bioavailability associated with the BCS class II drugs. Self-emulsifying formulations are ideally isotropic mixtures of oils, surfactants and co-solvents that emulsify to form fine oil in water emulsions when introduced in aqueous media. Fine oil droplets would pass rapidly from stomach and promote wide distribution of drug throughout the GI tract, thereby overcome the slow dissolution step typically observed with solid dosage forms. Recent advances in drug carrier technologies have promulgated the development of novel drug carriers such as control release self-emulsifying pellets, microspheres, tablets, capsules etc. that have boosted the use of "self-emulsification" in drug delivery. This article reviews the different types of formulations and excipients used in emulsion forming drug delivery system to enhance the bioavailability of lipophilic drugs.

  2. Dose error analysis for a scanned proton beam delivery system

    NASA Astrophysics Data System (ADS)

    Coutrakon, G.; Wang, N.; Miller, D. W.; Yang, Y.

    2010-12-01

    All particle beam scanning systems are subject to dose delivery errors due to errors in position, energy and intensity of the delivered beam. In addition, finite scan speeds, beam spill non-uniformities, and delays in detector, detector electronics and magnet responses will all contribute errors in delivery. In this paper, we present dose errors for an 8 × 10 × 8 cm3 target of uniform water equivalent density with 8 cm spread out Bragg peak and a prescribed dose of 2 Gy. Lower doses are also analyzed and presented later in the paper. Beam energy errors and errors due to limitations of scanning system hardware have been included in the analysis. By using Gaussian shaped pencil beams derived from measurements in the research room of the James M Slater Proton Treatment and Research Center at Loma Linda, CA and executing treatment simulations multiple times, statistical dose errors have been calculated in each 2.5 mm cubic voxel in the target. These errors were calculated by delivering multiple treatments to the same volume and calculating the rms variation in delivered dose at each voxel in the target. The variations in dose were the result of random beam delivery errors such as proton energy, spot position and intensity fluctuations. The results show that with reasonable assumptions of random beam delivery errors, the spot scanning technique yielded an rms dose error in each voxel less than 2% or 3% of the 2 Gy prescribed dose. These calculated errors are within acceptable clinical limits for radiation therapy.

  3. Nursing Services Delivery Theory: an open system approach

    PubMed Central

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

    2010-01-01

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

  4. PepFects and NickFects for the Intracellular Delivery of Nucleic Acids.

    PubMed

    Arukuusk, Piret; Pärnaste, Ly; Hällbrink, Mattias; Langel, Ülo

    2015-01-01

    Nucleic acids can be utilized in gene therapy to restore, alter, or silence gene functions. In order to reveal the biological activity nucleic acids have to reach their intracellular targets by passing through the plasma membrane, which is impermeable for these large and negatively charged molecules. Cell-penetrating peptides (CPPs) condense nucleic acids into nanoparticles using non-covalent complexation strategy and mediate their delivery into the cell, whereas the physicochemical parameters of the nanoparticles determine the interactions with the membranes, uptake mechanism, and subsequent intracellular fate. The nanoparticles are mostly internalized by endocytosis that leads to the entrapment of them in endosomal vesicles. Therefore design of new CPPs that are applicable for non-covalent complex formation strategy and harness endosomolytic properties is highly vital. Here we demonstrate that PepFects and NickFects are efficient vectors for the intracellular delivery of various nucleic acids.This chapter describes how to form CPP/pDNA nanoparticles, evaluate stable nanoparticles formation, and assess gene delivery efficacy.

  5. Enhancing polysaccharide-mediated delivery of nucleic acids through functionalization with secondary and tertiary amines.

    PubMed

    Ghosn, Bilal; Kasturi, Sudhir Pai; Roy, Krishnendu

    2008-01-01

    Chitosan is a polysaccharide that has generated significant interest as a non-viral gene delivery vehicle due to its cationic and biocompatible characteristics. However, transfection efficiency of chitosan is significantly lower compared to other cationic gene delivery agents, e.g. polyethyleneimine (PEI), dendrimers or cationic lipids. This is primarily attributed to its minimal solubility and low buffering capacity at physiological pH leading to poor endosomal escape of the gene carrier and inefficient cytoplasmic decoupling of the complexed nucleic acid. Here we have developed an imidazole acetic acid (IAA)-modified chitosan to introduce secondary and tertiary amines to the polymer in order to improve its endosomal buffering and solubility. The modified polymer was characterized by ninhydrin and (1)H NMR assays for degree of modification, while buffering and solubility were analyzed by acid titration. Nanocomplex formation, studied at various polymer-nucleic acid ratios, showed an increase in particle zeta potential for chitosan-IAA, as well as an increase in the effective diameter. Up to 100-fold increase in transfection efficiency of pDNA was seen for chitosan-IAA as compared to native chitosan, nearly matching that of PEI. In addition, transfection of siRNA by the modified polymers showed efficient gene knockdown equivalent to commercially available siPORT Amines. Collectively, these results demonstrate the potential of the imidazole-grafted chitosan as a biocompatible and effective delivery vehicle for both pDNA and siRNA.

  6. Integrated delivery systems: mergers and acquisitions.

    PubMed

    Pinkerton, S

    1999-01-01

    Mergers and acquisitions are usually the way an IDS is built. The CNO and/or CNOs/DONs have an integral role in the resolution of the M/A process. During this time of significant change, during which there may even be chaos, the CNOs work to maintain stability so there is as little impact as possible on patient outcomes, a core responsibility of the CNOs. The CNOs should focus on identifying and working with the highly skilled individuals in the organization to get to the recovery stage of the M/A process, at which time a high-performing organization is achieved. To build this new organization or IDS, the old organizations of the M/A must be changed (Moss Kanter, 1994). The successful CNOs will manage the trade-offs and will become experts in collaboration. The CNO's goals are to maximize the quality of patient care, the professional satisfaction of the nurse, and the goals of achieving cost effectiveness for the system (Clifford, 1998), and keeping this focus through the M/A process will yield success.

  7. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry PMID:23852646

  8. Chitosan-based delivery systems for diclofenac delivery: preparation and characterization

    NASA Astrophysics Data System (ADS)

    Dreve, Simina; Kacso, Irina; Bratu, Ioan; Indrea, Emil

    2009-08-01

    The preparation and characterization of novel materials for drug delivery has rapidly gained importance in development of innovative medicine. The paper concerns the uses of chitosan as an excipient in oral formulations and as a drug delivery vehicle for burnt painful injuries. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare liquid release systems as hydrogels and solid release systems as sponges is presented. In this paper the preparation of CTS hydrogels and sponges carrying diclofenac (DCF), as anti-inflammatory drug is reported. The immobilization of DCF in CTS is done by mixing the CTS hydrogel with the anti-inflammatory drug solutions. The concentration of anti-inflammatory drug in the CTS hydrogel generating the sponges was of 57 mg/l, 72 mg/l and 114 mg/l. The CTS sponges with anti-inflammatory drugs were prepared by freeze-drying at -610°C and 0,09 atm. The characterization of the hydrogels and sponges was done by infrared spectra (FTIR) and ultraviolet-visible spectroscopy (UV-VIS). The results indicated the formation of CTS-DCF intermediates. The DCF molecules are forming temporary chelates in CTS hydrogels and sponges and they are compatible with skin or some of biological fluids with satisfactory results.

  9. Preparation of Two Types of Polymeric Micelles Based on Poly(β-L-Malic Acid) for Antitumor Drug Delivery.

    PubMed

    Yang, Tiehong; Li, Wei; Duan, Xiao; Zhu, Lin; Fan, Li; Qiao, Youbei; Wu, Hong

    2016-01-01

    Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. In this work, two types of CPT-conjugated polymers were synthesized based on poly(β-L-malic acid) (PMLA) derivatives. Folic acid (FA) was introduced into the polymers as tumor targeting group. The micellization behaviors of these polymers and antitumor activity of different self-assembled micelles were investigated. Results indicate that poly(ethylene glycol)-poly(β-L-malic acid)-campotothecin-I (PEG-PMLA-CPT-I, P1) is a grafted copolymer, and could form star micelles in aqueous solution with a diameter of about 97 nm, also that PEG-PMLA-CPT-II (P2) is an amphiphilic block copolymer, and could form crew cut micelles with a diameter of about 76 nm. Both P1 and P2 micelles could improve the cellular uptake of CPT, especially the FA-modified micelles, while P2 micelles showed higher stability, higher drug loading efficiency, smaller size, and slower drug release rate than that of P1 micelles. These results suggested that the P2 (crew cut) micelles possess better stability than that of the P1 (star) micelles and might be a potential drug delivery system for cancer therapy.

  10. Preparation of Two Types of Polymeric Micelles Based on Poly(β-L-Malic Acid) for Antitumor Drug Delivery

    PubMed Central

    Duan, Xiao; Zhu, Lin; Fan, Li; Qiao, Youbei; Wu, Hong

    2016-01-01

    Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. In this work, two types of CPT-conjugated polymers were synthesized based on poly(β-L-malic acid) (PMLA) derivatives. Folic acid (FA) was introduced into the polymers as tumor targeting group. The micellization behaviors of these polymers and antitumor activity of different self-assembled micelles were investigated. Results indicate that poly(ethylene glycol)-poly(β-L-malic acid)-campotothecin-I (PEG-PMLA-CPT-I, P1) is a grafted copolymer, and could form star micelles in aqueous solution with a diameter of about 97 nm, also that PEG-PMLA-CPT-II (P2) is an amphiphilic block copolymer, and could form crew cut micelles with a diameter of about 76 nm. Both P1 and P2 micelles could improve the cellular uptake of CPT, especially the FA-modified micelles, while P2 micelles showed higher stability, higher drug loading efficiency, smaller size, and slower drug release rate than that of P1 micelles. These results suggested that the P2 (crew cut) micelles possess better stability than that of the P1 (star) micelles and might be a potential drug delivery system for cancer therapy. PMID:27649562

  11. Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel.

    PubMed

    Li, Jing; Huo, Meirong; Wang, Jing; Zhou, Jianping; Mohammad, Jumah M; Zhang, Yinlong; Zhu, Qinnv; Waddad, Ayman Y; Zhang, Qiang

    2012-03-01

    A targeted intracellular delivery system of paclitaxel (PTX) was successfully developed based on redox-sensitive hyaluronic acid-deoxycholic acid (HA-ss-DOCA) conjugates. The conjugates self-assembled into nano-size micelles in aqueous media and exhibited excellent drug-loading capacities (34.1%) and entrapment efficiency (93.2%) for PTX. HA-ss-DOCA micelles were sufficiently stable at simulated normal physiologic condition but fast disassembled in the presence of 20 mm reducing agent, glutathione. In vitro drug release studies showed that the PTX-loaded HA-ss-DOCA micelles accomplished rapid drug release under reducing condition. Intracellular release of fluorescent probe nile red indicated that HA-ss-DOCA micelles provide an effective approach for rapid transport of cargo into the cytoplasm. Enhanced cytotoxicity of PTX-loaded HA-ss-DOCA micelles further confirmed that the sensitive micelles are more potent for intracellular drug delivery as compared to the insensitive control. Based on flow cytometry and confocal microscopic analyses, observations revealed that HA-ss-DOCA micelles were taken up to human breast adenocarcinoma cells (MDA-MB-231) via HA-receptor mediated endocytosis. In vivo investigation of micelles in tumor-bearing mice confirmed that HA-ss-DOCA micelles possessed much higher tumor targeting capacity than the insensitive control. These results suggest that redox-sensitive HA-ss-DOCA micelles hold great potential as targeted intracellular delivery carriers of lipophilic anticancer drugs.

  12. Chronopharmaceutical Drug Delivery Systems: Hurdles, Hype or Hope?⊗

    PubMed Central

    Youan, Bi-Botti C.

    2010-01-01

    The current advances in chronobiology and the knowledge gained from chronotherapy of selected diseases strongly suggest that “the one size fits all at all times” approach to drug delivery is no longer substantiated, at least for selected bioactive agents and disease therapy or prevention. Thus, there is a critical and urgent need for chronopharmaceutical research (e.g., design and evaluation of robust, spatially and temporally controlled drug delivery systems that would be clinically intended for chronotherapy by different routes of administration). This review provides a brief overview of current delivery system intended for chronotherapy. In theory, such an ideal “magic pill” preferably with affordable cost, would improve the safety, efficacy and patient compliance of old and new drugs. However, currently, there are three major hurdles for the successful transition of such system from laboratory to patient bedside. These include the challenges to identify adequate (i) rhythmic biomaterials and systems, (ii) rhythm engineering modeling, perhaps using system biology and (iii) regulatory guidance. PMID:20438781

  13. Nanoscale drug delivery systems and the blood–brain barrier

    PubMed Central

    Alyautdin, Renad; Khalin, Igor; Nafeeza, Mohd Ismail; Haron, Muhammad Huzaimi; Kuznetsov, Dmitry

    2014-01-01

    The protective properties of the blood–brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain’s vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual’s age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS. PMID:24550672

  14. Porous hyaluronic acid hydrogels for localized nonviral DNA delivery in a diabetic wound healing model.

    PubMed

    Tokatlian, Talar; Cam, Cynthia; Segura, Tatiana

    2015-05-01

    The treatment of impaired wounds requires the use of biomaterials that can provide mechanical and biological queues to the surrounding environment to promote angiogenesis, granulation tissue formation, and wound closure. Porous hydrogels show promotion of angiogenesis, even in the absence of proangiogenic factors. It is hypothesized that the added delivery of nonviral DNA encoding for proangiogenic growth factors can further enhance this effect. Here, 100 and 60 μm porous and nonporous (n-pore) hyaluronic acid-MMP hydrogels with encapsulated reporter (pGFPluc) or proangiogenic (pVEGF) plasmids are used to investigate scaffold-mediated gene delivery for local gene therapy in a diabetic wound healing mouse model. Porous hydrogels allow for significantly faster wound closure compared with n-pore hydrogels, which do not degrade and essentially provide a mechanical barrier to closure. Interestingly, the delivery of pDNA/PEI polyplexes positively promotes granulation tissue formation even when the DNA does not encode for an angiogenic protein. And although transfected cells are present throughout the granulation tissue surrounding, all hydrogels at 2 weeks, pVEGF delivery does not further enhance the angiogenic response. Despite this, the presence of transfected cells shows promise for the use of polyplex-loaded porous hydrogels for local gene delivery in the treatment of diabetic wounds.

  15. Food Delivery System with the Utilization of Vehicle Using Geographical Information System (GIS) and A Star Algorithm

    NASA Astrophysics Data System (ADS)

    Siregar, B.; Gunawan, D.; Andayani, U.; Sari Lubis, Elita; Fahmi, F.

    2017-01-01

    Food delivery system is one kind of geographical information systems (GIS) that can be applied through digitation process. The main case in food delivery system is the way to determine the shortest path and food delivery vehicle movement tracking. Therefore, to make sure that the digitation process of food delivery system can be applied efficiently, it is needed to add shortest path determination facility and food delivery vehicle tracking. This research uses A Star (A*) algorithm for determining shortest path and location-based system (LBS) programming for moving food delivery vehicle object tracking. According to this research, it is generated the integrated system that can be used by food delivery driver, customer, and administrator in terms of simplifying the food delivery system. Through the application of shortest path and the tracking of moving vehicle, thus the application of food delivery system in the scope of geographical information system (GIS) can be executed.

  16. Synthesis and physicochemical characterization of a novel amphiphilic polylactic acid-hyperbranched polyglycerol conjugate for protein delivery.

    PubMed

    Gao, Xiujun; Zhang, Xinge; Wu, Zhongming; Zhang, Xuejiao; Wang, Zhen; Li, Chaoxing

    2009-12-03

    Amphiphilic copolymers with polylactic acid (PLA) chains grafted onto hyperbranched polyglycerol (HPG) have been synthesized and characterized. The copolymer nanoparticles with corona and core structure were formed by self-assembly in aqueous solution. The loading capacity and association efficiency were up to 23% and 86%, respectively. Protein release profiles with different copolymer compositions and BSA concentrations all showed a burst effect followed by a continuous release phase. The released BSA from the copolymer nanoparticles remained in its original structure over a period of 4 days, as testified by circular dichroism spectroscopy. Furthermore, cell viability research suggested good biocompatibility of the copolymer nanoparticles, which have a promising potential for protein delivery system.

  17. Porous tube plant nutrient delivery system development: A device for nutrient delivery in microgravity

    NASA Technical Reports Server (NTRS)

    Dreschel, T. W.; Brown, C. S.; Piastuch, W. C.; Hinkle, C. R.; Knott, W. M.

    1994-01-01

    The Porous Tube Plant Nutrient Delivery Systems or PTPNDS (U.S. Patent #4,926,585) has been under development for the past six years with the goal of providing a means for culturing plants in microgravity, specifically providing water and nutrients to the roots. Direct applications of the PTPNDS include plant space biology investigations on the Space Shuttle and plant research for life support in the Space Station Freedom. In the past, we investigated various configurations, the suitability of different porous materials, and the effects of pressure and pore size on plant growth. Current work is focused on characterizing the physical operation of the system, examining the effects of solution aeration, and developing prototype configurations for the Plant Growth Unit (PGU), the flight system for the Shuttle mid-deck. Future developments will involve testing on KC-135 parabolic flights, the design of flight hardware and testing aboard the Space Shuttle.

  18. Clinical and Community Delivery Systems for Preventive Care

    PubMed Central

    Krist, Alex H.; Shenson, Douglas; Woolf, Steven H.; Bradley, Cathy; Liaw, Winston R.; Rothemich, Stephen F.; Slonim, Amy; Benson, William; Anderson, Lynda A.

    2015-01-01

    Although clinical preventive services (CPS)—screening tests, immunizations, health behavior counseling, and preventive medications—can save lives, Americans receive only half of recommended services. This "prevention gap," if closed, could substantially reduce morbidity and mortality. Opportunities to improve delivery of CPS exist in both clinical and community settings, but these activities are rarely coordinated across these settings, resulting in inefficiencies and attenuated benefits. Through a literature review, semi-structured interviews with 50 national experts, field observations of 53 successful programs, and a national stakeholder meeting, a framework to fully integrate CPS delivery across clinical and community care delivery systems was developed. The framework identifies the necessary participants, their role in care delivery, and the infrastructure, support, and policies necessary to ensure success. Essential stakeholders in integration include clinicians; community members and organizations; spanning personnel and infrastructure; national, state, and local leadership; and funders and purchasers. Spanning personnel and infrastructure are essential to bring clinicians and communities together and to help patients navigate across care settings. The specifics of clinical–community integrations vary depending on the services addressed and the local context. Although broad establishment of effective clinical–community integrations will require substantial changes, existing clinical and community models provide an important starting point. The key policies and elements of the framework are often already in place or easily identified. The larger challenge is for stakeholders to recognize how integration serves their mutual interests and how it can be financed and sustained over time. PMID:24050428

  19. Use of liposomes as injectable-drug delivery systems.

    PubMed

    Ostro, M J; Cullis, P R

    1989-08-01

    The formation of liposomes and their application as delivery systems for injectable drugs are described. Liposomes are microscopic vesicles composed of one or more lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid-soluble drugs within the membrane itself. Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis, lipid exchange, or fusion. Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes. Liposomes also accumulate preferentially at the sites of inflammation and infection and in some solid tumors; however, the reason for this accumulation is not clear. Four major factors influence liposomes' in vivo behavior and biodistribution: (1) liposomes tend to leak if cholesterol is not included in the vesicle membrane, (2) small liposomes are cleared more slowly than large liposomes, (3) the half-life of a liposome increases as the lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of liposome-based therapy is in the treatment of systemic fungal infections, especially with amphotericin B. Liposomes are also under investigation for treatment of neoplastic disorders. Liposomes' uses in cancer therapy include encapsulation of known antineoplastic agents such as doxorubicin and methotrexate, delivery of immune modulators such as N-acetylmuramyl-L-alanine-D-isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into lipid bilayers. Liposomal formulations of injectable antimicrobial agents and antineoplastic agents already are undergoing clinical testing, and most probably will receive

  20. Nanoengineered drug delivery systems for enhancing antibiotic therapy.

    PubMed

    Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

    2015-03-01

    Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections.

  1. The Delivery System of Environmental Education at the Tertiary Level in the Asia-Pacific Region.

    ERIC Educational Resources Information Center

    Sato, Masahisa; Bhandari, Bishnu; Abe, Osamu

    2001-01-01

    Analyzes the delivery system of environmental education at the tertiary level in relation to higher education attendance rate. Describes the characteristics of the delivery system in countries such as China, India, Australia, Japan, South Korea, and Indonesia. (Author/MM)

  2. Receptor-Mediated Drug Delivery Systems Targeting to Glioma

    PubMed Central

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

    2015-01-01

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

  3. Systemic delivery of recombinant proteins by genetically modified myoblasts

    SciTech Connect

    Barr, E.; Leiden, J.M. )

    1991-12-06

    The ability to stably deliver recombinant proteins to the systemic circulation would facilitate the treatment of a variety of acquired and inherited diseases. To explore the feasibility of the use of genetically engineered myoblasts as a recombinant protein delivery system, stable transfectants of the murine C2C12 myoblast cell line were produced that synthesize and secrete high levels of human growth hormone (hGH) in vitro. Mice injected with hGH-transfected myoblasts had significant levels of hGH in both muscle and serum that were stable for at least 3 weeks after injection. Histological examination of muscles injected with {beta}-galactosidase-expressing C2C12 myoblasts demonstrated that many of the injected cells had fused to form multinucleated myotubes. Thus, genetically engineered myoblasts can be used for the stable delivery of recombinant proteins into the circulation.

  4. Inhaled formulations and pulmonary drug delivery systems for respiratory infections.

    PubMed

    Zhou, Qi Tony; Leung, Sharon Shui Yee; Tang, Patricia; Parumasivam, Thaigarajan; Loh, Zhi Hui; Chan, Hak-Kim

    2015-05-01

    Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'.

  5. Intelligent system design for bionanorobots in drug delivery.

    PubMed

    Fletcher, Mark; Biglarbegian, Mohammad; Neethirajan, Suresh

    A nanorobot is defined as any smart structure which is capable of actuation, sensing, manipulation, intelligence, and swarm behavior at the nanoscale. In this study, we designed an intelligent system using fuzzy logic for diagnosis and treatment of tumors inside the human body using bionanorobots. We utilize fuzzy logic and a combination of thermal, magnetic, optical, and chemical nanosensors to interpret the uncertainty associated with the sensory information. Two different fuzzy logic structures, for diagnosis (Mamdani structure) and for cure (Takagi-Sugeno structure), were developed to efficiently identify the tumors and treat them through delivery of effective dosages of a drug. Validation of the designed system with simulated conditions proved that the drug delivery of bionanorobots was robust to reasonable noise that may occur in the bionanorobot sensors during navigation, diagnosis, and curing of the cancer cells. Bionanorobots represent a great hope for successful cancer therapy in the near future.

  6. Polyglutamic Acid-Gated Mesoporous Silica Nanoparticles for Enzyme-Controlled Drug Delivery.

    PubMed

    Tukappa, Asha; Ultimo, Amelia; de la Torre, Cristina; Pardo, Teresa; Sancenón, Félix; Martínez-Máñez, Ramón

    2016-08-23

    Mesoporous silica nanoparticles (MSNs) are highly attractive as supports in the design of controlled delivery systems that can act as containers for the encapsulation of therapeutic agents, overcoming common issues such as poor water solubility and poor stability of some drugs and also enhancing their bioavailability. In this context, we describe herein the development of polyglutamic acid (PGA)-capped MSNs that can selectively deliver rhodamine B and doxorubicin. PGA-capped MSNs remain closed in an aqueous environment, yet they are able to deliver the cargo in the presence of pronase because of the hydrolysis of the peptide bonds in PGA. The prepared solids released less than 20% of the cargo in 1 day in water, whereas they were able to reach 90% of the maximum release of the entrapped guest in ca. 5 h in the presence of pronase. Studies of the PGA-capped nanoparticles with SK-BR-3 breast cancer cells were also undertaken. Rhodamine-loaded nanoparticles were not toxic, whereas doxorubicin-loaded nanoparticles were able to efficiently kill more than 90% of the cancer cells at a concentration of 100 μg/mL.

  7. Feasibility Study: Ductless Hydronic Distribution Systems with Fan Coil Delivery

    SciTech Connect

    Springer, D.; Dakin, B.; Backman, C.

    2012-07-01

    The primary objectives of this study are to estimate potential energy savings relative to conventional ducted air distribution, and to identify equipment requirements, costs, and barriers with a focus on ductless hydronic delivery systems that utilize water-to-air terminal units in each zone. Results indicate that annual heating and cooling energy use can be reduced by up to 27% assuming replacement of the conventional 13 SEER heat pump and coil with a similarly rated air-to-water heat pump.

  8. Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems

    PubMed Central

    2016-01-01

    Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases. PMID:27867663

  9. Amphiphilic poly(L-amino acids) - new materials for drug delivery.

    PubMed

    Lalatsa, Aikaterini; Schätzlein, Andreas G; Mazza, Mariarosa; Le, Thi Bich Hang; Uchegbu, Ijeoma F

    2012-07-20

    The formulation of drug compounds into medicines will increasingly rely on the use of specially tailored molecules, which fundamentally alter the drug's pharmacokinetics to enable its therapeutic activity. This is particularly true of the more challenging hydrophobic drugs or therapeutic biological molecules. The demand for such enabled medicines will translate into a demand for advanced highly functionalised drug delivery materials. Polymers have been used to formulate medicines for many decades and this is unlikely to change soon. Amphiphilic polymers based on amino acids are the subject of this review. These molecules, which present as either poly(L-amino acid) block copolymers or poly(L-amino acid) backbones with hydrophobic substituents, self assemble into micelles, vesicles, nanofibres and solid nanoparticles and such self assemblies, have drug delivery capabilities. The nature of the self-assembly depends on the chemistry of the constituent molecules, with the more hydrophilic molecules forming nanosized micellar aggregates including peptide nanofibres, molecules of intermediate hydrophobicity forming polymeric vesicles and the more hydrophobic variants forming amorphous polymeric nanoparticles of 100-1000 nm in diameter. The self-assemblies may be loaded with drugs or may present as micelle forming polymer-drug conjugates and the supramolecular aggregates have been employed as drug solubilisers, tumour targeting agents, gene delivery vectors and facilitators of intracellular drug uptake, with a more promising polymer-drug conjugate progressing to clinical testing.

  10. Novel targeted bladder drug-delivery systems: a review

    PubMed Central

    Zacchè, Martino Maria; Srikrishna, Sushma; Cardozo, Linda

    2015-01-01

    The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy. PMID:26649286

  11. Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System

    PubMed Central

    Ouyang, Mengxing; Hill, Winfield; Lee, Jung Hyun; Hur, Soojung Claire

    2017-01-01

    Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages. PMID:28317836

  12. Novel targeted bladder drug-delivery systems: a review.

    PubMed

    Zacchè, Martino Maria; Srikrishna, Sushma; Cardozo, Linda

    2015-01-01

    The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy.

  13. Leishmaniasis: focus on the design of nanoparticulate vaccine delivery systems.

    PubMed

    Doroud, Delaram; Rafati, Sima

    2012-01-01

    Although mass vaccination of the entire population of an endemic area would be the most cost-effective tool to diminish Leishmania burden, an effective vaccine is not yet commercially available. Practically, vaccines have failed to achieve the required level of protection, possibly owing to the lack of an appropriate adjuvant and/or delivery system. Therefore, there is still an imperative demand for an improved, safe and efficient delivery system to enhance the immunogenicity of available vaccine candidates. Nanoparticles are proficient in boosting the quality and magnitude of immune responses in a predictable fashion. Herein, we discuss how nanoparticulate vaccine delivery systems can be used to induce appropriate immune responses against leishmaniasis by controlling physicochemical properties of the vaccine. Stability, production reproducibility, low cost per dose and low risk-benefit ratios are desirable characteristics of an ideal vaccine formulation and solid lipid nanoparticles may serve as one of the most promising practical strategies to help to achieve such a leishmanial vaccine, at least in canine species in the developing world.

  14. Peptide/protein vaccine delivery system based on PLGA particles

    PubMed Central

    Allahyari, Mojgan; Mohit, Elham

    2016-01-01

    abstract Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

  15. Efficient siRNA delivery system using carboxilated single-wall carbon nanotubes in cancer treatment.

    PubMed

    Neagoe, Ioana Berindan; Braicu, Cornelia; Matea, Cristian; Bele, Constantin; Florin, Graur; Gabriel, Katona; Veronica, Chedea; Irimie, Alexandru

    2012-08-01

    Several functionalized carbon nanotubes have been designed and tested for the purpose of nucleic acid delivery. In this study, the capacity of SWNTC-COOH for siRNA deliverey were investigated delivery in parallel with an efficient commercial system. Hep2G cells were reverse-transfected with 50 nM siRNA (p53 siRNA, TNF-alphasiRNA, VEGFsiRNA) using the siPORT NeoFX (Ambion) transfection agent in paralel with SWNTC-COOH, functionalised with siRNA. The highest level of gene inhibition was observed in the cases treated with p53 siRNA gene; in the case of transfection with siPort, the NeoFX value was 33.8%, while in the case of SWNTC-COOH as delivery system for p53 siRNA was 37.5%. The gene silencing capacity for VEGF was 53.7%, respectively for TNF-alpha 56.7% for siPORT NeoFX delivery systems versus 47.7% (VEGF) and 46.5% (TNF-alpha) for SWNTC-COOH delivery system. SWNTC-COOH we have been showed to have to be an efficient carrier system. The results from the inhibition of gene expresion for both transfection systems were confirmed at protein level. Overall, the lowest mRNA expression was confirmed at protein level, especially in the case of p53 siRNA and TNF-alpha siRNA transfection. Less efficient reduction protein expressions were observed in the case of VEGF siRNA, for both transfection systems at 24 h; only at 48 h, there was a statistically significant reduction of VEGF protein expression. SWCNT-COOH determined an efficient delivery of siRNA. SWNTC-COOH, combined with suitable tumor markers like p53 siRNA, TNFalpha siRNA or VEGF siRNA can be used for the efficient delivery of siRNA.

  16. Overview on gastroretentive drug delivery systems for improving drug bioavailability.

    PubMed

    Lopes, Carla M; Bettencourt, Catarina; Rossi, Alessandra; Buttini, Francesca; Barata, Pedro

    2016-08-20

    In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems.

  17. Intrauterine levonorgestrel delivery with frameless fibrous delivery system: review of clinical experience

    PubMed Central

    Wildemeersch, Dirk; Andrade, Amaury; Goldstuck, Norman D; Hasskamp, Thomas; Jackers, Geert

    2017-01-01

    The concept of using a frameless intrauterine device (IUD) instead of the conventional plastic framed IUD is not new. Frameless copper IUDs have been available since the late 1990s. They rely on an anchoring system to retain in the uterine cavity. The clinical experience with these IUDs suggests that frameless IUDs fit better as they are thin and, therefore, do not disturb or irritate the uterus. High tolerance and continuation rates have been achieved as complaints of pain are virtually nonexistent and the impact on menstrual blood loss is minimal. Conventional levonorgestrel-releasing intrauterine systems (LNG-IUSs) are very popular as they significantly reduce menstrual bleeding and provide highly effective contraception. However, continuation of use remains problematic, particularly in young users. Total or partial expulsion and displacement of the LNG-IUS also occur too often due to spatial incompatibility within a small uterine cavity, as strong uterine contractions originate, attempting to get rid of the bothersome IUD/IUS. If not expelled, embedment ensues, often leading to chronic pain and early removal of the IUD/IUS. Several studies conducted recently have requested attention to the relationship between the LNG-IUS and the endometrial cavity. Some authors have proposed to measure the cavity width prior to inserting an IUD, as many uterine cavities are much smaller than the currently existing LNG-IUSs. A frameless fibrous drug delivery system fits, in principle, in all uterine cavities and may therefore be preferable to framed drug delivery systems. This review examines the clinical performance, acceptability, and potential of the frameless LNG-IUS (FibroPlant®) when used for contraception, treatment of heavy menstrual bleeding, dysmenorrhea, and endometrial suppression in women using estrogen replacement therapy, endometrial hyperplasia, and other gynecological conditions. The review concludes that FibroPlant LNG-IUS offers unique advantages in reducing

  18. Potential for layered double hydroxides-based, innovative drug delivery systems.

    PubMed

    Zhang, Kai; Xu, Zhi Ping; Lu, Ji; Tang, Zhi Yong; Zhao, Hui Jun; Good, David A; Wei, Ming Qian

    2014-04-29

    Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications.

  19. Potential for Layered Double Hydroxides-Based, Innovative Drug Delivery Systems

    PubMed Central

    Zhang, Kai; Xu, Zhi Ping; Lu, Ji; Tang, Zhi Yong; Zhao, Hui Jun; Good, David A.; Wei, Ming Qian

    2014-01-01

    Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications. PMID:24786098

  20. Targeted multidrug delivery system to overcome chemoresistance in breast cancer

    PubMed Central

    Tang, Yuan; Soroush, Fariborz; Tong, Zhaohui; Kiani, Mohammad F; Wang, Bin

    2017-01-01

    Chemotherapy has been widely used in breast cancer patients to reduce tumor size. However, most anticancer agents cannot differentiate between cancerous and normal cells, resulting in severe systemic toxicity. In addition, acquired drug resistance during the chemotherapy treatment further decreases treatment efficacy. With the proper treatment strategy, nanodrug carriers, such as liposomes/immunoliposomes, may be able to reduce undesired side effects of chemotherapy, to overcome the acquired multidrug resistance, and to further improve the treatment efficacy. In this study, a novel combinational targeted drug delivery system was developed by encapsulating antiangiogenesis drug bevacizumab into liposomes and encapsulating chemotherapy drug doxorubicin (DOX) into immunoliposomes where the human epidermal growth factor receptor 2 (HER2) antibody was used as a targeting ligand. This novel combinational system was tested in vitro using a HER2 positive and multidrug resistant breast cancer cell line (BT-474/MDR), and in vivo using a xenograft mouse tumor model. In vitro cell culture experiments show that immunoliposome delivery led to a high cell nucleus accumulation of DOX, whereas free DOX was observed mostly near the cell membrane and in cytoplasm due to the action of P-gp. Combining liposomal bevacizumab with immunoliposomal DOX achieved the best tumor growth inhibition and the lowest toxicity. Tumor size decreased steadily within a 60-day observation period indicating a potential synergistic effect between DOX and bevacizumab through the targeted delivery. Our findings clearly indicate that tumor growth was significantly delayed in the combinational liposomal drug delivery group. This novel combinational therapy has great potential for the treatment of patients with HER2/MDR double positive breast cancer. PMID:28176940

  1. MDCK cell permeability characteristics of a sulfenamide prodrug: strategic implications in considering sulfenamide prodrugs for oral delivery of NH-acids.

    PubMed

    Guarino, Victor R; Nti-Addae, Kwame; Stella, Valentino J

    2011-01-01

    The objective of this Letter is both to report the permeability results of a linezolid-based sulfenamide prodrug in an MDCK cell model (enterocyte surrogate system) and to discuss the strategic implications of these results for considering sulfenamide prodrugs to enhance the oral delivery of weakly acidic NH-acids (e.g., amides, ureas, etc.). The two main findings from this study are that the sulfenamide prodrug does not appear to survive intracellular transport due to conversion to linezolid and that there appears to be an apically-oriented surface conversion pathway that can additionally serve to convert the sulfenamide prodrug to linezolid upon approach of the apical membrane. It is hoped that these findings, along with the discussion of the strategic implications, will facilitate a greater awareness of the potential strengths and weaknesses inherent in the sulfenamide prodrug approach for enhancing the oral delivery of weakly acidic NH-acid drugs.

  2. Cross-linked, biodegradable, cytocompatible salicylic acid based polyesters for localized, sustained delivery of salicylic acid: an in vitro study.

    PubMed

    Chandorkar, Yashoda; Bhagat, Rajesh K; Madras, Giridhar; Basu, Bikramjit

    2014-03-10

    In order to suppress chronic inflammation while supporting cell proliferation, there has been a continuous surge toward development of polymers with the intention of delivering anti-inflammatory molecules in a sustained manner. In the above backdrop, we report the synthesis of a novel, stable, cross-linked polyester with salicylic acid (SA) incorporated in the polymeric backbone and propose a simple synthesis route by melt condensation. The as-synthesized polymer was hydrophobic with a glass transition temperature of 1 °C, which increases to 17 °C upon curing. The combination of NMR and FT-IR spectral techniques established the ester linkages in the as-synthesized SA-based polyester. The pH-dependent degradation rate and the rate of release of salicylic acid from the as-synthesized SA-based polymer were studied at physiological conditions in vitro. The polyester underwent surface erosion and exhibited linear degradation kinetics in which a change in degradation rate is observed after 4-10 days and 24% mass loss was recorded after 4 months at 37 °C and pH 7.4. The delivery of salicylic acid also showed a similar change in slopes, with a sustained release rate of 3.5% in 4 months. The cytocompatibility studies of these polyesters were carried out with C2C12 murine myoblast cells using techniques like MTT assay and flow cytometry. Our results strongly suggest that SA-based polyester supports cell proliferation for 3 days in culture and do not cause cell death (<7%), as quantified by propidium iodide (PI) stained cells. Hence, these polyesters can be used as implant materials for localized, sustained delivery of salicylic acid and have applications in adjuvant cancer therapy, chronic wound healing, and as an alternative to commercially available polymers like poly(lactic acid) and poly(glycolic acid) or their copolymers.

  3. Ex vivo investigation of magnetically targeted drug delivery system

    NASA Astrophysics Data System (ADS)

    Yoshida, Y.; Fukui, S.; Fujimoto, S.; Mishima, F.; Takeda, S.; Izumi, Y.; Ohtani, S.; Fujitani, Y.; Nishijima, S.

    2007-03-01

    In conventional systemic drug delivery the drug is administered by intravenous injection; it then travels to the heart from where it is pumped to all regions of the body. When the drug is aimed at a small target region, this method is extremely inefficient and leads to require much larger doses than those being necessary. In order to overcome this problem a number of targeted drug delivery methods are developed. One of these, magnetically targeted drug delivery system (MT-DDS) will be a promising way, which involves binding a drug to small biocompatible magnetic particles, injecting these into the blood stream and using a high gradient magnetic field to pull them out of suspension in the target region. In the present paper, we describe an ex vivo experimental work. It is also reported that navigation and accumulation test of the magnetic particles in the Y-shaped glass tube was performed in order to examine the threshold of the magnetic force for accumulation. It is found that accumulation of the magnetic particles was succeeded in the blood vessel when a permanent magnet was placed at the vicinity of the blood vessel. This result indicates the feasibility of the magnetically drug targeting in the blood vessel.

  4. 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

  5. New targets and delivery systems for antifungal therapy.

    PubMed

    Walsh, T J; Viviani, M A; Arathoon, E; Chiou, C; Ghannoum, M; Groll, A H; Odds, F C

    2000-01-01

    Development of new approaches for treatment of invasive fungal infections encompasses new delivery systems for approved and investigational compounds, as well as exploiting the cell membrane, cell wall and virulence factors as putative antifungal targets. Novel delivery systems consisting of cyclodextrins, cochleates, nanoparticles/nanospheres and long circulating ('stealth') liposomes, substantially modulate the pharmacokinetics of existing compounds, and may also be useful to enhance the delivery of antifungal agents to sites of infection. Further insights into the structure-activity relationship of the antifungal triazoles that target the biosynthesis of ergosterol in the fungal cell membrane have led to the development of highly potent broad spectrum agents, including posaconazole, ravuconazole and voriconazole. Similarly, a novel generation of cell-wall active semisynthetic echinocandin 1,3 beta-glucan inhibitors (caspofungin, FK463, and VER-002) has entered clinical development. These agents have potent and broad-spectrum activity against Candida spp, and potentially useful activity against Aspergillus spp. and Pneumocystis carinii. The ongoing convergence of the fields of molecular pathogenesis, antifungal pharmacology and vaccine development will afford the opportunity to develop novel targets to complement the existing antifungal armamentarium.

  6. A 400G optical wireless integration delivery system.

    PubMed

    Li, Xinying; Yu, Jianjun; Zhang, Junwen; Dong, Ze; Li, Fan; Chi, Nan

    2013-08-12

    We experimentally demonstrate a record 400G optical wireless integration system simultaneously delivering 2 × 112 Gb/s two-channel polarization-division-multiplexing 16-ary quadrature amplitude modulation (PDM-16QAM) signal at 37.5 GHz wireless carrier and 2 × 108 Gb/s two-channel PDM quadrature phase shift keying (PDM-QPSK) signal at 100 GHz wireless carrier, adopting two millimeter-wave (mm-wave) frequency bands, two orthogonal antenna polarizations, multiple-input multiple-output (MIMO), photonic mm-wave generation and advanced digital signal processing (DSP). In the case of no fiber transmission, the bit error ratios (BERs) for both the 112 Gb/s PDM-16QAM signal after 1.5 m wireless delivery at 37.5 GHz and the 108 Gb/s PDM-QPSK signal after 0.7 m wireless delivery at 100 GHz are below the pre-forward-error-correction (pre-FEC) threshold of 3.8 × 10(-3). To our knowledge, this is the first demonstration of a 400G optical wireless integration system in mm-wave frequency bands and also a capacity record of wireless delivery.

  7. 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.

  8. Recent advances in pulsatile oral drug delivery systems.

    PubMed

    Politis, Stavros N; Rekkas, Dimitrios M

    2013-08-01

    It is well established that several diseases exhibit circadian behavior, following the relevant rhythm of the physiological functions of the human body. Their study falls in the fields of chronobiology and chronotherapeutics, the latter being essentially the effort of timely matching the treatment with the disease expression, in order to maximize the therapeutic benefits and minimize side effects. Pulsatile drug delivery is one of the pillars of chronopharmaceutics, achieved through dosage form design that allows programmable release of active pharmaceutical ingredients (APIs) to follow the disease's time profile. Its major characteristic is the presence of lag phases, followed by drug release in a variety of rates, immediate, repeated or controlled. The scope of this review is to summarize the recent literature on pulsatile oral drug delivery systems and provide an overview of the ready to use solutions and early stage technologies, focusing on the awarded and pending patents in this technical field during the last few years.

  9. Potential and problems in ultrasound-responsive drug delivery systems

    PubMed Central

    Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

    2013-01-01

    Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

  10. Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery

    PubMed Central

    Torchilin, Vladimir P.

    2015-01-01

    The use of nanoparticulate pharmaceutical drug delivery systems (NDDSs) to enhance the in vivo effectiveness of drugs is now well established. The development of multifunctional and stimulus-sensitive NDDSs is an active area of current research. Such NDDSs can have long circulation times, target the site of the disease and enhance the intracellular delivery of a drug. This type of NDDS can also respond to local stimuli that are characteristic of the pathological site by, for example, releasing an entrapped drug or shedding a protective coating, thus facilitating the interaction between drug-loaded nanocarriers and target cells or tissues. In addition, imaging contrast moieties can be attached to these carriers to track their real-time biodistribution and accumulation in target cells or tissues. Here, I highlight recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases. PMID:25287120

  11. Development of a Production Ready Automated Wire Delivery System

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The current development effort is a Phase 3 research study entitled "A Production Ready Automated Wire Delivery System", contract number NAS8-39933, awarded to Nichols Research Corporation (NRC). The goals of this research study were to production harden the existing Automated Wire Delivery (AWDS) motion and sensor hardware and test the modified AWDS in a range of welding applications. In addition, the prototype AWDS controller would be moved to the VME bus platform by designing, fabricating and testing a single board VME bus AWDS controller. This effort was to provide an AWDS that could transition from the laboratory environment to production operations. The project was performed in two development steps. Step 1 modified and tested an improved MWG. Step 2 developed and tested the AWDS single board VME bus controller. Step 3 installed the Wire Pilot in a Weld Controller with the imbedded VME bus controller.

  12. Use of microwave in processing of drug delivery systems.

    PubMed

    Wong, T W

    2008-04-01

    Microwave has received a widespread application in pharmaceuticals and food processing, microbial sterilization, biomedical therapy, scientific and biomedical analysis, as well as, drug synthesis. This paper reviews the basis of application of microwave to prepare pharmaceutical dosage forms such as agglomerates, gel beads, microspheres, nanomatrix, solid dispersion, tablets and film coat. The microwave could induce drying, polymeric crosslinkages as well as drug-polymer interaction, and modify the structure of drug crystallites via its effects of heating and/or electromagnetic field on the dosage forms. The use of microwave opens a new approach to control the physicochemical properties and drug delivery profiles of pharmaceutical dosage forms without the need for excessive heat, lengthy process or toxic reactants. Alternatively, the microwave can be utilized to process excipients prior to their use in the formulation of drug delivery systems. The intended release characteristics of drugs in dosage forms can be met through modifying the physicochemical properties of excipients using the microwave.

  13. Potential applications of boron nitride nanotubes as drug delivery systems.

    PubMed

    Ciofani, Gianni

    2010-08-01

    In recent years, there has been an explosion of research in the 'bio-nano' field, with the discovery and introduction of ever more fascinating materials for applications as drug delivery systems, sensors, transducers, and so on. The author's group, for the first time in the literature, proposed boron nitride nanotubes as a valid alternative to carbon nanotubes and other kinds of inorganic materials, because of their improved chemical properties that theoretically guarantee better stability and compatibility in a biological context. In this paper, the bio-applications of boron nitride nanotubes that have emerged in the literature are summarized, with special attention given to their exploitation as safe drug delivery and targeting carriers. Finally, the possibility of combining their physical and chemical properties is approached, highlighting the features that render these innovative nanovectors unique and exceptional candidates for many bio-applications.

  14. Optimized Delivery System Achieves Enhanced Endomyocardial Stem Cell Retention

    PubMed Central

    Behfar, Atta; Latere, Jean-Pierre; Bartunek, Jozef; Homsy, Christian; Daro, Dorothee; Crespo-Diaz, Ruben J.; Stalboerger, Paul G.; Steenwinckel, Valerie; Seron, Aymeric; Redfield, Margaret M.; Terzic, Andre

    2014-01-01

    Background Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention. Methods and Results Stem cell retention was simulated in silico using one and three-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol – a nickel and titanium alloy displaying shape memory and super-elasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared to a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle, without impact on biocompatibility or safety. Conclusions Modeling guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention. PMID:24326777

  15. A clinician-driven home care delivery system.

    PubMed

    August, D A; Faubion, W C; Ryan, M L; Haggerty, R H; Wesley, J R

    1993-12-01

    The financial, entrepreneurial, administrative, and legal forces acting within the home care arena make it difficult for clinicians to develop and operate home care initiatives within an academic setting. HomeMed is a clinician-initiated and -directed home care delivery system wholly owned by the University of Michigan. The advantages of a clinician-directed system include: Assurance that clinical and patient-based factors are the primary determinants of strategic and procedural decisions; Responsiveness of the system to clinician needs; Maintenance of an important role for the referring physician in home care; Economical clinical research by facilitation of protocol therapy in ambulatory and home settings; Reduction of lengths of hospital stays through clinician initiatives; Incorporation of outcome analysis and other research programs into the mission of the system; Clinician commitment to success of the system; and Clinician input on revenue use. Potential disadvantages of a clinician-based system include: Entrepreneurial, financial, and legal naivete; Disconnection from institutional administrative and data management resources; and Inadequate clinician interest and commitment. The University of Michigan HomeMed experience demonstrates a model of clinician-initiated and -directed home care delivery that has been innovative, profitable, and clinically excellent, has engendered broad physician, nurse, pharmacist, and social worker enthusiasm, and has supported individual investigator clinical protocols as well as broad outcomes research initiatives. It is concluded that a clinician-initiated and -directed home care program is feasible and effective, and in some settings may be optimal.

  16. [A novel anticancer drug delivery system -DAC-70/CDDP].

    PubMed

    Sugitachi, Akio; Otsuka, Koki; Fujisawa, Kentaro; Itabashi, Tetsuya; Akiyama, Yuji; Sasaki, Akira; Ikeda, Kenichiro; Yoshida, Yasuo; Takamori, Yoshimori; Kurozumi, Seiji; Mori, Takatoshi; Wakabayashi, Go

    2007-11-01

    We devised a muco-adhesive anticancer drug delivery system using 70% deacetylated chitin (DAC-70) and cisplatin (CDDP) and 5-fluorouracil (5-FU). The adhesive force between the system and human colonic mucosa was measured ex vivo, and a release profile of each drug was examined in vitro. Each system demonstrated a stronger muco-adhesive force at 37 degrees C than that of 25 degrees C. The CDDP-loaded system showed a sustained release of the drug while the 5-FU-loaded system exhibited an initial bursting of the agent. We presume that the release profile of CDDP and 5-FU is closely related to both degradability of the chitin and interactions between the chitin and each drug. The DAC-70/CDDP system would be clinically promising in loco-regional cancer chemotherapy.

  17. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

    PubMed Central

    Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

    2017-01-01

    Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. PMID:28243062

  18. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

    PubMed

    Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

    2017-01-01

    Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

  19. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems.

    PubMed

    Kaur, Randeep; Badea, Ildiko

    2013-01-01

    Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.

  20. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems

    PubMed Central

    Kaur, Randeep; Badea, Ildiko

    2013-01-01

    Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans. PMID:23326195

  1. Cationic liposome–nucleic acid complexes for gene delivery and gene silencing

    PubMed Central

    Ewert, Kai K.; Majzoub, Ramsey N.; Leal, Cecília

    2014-01-01

    Cationic liposomes (CLs) are studied worldwide as carriers of DNA and short interfering RNA (siRNA) for gene delivery and gene silencing, and related clinical trials are ongoing. Optimization of transfection efficiency and silencing efficiency by cationic liposome carriers requires a comprehensive understanding of the structures of CL–nucleic acid complexes and the nature of their interactions with cell membranes as well as events leading to release of active nucleic acids within the cytoplasm. Synchrotron x-ray scattering has revealed that CL–nucleic acid complexes spontaneously assemble into distinct liquid crystalline phases including the lamellar, inverse hexagonal, hexagonal, and gyroid cubic phases, and fluorescence microscopy has revealed CL–DNA pathways and interactions with cells. The combining of custom synthesis with characterization techniques and gene expression and silencing assays has begun to unveil structure–function relations in vitro. As a recent example, this review will briefly describe experiments with surface-functionalized PEGylated CL–DNA nanoparticles. The functionalization, which is achieved through custom synthesis, is intended to address and overcome cell targeting and endosomal escape barriers to nucleic acid delivery faced by PEGylated nanoparticles designed for in vivo applications. PMID:25587216

  2. Oleoylethanolamide-based lyotropic liquid crystals as vehicles for delivery of amino acids in aqueous environment.

    PubMed

    Mohammady, Sayed Z; Pouzot, Matthieu; Mezzenga, Raffaele

    2009-02-18

    We have investigated the phase behavior of self-assembled lyotropic liquid crystals (LC) formed by ternary mixtures of oleoylethanolamide (OEA), water and arginine. OEA, a natural analog of the endogenous cannabinoid anandamide involved in the peripheral regulation of feeding, was selected as a main component due to its capacity to induce efficient decreases in food intake and gains in body mass. Arginine was selected as representative hydrophilic amino acid and added to the OEA-water mixture at different concentrations. The phase diagrams were determined by combining cross-polarized optical microscopy and small angle x-ray scattering. First, the phase diagram for the OEA-water system was determined. It was shown that these two compounds give rise to reverse Ia3d double gyroid and reverse Pn3m double diamond cubic phases existing in bulk over a large window of temperature and composition, and that for water content beyond 25% Pn3m coexisted with excess water. Successively, the influence of arginine as guest molecule in the water channels of the reverse LC was investigated. For the sake of comparison, results for the OEA-water-arginine system were compared with analog series of OEA-water-glucose. The results showed that, at a fixed water content and temperature, the phase behavior of the liquid crystalline phases is strongly dependent on arginine concentration. In more detail, arginine could be encapsulated in the bulk OEA-water LC up to 2.0% wt, whereas transitions from Ia3d to Pn3m cubic phase were observed with increasing arginine concentration. Interestingly, upon an increase of water concentration beyond 20-25%, Pn3m phase started to coexist with excess water releasing the arginine in external water solution. Quantitative measurements of arginine content inside the LC water channels and in the excess external water solution revealed a complete release of the amino acid, demonstrating that the investigated lyotropic liquid crystalline systems can be used as

  3. Single-walled carbon nanotube and graphene: Nano-delivery of Gambogic acid increases its cytotoxicty in various cancer cells

    NASA Astrophysics Data System (ADS)

    Saeed, Lamya M.

    Nanomedicine is a new branch of medicine that has been developed due to the critical need to treat challenging diseases, especially cancer since it remains a significant cause of morbidity and mortality worldwide and the second most common cause of death after heart disease in the USA. One of the most important health care applications of nanomedicine concerns the development of drug delivery systems. Graphene (Gn), an atom-thick carbon monolayer of sp2- bonded carbon atoms arranged in a two dimensional (2D) honeycomb crystal lattice, and single-walled carbon nanotubes (SWCNTs) (1D, tubular) are among the most promising nanomaterials with the capability of delivering drugs or small therapeutic molecules to cancerous cells. For example, they have been used as vehicles for the anti-cancer, low-toxicity drug Gambogic acid (GA). Here, the cytotoxicity of GA in breast (MCF-7), pancreatic (PANC-1), cervical (HELA), ovarian (NCI/ADR), and prostate (PC3) cancer cells was assessed to determine what effect nanodelivery by either Gn or SWCNTs had on the efficacy of this promising drug. The nanomaterials showed no toxicity at the concentrations used. The inhibition of cell proliferation and apoptosis of the cells was due to the effects of GA which was significantly enhanced by nanodelivery. Such delivery of GA by either Gn or SWCNTs represents a first step toward assessing their effectiveness in more complex, targeted nano-delivery in vivo settings and signals their potential application in the treatment of cancer.

  4. Issues and challenges in developing ruminal drug delivery systems.

    PubMed

    Vandamme, Th F; Ellis, K J

    2004-06-23

    Ruminants have a specialised digestive system that contains anaerobic bacteria and protozoa capable of digesting the cellulosic materials that are so common in plant materials. In addition, their distinct digestive system can change the metabolism and mode of action of some nutrients, medicines or other bioactive materials when delivered orally or may provide opportunities for alternative oral dosing strategies. In particular, there is interest in administering a relatively large depot of some drugs into the rumen, which then provides for a prolonged and sustained release of small quantities of these drugs over time. Any strategy to develop a new ruminal drug delivery system must take into account the characteristics of the digestive system of ruminants and its specific bioactive application. For example, in the case of products to control parasitic infections, the development of the host's immunity against the nematodes, which can be acquired during the pasture season, must be considered; likewise, where pharmacologically active materials are used to manipulate a particular metabolic or biochemical process, one must always be aware of interactions with other processes, which might eventuate. This article reviews the necessary concepts, the issues and the challenges to construct ruminal drug delivery systems.

  5. Recent trends in vaccine delivery systems: A review

    PubMed Central

    Saroja, CH; Lakshmi, PK; Bhaskaran, Shyamala

    2011-01-01

    Vaccines are the preparations given to patients to evoke immune responses leading to the production of antibodies (humoral) or cell-mediated responses that will combat infectious agents or noninfectious conditions such as malignancies. Alarming safety profile of live vaccines, weak immunogenicity of sub-unit vaccines and immunization, failure due to poor patient compliance to booster doses which should potentiate prime doses are few strong reasons, which necessitated the development of new generation of prophylactic and therapeutic vaccines to promote effective immunization. Attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and targeting. Hence, lower doses of weak immunogens can be effectively directed to stimulate immune responses and eliminate the need for the administration of prime and booster doses as a part of conventional vaccination regimen. This paper reviews carrier systems such as liposomes, microspheres, nanoparticles, dendrimers, micellar systems, ISCOMs, plant-derived viruses which are now being investigated and developed as vaccine delivery systems. This paper also describes various aspects of “needle-free technologies” used to administer the vaccine delivery systems through different routes into the human body. PMID:23071924

  6. Chitosan-modified lipid nanovesicles for efficient systemic delivery of l-asparaginase.

    PubMed

    Wan, Shengli; He, Dan; Yuan, Yuming; Yan, Zijun; Zhang, Xue; Zhang, Jingqing

    2016-07-01

    The goal of this study was to evaluate the enhanced catalytic activity, increased stability, in vitro anti-cancer effects on H446 cells and in vivo bioavailability of novel enzyme delivery nanovesicles (l-asparaginase containing chitosan modified lipid nanovesicles, ACLNs) when administered intravenously. It was the first time for the chitosan-modified lipid nanovesicles to be fabricated to deliver l-asparaginase (ASP, a therapeutic enzyme) efficiently. It was indicated that ACLNs markedly increased the enzymatic activity, improved the temperature/acid-base/proteolytic stabilities and favorably changed the in vivo kinetic characteristics. Moreover, ACLNs exhibited higher anti-lung-cancer activity than free ASP. The possible existence status of ASP in ACLNs and the fluorescence changes of ACLNs reflecting the conformational changes after heat treatment were preliminary explored. ACLNs might be novel promising nanovesicles for effective systemic delivery of therapeutic enzyme ASP.

  7. Healthcare delivery systems: designing quality into health information systems.

    PubMed

    Joyce, Phil; Green, Rosamund; Winch, Graham

    2007-01-01

    To ensure that quality is 'engineered in' a holistic, integrated and quality approach is required, and Total Quality Management (TQM) principles are the obvious foundations for this. This paper describes a novel approach to viewing the operations of a healthcare provider where electronic means could be used to distribute information (including electronic fund settlements), building around the Full Service Provider core. Specifically, an approach called the "triple pair flow" model is used to provide a view of healthcare delivery that is integrated, yet detailed, and that combines the strategic enterprise view with a business process view.

  8. Polymeric-based particulate systems for delivery of therapeutic proteins.

    PubMed

    Akash, Muhammad Sajid Hamid; Rehman, Kanwal; Chen, Shuqing

    2016-01-01

    Polymeric-based particulate systems have been intensively developed to increase the short biological half-life and prevent enzymatic degradation of therapeutic proteins. These techniques demonstrate the useful characteristics for the delivery of therapeutic proteins and peptides to the targeted site of application and prevent the interaction of encapsulated drug with the normal cells. In this article, we have described the in depth of different pharmaceutical-based techniques that are currently being practiced for efficient delivery of therapeutic proteins and peptides. A comprehensive English literature was searched using different electronic search databases including PubMed, Science Direct, Web of Science, google scholar and library search. Different search terms and advanced search were made by combining all the search fields in abstract, keywords and/or titles. Findings of various studies that have been discussed in this article clearly indicate that polymeric-based techniques can significantly increase the therapeutic potentials of incorporated proteins with no known toxic effects. These techniques have shown to maintain the stability and retain biological activity of protein therapeutics. Hence it can be suggested that pharmaceutical-based techniques are promising drug carriers for efficient delivery of therapeutic proteins.

  9. New Delivery Systems for Local Anaesthetics—Part 2

    PubMed Central

    Shipton, Edward A.

    2012-01-01

    Part 2 of this paper deals with the techniques for drug delivery of topical and injectable local anaesthetics. The various routes of local anaesthetic delivery (epidural, peripheral, wound catheters, intra-nasal, intra-vesical, intra-articular, intra-osseous) are explored. To enhance transdermal local anaesthetic permeation, additional methods to the use of an eutectic mixture of local anaesthetics and the use of controlled heat can be used. These methods include iontophoresis, electroporation, sonophoresis, and magnetophoresis. The potential clinical uses of topical local anaesthetics are elucidated. Iontophoresis, the active transportation of a drug into the skin using a constant low-voltage direct current is discussed. It is desirable to prolong local anaesthetic blockade by extending its sensory component only. The optimal release and safety of the encapsulated local anaesthetic agents still need to be determined. The use of different delivery systems should provide the clinician with both an extended range and choice in the degree of prolongation of action of each agent. PMID:22190921

  10. 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

  11. Comparison of SAGS I vs. SAGS II delivery systems in emerging implantation technologies

    NASA Astrophysics Data System (ADS)

    Despres, Joseph; Sweeney, Joseph

    2012-11-01

    The International Fire Code has classified Subatmospheric Gas Delivery Systems (SAGS) technologies into two main categories: SAGS Type I and SAGS Type II systems. SAGS Type I delivery systems both store and deliver gases at subatmospheric pressures. An example of this technology is ATMI's Safe Delivery Source (SDS®) adsorbent based cylinder. SAGS Type II delivery systems store fluids at high pressure and utilize mechanical devices internal to the cylinder to deliver the gas at subatmospheric pressures. Typical mechanical devices used to enable subatmospheric delivery are either set point regulators or mechanical capillary based systems. This paper focuses on how these delivery systems perform against the unique requirements of traditional beam line ion implantation as well as solar and flat panel applications. Specifically, data are provided showing the capability of these systems with respect to flow rate, residual gas left within the cylinder, and cylinder end-point flow and delivery pressure dynamics.

  12. Poly(N-vinylcaprolactam-co-methacrylic acid) hydrogel microparticles for oral insulin delivery.

    PubMed

    Mundargi, Raghavendra C; Rangaswamy, Vidhya; Aminabhavi, Tejraj M

    2011-01-01

    pH-sensitive copolymeric hydrogels prepared from N-vinylcaprolactam and methacrylic acid monomers by free radical polymerization offered 52% encapsulation efficiency and evaluated for oral delivery of human insulin. The in vitro experiments performed on insulin-loaded microparticles in pH 1.2 media (stomach condition) demonstrated no release of insulin in the first 2 h, but almost 100% insulin was released in pH 7.4 media (intestinal condition) in 6 h. The carrier was characterized by Fourier transform infrared, differential scanning calorimeter, thermogravimetry and nuclear magnetic resonance techniques to confirm the formation of copolymer, while scanning electron microscopy was used to assess the morphology of hydrogel microparticles. The in vivo experiments on alloxan-induced diabetic rats showed the biological inhibition up to 50% and glucose tolerance tests exhibited 44% inhibition. The formulations of this study are the promising carriers for oral delivery of insulin.

  13. Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    NASA Astrophysics Data System (ADS)

    Wan, Long; Jiao, Jian; Cui, Yu; Guo, Jingwen; Han, Ning; Di, Donghua; Chang, Di; Wang, Pu; Jiang, Tongying; Wang, Siling

    2016-04-01

    In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell-targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors.

  14. Electrohydrodynamic encapsulation of cisplatin in poly (lactic-co-glycolic acid) nanoparticles for controlled drug delivery.

    PubMed

    Parhizkar, Maryam; Reardon, Philip J T; Knowles, Jonathan C; Browning, Richard J; Stride, Eleanor; Barbara, Pedley R; Harker, Anthony H; Edirisinghe, Mohan

    2016-10-01

    Targeted delivery of potent, toxic chemotherapy drugs, such as cisplatin, is a significant area of research in cancer treatment. In this study, cisplatin was successfully encapsulated with high efficiency (>70%) in poly (lactic-co-glycolic acid) polymeric nanoparticles by using electrohydrodynamic atomization (EHDA) where applied voltage and solution flow rate as well as the concentration of cisplatin and polymer were varied to control the size of the particles. Thus, nanoparticles were produced with three different drug:polymer ratios (2.5, 5 and 10wt% cisplatin). It was shown that smaller nanoparticles were produced with 10wt% cisplatin. Furthermore, these demonstrated the best sustained release (smallest burst release). By fitting the experimental data with various kinetic models it was concluded that the release is dependent upon the particle morphology and the drug concentration. Thus, these particles have significant potential for cisplatin delivery with controlled dosage and release period that are crucial chemotherapy parameters.

  15. A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Gang; Dong, Zhi-Yue; Cheng, Hong; Wan, Shuang-Shuang; Chen, Wei-Hai; Zou, Mei-Zhen; Huo, Jia-Wei; Deng, He-Xiang; Zhang, Xian-Zheng

    2015-09-01

    Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects.Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose-related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free ``green'' post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects. Electronic supplementary information (ESI) available

  16. IceBreaker: Mars Drill and Sample Delivery System

    NASA Astrophysics Data System (ADS)

    Mellerowicz, B. L.; Paulsen, G. L.; Zacny, K.; McKay, C.; Glass, B. J.; Dave, A.; Davila, A. F.; Marinova, M.

    2012-12-01

    We report on the development and testing of a one meter class prototype Mars drill and cuttings sample delivery system. The IceBreaker drill consists of a rotary-percussive drill head, a sampling auger with a bit at the end having an integrated temperature sensor, a Z-stage for advancing the auger into the ground, and a sam-pling station for moving the augered ice shavings or soil cuttings into a sample cup. The drill is deployed from a 3 Degree of Freedom (DOF) robotic arm. The drill demonstrated drilling in ice-cemented ground, ice, and rocks at the 1-1-100-100 level; that is the drill reached 1 meter in 1 hour with 100 Watts of power and 100 Newton Weight on Bit. This cor-responds to an average energy of 100 Whr. The drill has been extensively tested in the Mars chamber to a depth of 1 meter, as well as in the Antarctic and the Arctic Mars analog sites. We also tested three sample delivery systems: 1) 4 DOF arm with a custom soil scoop at the end; 2) Pneumatic based, and 3) Drill based enabled by the 3 (DOF) drill deployment boom. In all approaches there is an air-gap between the sterilized drill (which penetrates subsurface) and the sample transfer hardware (which is not going to be sterilized). The air gap satisfies the planetary protection requirements. The scoop acquires cuttings sample once they are augered to the surface, and drops them into an in-strument inlet port. The system has been tested in the Mars chamber and in the Arctic. The pneumatic sample delivery system uses compressed gas to move the sample captured inside a small chamber inte-grated with the auger, directly into the instrument. The system was tested in the Mars chamber. In the third approach the drill auger captures the sample on its flutes, the 3 DOF boom positions the tip of the auger above the instrument, and then the auger discharges the sample into an instrument. This approach was tested in the labolatory (at STP). The above drilling and sample delivery tests have shown that drilling

  17. G2 Autonomous Control for Cryogenic Delivery Systems

    NASA Technical Reports Server (NTRS)

    Dito, Scott J.

    2014-01-01

    The Independent System Health Management-Autonomous Control (ISHM-AC) application development for cryogenic delivery systems is intended to create an expert system that will require minimal operator involvement and ultimately allow for complete autonomy when fueling a space vehicle in the time prior to launch. The G2-Autonomous Control project is the development of a model, simulation, and ultimately a working application that will control and monitor the cryogenic fluid delivery to a rocket for testing purposes. To develop this application, the project is using the programming language/environment Gensym G2. The environment is an all-inclusive application that allows development, testing, modeling, and finally operation of the unique application through graphical and programmatic methods. We have learned G2 through training classes and subsequent application development, and are now in the process of building the application that will soon be used to test on cryogenic loading equipment here at the Kennedy Space Center Cryogenics Test Laboratory (CTL). The G2 ISHM-AC application will bring with it a safer and more efficient propellant loading system for the future launches at Kennedy Space Center and eventually mobile launches from all over the world.

  18. Biodegradable PLGA- b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system

    NASA Astrophysics Data System (ADS)

    Locatelli, Erica; Comes Franchini, Mauro

    2012-12-01

    During the past decades many synthetic polymers have been studied for nanomedicine applications and in particular as drug delivery systems. For this purpose, polymers must be non-toxic, biodegradable, and biocompatible. Polylactic- co-glycolic acid (PLGA) is one of the most studied polymers due to its complete biodegradability and ability to self-assemble into nanometric micelles that are able to entrap small molecules like drugs and to release them into body in a time-dependent manner. Despite fine qualities, using PLGA polymeric nanoparticles for in vivo applications still remains an open challenge due to many factors such as poor stability in water, big diameter (150-200 nm), and the removal of these nanocarriers from the blood stream by the liver and spleen thus reducing the concentration of drugs drastically in tumor tissue. Polyethylene glycol (PEG) is the most used polymers for drug delivery applications and the first PEGylated product is already on the market for over 20 years. This is due to its stealth behavior that inhibits the fast recognition by the immune system (opsonization) and generally leads to a reduced blood clearance of nanocarriers increasing blood circulation time. Furthermore, PEG is hydrophilic and able to stabilize nanoparticles by steric and not ionic effects especially in water. PLGA-PEG block copolymer is an emergent system because it can be easily synthesized and it possesses all good qualities of PLGA and also PEG capability so in the last decade it arose as one of the most promising systems for nanoparticles formation, drug loading, and in vivo drug delivery applications. This review will discuss briefly on PLGA- b-PEG synthesis and physicochemical properties, together with its improved qualities with respect to the single PLGA and PEG polymers. Moreover, we will focus on but in particular will treat nanoparticles formation and uses as new drug delivery system for nanomedical applications.

  19. Characterisation of zinc delivery from a nipple shield delivery system using a breastfeeding simulation apparatus

    PubMed Central

    Bruggraber, Sylvaine F. A.; Gerrard, Stephen E.; Kendall, Richard A.; Tuleu, Catherine; Slater, Nigel K. H.

    2017-01-01

    Zinc delivery from a nipple shield delivery system (NSDS), a novel platform for administering medicines to infants during breastfeeding, was characterised using a breastfeeding simulation apparatus. In this study, human milk at flow rates and pressures physiologically representative of breastfeeding passed through the NSDS loaded with zinc-containing rapidly disintegrating tablets, resulting in release of zinc into the milk. Inductively coupled plasma optical emission spectrometry was used to detect the zinc released, using a method that does not require prior digestion of the samples and that could be applied in other zinc analysis studies in breast milk. Four different types of zinc-containing tablets with equal zinc load but varying excipient compositions were tested in the NSDS in vitro. Zinc release measured over 20 minutes ranged from 32–51% of the loaded dose. Total zinc release for sets tablets of the same composition but differing hardness were not significantly different from one another with P = 0.3598 and P = 0.1270 for two tested pairs using unpaired t tests with Welch’s correction. By the same test total zinc release from two sets of tablets having similar hardness but differing composition were also not significantly significant with P = 0.2634. Future zinc tablet composition and formulation optimisation could lead to zinc supplements and therapeutics with faster drug release, which could be administered with the NSDS during breastfeeding. The use of the NSDS to deliver zinc could then lead to treatment and prevention of some of the leading causes of child mortality, including diarrheal disease and pneumonia. PMID:28158283

  20. Characterisation of zinc delivery from a nipple shield delivery system using a breastfeeding simulation apparatus.

    PubMed

    Scheuerle, Rebekah L; Bruggraber, Sylvaine F A; Gerrard, Stephen E; Kendall, Richard A; Tuleu, Catherine; Slater, Nigel K H

    2017-01-01

    Zinc delivery from a nipple shield delivery system (NSDS), a novel platform for administering medicines to infants during breastfeeding, was characterised using a breastfeeding simulation apparatus. In this study, human milk at flow rates and pressures physiologically representative of breastfeeding passed through the NSDS loaded with zinc-containing rapidly disintegrating tablets, resulting in release of zinc into the milk. Inductively coupled plasma optical emission spectrometry was used to detect the zinc released, using a method that does not require prior digestion of the samples and that could be applied in other zinc analysis studies in breast milk. Four different types of zinc-containing tablets with equal zinc load but varying excipient compositions were tested in the NSDS in vitro. Zinc release measured over 20 minutes ranged from 32-51% of the loaded dose. Total zinc release for sets tablets of the same composition but differing hardness were not significantly different from one another with P = 0.3598 and P = 0.1270 for two tested pairs using unpaired t tests with Welch's correction. By the same test total zinc release from two sets of tablets having similar hardness but differing composition were also not significantly significant with P = 0.2634. Future zinc tablet composition and formulation optimisation could lead to zinc supplements and therapeutics with faster drug release, which could be administered with the NSDS during breastfeeding. The use of the NSDS to deliver zinc could then lead to treatment and prevention of some of the leading causes of child mortality, including diarrheal disease and pneumonia.

  1. Comparative Effectiveness Topics from a Large, Integrated Delivery System

    PubMed Central

    Danforth, Kim N; Patnode, Carrie D; Kapka, Tanya J; Butler, Melissa G; Collins, Bernadette; Compton-Phillips, Amy; Baxter, Raymond J; Weissberg, Jed; McGlynn, Elizabeth A; Whitlock, Evelyn P

    2013-01-01

    Objective: To identify high-priority comparative effectiveness questions directly relevant to care delivery in a large, US integrated health care system. Methods: In 2010, a total of 792 clinical and operational leaders in Kaiser Permanente were sent an electronic survey requesting nominations of comparative effectiveness research questions; most recipients (83%) had direct clinical roles. Nominated questions were divided into 18 surveys of related topics that included 9 to 23 questions for prioritization. The next year, 648 recipients were electronically sent 1 of the 18 surveys to prioritize nominated questions. Surveys were assigned to recipients on the basis of their nominations or specialty. High-priority questions were identified by comparing the frequency a question was selected to an “expected” frequency, calculated to account for the varying number of questions and respondents across prioritization surveys. High-priority questions were those selected more frequently than expected. Results: More than 320 research questions were nominated from 181 individuals. Questions most frequently addressed cardiovascular and peripheral vascular disease; obesity, diabetes, endocrinology, and metabolic disorders; or service delivery and systems-level questions. Ninety-five high-priority research questions were identified, encompassing a wide range of health questions that ranged from prevention and screening to treatment and quality of life. Many were complex questions from a systems perspective regarding how to deliver the best care. Conclusions: The 95 questions identified and prioritized by leaders on the front lines of health care delivery may inform the national discussion regarding comparative effectiveness research. Additionally, our experience provides insight in engaging real-world stakeholders in setting a health care research agenda. PMID:24361013

  2. Paclitaxel Nano-Delivery Systems: A Comprehensive Review

    PubMed Central

    Ma, Ping; Mumper, Russell J.

    2013-01-01

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

  3. Reliability review of the remote tool delivery system locomotor

    SciTech Connect

    Chesser, J.B.

    1999-04-01

    The locomotor being built by RedZone Robotics is designed to serve as a remote tool delivery (RID) system for waste retrieval, tank cleaning, viewing, and inspection inside the high-level waste tanks 8D-1 and 8D-2 at West Valley Nuclear Services (WVNS). The RTD systm is to be deployed through a tank riser. The locomotor portion of the RTD system is designed to be inserted into the tank and is to be capable of moving around the tank by supporting itself and moving on the tank internal structural columns. The locomotor will serve as a mounting platform for a dexterous manipulator arm. The complete RTD system consists of the locomotor, dexterous manipulator arm, cameras, lights, cables, hoses, cable/hose management system, power supply, and operator control station.

  4. THE SUPERCONDUCTION MAGNETS OF THE ILC BEAM DELIVERY SYSTEM.

    SciTech Connect

    PARKER,B.; ANEREELA, M.; ESCALLIE, J.; HE, P.; JAIN, A.; MARONE, A.; NOSOCHKOV, Y.; SERYI, A.

    2007-06-25

    The ILC Reference Design Report was completed early in February 2007. The Magnet Systems Group was formed to translate magnetic field requirements into magnet designs and cost estimates for the Reference Design. As presently configured, the ILC will have more than 13,000 magnetic elements of which more than 2300 will be based on superconducting technology. This paper will describe the major superconducting magnet needs for the ILC as presently determined by the Area Systems Groups, responsible for beam line design, working with the Magnet Systems Group. The superconducting magnet components include Main Linac quadrupoles, Positron Source undulators, Damping Ring wigglers, a complex array of Final Focus superconducting elements in the Beam Delivery System, and large superconducting solenoids in the e{sup +} and e{sup -} Sources, and the Ring to Main Linac lines.

  5. Demonstrations of Alternative Delivery Systems Under Medicare and Medicaid

    PubMed Central

    Galblum, Trudi W.; Trieger, Sidney

    1982-01-01

    The current Administration supports competition as one method of helping to contain escalating costs. Proponents of competition claim many advantages to its implementation, but their claims have yet to be widely tested. Over the past several years, however, the Health Care Financing Administration has supported a number of Medicare and Medicaid demonstrations to yield information on plan participation, marketing, and reimbursement under alternative delivery systems. Much of these data are applicable to the competitive plans being considered by the Administration and Congress. This paper discusses recent findings from these projects. PMID:10309599

  6. Power Delivery from an Actual Thermoelectric Generation System

    NASA Astrophysics Data System (ADS)

    Kaibe, Hiromasa; Kajihara, Takeshi; Nagano, Kouji; Makino, Kazuya; Hachiuma, Hirokuni; Natsuume, Daisuke

    2014-06-01

    Similar to photovoltaic (PV) and fuel cells, thermoelectric generators (TEGs) supply direct-current (DC) power, essentially requiring DC/alternating current (AC) conversion for delivery as electricity into the grid network. Use of PVs is already well established through power conditioning systems (PCSs) that enable DC/AC conversion with maximum-power-point tracking, which enables commercial use by customers. From the economic, legal, and regulatory perspectives, a commercial PCS for PVs should also be available for TEGs, preferably as is or with just simple adjustment. Herein, we report use of a PV PCS with an actual TEG. The results are analyzed, and proper application for TEGs is proposed.

  7. The Superconducting Magnets of the ILC Beam Delivery System

    SciTech Connect

    Parker, B.; Anerella, M.; Escallier, J.; He, P.; Jain, A.; Marone, A.; Nosochkov, Y.; Seryi, Andrei; /SLAC

    2007-09-28

    The ILC Beam Delivery System (BDS) uses a variety of superconducting magnets to maximize luminosity and minimize background. Compact final focus quadrupoles with multifunction correction coils focus incoming beams to few nanometer spot sizes while focusing outgoing disrupted beams into a separate extraction beam line. Anti-solenoids mitigate effects from overlapping focusing and the detector solenoid field. Far from the interaction point (IP) strong octupoles help minimize IP backgrounds. A low-field but very large aperture dipole is integrated with the detector solenoid to reduce backgrounds from beamstrahlung pairs generated at the IP. Physics requirements and magnetic design solutions for the BDS superconducting magnets are reviewed in this paper.

  8. Instrumentation system upgrade supports mobile personalized healthcare delivery.

    PubMed

    Ellingson, Roger M; Helt, Wendy J; Kelt, Patrick V; Fausti, Stephen A

    2006-01-01

    Clinicians and patients need mobile tools to detect ototoxic change early and prevent hearing loss. We report on the development of an upgrade of our existing desktop-based clinical-audiological instrumentation into a mobile instrument platform which efficiently supports personalized ototoxicity monitoring on the hospital wards as well as clinic by a trained clinician. Our new wireless-enabled system also serves as the instrumentation platform for the next phase of our work which is remote healthcare delivery with patient-guided at-home ototoxicity monitoring using an evidence-based individualized SRO protocol.

  9. Biocompatible polymers coated on carboxylated nanotubes functionalized with betulinic acid for effective drug delivery.

    PubMed

    Tan, Julia M; Karthivashan, Govindarajan; Abd Gani, Shafinaz; Fakurazi, Sharida; Hussein, Mohd Zobir

    2016-02-01

    Chemically functionalized carbon nanotubes are highly suitable and promising materials for potential biomedical applications like drug delivery due to their distinct physico-chemical characteristics and unique architecture. However, they are often associated with problems like insoluble in physiological environment and cytotoxicity issue due to impurities and catalyst residues contained in the nanotubes. On the other hand, surface coating agents play an essential role in preventing the nanoparticles from excessive agglomeration as well as providing good water dispersibility by replacing the hydrophobic surfaces of nanoparticles with hydrophilic moieties. Therefore, we have prepared four types of biopolymer-coated single walled carbon nanotubes systems functionalized with anticancer drug, betulinic acid in the presence of Tween 20, Tween 80, polyethylene glycol and chitosan as a comparative study. The Fourier transform infrared spectroscopy studies confirm the bonding of the coating molecules with the SWBA and these results were further supported by Raman spectroscopy. All chemically coated samples were found to release the drug in a slow, sustained and prolonged fashion compared to the uncoated ones, with the best fit to pseudo-second order kinetic model. The cytotoxic effects of the synthesized samples were evaluated in mouse embryonic fibroblast cells (3T3) at 24, 48 and 72 h. The in vitro results reveal that the cytotoxicity of the samples were dependent upon the drug release profiles as well as the chemical components of the surface coating agents. In general, the initial burst, drug release pattern and cytotoxicity could be well-controlled by carefully selecting the desired materials to suit different therapeutic applications.

  10. Current approaches for drug delivery to central nervous system.

    PubMed

    Hossain, Sharif; Akaike, Toshihiro; Chowdhury, Ezharul Hoque

    2010-12-01

    Brain, the center of the nervous system in all vertebrate, plays the most vital role in every function of human body. However, many neurodegenerative diseases, cancer and infections of the brain become more prevalent as populations become older. In spite of the major advances in neuroscience, many potential therapeutics are still unable to reach the central nervous system (CNS) due to the blood-brain barrier (BBB) which is formed by the tight junctions within the capillary endothelium of the vertebrate brain. This results in the capillary wall behaving as a continuous lipid bilayer and preventing the passage of polar and lipid insoluble substances. Several approaches for delivering drugs to the CNS have been developed to enhance the capacity of therapeutic molecules to cross the BBB by modifying the drug itself, or by coupling it to a vector for receptor-mediated, carrier mediated or adsorption-mediated transcytosis. The current challenge is to develop drug delivery systems that ensure the safe and effective passage of drugs across the BBB. This review focuses on the strategies and approaches developed to enhance drug delivery to the CNS.

  11. Systems approaches to design of targeted therapeutic delivery.

    PubMed

    Myerson, Jacob W; Brenner, Jacob S; Greineder, Colin F; Muzykantov, Vladimir R

    2015-01-01

    Targeted drug delivery aims to improve therapeutic effects and enable mechanisms that are not feasible for untargeted agents (e.g., due to impermeable biological barriers). To achieve targeting, a drug or its carrier should possess properties providing specific accumulation from circulation at the desired site. There are several examples of systems-inspired approaches that have been applied to achieve this goal. First, proteomics analysis of plasma membrane fraction of the vascular endothelium has identified a series of target molecules and their ligands (e.g., antibodies) that deliver conjugated cargoes to well-defined vascular cells and subcellular compartments. Second, selection of ligands binding to cells of interest using phage display libraries in vitro and in vivo has provided peptides and polypeptides that bind to normal and pathologically altered cells. Finally, large-scale high-throughput combinatorial synthesis and selection of lipid- and polymer-based nanocarriers varying their chemical components has yielded a series of carriers accumulating in diverse organs and delivering RNA interference agents to diverse cells. Together, these approaches offer a basis for systems-based design and selection of targets, targeting molecules, and targeting vehicles. Current studies focus on expanding the arsenal of these and alternative targeting strategies, devising drug delivery systems capitalizing on these strategies and evaluation of their benefit/risk ratio in adequate animal models of human diseases. These efforts, combined with better understanding of mechanisms and unintended consequences of these targeted interventions, need to be ultimately translated into industrial development and the clinical domain.

  12. Liposomal Conjugates for Drug Delivery to the Central Nervous System

    PubMed Central

    Helm, Frieder; Fricker, Gert

    2015-01-01

    Treatments of central nervous system (CNS) diseases often fail due to the blood–brain barrier. Circumvention of this obstacle is crucial for any systemic treatment of such diseases to be effective. One approach to transfer drugs into the brain is the use of colloidal carrier systems—amongst others, liposomes. A prerequisite for successful drug delivery by colloidal carriers to the brain is the modification of their surface, making them invisible to the reticuloendothelial system (RES) and to target them to specific surface epitopes at the blood–brain barrier. This study characterizes liposomes conjugated with cationized bovine serum albumin (cBSA) as transport vectors in vitro in porcine brain capillary endothelial cells (PBCEC) and in vivo in rats using fluorescently labelled liposomes. Experiments with PBCEC showed that sterically stabilized (PEGylated) liposomes without protein as well as liposomes conjugated to native bovine serum albumin (BSA) were not taken up. In contrast, cBSA-liposomes were taken up and appeared to be concentrated in intracellular vesicles. Uptake occurred in a concentration and time dependent manner. Free BSA and free cBSA inhibited uptake. After intravenous application of cBSA-liposomes, confocal fluorescence microscopy of brain cryosections from male Wistar rats showed fluorescence associated with liposomes in brain capillary surrounding tissue after 3, 6 and 24 h, for liposomes with a diameter between 120 and 150 nm, suggesting successful brain delivery of cationized-albumin coupled liposomes. PMID:25835091

  13. Delivery of Probiotics in the Space Food System</