Science.gov

Sample records for acid delivery systems

  1. Amino acids as cryoprotectants for liposomal delivery systems.

    PubMed

    Mohammed, Afzal R; Coombes, Allan G A; Perrie, Yvonne

    2007-04-01

    Liposomes provide an efficient delivery system for solubilisation and delivery of both small and macro molecules. However, they suffer from the disadvantage of instability when stored as aqueous dispersions. Cryoprotection of the liposomal systems provides an effective approach to overcome poor stability whilst maintaining formulation characteristics, although, the formulation of a freeze-dried product requires the consideration of not only the selection of an appropriate cryoprotectant, but also needs careful consideration of the processing parameters including pre-freezing conditions, primary and secondary drying protocols along with optimisation of cryoprotectant concentration. This current work investigates the application of amino acids as potential cryoprotectants for the stabilisation of liposomes, and results indicate that amino acids show biphasic nature of stabilisation with 4 mol of cryoprotectant per mole of the lipid exhibiting optimum cryoprotection. The investigations of process parameters showed that the pre-freezing temperatures below the glass transition of the amino acids followed by drying for over 6h resulted in stable formulations. Studies investigating the efficiency of drug retention showed that the cryoprotection offered by lysine was similar to that shown by trehalose, suggesting that amino acids act as effective stabilizers. ESEM analysis was carried out to monitor morphology of the rehydrated liposomes. PMID:17317117

  2. Delivery Systems for In Vivo Use of Nucleic Acid Drugs

    PubMed Central

    Resende, R.R; Torres, H.A.M; Yuahasi, K.K; Majumder, P; Ulrich, H

    2007-01-01

    The notorious biotechnological advance of the last few decades has allowed the development of experimental methods for understanding molecular mechanisms of genes and new therapeutic approaches. Gene therapy is maturing into a viable, practical method with the potential to cure a variety of human illnesses. Some nucleic-acid-based drugs are now available for controlling the progression of genetic diseases by inhibiting gene expression or the activity of their gene products. New therapeutic strategies employ a wide range of molecular tools such as bacterial plasmids containing transgenic inserts, RNA interference and aptamers. A nucleic-acid based constitution confers a lower immunogenic potential and as result of the high stringency selection of large molecular variety, these drugs have high affinity and selectivity for their targets. However, nucleic acids have poor biostability thus requiring chemical modifications and delivery systems to maintain their activity and ease their cellular internalization. This review discusses some of the mechanisms of action and the application of therapies based on nucleic acids such as aptamers and RNA interference as well as platforms for cellular uptake and intracellular delivery of therapeutic oligonucleotides and their trade-offs. PMID:21901073

  3. 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. PMID:21329050

  4. Silica nanoparticles as a delivery system for nucleic acid-based reagents

    PubMed Central

    Hom, Christopher; Lu, Jie

    2010-01-01

    The transport of nucleic acid-based reagents is predicated upon developing structurally stable delivery systems that can preferentially bind and protect DNA and RNA, and release their cargo upon reaching their designated sites. Recent advancements in tailoring the size, shape, and external surface functionalization of silica materials have led to increased biocompatibility and efficiency of delivery. In this Feature Article, we highlight recent research progress in the use of silica nanoparticles as a delivery vehicle for nucleic acid-based reagents. PMID:20740060

  5. 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. PMID:25578828

  6. Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: design and evaluation

    PubMed Central

    Yang, Rui; Huang, Xin; Dou, Jinfeng; Zhai, Guangxi; Su, Lequn

    2013-01-01

    Oleanolic acid is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance the solubility and oral bioavailability of oleanolic acid. The formulation design was optimized by solubility assay, compatibility tests, and pseudoternary phase diagrams. The morphology, droplet size distribution, zeta potential, viscosity, electrical conductivity, and refractive index of a SMEDDS loaded with oleanolic acid were studied in detail. Compared with oleanolic acid solution, the in vitro release of oleanolic acid from SMEDDS showed that the drug could be released in a sustained manner. A highly selective and sensitive high-performance liquid chromatographymass spectrometry method was developed for determination of oleanolic acid in rat plasma. This method was used for a pharmacokinetic study of an oleanolic acid-loaded SMEDDS compared with the conventional tablet in rats. Promisingly, a 5.07-fold increase in oral bioavailability of oleanolic acid was achieved for the SMEDDS compared with the marketed product in tablet form. Our studies illustrate the potential use of a SMEDDS for delivery of oleanolic acid via the oral route. PMID:23966781

  7. Skin delivery of kojic acid-loaded nanotechnology-based drug delivery systems for the treatment of skin aging.

    PubMed

    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

  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. Oleic acid based heterolipid synthesis, characterization and application in self-microemulsifying drug delivery system.

    PubMed

    Kalhapure, Rahul S; Akamanchi, Krishnacharya G

    2012-04-01

    There is increasing demand for lipids owing to their use in formulating lipid based drug delivery systems of poorly soluble drugs. The present work discusses the synthesis, characterization of oleic acid based heterolipid and its use as oil in the development of self-microemulsifying drug delivery system (SMEDDS) for parenteral delivery. Synthesis was carried out by Michael addition of tert-butyl acrylate to 3-amino-1-propanol to obtain di-tert-butyl aminopropanol derivative. Reaction of this di-tert-butyl aminopropanol derivative with oleoyl chloride using p-dimethylaminopyridine as a coupling agent gave the desired heterolipid. It was characterized by (1)H NMR, (13)C NMR and MS to confirm the structure. It did not exhibit any measurable cytotoxicity, even up to 80μg/ml concentration. Application in parenteral drug delivery was explored using furosemide (FUR), a BCS class IV drug, as a model. FUR showed three times greater solubility in the heterolipid as compared to oleic acid. SMEDDSs were developed using heterolipid as oily phase, Solutol HS 15(®) as surfactant and ethanol as a co-surfactant. Developed SMEDDS could form spontaneous microemulsion on addition to various aqueous phases with mean globule size <70nm without any phase separation or drug precipitation even after 24h, and exhibited negligible hemolytic potential. PMID:22266534

  10. 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. PMID:21902630

  11. 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

  12. 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

  13. Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems.

    PubMed

    Pan, Qixia; Lv, Yao; Williams, Gareth R; Tao, Lei; Yang, Huihui; Li, Heyu; Zhu, Limin

    2016-10-20

    In this work, we report a targeted drug delivery system built by functionalizing graphene oxide (GO) with carboxymethyl chitosan (CMC), fluorescein isothiocyanate and lactobionic acid (LA). Analogous systems without LA were prepared as controls. Doxorubicin (DOX) was loaded onto the composites through adsorption. The release behavior from both the LA-functionalized and the LA-free material is markedly pH sensitive. The modified GOs have high biocompatibility with the liver cancer cell line SMMC-7721, but can induce cell death after 24h incubation if loaded with DOX. Tests with shorter (2h) incubation times were undertaken to investigate the selectivity of the GO composites: under these conditions, neither DOX-loaded system was found to be toxic to the non-cancerous L929 cell line, but the LA-containing composite showed the ability to selectively induce cell death in cancerous (SMMC-7721) cells while the LA-free analogue was inactive here also. These findings show that the modified GO materials are strong potential candidates for targeted anticancer drug delivery systems. PMID:27474628

  14. Statistical optimization of ranitidine HCl floating pulsatile delivery system for chronotherapy of nocturnal acid breakthrough.

    PubMed

    Roy, Pallab; Shahiwala, Aliasgar

    2009-06-28

    Present work conceptualizes a specific technology, based on combining floating and pulsatile principles to develop drug delivery system, intended for chronotherapy in nocturnal acid breakthrough. This approach will be achieved by using a programmed delivery of ranitidine hydrochloride from a floating tablet with time-lagged coating. In this study, investigation of the functionality of the outer polymer coating to predict lag time and drug release was statistically analyzed using the response surface methodology (RSM). RSM was employed for designing of the experiment, generation of mathematical models and optimization study. The chosen independent variables, i.e. percentage weight ratios of ethyl cellulose to hydroxypropyl methyl cellulose in the coating formulation and coating level (% weight gain) were optimized with a 3(2) full factorial design. Lag time prior to drug release and cumulative percentage drug release in 7h were selected as responses. Results revealed that both, the coating composition and coating level, are significant factors affecting drug release profile. A second-order polynomial equation fitted to the data was used to predict the responses in the optimal region. The optimized formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. The proposed mathematical model is found to be robust and accurate for optimization of time-lagged coating formulations for programmable pulsatile release of ranitidine hydrochloride, consistent with the demands of nocturnal acid breakthrough. PMID:19491027

  15. Experience of using heat citric acid disinfection method in central dialysis fluid delivery system.

    PubMed

    Sakuma, Koji; Uchiumi, Nobuko; Sato, Sumihiko; Aida, Nobuhiko; Ishimatsu, Taketo; Igoshi, Tadaaki; Kodama, Yoshihiro; Hotta, Hiroyuki

    2010-09-01

    We applied the heat citric acid disinfection method in the main part of the central dialysis fluid delivery system (MPCDDS), which consists of a multiple-patient dialysis fluid supply unit, dialysis console units, and dialysis fluid piping. This disinfection method has been used for single-patient dialysis machines, but this is the first trial in the MPCDDS. We examined, by points of safety and disinfection effect, whether this disinfection method is comparable to conventional disinfection methods in Japan. The conventional disinfection method is a combination of two disinfectants, sodium hypochlorite and acetic acid, used separately for protein removal and decalcification. Consequently, total microbial counts and endotoxin concentrations fully satisfied the microbiological requirements for standard dialysis fluid of ISO 11663. From our results and discussion, this heat citric acid disinfection method is proved to be safe and reliable for MPCDDS. However, to satisfy the microbiological requirements for ultrapure dialysis fluid, further consideration for this method in MPCDDS including the reverse osmosis device composition and piping is necessary. PMID:20514548

  16. Cationic Mucic Acid Polymer-Based siRNA Delivery Systems.

    PubMed

    Pan, Dorothy W; Davis, Mark E

    2015-08-19

    Nanoparticle (NP) delivery systems for small interfering RNA (siRNA) that have good systemic circulation and high nucleic acid content are highly desired for translation into clinical use. Here, a family of cationic mucic acid-containing polymers is synthesized and shown to assemble with siRNA to form NPs. A cationic mucic acid polymer (cMAP) containing alternating mucic acid and charged monomers is synthesized. When combined with siRNA, cMAP forms NPs that require steric stabilization by poly(ethylene glycol) (PEG) that is attached to the NP surface via a 5-nitrophenylboronic acid linkage (5-nitrophenylboronic acid-PEGm (5-nPBA-PEGm)) to diols on mucic acid in the cMAP in order to inhibit aggregation in biological fluids. As an alternative, cMAP is covalently conjugated with PEG via two methods. First, a copolymer is prepared with alternating cMAP-PEG units that can form loops of PEG on the surface of the formulated siRNA-containing NPs. Second, an mPEG-cMAP-PEGm triblock polymer is synthesized that could lead to a PEG brush configuration on the surface of the formulated siRNA-containing NPs. The copolymer and triblock polymer are able to form stable siRNA-containing NPs without and with the addition of 5-nPBA-PEGm. Five formulations, (i) cMAP with 5-nPBA-PEGm, (ii) cMAP-PEG copolymer both (a) with and (b) without 5-nPBA-PEGm, and (iii) mPEG-cMAP-PEGm triblock polymer both (a) with and (b) without 5-nPBA-PEGm, are used to produce NPs in the 30-40 nm size range, and their circulation times are evaluated in mice using tail vein injections. The mPEG-cMAP-PEGm triblock polymer provides the siRNA-containing NP with the longest circulation time (5-10% of the formulation remains in circulation at 60 min postdosing), even when a portion of the excess cationic components used in the formulation is filtered away prior to injection. A NP formulation using the mPEG-cMAP-PEGm triblock polymer that is free of excess components could contain as much as ca. 30 wt % siRNA. PMID

  17. Bicellar systems as new delivery strategy for topical application of flufenamic acid.

    PubMed

    Rubio, L; Alonso, C; Rodríguez, G; Cócera, M; López-Iglesias, C; Coderch, L; De la Maza, A; Parra, J L; López, O

    2013-02-28

    In this work, bicellar systems, bilayered disc-shaped nanoaggregates formed in water by phospholipids, are proposed as a novel strategy for delivery of the anti-inflammatory flufenamic acid (FFA) to the skin. A comparative percutaneous penetration study of this drug in bicellar systems and other vehicles was conducted. The effects induced on the skin by the application of FFA in the different vehicles were analyzed by attenuated total reflectance-fourier transform infrared (ATR-FTIR). Additionally, using the microscopic technique freeze-substitution transmission electron microscopy (FSTEM) and X-ray scattering technique using synchrotron radiation (SAXS-SR), we studied the possible microstructural and organizational changes that were induced in the stratum corneum (SC) lipids and the collagen of the skin by the application of FFA bicellar systems. Bicellar systems exhibited a retarder effect on the percutaneous absorption of FFA with respect to the other vehicles without promoting disruption in the SC barrier function of the skin. Given that skin disruption is one of the main effects caused by inflammation, prevention of disruption and repair of the skin microstructure should be prioritized in anti-inflammatory formulations. PMID:23357252

  18. Nucleic acid delivery with microbubbles and ultrasound.

    PubMed

    Rychak, Joshua J; Klibanov, Alexander L

    2014-06-01

    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, and 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. The 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, and pancreas) proves the potential usefulness of this technique for nucleic acid drug delivery. PMID:24486388

  19. 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

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

    PubMed

    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

  1. 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

  2. An injectable hyaluronic acid-tyramine hydrogel system for protein delivery.

    PubMed

    Lee, Fan; Chung, Joo Eun; Kurisawa, Motoichi

    2009-03-19

    Previously, we reported the independent tuning of mechanical strength (crosslinking density) and gelation rate of an injectable hydrogel system composed of hyaluronic acid-tyramine (HA-Tyr) conjugates. The hydrogels were formed through the oxidative coupling of tyramines which was catalyzed by hydrogen peroxide (H(2)O(2)) and horseradish peroxidase (HRP). Herein, we studied the encapsulation and release of model proteins using the HA-Tyr hydrogel. It was shown that the rapid gelation achieved by an optimal concentration of HRP could effectively encapsulate the proteins within the hydrogel network and thus prevented the undesired leakage of proteins into the surrounding tissues after injection. Hydrogels with different mechanical strengths were formed by changing the concentration of H(2)O(2) while maintaining the rapid gelation rate. The mechanical strength of the hydrogel controlled the release rate of proteins: stiff hydrogels released proteins slower compared to weak hydrogels. In phosphate buffer saline, alpha-amylase (negatively charged) was released sustainably from the hydrogel. Conversely, the release of lysozyme (positively charged) discontinued after the fourth hour due to electrostatic interactions with HA. In the presence of hyaluronidase, lysozymes were released continuously and completely from the hydrogel due to degradation of the hydrogel network. The activities of the released proteins were mostly retained which suggested that the HA-Tyr hydrogel is a suitable injectable and biodegradable system for the delivery of therapeutic proteins. PMID:19121348

  3. 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

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

    PubMed

    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

  5. Gold Nanoparticles for Nucleic Acid Delivery

    PubMed Central

    Ding, Ya; Jiang, Ziwen; Saha, Krishnendu; Kim, Chang Soo; Kim, Sung Tae; Landis, Ryan F; Rotello, Vincent M

    2014-01-01

    Gold nanoparticles provide an attractive and applicable scaffold for delivery of nucleic acids. In this review, we focus on the use of covalent and noncovalent gold nanoparticle conjugates for applications in gene delivery and RNA-interference technologies. We also discuss challenges in nucleic acid delivery, including endosomal entrapment/escape and active delivery/presentation of nucleic acids in the cell. PMID:24599278

  6. 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

  7. pH-Activated Targeting Drug Delivery System Based on the Selective Binding of Phenylboronic Acid.

    PubMed

    Zhao, Dan; Xu, Jia-Qi; Yi, Xiao-Qing; Zhang, Quan; Cheng, Si-Xue; Zhuo, Ren-Xi; Li, Feng

    2016-06-15

    Phenylboronic acid (PBA) is a tumor-targeting molecule, but its nonspecific interaction with normal cells or other components containing cis-diol residues undoubtedly limits its potential application in tumor-targeting drug delivery. Herein, we developed fructose-coated mixed micelles via PBA-terminated polyethylene glycol monostearate (PBA-PEG-C18) and Pluronic P123 (PEG20-PPG70-PEG20) to solve this problem, as the stability of borate formed by PBA and fructose was dramatically dependent on pH. The fluorescence spectroscopic results indicated that the borate formed by PBA and fructose decomposed at a decreased pH, and better binding between PBA and sialic acid (SA) was observed at a low pH. These results implied that the fructose groups decorated on the surface of the micelles could be out-competed by SA at a low pH. In vitro uptake and cytotoxicity studies demonstrated that the fructose coating on the mixed micelles improved the endocytosis and enhanced the cytotoxicity of drug-loaded mixed micelles in HepG2 cells but reduced the cytotoxicity in normal cells. These results demonstrate that a simple decorating strategy may facilitate PBA-targeted nanoparticles for tumor-specific drug delivery. PMID:27229625

  8. Synthesis and characterization of a pH responsive folic acid functionalized polymeric drug delivery system.

    PubMed

    Li, Xia; McTaggart, Matt; Malardier-Jugroot, Cecile

    2016-01-01

    We report the computational analysis, synthesis and characterization of folate functionalized poly(styrene-alt-maleic anhydride), PSMA for drug delivery purpose. The selection of the proper linker between the polymer and the folic acid group was performed before conducting the synthesis using Density Functional Theory (DFT). The computational results showed the bio-degradable linker 2, 4-diaminobutyric acid, DABA as a good candidate allowing flexibility of the folic acid group while maintaining the pH sensitivity of PSMA, used as a trigger for drug release. The synthesis was subsequently carried out in multi-step experimental procedures. The functionalized polymer was characterized using InfraRed spectroscopy, Nuclear Magnetic Resonance and Dynamic Light Scattering confirming both the chemical structure and the pH responsiveness of PSMA-DABA-Folate polymers. This study provides an excellent example of how computational chemistry can be used in selection process for the functional materials and product characterization. The pH sensitive polymers are expected to be used in delivering anti-cancer drugs to solid tumors with overly expressed folic acid receptors. PMID:27183249

  9. Multifunctional materials such as MCM-41÷Fe3O4÷folic acid as drug delivery system.

    PubMed

    Popescu, Simona; Ardelean, Ioana Lavinia; Gudovan, Dragoş; Rădulescu, Marius; Ficai, Denisa; Ficai, Anton; Vasile, Bogdan Ştefan; Andronescu, Ecaterina

    2016-01-01

    In this study, MCM-41 mesoporous silica nanoparticles (NPs) and MCM-41÷Fe3O4 mesoporous silica NPs were prepared by sol-gel method using CTAB (cetyltrimethylammonium bromide) as template and TEOS (tetraethyl orthosilicate) as silica precursor in order to use these materials as drug delivery system (DDS) for different biologically active agents. The MCM-41 and MCM-41÷Fe3O4 mesoporous silica NPs were characterized using specific physico-chemical methods [transmission electron microscopy (TEM), scanning electron microscopy (SEM), nitrogen adsorption and desorption studies - BET (Brunauer-Emmett-Teller) method, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy], while the release studies were done by a high-performance liquid chromatography (HPLC)-modified method. The pH dependence of the delivery of folic acid from the mesoporous structures was analyzed and found that the release is pH sensitive. The lower delivery at strongly acid pH comparing with neutral/slightly alkaline pH could be beneficial because in stomach the folic acid can be destroyed. PMID:27516022

  10. 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. PMID:23910307

  11. 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. PMID:26764107

  12. 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

  13. Biodistribution profiling of the chemical modified hyaluronic acid derivatives used for oral delivery system.

    PubMed

    Hsieh, Chien-Ming; Huang, Yu-Wen; Sheu, Ming-Thau; Ho, Hsiu-O

    2014-03-01

    A series of adipic acid dihydrazide (ADH)-modified hyaluronic acid (HA-ADH) compounds were synthesized and conjugated with QDots (QDots-HA conjugates) to assess the effects of the molecular weight (MW) and extent of chemical modification of HA on its biodistribution. Their physicochemical structures were confirmed by complementary application of GPC, (1)H NMR, FTIR, and UV-vis spectroscopic methods. In vivo imaging of QDots-HA conjugates after oral administration was analyzed to investigate their biodistribution in nude mice. Simultaneously, real-time bioimaging was confirmed by an anatomical analysis to investigate the organ-specific accumulation of conjugates. QDot-HA conjugates with a higher MW of HA or high modification presented relatively slow clearance leading to an extension of the retention time for up to 10 days, whereas those with lower MWs of HA or a low modification extent exhibited quick absorption and elimination after oral administration. Taken together, HA derivatives with suitable MWs and chemical modification extents can be used to design new, more-sophisticated, and intelligent HA-based vehicles for oral delivery with diverse characteristics. PMID:24315950

  14. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

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

  15. A pH- and thermo-responsive poly(amino acid)-based drug delivery system.

    PubMed

    Liu, Na; Li, Bingqiang; Gong, Chu; Liu, Yuan; Wang, Yanming; Wu, Guolin

    2015-12-01

    A pH- and thermo-responsive poly(amino acid)-based amphiphilic copolymer was developed, functioning as a tumour targeting drug delivery system with good biocompatibility and biodegradability. To provide multi-stimuli sensitivity characteristics to the poly(amino acid)s, the polyaspartamide scaffold has been functionalized with N,N-diisopropylamide groups via aminolysis reaction of polysuccinimide. PEG chains have also been chemically grafted to the poly(amino acid) backbone through acid-labile hydrazone linkages, providing a removable shield for the poly(amino acid) based nanoparticles. Furthermore, doxorubicin was chemically linked to the copolymer chain via hydrazone bonds, acting as the hydrophobic moiety to drive the polymeric self-assembly. Free doxorubicin molecules could be encapsulated into the self-assembled nanoparticles via hydrophobic interactions and molecular π-π stacking. The results obtained show that the drug release can be triggered by the temperature with a significantly increased release being observed under acidic conditions. The cytotoxicity behaviour of the copolymers and drug-loaded nanoparticles was investigated in vitro at varying pH values and different temperatures. In doing so, superior characteristics concerning compatibility and anti-cancer activity could be observed. PMID:26454546

  16. 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

  17. Carbohydrate polymers for nonviral nucleic acid delivery.

    PubMed

    Sizovs, Antons; McLendon, Patrick M; Srinivasachari, Sathya; Reineke, Theresa M

    2010-01-01

    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

  18. Drug delivery systems.

    PubMed

    Robinson, D H; Mauger, J W

    1991-10-01

    New and emerging drug delivery systems for traditional drugs and the products of biotechnology are discussed, and the role of the pharmacist in ensuring the appropriate use of these systems is outlined. Advantages of advanced drug delivery systems over traditional systems are the ability to deliver a drug more selectively to a specific site; easier, more accurate, less frequent dosing; decreased variability in systemic drug concentrations; absorption that is more consistent with the site and mechanism of action; and reductions in toxic metabolites. Four basic strategies govern the mechanisms of advanced drug delivery: physical, chemical, biological, and mechanical. Oral drug delivery systems use natural and synthetic polymers to deliver the product to a specific region in the gastrointestinal tract in a timely manner that minimizes adverse effects and increases drug efficacy. Innovations in injectable and implantable delivery systems include emulsions, particulate delivery systems, micromolecular products and macromolecular drug adducts, and enzymatic-controlled delivery. Options for noninvasive drug delivery include the transdermal, respiratory, intranasal, ophthalmic, lymphatic, rectal, intravaginal, and intrauterine routes as well as topical application. Rapid growth is projected in the drug delivery systems market worldwide in the next five years. Genetic engineering has mandated the development of new strategies to deliver biotechnologically derived protein and peptide drugs and chemoimmunoconjugates. The role of the pharmacist in the era of advanced drug delivery systems will be broad based, including administering drugs, compounding, calculating dosages based on pharmacokinetic and pharmacodynamic monitoring, counseling, and research. The advent of advanced drug delivery systems offers pharmacists a new opportunity to assume an active role in patient care. PMID:1772110

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

    PubMed

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

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery. PMID:23662604

  20. 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

  1. 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. PMID:26840601

  2. Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation

    PubMed Central

    Selmin, Francesca; Puoci, Francesco; Parisi, Ortensia I.; Franzé, Silvia; Musazzi, Umberto M.; Cilurzo, Francesco

    2015-01-01

    This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA) to design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin (OVA) was selected as model compound because of its sensitiveness of γ-radiation. The adopted grafting procedure allowed us to obtain a material with good free radical scavenging properties, without a significant modification of Mw and Tg of the starting PLGA (Mw PLGA = 26.3 ± 1.3 kDa vs. Mw g-CA-PLGA = 22.8 ± 0.7 kDa; Tg PLGA = 47.7 ± 0.8 °C vs. Tg g-CA-PLGA = 47.4 ± 0.2 °C). By using a W1/O/W2 technique, g-CA-PLGA improved the encapsulation efficiency (EE), suggesting that the presence of caffeic residues improved the compatibility between components (EEPLGA = 35.0% ± 0.7% vs. EEg-CA-PLGA = 95.6% ± 2.7%). Microspheres particle size distribution ranged from 15 to 50 µm. The zeta-potential values of placebo and loaded microspheres were −25 mV and −15 mV, respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less than 1% variation of Mw and the degradation patterns of the non-irradiated and irradiated microspheres were superimposable. The OVA content in g-CA-PLGA microspheres decreased to a lower extent with respect to PLGA microspheres. These results suggest that g-CA-PLGA is a promising biodegradable material to microencapsulate biological drugs. PMID:25569163

  3. Pulmonary delivery of nucleic acids.

    PubMed

    Birchall, James

    2007-11-01

    The lung is an appropriate present and future target for gene therapy approaches designed to treat inherited monogenic diseases, eradicate bronchial tumours, transfer pharmacologically active products to the general circulation, express enzymes to catabolise toxins, manage pulmonary hypertension and lung injury and vaccinate against infection. Despite 35 years of gene therapy research and some significant milestones in molecular biology, the clinical potential of gene therapy has yet to be realised. In pulmonary gene therapy the nucleic acid cargo needs to be delivered to cells in the target region of the lung, and even in cases when these targets are well defined this is severely limited by the pulmonary architecture, clearance mechanisms, immune activation, the presence of respiratory mucus and the availability of a truly representative biological model. The challenge from a drug delivery perspective is to consider the suitability of conventional nebulisers and inhalers for delivering DNA to the lung and design and apply integrated formulation and device solutions specific to nucleic acid delivery. PMID:17970661

  4. An Acid-Triggered Degradable and Fluorescent Nanoscale Drug Delivery System with Enhanced Cytotoxicity to Cancer Cells.

    PubMed

    An, Jinxia; Dai, Xiaomei; Wu, Zhongming; Zhao, Yu; Lu, Zhentan; Guo, Qianqian; Zhang, Xinge; Li, Chaoxing

    2015-08-10

    To reduce side-effects of anticancer drugs, development of nanocarriers with precise biological functions is a critical requirement. In this study, the multifunctional nanoparticles combining imaging and therapy for tumor-targeted delivery of hydrophobic anticancer drugs were prepared via self-assembly of amphiphilic copolymers obtained using RAFT polymerization, specifically, acid-labile ortho ester and galactose. First, boron-dipyrromethene dye-conjugated chain transfer agent provides fluorescent imaging capability for diagnostic application. Second, nanoparticles were stable under physiological conditions but degraded in acidic tumor microenvironment, leading to enhanced anticancer efficacy. Third, the application of biocompatible glycopolymers efficiently increased the target-to-background ratio through carbohydrate-protein interactions. Data from cell viability, cellular internalization, flow cytometry, biodistribution and anticancer efficacy tests showed that the drug-loaded nanoparticles were capable of inhibiting cancer cell proliferation with significantly enhanced capacity. Our newly developed multifunctional nanoparticles may thus facilitate the development of effective drug delivery systems for application in diagnosis and therapy of cancer. PMID:26213802

  5. GONAD: Genome-editing via Oviductal Nucleic Acids Delivery system: a novel microinjection independent genome engineering method in mice.

    PubMed

    Takahashi, Gou; Gurumurthy, Channabasavaiah B; Wada, Kenta; Miura, Hiromi; Sato, Masahiro; Ohtsuka, Masato

    2015-01-01

    Microinjection is considered the gold standard technique for delivery of nucleic acids (NAs; transgenes or genome editing tools such as CRISPR/Cas9 systems) into embryos, for creating genetically modified organisms. It requires sophisticated equipment as well as well-trained and highly skilled personnel to perform the micro-injection technique. Here, we describe a novel and simple microinjection-independent technique, called Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). Using GONAD, we show that NAs (e.g., eGFP mRNA or Cas9 mRNA/sgRNAs) can be effectively delivered to pre-implantation embryos within the intact mouse oviduct by a simple electroporation method, and result in the desired genetic modification in the embryos. Thus GONAD can bypass many complex steps in transgenic technology such as isolation of zygotes, microinjection of NAs into them, and their subsequent transfer to pseudo-pregnant animals. Furthermore, this method can potentially be used for genome editing in species other than mice. PMID:26096991

  6. GONAD: Genome-editing via Oviductal Nucleic Acids Delivery system: a novel microinjection independent genome engineering method in mice

    PubMed Central

    Takahashi, Gou; Gurumurthy, Channabasavaiah B; Wada, Kenta; Miura, Hiromi; Sato, Masahiro; Ohtsuka, Masato

    2015-01-01

    Microinjection is considered the gold standard technique for delivery of nucleic acids (NAs; transgenes or genome editing tools such as CRISPR/Cas9 systems) into embryos, for creating genetically modified organisms. It requires sophisticated equipment as wel as well-trained and highly skilled personnel to perform the micro-injection technique. Here, we describe a novel and simple microinjection-independent technique, called Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). Using GONAD, we show that NAs (e.g., eGFP mRNA or Cas9 mRNA/sgRNAs) can be effectively delivered to pre-implantation embryos within the intact mouse oviduct by a simple electroporation method, and result in the desired genetic modification in the embryos. Thus GONAD can bypass many complex steps in transgenic technology such as isolation of zygotes, microinjection of NAs into them, and their subsequent transfer to pseudo-pregnant animals. Furthermore, this method can potentially be used for genome editing in species other than mice. PMID:26096991

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

    PubMed

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

    2015-03-01

    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. PMID:25660501

  8. 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. PMID:26923270

  9. 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

  10. 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. PMID:27451154

  11. 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.

  12. Salicylic acid derivatives as potential anti asthmatic agents using disease responsive drug delivery system for prophylactic therapy of allergic asthma.

    PubMed

    Raju, Kalidhindi Rama Satyanarayana; Ambhore, Nilesh S; Mulukutla, Shashank; Gupta, Saurabh; Murthy, Vishakantha; Kumar, M N Kiran; Madhunapantula, Subba Rao V; Kuppuswamy, Gowthamarajan; Elango, Kannan

    2016-02-01

    Asthma is a multi-factorial and complicated lung disorder of the immune system which has expanded to a wider ambit unveiling its etiology to be omnipresent at both ends of the spectrum involving basic pharmacology and in-depth immunology. As asthma occurs through triggered activation of various immune cells due to different stimuli, it poses a great challenge to uncover specific targets for therapeutic interventions. Recent pharmacotherapeutic approaches for asthma have been focused on molecular targeting of transcription factors and their signaling pathways; mainly nucleus factor kappa B (NFκB) and its associated pathways which orchestrate the synthesis of pro-inflammatory cytokines (IL-1β, TNF-α, GM-CSF), chemokines (RANTES, MIP-1a, eotaxin), adhesion molecules (ICAM-1, VCAM-1) and inflammatory enzymes (cyclooxygenase-2 and iNOS). 5-aminosalicylic acid (5-ASA) and sodium salicylate are known to suppress NFκB activation by inhibiting inhibitor of kappa B kinase (IKκB). In order to target the transcription factor, a suitable carrier system for delivering the drug to the intracellular space is essential. 5-ASA and sodium salicylate loaded liposomes incorporated into PEG-4-acrylate and CCRGGC microgels (a polymer formed by crosslinking of trypsin sensitive peptide and PEG-4-acrylate) could probably suit the needs for developing a disease responsive drug delivery system which will serve as a prophylactic therapy for asthmatic patients. PMID:26643666

  13. 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

  14. Technological Delivery Systems.

    ERIC Educational Resources Information Center

    Kennedy, Don; And Others

    A section on technological delivery systems, presented as part of the second Australian National Workshop on Distance Education (Perth, 1983), contains four papers on using technological resources to provide educational services to persons in isolated locations. The first paper, by Don Kennedy, covers the use of satellite broadcasting of course…

  15. [Development of an ultrasound-mediated nucleic acid delivery system for treating muscular dystrophies].

    PubMed

    Negishi, Yoichi; Hamano, Nobuhito; Shiono, Hitomi; Akiyama, Saki; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo; Aramaki, Yukihiko

    2012-01-01

    Muscular dystrophies are a group of heterogeneous diseases that are characterized by progressive muscle weakness, wasting and degeneration. These muscular deficiencies are often caused by the loss of the protein dystrophin, a crucial element of the dystrophin-glycoprotein complex of muscle fibers. Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscular disease that occurs in 1 out of every 3500 males. Therefore, feasible strategies for replacing or repairing the defective gene are required; however, to date, no effective therapeutic strategies for muscular dystrophies have been established. In this review, we first introduce gene therapies mediated by adeno-associated viruses (AAVs) including a functional dystrophin cDNA or antisense oligonucleotide (AO)-induced exon-skipping therapies, which are designed to exclude the mutated or additional exon(s) in the defective gene and thereby correct the translational reading frame. Recently, we developed "Bubble liposomes" (BLs), which are polyethylene glycol (PEG)-modified liposomes entrapping echo-contrast gas that is known as ultrasound (US) imaging gas. BL application combined with US exposure can function as a novel gene delivery tool, and we demonstrate that the US-mediated eruption of BLs is a feasible and efficient technique to deliver plasmid DNA or AOs for the treatment of muscular dystrophies. PMID:23208045

  16. Terplex Gene Delivery System.

    PubMed

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16243067

  17. Terplex gene delivery system.

    PubMed

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16240997

  18. 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

  19. Poly(hydroxy acids) in drug delivery.

    PubMed

    Juni, K; Nakano, M

    1987-01-01

    Poly(hydroxy acids) so far have been examined for use in drug delivery in limited number, while the advantageous use of the polymers has been recognized due to their biodegradability and biocompatibility. Homo- and copolymers of lactic acid and glycolic acid have been studied in drug delivery by many workers, while homo- and copolymers of epsilon-caprolactone have been studied by only one group of workers. Although poly-hydroxybutyric acid had been found to be a naturally occurring polymer, examination as to the use of the polymer in drug delivery is rather recent and reports are still limited. In the present article, the use of poly(hydroxy acids) including homo- and copolymers of lactic acid and glycolic acid, polycaprolactone, and poly-beta-hydroxybutyric acid in drug delivery is reviewed. Physicochemical properties, biodegradability, and biocompatibility of the polymers, and evaluations in vitro and in vivo of specific dosage forms using the polymers, are included. The most recent work in our laboratories on the use of polyactic acid and poly-beta-hydroxybutyric acid is also included. PMID:3549007

  20. Novel antigen delivery systems.

    PubMed

    Trovato, Maria; De Berardinis, Piergiuseppe

    2015-08-12

    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

  1. Continuing Professional Education Delivery Systems.

    ERIC Educational Resources Information Center

    Weeks, James P.

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

  2. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. PMID:25703045

  3. 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. PMID:19925443

  4. Nanovehicular intracellular delivery systems.

    PubMed

    Prokop, Ales; Davidson, Jeffrey M

    2008-09-01

    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

  5. 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

  6. Transmembrane heme delivery systems

    PubMed Central

    Goldman, Barry S.; Beck, David L.; Monika, Elizabeth M.; Kranz, Robert G.

    1998-01-01

    Heme proteins play pivotal roles in a wealth of biological processes. Despite this, the molecular mechanisms by which heme traverses bilayer membranes for use in biosynthetic reactions are unknown. The biosynthesis of c-type cytochromes requires that heme is transported to the bacterial periplasm or mitochondrial intermembrane space where it is covalently ligated to two reduced cysteinyl residues of the apocytochrome. Results herein suggest that a family of integral membrane proteins in prokaryotes, protozoans, and plants act as transmembrane heme delivery systems for the biogenesis of c-type cytochromes. The complete topology of a representative from each of the three subfamilies was experimentally determined. Key histidinyl residues and a conserved tryptophan-rich region (designated the WWD domain) are positioned at the site of cytochrome c assembly for all three subfamilies. These histidinyl residues were shown to be essential for function in one of the subfamilies, an ABC transporter encoded by helABCD. We believe that a directed heme delivery pathway is vital for the synthesis of cytochromes c, whereby heme iron is protected from oxidation via ligation to histidinyl residues within the delivery proteins. PMID:9560218

  7. 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

  8. Biocompatible hydrogels based on hyaluronic acid cross-linked with a polyaspartamide derivative as delivery systems for epithelial limbal cells.

    PubMed

    Fiorica, Calogero; Senior, Richard A; Pitarresi, Giovanna; Palumbo, Fabio Salvatore; Giammona, Gaetano; Deshpande, Pallavi; MacNeil, Sheila

    2011-07-29

    The aim of this work was to evaluate the potential use of hydrogels based on hyaluronic acid (HA) chemically cross-linked with α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) as substitutes for the amniotic membrane able to release limbal cells for corneal regeneration. Hydrogels, shaped as films, with three different molar ratios (X) between PHEA-EDA and HA (X = 0.5, 1.0 and 1.5) have been investigated. First, it has been evaluated their swelling ability, hydrolytic resistance in simulated physiological fluid and cell compatibility by using human dermal fibroblasts chosen as a model cell line. Then adhesion studies in comparison with collagen gel, have been performed by using immortalized cells, such as human corneal epithelial cells (HCEC) or primary cells, such as rabbit limbal epithelial cells (RLEC) and/or rabbit limbal fibroblasts (RLF). HA/PHEA-EDA hydrogels allow a moderate/poor adhesion of all investigated cells thus suggesting their potential ability to act as cell delivery systems. Finally, commercial contact lenses have been coated, in their inner surface, with each HA/PHEA-EDA film and it has been found that in these conditions, a greater cell adhesion occurs, particularly when RLEC are in co-culture with RLF. However, this adhesion is only transitory, in fact after three days, viable cells are released in the culture medium thus suggesting a potential application of HA/PHEA-EDA hydrogels, for delivering limbal cells in the treatment of corneal damage. PMID:21596121

  9. 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.

  10. Imaging Functional Nucleic Acid Delivery to Skin.

    PubMed

    Kaspar, Roger L; Hickerson, Robyn P; González-González, Emilio; Flores, Manuel A; Speaker, Tycho P; Rogers, Faye A; Milstone, Leonard M; Contag, Christopher H

    2016-01-01

    Monogenic skin diseases arise from well-defined single gene mutations, and in some cases a single point mutation. As the target cells are superficial, these diseases are ideally suited for treatment by nucleic acid-based therapies as well as monitoring through a variety of noninvasive imaging technologies. Despite the accessibility of the skin, there remain formidable barriers for functional delivery of nucleic acids to the target cells within the dermis and epidermis. These barriers include the stratum corneum and the layered structure of the skin, as well as more locally, the cellular, endosomal and nuclear membranes. A wide range of technologies for traversing these barriers has been described and moderate success has been reported for several approaches. The lessons learned from these studies include the need for combinations of approaches to facilitate nucleic acid delivery across these skin barriers and then functional delivery across the cellular and nuclear membranes for expression (e.g., reporter genes, DNA oligonucleotides or shRNA) or into the cytoplasm for regulation (e.g., siRNA, miRNA, antisense oligos). The tools for topical delivery that have been evaluated include chemical, physical and electrical methods, and the development and testing of each of these approaches has been greatly enabled by imaging tools. These techniques allow delivery and real time monitoring of reporter genes, therapeutic nucleic acids and also triplex nucleic acids for gene editing. Optical imaging is comprised of a number of modalities based on properties of light-tissue interaction (e.g., scattering, autofluorescence, and reflectance), the interaction of light with specific molecules (e.g., absorbtion, fluorescence), or enzymatic reactions that produce light (bioluminescence). Optical imaging technologies operate over a range of scales from macroscopic to microscopic and if necessary, nanoscopic, and thus can be used to assess nucleic acid delivery to organs, regions, cells

  11. Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio.

    PubMed

    Lai, Jui-Yang

    2013-01-01

    Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations. PMID:24187486

  12. Biodegradable in situ gelling delivery systems containing pilocarpine as new antiglaucoma formulations: effect of a mercaptoacetic acid/N-isopropylacrylamide molar ratio

    PubMed Central

    Lai, Jui-Yang

    2013-01-01

    Ocular drug delivery is one of the most commonly used treatment modalities in the management of glaucoma. We have recently proposed the use of gelatin and poly(N-isopropylacrylamide) (PNIPAAm) graft copolymers as biodegradable in situ forming delivery systems for the intracameral administration of antiglaucoma medications. In this study, we further investigated the influence of carrier characteristics on drug delivery performance. The carboxyl-terminated PNIPAAm samples with different molecular weights were synthesized by varying the molar ratio of mercaptoacetic acid (MAA)/N-isopropylacrylamide (NIPAAm) from 0.05 to 1.25, and were determined by end-group titration. The preparation of gelatin-g-PNIPAAm (GN) copolymers from these thermoresponsive polymers was achieved using carbodiimide chemistry. Our results showed that the carboxylic end-capped PNIPAAm of high molecular weight may lead to the lower thermal phase transition temperature and slower degradation rate of GN vehicles than its low molecular weight counterparts. With a decreasing MAA/NIPAAm molar ratio, the drug encapsulation efficiency of copolymers was increased due to fast temperature-triggered capture of pilocarpine nitrate. The degradation of the gelatin network could greatly affect the drug release profiles. All of the GN copolymeric carriers demonstrated good corneal endothelial cell and tissue compatibility. It is concluded that different types of GN-based delivery systems exhibit noticeably distinct intraocular pressure-lowering effect and miosis action, thereby reflecting the potential value of a MAA/NIPAAm molar ratio in the development of new antiglaucoma formulations. PMID:24187486

  13. A designed 5-fluorouracil-based bridged silsesquioxane as an autonomous acid-triggered drug-delivery system.

    PubMed

    Giret, Simon; Théron, Christophe; Gallud, Audrey; Maynadier, Marie; Gary-Bobo, Magali; Garcia, Marcel; Wong Chi Man, Michel; Carcel, Carole

    2013-09-16

    Two new prodrugs, bearing two and three 5-fluorouracil (5-FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5-FU, they were intended to form complexes through H-bonds to an organo-bridged silane prior to hydrolysis-condensation through sol-gel processes to construct acid-responsive bridged silsesquioxanes (BS). Whereas 5-FU itself and the prodrug bearing two 5-FU units completely leached out from the corresponding materials, the prodrug bearing three 5-FU units was successfully maintained in the resulting BS. Solid-state NMR ((29) Si and (13) C) spectroscopy show that the organic fragments of the organo-bridged silane are retained in the hybrid through covalent bonding and the (1) H NMR spectroscopic analysis provides evidence for the hydrogen-bonding interactions between the prodrug bearing three 5-FU units and the triazine-based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and (13) C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5-FU thanks to a controlled and targeted drug delivery. PMID:23929826

  14. 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

  15. Delivery methods for LVSD systems

    NASA Astrophysics Data System (ADS)

    Kasner, James H.; Brower, Bernard V.

    2011-06-01

    In this paper we present formats and delivery methods of Large Volume Streaming Data (LVSD) systems. LVSD systems collect TBs of data per mission with aggregate camera sizes in the 100 Mpixel to several Gpixel range at temporal rates of 2 - 60 Hz. We present options and recommendations for the different stages of LVSD data collection and delivery, to include the raw (multi-camera) data, delivery of processed (stabilized mosaic) data, and delivery of user-defined region of interest windows. Many LVSD systems use JPEG 2000 for the compression of raw and processed data. We explore the use of the JPEG 2000 Interactive Protocol (JPIP) for interactive client/server delivery to thick-clients (desktops and laptops) and MPEG-2 and H.264 to handheld thin-clients (tablets, cell phones). We also explore the use of 3D JPEG 2000 compression, defined in ISO 15444-2, for storage and delivery as well. The delivery of raw, processed, and region of interest data requires different metadata delivery techniques and metadata content. Beyond the format and delivery of data and metadata we discuss the requirements for a client/server protocol that provides data discovery and retrieval. Finally, we look into the future as LVSD systems perform automated processing to produce "information" from the original data. This information may include tracks of moving targets, changes of the background, snap shots of targets, fusion of multiple sensors, and information about "events" that have happened.

  16. Transmucosal delivery systems for calcitonin: a review.

    PubMed

    Torres-Lugo, M; Peppas, N A

    2000-06-01

    The commercial availability of peptides and proteins and their advantages as therapeutic agents have been the basis for tremendous efforts in designing delivery systems for such agents. The protection of these agents from biological fluids and physiological interactions is crucial for the treatment efficacy. One such agent is salmon calcitonin, a 32 amino-acid polypeptide hormone used in the treatment of bone diseases such as Paget's disease, hypercalcemia and osteoporosis. Researchers have studied different routes to deliver salmon calcitonin more effectively, including nasal, oral, vaginal and rectal delivery. These systems are designed to protect the polypeptide from the biological barriers that each delivery route imposes. Oil-based and polymer-based delivery systems are discussed. PMID:10811300

  17. Electronic Nicotine Delivery Systems

    PubMed Central

    Adkison, Sarah E.; O’Connor, Richard J.; Bansal-Travers, Maansi; Hyland, Andrew; Borland, Ron; Yong, Hua-Hie; Cummings, K. Michael; McNeill, Ann; Thrasher, James F.; Hammond, David; Fong, Geoffrey T.

    2013-01-01

    Background Electronic nicotine delivery systems (ENDS) initially emerged in 2003 and have since become widely available globally, particularly over the Internet. Purpose Data on ENDS usage patterns are limited. The current paper examines patterns of ENDS awareness, use, and product-associated beliefs among current and former smokers in four countries. Methods Data come from Wave 8 of the International Tobacco Control Four-Country Survey, collected July 2010 to June 2011 and analyzed through June 2012. Respondents included 5939 current and former smokers in Canada (n=1581); the U.S. (n=1520); the United Kingdom (UK; n=1325); and Australia (n=1513). Results Overall, 46.6% were aware of ENDS (U.S.: 73%, UK: 54%, Canada: 40%, Australia: 20%); 7.6% had tried ENDS (16% of those aware of ENDS); and 2.9% were current users (39% of triers). Awareness of ENDS was higher among younger, non-minority smokers with higher incomes who were heavier smokers. Prevalence of trying ENDS was higher among younger, nondaily smokers with a high income and among those who perceived ENDS as less harmful than traditional cigarettes. Current use was higher among both nondaily and heavy (≥20 cigarettes per day) smokers. In all, 79.8% reported using ENDS because they were considered less harmful than traditional cigarettes; 75.4% stated that they used ENDS to help them reduce their smoking; and 85.1% reported using ENDS to help them quit smoking. Conclusions Awareness of ENDS is high, especially in countries where they are legal (i.e., the U.S. and UK). Because trial was associated with nondaily smoking and a desire to quit smoking, ENDS may have potential to serve as a cessation aid. PMID:23415116

  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. PMID:26577995

  19. 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

  20. 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.

  1. 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.

  2. A novel pulsatile drug delivery system based on the physiochemical reaction between acrylic copolymer and organic acid: in vitro and in vivo evaluation.

    PubMed

    Zhang, Ziwei; Qi, Xiaole; Li, Xiangbo; Xing, Jiayu; Zhu, Xuehua; Wu, Zhenghong

    2014-02-28

    Multilayer-coating technology is the traditional method to achieve pulsatile drug release with the drawbacks of time consuming, more materials demanding and lack of efficiency. The purpose of this study was to design a novel pulsatile drug delivery system based on the physiochemical interaction between acrylic copolymer and organic acid with relatively simpler formulation and manufacturing process. The Enalapril Maleate (EM) pulsatile release pellets were prepared using extruding granulation, spheronization and fluid-bed coating technology. The ion-exchange experiment, hydration study and determination of glass transition temperature were conducted to explore the related drug release mechanism. Bioavailability experiment was carried out by administering the pulsatile release pellets to rats compared with marketed rapid release tablets Yisu. An obvious 4h lag time period and rapid drug release was observed from in vitro dissolution profiles. The release mechanism was a combination of both disassociated and undisassociated forms of succinic acid physiochemically interacting with Eudragit RS. The AUC0-τ of the EM pulsatile pellets and the market tablets was 702.384 ± 96.89 1 hn g/mL and 810.817 ± 67.712 h ng/mL, while the relative bioavailability was 86.62%. These studies demonstrate this novel pulsatile release concept may be a promising strategy for oral pulsatile delivery system. PMID:24368107

  3. 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

  4. Development of insulin delivery systems.

    PubMed

    Siddiqui, N I; Siddiqui, Ni; Rahman, S; Nessa, A

    2008-01-01

    Delivery system of insulin is vital for its acceptance and adherence to therapy for achieving the glycemic targets. Enormous developments have occurred in the delivery system of insulin during the last twenty years and each improvement was aimed at two common goals: patients convenience and better glycemic control. Till to date, the various insulin delivery systems are: syringes/vials, injection aids, jet injectors, transmucosal delivery, transdermal delivery, external insulin infusion pump, implantable insulin pumps, insulin pens and insulin inhalers. Syringe/vial is the oldest and conventional method, still widely used and relatively cheaper. Modern plastic syringes are disposable, light weight with microfine needle for patients convenience and comfort. Oral route could be the most acceptable and viable, if the barriers can be overcome and under extensive trial. Insulin pen device is an important milestone in the delivery system of insulin as it is convenient, discrete, painless, attractive, portable with flexible life style and improved quality of life. More than 80% of European diabetic patients are using insulin pen. Future digital pen will have better memory option, blood glucose monitoring system, insulin dose calculator etc. Insulin infusion pump is a good option for the children, busy patients with flexible lifestyle and those who want to avoid multiple daily injections. Pulmonary route of insulin delivery is a promising, effective, non-invasive and acceptable alternative method. Exubera, the world first insulin inhaler was approved by FDA in 28 January 2006. But due to certain limitations, it has been withdrawn from the market in October 2007. The main concern of inhaled insulin are: long term pulmonary safety issues, cost effectiveness and user friendly device. In future, more acceptable and cost effective insulin inhaler will be introduced. Newer avenues are under extensive trial for better future insulin delivery systems. PMID:18285745

  5. Nanoparticulate systems for polynucleotide delivery

    PubMed Central

    Basarkar, Ashwin; Singh, Jagdish

    2007-01-01

    Nanotechnology has tremendously influenced gene therapy research in recent years. Nanometer-size systems have been extensively investigated for delivering genes at both local and systemic levels. These systems offer several advantages in terms of tissue penetrability, cellular uptake, systemic circulation, and cell targeting as compared to larger systems. They can protect the polynucleotide from a variety of degradative and destabilizing factors and enhance delivery efficiency to the cells. A variety of polymeric and non-polymeric nanoparticles have been investigated in an effort to maximize the delivery efficiency while minimizing the toxic effects. This article provides a review on the most commonly used nanoparticulate systems for gene delivery. We have discussed frequently used polymers, such as, polyethyleneimine, poly (lactide-co-glycolide), chitosan, as well as non-polymeric materials such as cationic lipids and metallic nanoparticles. The advantages and limitations of each system have been elaborated. PMID:18019834

  6. 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. PMID:24325540

  7. 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. PMID:25753198

  8. Intracisternal delivery of NFκB-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment.

    PubMed

    Bockstael, Olivier; Tenenbaum, Liliane; Dalkara, Deniz; Melas, Catherine; De Witte, Olivier; Levivier, Marc; Chtarto, Abdelwahed

    2014-01-01

    We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NFκB activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic kainic acid (KA) injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions, respectively, known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions. We show that self-complementary AAV2/9 (scAAV2/9) delivery in the adult rat cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e., cortex, hippocampus, and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF) into the brain is a limiting factor. Interestingly, AAV2/9-2YF a rationally designed capsid mutant (affecting surface tyrosines) increased gene transfer efficiency approximately fivefold. Neurons, astrocytes, and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid. Finally, after a single intracisternal injection of scAAV2/9-2YF using the NFκB-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the CD11b marker of microglial activation. These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or transgenic disease models. However, further improvements are

  9. 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…

  10. Advances in Gene Delivery Systems

    PubMed Central

    Kamimura, Kenya; Suda, Takeshi; Zhang, Guisheng; Liu, Dexi

    2011-01-01

    The transfer of genes into cells, both in vitro and in vivo, is critical for studying gene function and conducting gene therapy. Methods that utilize viral and nonviral vectors, as well as physical approaches, have been explored. Viral vector-mediated gene transfer employs replication-deficient viruses such as retro-virus, adenovirus, adeno-associated virus and herpes simplex virus. A major advantage of viral vectors is their high gene delivery efficiency. The nonviral vectors developed so far include cationic liposomes, cationic polymers, synthetic peptides and naturally occurring compounds. These nonviral vectors appear to be highly effective in gene delivery to cultured cells in vitro but are significantly less effective in vivo. Physical methods utilize mechanical pressure, electric shock or hydrodynamic force to transiently permeate the cell membrane to transfer DNA into target cells. They are simpler than viral- and nonviral-based systems and highly effective for localized gene delivery. The past decade has seen significant efforts to establish the most desirable method for safe, effective and target-specific gene delivery, and good progress has been made. The objectives of this review are to (i) explain the rationale for the design of viral, nonviral and physical methods for gene delivery; (ii) provide a summary on recent advances in gene transfer technology; (iii) discuss advantages and disadvantages of each of the most commonly used gene delivery methods; and (iv) provide future perspectives. PMID:22200988

  11. Chemical functionalization of hyaluronic acid for drug delivery applications.

    PubMed

    Vasi, Ana-Maria; Popa, Marcel Ionel; Butnaru, Maria; Dodi, Gianina; Verestiuc, Liliana

    2014-05-01

    Functionalized hyaluronic acid (HA) derivatives were obtained by ring opening mechanism of maleic anhydride (MA). FTIR and H(1) NMR spectroscopy were used to confirm the chemical linkage of MA on the hyaluronic acid chains. Thermal analysis (TG-DTG and DSC) and GPC data for the new products revealed the formation of new functional groups, without significant changes in molecular weight and thermal stability. New gels based on hyaluronic acid modified derivatives were obtained by acrylic acid copolymerization in the presence of a redox initiation system. The resulted circular and interconnected pores of the gels were visualized by SEM. The release profiles of an ophthalmic model drug, pilocarpine from tested gels were studied in simulated media. Evaluation of the cytotoxicity and cell proliferation properties indicates the potential of the new systems to be used in contact with biological media in drug delivery applications. PMID:24656366

  12. Styrene maleic acid micelles as a nanocarrier system for oral anticancer drug delivery – dual uptake through enterocytes and M-cells

    PubMed Central

    Parayath, Neha N; Nehoff, Hayley; Müller, Philipp; Taurin, Sebastien; Greish, Khaled

    2015-01-01

    Drug delivery systems could potentially overcome low bioavailability and gastrointestinal toxicity, which are the major challenges for the development of oral anticancer drugs. Herein, we demonstrate the ability of styrene maleic acid (SMA) nanomicelles encapsulating epirubicin to traverse in vitro and ex vivo models of the intestinal epithelium without affecting the tissue integrity. Further, SMA micelles encapsulating a fluorescent dye dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) showed twofold higher accumulation in the liver and spleen, 15-fold higher accumulation in the tumor, and sixfold higher accumulation in the lung as compared with the free DiI, following oral administration in a mice xenograft breast cancer model. Additionally, SMA micelles showed colocalization with microfold (M)-cells and accumulation in Peyer’s patches, which together confirms the M-cell mediated uptake and transport of SMA micelles. Our results indicate that SMA micelles, showing dual uptake by enterocytes and M-cells, are a potential tool for safe oral anticancer drug delivery. PMID:26229468

  13. Physical Characterisation as an Insight into a Gene Delivery System Containing Cyclodextrins with Pluronic®-F127 and Folic acid as Non-Viral Vectors.

    PubMed

    Eng, Matthew; Elkordy, Amal A; McCarron, Paul A; Elkordy, Eman A; Faheem, Ahmed

    2014-01-01

    Gene delivery into cells offers opportunities to treat various human genetic diseases. Effective gene delivery is dependent on its stability and ability to transfect across cells. DNA is susceptible to enzymatic degradation and its negatively charge are barriers towards successful transfection. DNA has to be protected from degradation and neutralised. Non-viral vectors are preferred carrier systems, therefore, the use of cyclodextrins with Pluronic(®)-F127 and folic acid at different concentrations to stabilise the formulation was investigated. Formulations were characterised in fresh and freeze dried forms. DNA stability in formulations was tested by determining the stability of DNA against enzymatic degradation. Degree of DNA inclusion into cyclodextrins was investigated using fluorescence spectroscopy. Thermal behaviour was studied using Differential Scanning Calorimetry (DSC). Incorporation of Pluronic(®)-F127 produced most stable formulations regarding enzymatic degradation. These formulations show high percentage inclusion. Shift of peaks in FTIR data, appearance of uniform particulate as detected by SEM and changing in the denaturation temperature as demonstrated by DSC data for Pluronic(®)-F127 containing formulations confirm clear interaction between Pluronic(®)-F127 and cyclodextrin/ DNA complex. It was noted that γ-cyclodextrin provide better protection and inclusion compared to β-cyclodextrin. Pluronic(®)-F127 with cyclodextrins is a promising combination to improve stability. PMID:25158973

  14. Formulation and evaluation of mefenamic acid emulgel for topical delivery

    PubMed Central

    Khullar, Rachit; Kumar, Deepinder; Seth, Nimrata; Saini, Seema

    2011-01-01

    Emulgels have emerged as a promising drug delivery system for the delivery of hydrophobic drugs. The objective of the study was to prepare emulgel of mefenamic acid, a NSAID, using Carbapol 940 as a gelling agent. Mentha oil and clove oil were used as penetration enhancers. The emulsion was prepared and it was incorporated in gel base. The formulations were evaluated for rheological studies, spreading coefficient studies, bioadhesion strength, skin irritation studies, in vitro release, ex vivo release studies, anti-inflammatory activity and analgesic activity. Formulation F2 and F4 showed comparable analgesic and anti-inflammatory activity when they compared with marketed diclofenac sodium gel. So, it can be concluded that topical emulgel of mefenamic acid posses an effective anti-inflammatory and analgesic activity. PMID:23960777

  15. Special Delivery Systems. Final Report.

    ERIC Educational Resources Information Center

    Molek, Carol

    The Special Delivery Systems project developed a curriculum for students with learning disabilities (LD) in an adult basic education program. The curriculum was designed to assist and motivate the students in the educational process. Fourteen students with LD were recruited and screened. The curriculum addressed varied learning styles combined…

  16. 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. PMID:26891564

  17. 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.

  18. 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

  19. Planning health care delivery systems.

    PubMed Central

    Baum, M A; Bergwall, D F; Reeves, P N

    1975-01-01

    The increasing concern and interest in the health delivery system in the United States has placed the health system planners in a difficult position. They are inadequately prepared, in many cases, to deal with the management techniques that have been designed for use with system problems. This situation has been compounded by the failure, until recently, of educational programs to train new health professionals in these techniques. Computer simulation is a technique that allows the planners dynamic feedback on his proposed plans. This same technique provides the planning student with a better understanding of the systems planning process. PMID:1115292

  20. 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 Central

    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. PMID:27471381

  1. 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. PMID:27471381

  2. 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. PMID:26948622

  3. Recent Developments in Peptide-Based Nucleic Acid Delivery

    PubMed Central

    Veldhoen, Sandra; Laufer, Sandra D.; Restle, Tobias

    2008-01-01

    Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10–30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls. PMID:19325804

  4. 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. PMID:24901208

  5. Recent developments in peptide-based nucleic acid delivery.

    PubMed

    Veldhoen, Sandra; Laufer, Sandra D; Restle, Tobias

    2008-06-01

    Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls. PMID:19325804

  6. Oleic acid-enhanced transdermal delivery pathways of fluorescent nanoparticles

    NASA Astrophysics Data System (ADS)

    Lo, Wen; Ghazaryan, Ara; Tso, Chien-Hsin; Hu, Po-Sheng; Chen, Wei-Liang; Kuo, Tsung-Rong; Lin, Sung-Jan; Chen, Shean-Jen; Chen, Chia-Chun; Dong, Chen-Yuan

    2012-05-01

    Transdermal delivery of nanocarriers provides an alternative pathway to transport therapeutic agents, alleviating pain, improving compliance of patients, and increasing overall effectiveness of delivery. In this work, enhancement of transdermal delivery of fluorescent nanoparticles and sulforhodamine B with assistance of oleic acid was visualized utilizing multiphoton microscopy (MPM) and analyzed quantitatively using multi-photon excitation-induced fluorescent signals. Results of MPM imaging and MPM intensity-based spatial depth-dependent analysis showed that oleic acid is effective in facilitating transdermal delivery of nanoparticles.

  7. 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.

  8. Self-nanoemulsifying drug delivery system of trans-cinnamic acid: formulation development and pharmacodynamic evaluation in alloxan-induced type 2 diabetic rat model.

    PubMed

    Wang, Houyong; Li, Qiang; Deng, Wenwen; Omari-Siaw, E; Wang, Qilong; Wang, Shicheng; Wang, Shengli; Cao, Xia; Xu, Ximing; Yu, Jiangnan

    2015-03-01

    The objective of this study was to formulate a self-nanoemulsifying oral drug delivery system (SNEDDS) for the poorly water-soluble trans-Cinnamic acid (t-CA SNEDDS) that could be evaluated for its antihyperglycemic efficacy in comparison to the parent t-CA in an alloxan-induced diabetic rat model. A SNEDDS formulation consisting of 60% surfactant (Kolliphor EL), 10% co-surfactant (PEG 400) and 30% oil (isopropyl myristate) proved to be optimal. t-CA SNEDDS (80 mg/kg, p.o.), t-CA suspension (80 mg/kg, p.o.), and Metformin Hydrochloride Tablets (230 mg/kg, p.o.) were administer qdfor 30 days to diabetic rats. After treatment the body weight of diabetic rats was increased, blood glucose levels, total cholesterol, and triglyceride in the serum tended to be normalized, while the levels of alanine aminotransferase and aspartate aminotransferase were markedly decreased. The effects of t-CA SNEDDS were superior to that of the t-CA suspension. The present study demonstrated that t-CA was effective in attenuating the effects of alloxan treatment and that t-CA SNEDDS with a more favorable absorption and enhanced bioavailability is more effective than t-CA. PMID:25847843

  9. Electroporation-enhanced delivery of nucleic acid vaccines.

    PubMed

    Broderick, Kate E; Humeau, Laurent M

    2015-02-01

    The naked delivery of nucleic acid vaccines is notoriously inefficient, and an enabling delivery technology is required to direct efficiently these constructs intracellularly. A delivery technology capable of enhancing nucleic acid uptake in both cells in tissues and in culture is electroporation (EP). EP is a physical delivery mechanism that increases the permeability of mammalian cell membranes and allows the trafficking of large macromolecules into the cell. EP has now been used extensively in the clinic and been shown to be an effective method to increase both the uptake of the construct and the breadth and magnitude of the resulting immune responses. Excitingly, 2014 saw the announcement of the first EP-enhanced DNA vaccine Phase II trial demonstrating clinical efficacy. This review seeks to introduce the reader to EP as a technology to enhance the delivery of DNA and RNA vaccines and highlight several published clinical trials using this delivery modality. PMID:25487734

  10. 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. PMID:26652353

  11. MATra - Magnet Assisted Transfection: combining nanotechnology and magnetic forces to improve intracellular delivery of nucleic acids.

    PubMed

    Bertram, J

    2006-08-01

    Recent efforts combining nanotechnology and magnetic properties resulted in the development and commercialization of magnetic nanoparticles that can be used as carriers for nucleic acids for in vitro transfection and for gene therapy approaches including DNA-based vaccination strategies. The efficiency of intracellular delivery is still a limiting factor for basic cell biological research and also for emerging technologies such as temporary gene silencing based on inhibitory RNA/siRNA. Nanotechnology has resulted in a variety of different nanostructures and especially nanoparticles as carriers in a wide range of new drug delivery systems for conventional drugs, recombinant proteins, vaccines and more recently nucleic acids. It is possible to combine superparamagnetic nanoparticles with magnetic forces to increase, direct and optimize intracellular delivery of biomolecules. This article discusses the main approaches in the field of magnet assisted transfection (MATra) focusing on the transfection or intracellular delivery of nucleic acids, although also suitable to improve the intracellular delivery of other biomolecules. PMID:16918404

  12. 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

  13. 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 Central

    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/58S-bioactive glass (58S-BG) containing poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been prepared and then characterized. The effects of further addition of 58S-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 58S-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. PMID:24949477

  14. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-04-01

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

  15. Integrated delivery systems. Evolving oligopolies.

    PubMed

    Malone, T A

    1998-01-01

    The proliferation of Integrated Delivery Systems (IDSs) in regional health care markets has resulted in the movement of these markets from a monopolistic competitive model of behavior to an oligopoly. An oligopoly is synonymous with competition among the few, as a small number of firms supply a dominant share of an industry's total output. The basic characteristics of a market with competition among the few are: (1) A mutual interdependence among the actions and behaviors of competing firms; (2) competition tends to rely on the differentiation of products; (3) significant barriers to entering the market exist; (4) the demand curve for services may be kinked; and (5) firms can benefit from economies of scale. An understanding of these characteristics is essential to the survival of IDSs as regional managed care markets mature. PMID:10180497

  16. 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.

  17. 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

  18. Physically facilitating drug-delivery systems

    PubMed Central

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

    2012-01-01

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

  19. 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.

  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. Gastroretentive delivery systems: hollow beads.

    PubMed

    Talukder, R; Fassihi, R

    2004-04-01

    The objective of this study was to develop a floatable multiparticulate system with potential for intragastric sustained drug delivery. Cross-linked beads were made by using calcium and low methoxylated pectin (LMP), which is an anionic polysaccharide, and calcium, LMP, and sodium alginate. Beads were dried separately in an air convection type oven at 40 degrees C for 6 hours and in a freeze dryer to evaluate the changes in bead characteristics due to process variability. Riboflavin (B-2), tetracycline (TCN), and Methotrexate (MTX) were used as model drugs for encapsulation. Ionic and nonionic excipients were added to study their effects on the release profiles of the beads. The presence of noncross linking agents in low amounts (less than 2%) did not significantly interfere with release kinetics. For an amphoteric drug like TCN, which has pH dependent solubility, three different pHs (1.5, 5.0, and 8.0) of cross-linking media were used to evaluate the effects of pH on the drug entrapment capacity of the beads. As anticipated, highest entrapment was possible when cross-linking media pH coincided with least drug solubility. Evaluation of the drying process demonstrated that the freeze-dried beads remained buoyant over 12 hours in United States Pharmacopeia (USP) hydrochloride buffer at pH 1.5, whereas the air-dried beads remained submerged throughout the release study. Confocal laser microscopy revealed the presence of air-filled hollow spaces inside the freeze dried beads, which was responsible for the flotation property of the beads. However, the release kinetics from freeze dried beads was independent of hydrodynamic conditions. Calcium-pectinate-alginate beads released their contents at much faster rates than did calcium-pectinate beads (100% in 10 hours vs. 50% in 10 hours). It appears that the nature of cross-linking, drying method, drug solubility, and production approach are all important and provide the opportunity and potential for development of a

  2. Viral and nonviral delivery systems for gene delivery.

    PubMed

    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

  3. 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

  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. Microneedles As a Delivery System for Gene Therapy.

    PubMed

    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

  6. 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.

  7. 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

  8. Self-assembled nucleolipids: from supramolecular structure to soft nucleic acid and drug delivery devices

    PubMed Central

    Allain, Vanessa; Bourgaux, Claudie; Couvreur, Patrick

    2012-01-01

    This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly. High-resolution structural investigations reveal the diversity and complexity of assemblies formed by these bioinspired amphiphiles, resulting from the interplay between aggregation of the lipid chains and base–base interactions. Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids. Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs. PMID:22075995

  9. Fibrin Glue as a Drug Delivery System

    PubMed Central

    Spicer, Patrick P.; Mikos, Antonios G.

    2010-01-01

    Fibrin glue has been used surgically for decades for hemostasis as well as a sealant. It has also been researched as both a gel for cell delivery and a vehicle for drug delivery. The drug delivery applications for fibrin glue span tissue engineering to chemotherapy and involve several mechanisms for drug matrix interactions and control of release kinetics. Additionally, drugs or factors can be loaded in the gel via impregnation and tethering to the gel through covalent linkages or affinity based systems. This review highlights recent research of fibrin glue as a drug delivery vehicle. PMID:20637815

  10. 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.

  11. Polyethylenimine: A versatile, multifunctional non-viral vector for nucleic acid delivery.

    PubMed

    Pandey, Abhijeet P; Sawant, Krutika K

    2016-11-01

    Polyethylenimine (PEI) has recently been widely studied for the design of nucleic acid delivery vehicles. Gene delivery using PEI involves condensation of DNA into compact particles, uptake into the cells, release from the endosomal compartment into the cytoplasm, and uptake of the DNA into the nucleus. PEIs being positively charged, linear or branched polymers are able to form nanoscale complexes with small RNAs, leading to RNA protection, cellular delivery, and intracellular release. This review highlights the important properties of various PEIs with regard to their use for nucleic acid delivery. Brief discussion on cellular uptake mechanism of non-viral vector is included to understand its utility for gene delivery. Applications of modified PEI for increased efficacy, altered pharmacokinetic properties; improved biocompatibility and targeted delivery have also been discussed. An overview of simulation studies which can help in understanding the underlying complexation mechanism has also been included. The review provides a brief discussion about clinical trials and patents related to nucleic acid delivery using PEI based systems. PMID:27524093

  12. Delivery system for laser medical instrument

    NASA Astrophysics Data System (ADS)

    Jelinkova, Helena; Nemec, Michal; Sulc, Jan; Cerny, Pavel; Miyagi, Mitsunobu; Shi, Yi-Wei; Matsuura, Yuji

    2003-10-01

    Investigation of the special constructed hollow glass waveguides was realized. Maximum mean power transmitted via this delivery system was 5.8 W (for alexandrite radiation) or 5.1 W (for mid infrared Er.YAG light). Maximum output intensity 173 GW/cm2 was reached for delivery of 55 psec long Nd:YAG pulses.

  13. 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. PMID:25042710

  14. Nucleic-Acid Delivery Using Lipid Nanocapsules.

    PubMed

    Lagarce, Frederic; Passirani, Catherine

    2016-01-01

    Lipid nanocapsules (LNCs) were designed more than 15 years ago to deliver lipophilic drugs to cells with non toxic excipients by mimicking lipoproteins. During the last 5 years these promising nanocarriers were re-designed to deliver nucleic acids to cancer cells. This short review sums up the features of LNCs and describes how DNAs or RNAs can be associated or encapsulated in these lipid carriers. The results of transfection effects on cells in vitro or in vivo are also presented. These new therapeutic strategies have been mainly proposed for glioma and melanoma treatment because these cancers are characterized by multiple acquired resistances, which can be reversed by DNA transfection or siRNA interference as it is discussed in this paper. In conclusion, LNCs are very good candidates to deliver nucleic acids to cells in the course of anti-cancer therapies. PMID:27033510

  15. In vivo Evaluation of Self Emulsifying Drug Delivery System for Oral Delivery of Nevirapine

    PubMed Central

    Chudasama, A. S.; Patel, V. V.; Nivsarkar, M.; Vasu, Kamala K.; Shishoo, C. J.

    2014-01-01

    Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation. However, HIV/AIDS patients experience a variety of functional and anatomical abnormalities in gastrointestinal tract that result in diarrhoea and nutrient malabsorption. Medium chain triglycerides are readily absorbed from the small bowel under conditions in which the absorption of long chain triglycerides is impaired. Therefore, nevirapine self-emulsifying drug delivery system containing medium chain fatty acid, caprylic acid and a solubilizer, Soluphor® P (2-pyrrolidone) was developed and found to be superior to the marketed conventional suspension with respect to in vitro diffusion and ex vivo intestinal permeability. This self-emulsifying drug delivery system has now been further investigated for in vivo absorption in an animal model. The contribution of caprylic acid and Soluphor® P on in vivo absorption of nevirapine was also studied in the present study. The bioavailability of nevirapine from self-emulsifying drug delivery system, after oral administration, was 2.69 times higher than that of the marketed suspension. The improved bioavailability could be due to absorption of nevirapine via both portal and intestinal lymphatic routes. The study indicates that medium chain or structured triglycerides can be a better option to develop self-emulsifying drug delivery system for lipophilic and extensively metabolised drugs like nevirapine for patients with AIDS-associated malabsorption. PMID:25035533

  16. In vivo Evaluation of Self Emulsifying Drug Delivery System for Oral Delivery of Nevirapine.

    PubMed

    Chudasama, A S; Patel, V V; Nivsarkar, M; Vasu, Kamala K; Shishoo, C J

    2014-05-01

    Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation. However, HIV/AIDS patients experience a variety of functional and anatomical abnormalities in gastrointestinal tract that result in diarrhoea and nutrient malabsorption. Medium chain triglycerides are readily absorbed from the small bowel under conditions in which the absorption of long chain triglycerides is impaired. Therefore, nevirapine self-emulsifying drug delivery system containing medium chain fatty acid, caprylic acid and a solubilizer, Soluphor(®) P (2-pyrrolidone) was developed and found to be superior to the marketed conventional suspension with respect to in vitro diffusion and ex vivo intestinal permeability. This self-emulsifying drug delivery system has now been further investigated for in vivo absorption in an animal model. The contribution of caprylic acid and Soluphor(®) P on in vivo absorption of nevirapine was also studied in the present study. The bioavailability of nevirapine from self-emulsifying drug delivery system, after oral administration, was 2.69 times higher than that of the marketed suspension. The improved bioavailability could be due to absorption of nevirapine via both portal and intestinal lymphatic routes. The study indicates that medium chain or structured triglycerides can be a better option to develop self-emulsifying drug delivery system for lipophilic and extensively metabolised drugs like nevirapine for patients with AIDS-associated malabsorption. PMID:25035533

  17. 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.

  18. 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

  19. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

    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. PMID:24936306

  20. Delivery systems for intradermal vaccination.

    PubMed

    Kim, Y C; Jarrahian, C; Zehrung, D; Mitragotri, S; Prausnitz, M R

    2012-01-01

    Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development. PMID:21472533

  1. Cationic lipid-mediated nucleic acid delivery: beyond being cationic.

    PubMed

    Rao, N Madhusudhana

    2010-03-01

    Realization of the potential of nucleic acids as drugs is intricately linked to their in vivo delivery. Cationic lipids demonstrated tremendous potential as safe, efficient and scalable in vitro carriers of nucleic acids. For in vivo delivery of nucleic acids, the extant two component liposomal preparations consisting of cationic lipids and nucleic acids have been largely found to be insufficient. Being a soft matter, liposomes readily respond to many physiological variables leading to complex component and morphological changes, thus confounding the efforts in a priori identification of a "competent" formulation. In the recent past many chemical moieties that provide advantage in facing the challenges of barriers in vivo, were incorporated into cationic lipids to improve the transfection efficiency. The cationic lipids, essential for DNA condensation and protection, definitely require additional components to be efficient in vivo. In addition, formulations of cationic lipid carriers with non-lipidic components, mainly peptides, have demonstrated success in in vivo transfection. The present review describes some recent successes of in vivo nucleic acid delivery by cationic lipids. PMID:20060819

  2. 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

  3. 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.

  4. Amino Acid-Functionalized Dendritic Polyglycerol for Safe and Effective siRNA Delivery.

    PubMed

    Zeng, Hanxiang; Schlesener, Cathleen; Cromwell, Olivia; Hellmund, Markus; Haag, Rainer; Guan, Zhibin

    2015-12-14

    The development of safe and effective delivery vectors is a great challenge for the medicinal application of RNA interference (RNAi). In this study, we aimed to develop new synthetic transfection agents based on dendritic polyglycercol (dPG), which has shown great biocompatibility in several biomaterial applications. Histidine and aromatic amino acids were conjugated to the amine-terminated dPGs through amide bonds. We systematically tuned the amino acid combination, functionalization ratio, ligand density, and dPG core size to find optimal vectors. It was found that histidine-tryptophan-functionalized dPGs exhibited improved delivery efficiency and greatly reduced toxicity over simple amine-terminated dPGs. Furthermore, the optimized vectors exhibited strong siRNA binding and high transfection efficiency in serum containing media. The results indicate that the current amino acid-functionalized dPG system is a promising candidate for in vivo siRNA delivery applications. PMID:26569043

  5. Microwell array-mediated delivery of lipoplexes containing nucleic acids for enhanced therapeutic efficacy.

    PubMed

    Wu, Yun; Gallego-Perez, Daniel; Lee, L James

    2015-01-01

    Many delivery methods have been developed to improve the therapeutic efficacy and facilitate the clinical translation of nucleic acids-based therapeutics. We present a facile microwell array to mediate the delivery of nucleic acids carried by lipoplexes, which combines the advantages of lipoplexes as an efficient carrier system, the surface mediated delivery, and the control of surface topography. This method shows much higher transfection efficiency than conventional transfection method for oligodeoxynucleotides and microRNAs, and thus significantly reduces the effective therapeutic dosages. Microwell array is also a very flexible platform. Multifunctional lipoplexes containing both nucleic acid therapeutics and imaging reagents can be easily prepared in the microwell array and efficiently delivered to cells, demonstrating its potential applications in theranostic medicine. PMID:25319649

  6. 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

  7. Novel drug delivery systems for glaucoma

    PubMed Central

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

    2011-01-01

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

  8. Poly (lactic acid)-poly (ethylene glycol) nanoparticles provide sustained delivery of a Chlamydia trachomatis recombinant MOMP peptide and potentiate systemic adaptive immune responses in mice

    PubMed Central

    Dixit, Saurabh; Singh, Shree R.; Yilma, Abebayehu N.; Agee, Ronald D.; Taha, Murtada; Dennis, Vida A.

    2014-01-01

    PLA-PEG [poly (lactic acid)-poly (ethylene glycol)], a biodegradable copolymer, is underexploited for vaccine delivery although it exhibits enhanced biocompatibility and slow release immune-potentiating properties. We document here successful encapsulation of M278, a Chlamydia trachomatis MOMP (major outer membrane protein) peptide, within PLA-PEG nanoparticles by size (~73–100 nm), zeta potential (−16 mV), smooth morphology, encapsulation efficiency (~60%), slow release pattern, and non-toxicity to macrophages. Immunization of mice with encapsulated-M278 elicited higher M278-specific T-cell cytokines [Th1 (IFN-γ, IL-2), Th17 (IL-17)] and antibodies [Th1 (IgG2a), Th2 (IgG1, IgG2b)] compared to bare M278. Encapsulated-M278 mouse serum inhibited Chlamydia infectivity of macrophages, with a concomitant transcriptional down-regulation of MOMP, its cognate TLR2 and CD80 co-stimulatory molecule. Collectively, encapsulated-M278 potentiated crucial adaptive immune responses, which are required by a vaccine candidate for protective immunity against Chlamydia. Our data highlights PLA-PEG’s potential for vaccines, which resides in its slow release and potentiating effects to bolster immune responses. PMID:24602605

  9. Development of a controlled release of salicylic acid loaded stearic acid-oleic acid nanoparticles in cream for topical delivery.

    PubMed

    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

  10. 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

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

    DOEpatents

    Frechet, Jean M. J.; Standley, Stephany M.; Jain, Rachna; Lee, Cameron C.

    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.

  12. Albumin-based nanocomposite spheres for advanced drug delivery systems.

    PubMed

    Misak, Heath E; Asmatulu, Ramazan; Gopu, Janani S; Man, Ka-Poh; Zacharias, Nora M; Wooley, Paul H; Yang, Shang-You

    2014-01-01

    A novel drug delivery system incorporating human serum albumin, poly(lactic-co-glycolic acid, magnetite nanoparticles, and therapeutic agent(s) was developed for potential application in the treatment of diseases such as rheumatoid arthritis and skin cancer. An oil-in-oil emulsion/solvent evaporation (O/OSE) method was modified to produce a drug delivery system with a diameter of 0.5–2 μm. The diameter was mainly controlled by adjusting the viscosity of albumin in the discontinuous phase of the O/OSE method. The drug-release study showed that the release of drug and albumin was mostly dependent on the albumin content of the drug delivery system, which is very similar to the drug occlusion-mesopore model. Cytotoxicity tests indicated that increasing the albumin content in the drug delivery system increased cell viability, possibly due to the improved biocompatibility of the system. Overall, these studies show that the proposed system could be a viable option as a drug delivery system in the treatment of many illnesses, such as rheumatoid arthritis, and skin and breast cancers. PMID:24106002

  13. Application of Controlled Radical Polymerization for Nucleic Acid Delivery

    PubMed Central

    CHU, DAVID S.H.; SCHELLINGER, JOAN G.; SHI, JULIE; CONVERTINE, ANTHONY J.; STAYTON, PATRICK S.; PUN, SUZIE H.

    2012-01-01

    CONSPECTUS Nucleic acid-based therapeutics can potentially address otherwise untreatable genetic disorders and have significant potential for a wide range of diseases. Therapeutic gene delivery can restore protein function by replacing defunct genes to restore cellular health while RNA interference (RNAi) can mask mutated and harmful genes. Cationic polymers have been extensively studied for nucleic acid delivery applications due to their self-assembly with nucleic acids into virus-sized nanoparticles and high transfection efficiency in vitro, but toxicity and particle stability have limited their clinical applications. The advent of controlled radical polymerization has improved the quality, control and reproducibility of synthesized materials. Controlled radical polymerization yields well-defined, narrowly disperse materials of designable architectures and molecular weight, allowing study of the effects of polymer architecture and molecular weight on transfection efficiency and cytotoxicity for improved design of next-generation vectors. Robust methods such as atom transfer radical polymerization (ATRP), reverse addition-fragmentation chain transfer polymerization (RAFT), and ring-opening metastasis polymerization (ROMP) have been used to engineer materials that specifically enhance extracellular stability, cellular specificity, and decrease toxicity. This Account reviews findings from structure-function studies that have elucidated key design motifs necessary for the development of effective nucleic acid vectors. In addition, polymers that are biodegradable, form supramolecular structures, target specific cells, or facilitate endosomal release are also discussed. Finally, promising materials with in vivo applications ranging from pulmonary gene delivery to DNA vaccines are described. PMID:22242774

  14. 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.

  15. Phenylboronic-Acid-Based Polymeric Micelles for Mucoadhesive Anterior Segment Ocular Drug Delivery.

    PubMed

    Prosperi-Porta, Graeme; Kedzior, Stephanie; Muirhead, Benjamin; Sheardown, Heather

    2016-04-11

    Topical drug delivery to the front of the eye is extremely inefficient due to effective natural protection mechanisms such as precorneal tear turnover and the relative impermeability of the cornea and sclera tissues. This causes low ocular drug bioavailability, requiring large frequent doses that result in high systemic exposure and side effects. Mucoadhesive drug delivery systems have the potential to improve topical drug delivery by increasing pharmaceutical bioavailability on the anterior eye surface. We report the synthesis and characterization of a series of poly(l-lactide)-b-poly(methacrylic acid-co-3-acrylamidophenylboronic acid) block copolymer micelles for use as mucoadhesive drug delivery vehicles. Micelle properties, drug release rates, and mucoadhesion were shown to depend on phenylboronic acid content. The micelles showed low in vitro cytotoxicity against human corneal epithelial cells and undetectable acute in vivo ocular irritation in Sprague-Dawley rats, suggesting good biocompatibility with the corneal surface. The micelles show the potential to significantly improve the bioavailability of topically applied ophthalmic drugs, which could reduce dosage, frequency of administration, and unintentional systemic exposure. This would greatly improve the delivery of the ocular drugs such as the potent immunosuppressive cyclosporine A used in the treatment of severe dry eye disease. PMID:26963738

  16. Star polymers with a cationic core prepared by ATRP for cellular nucleic acids delivery.

    PubMed

    Cho, Hong Y; Averick, Saadyah E; Paredes, Eduardo; Wegner, Katarzyna; Averick, Amram; Jurga, Stefan; Das, Subha R; Matyjaszewski, Krzysztof

    2013-05-13

    Poly(ethylene glycol) (PEG)-based star polymers with a cationic core were prepared by atom transfer radical polymerization (ATRP) for in vitro nucleic acid (NA) delivery. The star polymers were synthesized by ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and ethylene glycol dimethacrylate (EGDMA). Star polymers were characterized by gel permeation chromatography, zeta potential, and dynamic light scattering. These star polymers were combined with either plasmid DNA (pDNA) or short interfering RNA (siRNA) duplexes to form polyplexes for intracellular delivery. These polyplexes with either siRNA or pDNA were highly effective in NA delivery, particularly at relatively low star polymer weight or molar ratios, highlighting the importance of NA release in efficient delivery systems. PMID:23560989

  17. 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. PMID:26022888

  18. A tumoral acidic pH-responsive drug delivery system based on a novel photosensitizer (fullerene) for in vitro and in vivo chemo-photodynamic therapy.

    PubMed

    Shi, Jinjin; Liu, Yan; Wang, Lei; Gao, Jun; Zhang, Jing; Yu, Xiaoyuan; Ma, Rou; Liu, Ruiyuan; Zhang, Zhenzhong

    2014-03-01

    Fullerene has shown great potential both in drug delivery and photodynamic therapy. Herein, we developed a doxorubicin (DOX)-loaded poly(ethyleneimine) (PEI) derivatized fullerene (C60-PEI-DOX) to facilitate combined chemotherapy and photodynamic therapy in one system, and DOX was covalently conjugated onto C60-PEI by the pH-sensitive hydrazone linkage. The release profiles of DOX from C60-PEI-DOX showed a strong dependence on the environmental pH value. The biodistributions of C60-PEI-DOX were investigated by injecting CdSe/ZnS (Qds) labeled conjugates (C60-PEI-DOX/Qds) into tumor-bearing mice. C60-PEI-DOX/Qds showed a higher tumor targeting efficiency compared with Qds alone. Compared with free DOX in an in vivo murine tumor model, C60-PEI-DOX afforded higher antitumor efficacy without obvious toxic effects to normal organs owing to its good tumor targeting efficacy and the 2.4-fold greater amount of DOX released in the tumor than in the normal tissues. C60-PEI-DOX also showed high antitumor efficacy during photodynamic therapy. The ability of C60-PEI-DOX nanoparticles to combine local specific chemotherapy with external photodynamic therapy significantly improved the therapeutic efficacy of the cancer treatment, the combined treatment demonstrating a synergistic effect. These results suggest that C60-PEI-DOX may be promising for high treatment efficacy with minimal side effects in future therapy. PMID:24211343

  19. Preparation and characterization of microemulsion formulations of nicotinic acid and its prodrugs for transdermal delivery.

    PubMed

    Tashtoush, Bassam M; Bennamani, Amina N; Al-Taani, Bashar M

    2013-01-01

    At pharmacological doses, nicotinic acid has a lipid-regulating effect and is in use clinically for that purpose. However, despite of all features, its utility is strongly limited by several disadvantages such as, extensive hepatic metabolism and flushing. Transdermal delivery of nicotinic acid may, therefore, be the solution to reducing side effects associated with oral administration, and to maintaining constant therapeutic blood levels for longer duration. The aim of this investigation was to develop a suitable formulation or select a suitable vehicle for the transdermal delivery of highly lipophilic prodrugs of nicotinic acid (dodecyl and myristyl nicotinate) designed to deliver nicotinic acid through skin without causing vasodilatation and flushing and optimizing its delivery to the blood stream. A microemulsion system and penetration enhancers have been attempted in this study. The microemulsion system was composed of isopropyl myristate (IPM), water and a 4:1 (w/w) mixture of Labrasol and Peceol where a pseudoternary phase diagram was constructed. Furthermore, the microemulsion formulations with different component ratios were characterized by determination of conductivity, pH, particle size, viscosity and refractive index. According to the particle size analysis, conductivity and viscosity measurements, the microemulsion formulations that formed were of oil-in-water type. The transdermal permeability of nicotinic acid and its prodrugs was evaluated in vitro using Franz diffusion cells fitted with mice skin and nicotinic acid concentration was analyzed by high performance liquid chromatography. A theoretical design of percutaneous penetration optimization in which prodrugs derivation and enhancer application are combined based on the skin diffusion model was experimentally verified. The selected formulations seemed promising for developing a transdermal drug delivery system of nicotinic acid from dodecyl nicotinate that would offer advantages like possible

  20. 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.

  1. 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.

  2. Development of antimigraine transdermal delivery systems of pizotifen malate.

    PubMed

    Serna-Jiménez, C E; del Rio-Sancho, S; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; López-Castellano, A; Merino, V

    2015-08-15

    The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate. PMID:26196273

  3. 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. PMID:23016644

  4. 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. PMID:27305810

  5. [Progression of drug delivery system for glaucoma].

    PubMed

    Xu, Yan; Lyu, Liu

    2014-12-01

    Reduction of intraocular pressure (IOP) by drugs is a major treatment for glaucoma. Clinically, diverse antiglaucoma drugs take effect to decrease the IOP through different mechanisms.However, due to limitations of traditional form of eye drops, the bioavailability of the drug and the patient compliance is lowered, the clinical efficacy is not good and also some toxic and side-effects come out.Otherwise, traditional medication is not suitable for neuroprotective drugs to work on both retina and optic nerve. Drug delivery system has the potential to improve the bioavailability of the drug, prolong the time of drug action, decrease the dosage and frequency of drugs, reduce the side-effects, and improve the patient compliance and efficacy.It is one of the most important studies in glaucoma medication development because it is valuable for patients' neuroprotection.Nowadays, several novel delivery systems have been designed. This review will focus on the progressions of some of the sustained-release antiglaucoma eye drops, polymeric gels, colloidal systems, membrane-controlled drug delivery system, ocular implants, and transscleral drug delivery systems. PMID:25619186

  6. 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

  7. Incorporation of Naked Peptide Nucleic Acids into Liposomes Leads to Fast and Efficient Delivery.

    PubMed

    Avitabile, Concetta; Accardo, Antonella; Ringhieri, Paola; Morelli, Giancarlo; Saviano, Michele; Montagner, Giulia; Fabbri, Enrica; Gallerani, Eleonora; Gambari, Roberto; Romanelli, Alessandra

    2015-08-19

    The delivery of peptide nucleic acids (PNAs) to cells is a very challenging task. We report here that a liposomal formulation composed of egg PC/cholesterol/DSPE-PEG2000 can be loaded, according to different encapsulation techniques, with PNA or fluorescent PNA oligomers. PNA loaded liposomes efficiently and quickly promote the uptake of a PNA targeting the microRNA miR-210 in human erythroleukemic K562 cells. By using this innovative delivery system for PNA, down-regulation of miR-210 is achieved at a low PNA concentration. PMID:26176882

  8. 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.

  9. Drug Delivery Systems: Entering the Mainstream

    NASA Astrophysics Data System (ADS)

    Allen, Theresa M.; Cullis, Pieter R.

    2004-03-01

    Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.

  10. 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. PMID:27016914

  11. Human Services Course Delivery Systems.

    ERIC Educational Resources Information Center

    Soong, Robert K.; And Others

    This paper deals with various teaching methods and techniques currently is use in junior colleges in the Chicago area including traditional as well as innovative methods. The basic assumption is that teaching and learning are both essential aspects of the same system. The human services field is defined as encompassing the basic area of social…

  12. Systemic delivery of artemether by dissolving microneedles.

    PubMed

    Qiu, Yuqin; Li, Chun; Zhang, Suohui; Yang, Guozhong; He, Meilin; Gao, Yunhua

    2016-07-11

    Dissolving microneedles (DMNs) based transdermal delivery is an attractive drug delivery approach with minimal invasion. However, it is still challenging to load poorly water-soluble drugs in DMNs for systemic delivery. The aim of the study was to develop DMNs loaded with artemether (ARM) as a model drug, to enable efficient drug penetration through skin for systemic absorption and distribution. The micro-conduits created by microneedles were imaged by confocal laser scanning microscopy (CLSM), and the insertion depth was suggested to be about 270μm. The maximum amount of ARM delivered into skin was 72.67±2.69% of the initial dose loaded on DMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma ARM concentrations, after ARM-loaded DMNs treatment. In contrast to intramuscular injection, DMNs application resulted in lower peak plasma levels, but higher plasma ARM concentration at 8h after administration. There were no significant difference in area under the curve and bioavailability between DMNs group and intramuscular group (P>0.05). Pharmacodynamics studies performed in collagen-induced arthritis (CIA) rats showed that ARM-loaded DMNs could reverse paw edema, similar to ARM intramuscular injection. In conclusion, developed DMNs provided a potential minimally invasive route for systemic delivery of poorly water-soluble drugs. PMID:27150946

  13. 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

  14. 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. PMID:15889632

  15. Nanoscaled poly(L-glutamic acid)/doxorubicin-amphiphile complex as pH-responsive drug delivery system for effective treatment of nonsmall cell lung cancer.

    PubMed

    Li, Mingqiang; Song, Wantong; Tang, Zhaohui; Lv, Shixian; Lin, Lin; Sun, Hai; Li, Quanshun; Yang, Yan; Hong, Hua; Chen, Xuesi

    2013-03-13

    Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Herein, we develop a polypeptide-based block ionomer complex formed by anionic methoxy poly(ethylene glycol)-b-poly(L-glutamic acid) (mPEG-b-PLG) and cationic anticancer drug doxorubicin hydrochloride (DOX·HCl) for NSCLC treatment. This complex spontaneously self-assembled into spherical nanoparticles (NPs) in aqueous solutions via electrostatic interaction and hydrophobic stack, with a high loading efficiency (almost 100%) and negative surface charge. DOX·HCl release from the drug-loaded micellar nanoparticles (mPEG-b-PLG-DOX·HCl) was slow at physiological pH, but obviously increased at the acidic pH mimicking the endosomal/lysosomal environment. In vitro cytotoxicity and hemolysis assays demonstrated that the block copolypeptide was cytocompatible and hemocompatible, and the presence of copolypeptide carrier could reduce the hemolysis ratio of DOX·HCl significantly. Cellular uptake and cytotoxicity studies suggested that mPEG-b-PLG-DOX·HCl was taken up by A549 cells via endocytosis, with a slightly slower cellular internalization and lower cytotoxicity compared with free DOX·HCl. The pharmacokinetics study in rats showed that DOX·HCl-loaded micellar NPs significantly prolonged the blood circulation time. Moreover, mPEG-b-PLG-DOX·HCl exhibited enhanced therapeutic efficacy, increased apoptosis in tumor tissues, and reduced systemic toxicity in nude mice bearing A549 lung cancer xenograft compared with free DOX·HCl, which were further confirmed by histological and immunohistochemical analyses. The results demonstrated that mPEG-b-PLG was a promising vector to deliver DOX·HCl into tumors and achieve improved pharmacokinetics, biodistribution and efficacy of DOX·HCl with reduced toxicity. These features strongly supported the interest of developing mPEG-b-PLG-DOX·HCl as a valid therapeutic modality in the therapy of human NSCLC and other solid tumors. PMID:23410916

  16. Effect of Varying Magnetic Fields on Targeted Gene Delivery of Nucleic Acid-Based Molecules.

    PubMed

    Oral, Ozlem; Cıkım, Taha; Zuvin, Merve; Unal, Ozlem; Yagci-Acar, Havva; Gozuacik, Devrim; Koşar, Ali

    2015-11-01

    Several physical methods have been developed to introduce nucleic acid expression vectors into mammalian cells. Magnetic transfection (magnetofection) is one such transfection method, and it involves binding of nucleic acids such as DNA, RNA or siRNA to magnetic nanoparticles followed by subsequent exposure to external magnetic fields. However, the challenge between high efficiency of nucleic acid uptake by cells and toxicity was not totally resolved. Delivery of nucleic acids and their transport to the target cells require carefully designed and controlled systems. In this study, we introduced a novel magnetic system design providing varying magnet turn speeds and magnetic field directions. The system was tested in the magnetofection of human breast (MCF-7), prostate (DU-145, PC-3) and bladder (RT-4) cancer cell lines using green fluorescent protein DNA as a reporter. Polyethylenimine coated superparamagnetic iron oxide nanoparticles (SPIONs) were used as nucleic acid carriers. Adsorption of PEI on SPION improved the cytocompatibility dramatically. Application of external magnetic field increased intracellular uptake of nanoparticles and transfection efficiency without any additional cytotoxicity. We introduce our novel magnetism-based method as a promising tool for enhanced nucleic acid delivery into mammalian cells. PMID:25963582

  17. 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

  18. Challenges in media delivery systems and servers

    NASA Astrophysics Data System (ADS)

    Swaminathan, Viswanathan

    2005-03-01

    Although multimedia compression formats and protocols to stream such content have been around for a long time, there has been limited success in the adoption of open standards for streaming over IP (Internet Protocol) networks. The elements of such an end-to-end system will be introduced outlining the responsibilities of each element. The technical and financial challenges in building a viable multimedia streaming end-to-end system will be analyzed in detail in this paper outlining some solutions and areas for further research. Also, recent migration to IP in the backend video delivery network infrastructures have made it possible to use IP based media streaming solutions in non-IP last mile access networks like cable and wireless networks in addition to the DSL networks. The advantages of using IP streaming solutions in such networks will be outlined. However, there is a different set of challenges posed by such applications. The real time constraints are acute in each element of the media delivery end-to-end system. Meeting these real time constraints in general purpose non real time server systems is quite demanding. Quality of service, resource management, session management, fail-over, reliability, and cost are some important but challenging requirements in such systems. These will also be analyzed with suggested solutions. Content protection and rights management requirements are also very challenging for open standards based multimedia delivery systems. Interoperability unfortunately interferes with security in most of the current day systems. Some approaches to solve the interoperability problems will also be presented. The requirements, challenges, and possible solutions for delivering broadcast, on demand, and interactive video delivery applications for IP based media streaming systems will be analyzed in detail.

  19. 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

  20. Polyacrylic acid modified upconversion nanoparticles for simultaneous pH-triggered drug delivery and release imaging.

    PubMed

    Jia, Xuekun; Yin, Jinjin; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Chen, Mian; Li, Yuhong

    2013-12-01

    A poly(acrylicacid)-modified NaYF4:Yb, Er upconversion nanoparticles (PAA-UCNPs) with dual functions of drug delivery and release imaging have been successfully developed. The PAA polymer coated on the surface of UCNPs serve as a pH-sensitive nanovalve for loading drug molecules via electrostatic interaction. The drug-loading efficiency of the PAA-UCNPs was investigated by using doxorubicin hydrochloride (DOX) as a model anticancer drug to evaluate their potential as a delivery system. Results showed loading and releasing of DOX from PAA-UCNPs were controlled by varying pH, with high encapsulation rate at weak alkaline conditions and an increased drug dissociation rate in acidic environment, which is favorable for construct a pH-responsive controlled drug delivery system. The in vitro cytotoxicity test using HeLa cell line indicated that the DOX loaded PAA-UCNPs (DOX@PAA-UCNPs) were distinctly cytotoxic to HeLa cells, while the PAA-UCNPs were highly biocompatible and suitable to use as drug carriers. Furthermore, the upconversion fluorescence resonance energy transfer (UFRET) imaging through the two-photon laser scanning microscopy (TLSM) revealed the time course of intracellular delivery of DOX from DOX@PAA-UCNPs. Thus, PAA-UCNPs are effective for constructing pH-responsive controlled drug delivery systems for multi-functional cancer therapy and imaging. PMID:24266261

  1. 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.

  2. HDL as a drug and nucleic acid delivery vehicle

    PubMed Central

    Lacko, Andras G.; Sabnis, Nirupama A.; Nagarajan, Bhavani; McConathy, Walter J.

    2015-01-01

    This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s) of high density lipoprotein type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload) in their natural/physiological environment. The ability to accommodate highly water insoluble constituents in their core regions enables High density lipoproteins (HDL) type nanoparticles to effectively transport hydrophobic drugs subsequent to systemic administration. Even though the application of reconstituted HDL in the treatment of a number of diseases is reviewed, the primary focus is on the application of HDL type drug delivery agents in cancer chemotherapy. The use of both native and synthetic HDL as drug delivery agents is compared to evaluate their respective potentials for commercial and clinical development. The current status and future perspectives for HDL type nanoparticles are discussed, including current obstacles and future applications in therapeutics. PMID:26578957

  3. 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. PMID:26508855

  4. 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

  5. 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. PMID:22196902

  6. Propaedeutic study for the delivery of nucleic acid-based molecules from PLGA microparticles and stearic acid nanoparticles

    PubMed Central

    Grassi, G; Coceani, N; Farra, R; Dapas, B; Racchi, G; Fiotti, N; Pascotto, A; Rehimers, B; Guarnieri, G; Grassi, M

    2006-01-01

    We studied the mechanism governing the delivery of nucleic acid-based drugs (NABD) from microparticles and nanoparticles in zero shear conditions, a situation occurring in applications such as in situ delivery to organ parenchyma. The delivery of a NABD molecule from poly(DL-lactide-co-glycolide) (PLGA) microparticles and stearic acid (SA) nanoparticles was studied using an experimental apparatus comprising a donor chamber separated from the receiver chamber by a synthetic membrane. A possible toxic effect on cell biology, as evaluated by studying cell proliferation, was also conducted for just PLGA microparticles. A mathematical model based on the hypothesis that NABD release from particles is due to particle erosion was used to interpret experimental release data. Despite zero shear conditions imposed in the donor chamber, particle erosion was the leading mechanism for NABD release from both PLGA microparticles and SA nanoparticles. PLGA microparticle erosion speed is one order of magnitude higher than that of competing to SA nanoparticles. Finally, no deleterious effects of PLGA microparticles on cell proliferation were detected. Thus, the data here reported can help optimize the delivery systems aimed at release of NABD from micro- and nanoparticles. PMID:17722283

  7. 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

  8. 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.

  9. 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

  10. Recent technologies in pulsatile drug delivery systems

    PubMed Central

    Jain, Deepika; Raturi, Richa; Jain, Vikas; Bansal, Praveen; Singh, Ranjit

    2011-01-01

    Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period. These systems are beneficial for drugs with chronopharmacological behavior, where nocturnal dosing is required, and for drugs that show the first-pass effect. This review covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Marketed technologies, such as PulsincapTM, Diffucaps®, CODAS®, OROS® and PULSYSTM, follow the above mechanism to render a sigmoidal drug release profile. Diseases wherein PDDS are promising include asthma, peptic ulcers, cardiovascular ailments, arthritis and attention deficit syndrome in children and hypercholesterolemia. Pulsatile drug delivery systems have the potential to bring new developments in the therapy of many diseases. PMID:23507727

  11. Resistive-wall wake effect in the beam delivery system

    SciTech Connect

    J.R. Delayen; Juhao Wu; T.O. Raubenheimer; Jiunn-Ming Wang

    2004-08-16

    General formulae for resistive-wall induced beam dilution are presented and then applied to the final beam delivery system of linear colliders. Criteria for the design of final beam delivery systems are discussed.

  12. Lactic acid bacteria as mucosal delivery vehicles: a realistic therapeutic option.

    PubMed

    Wang, Miao; Gao, Zeqian; Zhang, Yongguang; Pan, Li

    2016-07-01

    Recombinant lactic acid bacteria (LAB), in particular lactococci and lactobacilli, have gained increasing interest as mucosal delivery vehicles in recent years. With the development of mucosal vaccines, studies on LAB expression systems have been mainly focused on the generation of genetic tools for antigen expression in different locations. Recombinant LAB show advantages in a wide range of aspects over other mucosal delivery systems and represent an attractive candidate for the delivery of therapeutic and prophylactic molecules in different applications. Here, we review the recent data on the use of recombinant LAB as mucosal delivery vectors and the associated health benefits, including the prevention and treatment of inflammatory bowel diseases (IBDs), autoimmune disorders, and infections by pathogenic microorganisms from mucosal surfaces. In addition, we discuss the use of LAB as vehicles to deliver DNA directly to eukaryotic cells. Researches from the last 5 years demonstrate that LAB as vectors for mucosal delivery of therapeutic molecules seem to be a realistic therapeutic option both in human and animal diseases. PMID:27154346

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

    PubMed Central

    Kooijmans, Sander AA; 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. PMID:22619510

  14. 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

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

    PubMed

    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

  16. 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

  17. 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.

  18. 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.

  19. Light-Induced Acid Generation on a Gatekeeper for Smart Nitric Oxide Delivery.

    PubMed

    Choi, Hyung Woo; Kim, Jihoon; Kim, Jinhwan; Kim, Yonghwi; Song, Hyun Beom; Kim, Jeong Hun; Kim, Kimoon; Kim, Won Jong

    2016-04-26

    We report herein the design of a light-responsive gatekeeper for smart nitric oxide (NO) delivery. The gatekeeper is composed of a pH-jump reagent as an intermediary of stimulus and a calcium phosphate (CaP) coating as a shielding layer for NO release. The light irradiation and subsequent acid generation are used as triggers for uncapping the gatekeeper and releasing NO. The acids generated from a light-activated pH-jump agent loaded in the mesoporous nanoparticles accelerated the degradation of the CaP-coating layers on the nanoparticles, facilitating the light-responsive NO release from diazeniumdiolate by exposing a NO donor to physiological conditions. Using the combination of the pH-jump reagent and CaP coating, we successfully developed a light-responsive gatekeeper system for spatiotemporal-controlled NO delivery. PMID:26953516

  20. 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

  1. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

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

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems. PMID:26898739

  2. Towards more effective advanced drug delivery systems.

    PubMed

    Crommelin, Daan J A; Florence, Alexander T

    2013-09-15

    This position paper discusses progress made and to be made with so-called advanced drug delivery systems, particularly but not exclusively those in the nanometre domain. The paper has resulted from discussions with a number of international experts in the field who shared their views on aspects of the subject, from the nomenclature used for such systems, the sometimes overwrought claims made in the era of nanotechnology, the complex nature of targeting delivery systems to specific destinations in vivo, the need for setting standards for the choice and characterisation of cell lines used in in vitro studies, to attention to the manufacturability, stability and analytical profiling of systems and more relevant studies on toxicology. The historical background to the development of many systems is emphasised. So too is the stochastic nature of many of the steps to successful access to and action in targets. A lacuna in the field is the lack of availability of data on a variety of carrier systems using the same models in vitro and in vivo using standard controls. The paper asserts that greater emphasis must also be paid to the effective levels of active attained in target organs, for without such crucial data it will be difficult for many experimental systems to enter the clinic. This means the use of diagnostic/imaging technologies to monitor targeted drug delivery and stratify patient groups, identifying patients with optimum chances for successful therapy. Last, but not least, the critical importance of the development of science bases for regulatory policies, scientific platforms overseeing the field and new paradigms of financing are discussed. PMID:23415662

  3. 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. PMID:22124008

  4. [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. PMID:25898576

  5. 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

  6. 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

    2016-01-01

    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. PMID:27483234

  7. 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,…

  8. 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

  9. Advances in Systemic siRNA Delivery

    PubMed Central

    Leng, Qixin; Woodle, Martin C; Lu, Patrick Y; Mixson, A James

    2009-01-01

    Sequence-specific gene silencing with small interfering RNA (siRNA) has transformed basic science research, and the efficacy of siRNA therapeutics toward a variety of diseases is now being evaluated in pre-clinical and clinical trials. Despite its potential value, the highly negatively charged siRNA has the classic delivery problem of requiring transport across cell membranes to the cytosol. Consequently, carrier development for siRNA delivery is one of the most important problems to solve before siRNA can achieve widespread clinical use. An assortment of non-viral carriers including liposomes, peptides, polymers, and aptamers are being evaluated for their ability to shepherd siRNA to the target tissue and cross the plasma membrane barrier into the cell. Several promising carriers with low toxicity and increased specificity for disease targets have emerged for siRNA-based therapeutics. This review will discuss non-viral approaches for siRNA therapeutics, with particular focus on synthetic carriers for in vivo systemic delivery of siRNA. PMID:20161621

  10. 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. PMID:25466399

  11. Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear.

    PubMed

    El Kechai, Naila; Mamelle, Elisabeth; Nguyen, Yann; Huang, Nicolas; Nicolas, Valérie; Chaminade, Pierre; Yen-Nicolaÿ, Stéphanie; Gueutin, Claire; Granger, Benjamin; Ferrary, Evelyne; Agnely, Florence; Bochot, Amélie

    2016-03-28

    The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model. The liposomal gel was easily injectable as a result of the shear-thinning behavior of hyaluronic acid. A prolonged residence time at the site of injection as well as in the round window were achieved without any negative effect on the hearing thresholds of the animals. The presence of liposomes in the formulation resulted in sustained release of the drug in the perilymph for 30days and promoted the conversion of the prodrug loaded within the liposomes (dexamethasone phosphate) into its active form (dexamethasone). In this way, therapeutic doses were attained in the perilymph. A small amount of intact liposomes was visualized in the perilymph, whereas the main proportion of liposomes seemed to be trapped in the round window resulting in a reservoir effect. Thus, the administration of hyaluronic acid liposomal gel to the middle ear is an efficient strategy for delivering corticoids to the inner ear in a sustained manner. PMID:26860286

  12. Protamine-based nanoparticles as new antigen delivery systems.

    PubMed

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

    2015-11-01

    The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. PMID:26455338

  13. Oral delivery of taurocholic acid linked heparin-docetaxel conjugates for cancer therapy.

    PubMed

    Khatun, Zehedina; Nurunnabi, Md; Reeck, Gerald R; Cho, Kwang Jae; Lee, Yong-Kyu

    2013-08-28

    We have synthesized taurocholic acid (TCA) linked heparin-docetaxel (DTX) conjugates for oral delivery of anticancer drug. The ternary biomolecular conjugates formed self-assembly nanoparticles where docetaxel was located inside the core and taurocholic acid was located on the surface of the nanoparticles. The coupled taurocholic acid in the nanoparticles had enhanced oral absorption, presumably through the stimulation of a bile acid transporter of the small intestine. The oral absorption profile demonstrated that the concentration of the conjugates in plasma is about 6 fold higher than heparin alone. An anti-tumor study in MDA-MB231 and KB tumor bearing mice showed significant tumor growth inhibition activity by the ternary biomolecular conjugates. Ki-67 histology study also showed evidence of anticancer activity of the nanoparticles. Finally, noninvasive imaging using a Kodak Molecular Imaging System demonstrated that the nanoparticles were accumulated efficiently in tumors. Thus, this approach for oral delivery using taurocholic acid in the ternary biomolecular conjugates is promising for treatment of various types of cancer. PMID:23665255

  14. 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.

  15. 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.

  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. PMID:12378965

  17. 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. PMID:26920318

  18. 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.

  19. A mucoadhesive in situ gel delivery system for paclitaxel.

    PubMed

    Jauhari, Saurabh; Dash, Alekha K

    2006-01-01

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% +/- 0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/- 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell. PMID:16796370

  20. 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.

  1. Lysosomal delivery of a lipophilic gemcitabine prodrug using novel acid-sensitive micelles improved its antitumor activity

    PubMed Central

    Zhu, Saijie; Lansakara-P, Dharmika S.P.; Li, Xinran; Cui, Zhengrong

    2012-01-01

    Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein we reported a novel strategy to engineer acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic polyethylene glycol (PEG) with a hydrophobic stearic acid derivative (C18) using an acid-sensitive hydrazone bond (PHC). An acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analog gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the acid-sensitive PHC micelles was more cytotoxic than in the acid-insensitive PAC micelles, which may be attributed to the acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16-F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed a stronger antitumor activity than GemC18 or gemcitabine solution, likely because of the prolonged circulation time and increased tumor accumulation of the GemC18 by the micelles. Importantly, the in vivo antitumor activity of GemC18-loaded PHC micelles was significantly stronger than that of the PAC micelles, demonstrating the potential of the novel acid-sensitive micelles as an anticancer drug delivery system. PMID:22471294

  2. 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. PMID:25178824

  3. All-trans retinoic acid-loaded lipid nanoparticles as a transdermal drug delivery carrier.

    PubMed

    Charoenputtakhun, Ponwanit; Opanasopit, Praneet; Rojanarata, Theerasak; Ngawhirunpat, Tanasait

    2014-03-01

    The objective of this study was to investigate the effects of drug amounts (0.1%, 0.2% and 0.3% w/w), amounts of the oil (10%, 15% and 20% w/w of lipid matrix) and types of the oil (soybean oil (S), medium chain triglycerides (M), oleic acids (O) and linoleic acids (L)) in lipid matrix of all-trans retinoic acid (ATRA)-loaded nanostructured lipid carriers (NLCs) for transdermal drug delivery. The ATRA-loaded solid lipid nanoparticles (SLNs) were formulated with 30% w/w cetyl palmitate. All lipid nanoparticles had average sizes between 130 and 241 nm and had negative zeta potentials. The drug loading of all formulations was higher than 95%. The release of drug from all lipid nanoparticles followed zero-order kinetics. The amount of drug released from all the NLCs and SLNs was significantly greater than the drug released from the ATRA suspension. The ATRA flux of the SLNs was higher than the NLCs. The flux of the NLCs containing oleic acid was significantly higher than the other types of oils. The chemical stability at 4 °C, the percentage of ATRA remaining in all the lipid nanoparticles tested was higher than 80%. It can be concluded that both the SLNs and NLCs are promising dermal drug delivery systems for ATRA. PMID:23356887

  4. 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. PMID:26433349

  5. 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. PMID:26318978

  6. 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

  7. Turbomachine injection nozzle including a coolant delivery system

    DOEpatents

    Zuo, Baifang

    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.

  8. 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.

  9. Fluid Delivery System For Capillary Electrophoretic Applications.

    DOEpatents

    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.

  10. 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. PMID:25513958

  11. 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

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

    PubMed

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

    2015-11-28

    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

  13. 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…

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

    PubMed

    Ling, Hui

    2016-01-01

    The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer. PMID:27573903

  15. 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

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

    PubMed

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

    2016-01-01

    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

  17. Synthesis and characterization of polyaspartamide copolymers obtained by ATRP for nucleic acid delivery.

    PubMed

    Cavallaro, G; Licciardi, M; Amato, G; Sardo, C; Giammona, G; Farra, R; Dapas, B; Grassi, M; Grassi, G

    2014-05-15

    Nucleic acid molecules such as small interfering RNAs (siRNAs) and plasmidic DNAs (pDNAs) have been shown to have the potential to be of therapeutic value in different human diseases. Their practical use is however compromised by the lack of appropriate release systems. Delivered as naked molecules, siRNAs/pDNAs are rapidly degraded by extracellular nucleases thus considerably reducing the amount of molecule which can reach the target cells. Additionally, the anionic charge of the phosphate groups present on the siRNAs/pDNAs backbone, disfavors the interaction with the negatively charged surface of the cell membrane. In this paper we describe the generation of a novel polymer able to deliver both siRNAs and pDNAs. The combined release of these molecules is used in many different experimental settings such as the evaluation of the silencing efficiency of a given siRNA targeted against a given RNA, encoded by the pDNA. The possibility to use the same delivery system is very convenient from the technical point of view and it allows minimizing possible artifacts introduced by the use of different delivery agents for siRNAs and pDNA. The copolymer described here is based on α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) bearing positively chargeable side oligochains, with diethylamino ethyl methacrylate (DEAEMA) as monomer. Monomer polymerization has been obtained by atom transfer radical polymerization (ATRP), a technique which allows the precise polymerization of the monomer. In addition to the chemical-physical characterization of the polymer, we provide evidences of the polymer ability to delivery both siRNAs and pDNA to cultured cells. Whereas additional investigations are necessary to study the delivery mechanisms of this polyplex, the polymer generated represents a novel and convenient device for the delivery of both siRNAs and pDNA. PMID:24631053

  18. Formulation of a Peptide Nucleic Acid Based Nucleic Acid Delivery Construct

    PubMed Central

    Millili, Peter G.; Yin, Daniel H.; Fan, Haihong; Naik, Ulhas P.; Sullivan, Millicent O.

    2010-01-01

    Gene delivery biomaterials need to be designed to efficiently achieve nuclear delivery of plasmid DNA. Polycations have been used to package DNA and other nucleic acids within sub-micron sized particles, offering protection from shear-induced or enzymatic degradation. However, cytotoxicity issues coupled with limited in vivo transfection efficiencies minimize the effectiveness of this approach. In an effort to improve upon existing technologies aimed at delivering nucleic acids, an alternative approach to DNA packaging was explored. Peptide nucleic acids (PNAs) were used to directly functionalize DNA with poly(ethylene glycol) (PEG) chains that provide a steric layer and inhibit multimolecular aggregation during complexation. DNA prePEGylation by this strategy was predicted to enable the formation of more homogeneous and efficiently packaged polyplexes. In this work, DNA-PNA-peptide-PEG (DP3) conjugates were synthesized and self-assembled with 25 kDa poly(ethylenimine) (PEI). Complexes with small standard deviations and average diameters ranging from 30 – 50 nm were created, with minimal dependence of complex size on N:P ratio (PEI amines to DNA phosphates). Furthermore, PEI-DNA interactions were altered by the derivitization strategy, resulting in tighter compaction of the PEI-DP3 complexes in comparison with PEI-DNA complexes. Transfection experiments in Chinese Hamster Ovary (CHO) cells revealed comparable transfection efficiencies but reduced cytotoxicities of the PEI-DP3 complexes relative to PEI-DNA complexes. The enhanced cellular activities of the PEI-DP3 complexes were maintained following the removal of free PEI from the PEI-DP3 formulations, whereas the cellular activity of the conventional PEI-DNA formulations was reduced by free PEI removal. These findings suggest that DNA prePEGylation by the PNA-based strategy might provide a way to circumvent cytotoxicity and formulation issues related to the use of PEI for in vivo gene delivery. PMID:20131756

  19. Moxifloxacin in situ gelling microparticles-bioadhesive delivery system.

    PubMed

    Guo, Qiongyu; Aly, Ahmed; Schein, Oliver; Trexler, Morgana M; Elisseeff, Jennifer H

    2012-01-01

    Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye. PMID:25755996

  20. Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

    PubMed Central

    Guo, Qiongyu; Aly, Ahmed; Schein, Oliver; Trexler, Morgana M.; Elisseeff, Jennifer H.

    2012-01-01

    Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye. PMID:25755996

  1. 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

  2. A motion maintaining antibiotic delivery system.

    PubMed

    Lombardi, Adolph V; Karnes, Jonathan M; Berend, Keith R

    2007-06-01

    Two-stage radical debridement with implant removal, antibiotic therapy, and delayed reimplantation remains the treatment of choice for deep infection in total joint arthroplasty. Studies have shown that articulating vs static spacers better improve functional results, increase patient satisfaction, prevent bone loss, and facilitate reimplantation without increasing risk of infection. Articulating spacers fabricated from cement provide a vehicle for prolonged local delivery of antibiotics. We currently use a mold system for creating antibiotic-laden articulating cement spacers. Disposable femoral and tibial molds are injection-filled with low-viscosity cement vacuum mixed with 3.6 to 4.8 g of tobramycin or gentamicin and 3.0 to 4.0 g of vancomycin per 40-g unit and massaged to fill any voids. After curing, the temporary spacers are removed from the molds, trimmed smooth, and cemented loosely into the joint space. PMID:17570278

  3. Pyrolytic Behavior of Amino Acids and Nucleic Acid Bases: Implications for Their Survival during Extraterrestrial Delivery

    NASA Astrophysics Data System (ADS)

    Basiuk, Vladimir A.; Navarro-González, Rafael

    1998-08-01

    The idea of extraterrestrial delivery of organic matter (by comets, asteroids, meteorites, and interplanetary dust particles) to the early Earth is very popular at present. A strong argument for its favor is the detection of a large variety of organic compounds, including amino acids and nucleic acid bases, in carbonaceous chondrites. Whether these compounds can be delivered by other space bodies is unclear and depends primarily on capability of the biomolecules to survive high temperature regimes during atmospheric deceleration and impacts to the terrestrial surface. Although some indirect estimates of simple biomolecules' survivability have been reported, there is an evident lack of experimental data. In the present study we demonstrate that some simple amino acids, purines, and pyrimidines do not completely decompose even under volatilization at 500°C in a nitrogen atmosphere at normal pressure, with the percentage of survival of the order of 1-10%. In the case of amino acids, several types of condensation products form (piperazine-2,5-diones, bicyclic amidines, hydantoins, etc.) with total yields in the same percentage range, preserving amino acid residues intact and being able to release free amino acids upon hydrolysis. Taking into account the property of amino acids as well as nucleic acid bases to sublime in vacuum under temperatures of about 200°C, one should expect that the biomolecules in the dust particles actually do not experience the temperatures as much as 400-500°C and rapidly sublime during the atmospheric passage, dissipating in the upper atmosphere. The biomolecules' survival during catastrophic airbursts of comets is also possible, but very unlikely for asteroidal impacts to the terrestrial surface (at least for those resulting in complete pulverization and evaporation of the projectiles).

  4. Linolenic acid-modified PEG-PCL micelles for curcumin delivery.

    PubMed

    Song, Zhimei; Zhu, Wenxia; Liu, Na; Yang, Fengying; Feng, Runliang

    2014-08-25

    In this study, a novel linolenic acid-modified poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer was prepared through radical addition, ring-opening polymerization, and N-acylation reactions. Its structure was characterized by (1)H NMR and GPC. Micelles were developed by thin-film hydration and used as a delivery system for curcumin with high drug loading capacity of 12.80% and entrapment efficiency of 98.53%. The water solubility of curcumin was increased to 2.05 mg/mL, which was approximately 1.87×10(5) times higher than that of free curcumin. The micelles were spherical shape with an average diameter of 20.8±0.8 nm. X-ray diffraction and FT-IR studies suggested that curcumin existed in the polymeric matrices under π-π conjugation and hydrogen bond interaction with the copolymer. In vitro drug release studies indicated that the curcumin release from linolenic acid-modified copolymer micelles met controlled release, and its release rate was less than that from the linolenic acid-unmodified copolymer micelles. Cytotoxicities against Hela and A-549cells demonstrated that the additional π-π conjugation could affect curcumin's anticancer activity through reducing its release from micelles. Hemolysis test and intravenous irritation test results revealed that the linolenic acid-modified copolymer was safe for intravenous injection. The plasma AUC0-∞ and MRT0-∞ of curcumin-loaded linolenic acid-conjugated poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer micelles were 2.75- and 3.49-fold higher than that of control solution, respectively. The CLz was also decreased by 2.75-fold. So, this linolenic acid-modified copolymer might be a carrier candidate for curcumin delivery. PMID:24939613

  5. Formulation of microemulsion systems for dermal delivery of silymarin.

    PubMed

    Panapisal, Vipaporn; Charoensri, Sawitree; Tantituvanont, Angkana

    2012-06-01

    Silymarin is a standardized extract from Silybum marianum seeds, known for its many skin benefits such as antioxidant, anti-inflammatory, and immunomodulatory properties. In this study, the potential of several microemulsion formulations for dermal delivery of silymarin was evaluated. The pseudo-ternary phase diagrams were constructed for the various microemulsion formulations which were prepared using glyceryl monooleate, oleic acid, ethyl oleate, or isopropyl myristate as the oily phase; a mixture of Tween 20®, Labrasol®, or Span 20® with HCO-40® (1:1 ratio) as surfactants; and Transcutol® as a cosurfactant. Oil-in-water microemulsions were selected to incorporate 2% w/w silymarin. After six heating-cooling cycles, physical appearances of all microemulsions were unchanged and no drug precipitation occurred. Chemical stability studies showed that microemulsion containing Labrasol® and isopropyl myristate stored at 40°C for 6 months showed the highest silybin remaining among others. The silybin remainings depended on the type of surfactant and were sequenced in the order of: Labrasol® > Tween 20® > Span 20®. In vitro release studies showed prolonged release for microemulsions when compared to silymarin solution. All release profiles showed the best fits with Higuchi kinetics. Non-occlusive in vitro skin permeation studies showed absence of transdermal delivery of silybin. The percentages of silybin in skin extracts were not significantly different among the different formulations (p > 0.05). Nevertheless, some silybin was detected in the receiver fluid when performing occlusive experiments. Microemulsions containing Labrasol® also were found to enhance silymarin solubility. Other drug delivery systems with occlusive effect could be further developed for dermal delivery of silymarin. PMID:22350738

  6. 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. PMID:24758139

  7. 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

  8. Description and Documentation of the Dental School Dental Delivery System.

    ERIC Educational Resources Information Center

    Chase, Rosen and Wallace, Inc., Alexandria, VA.

    A study was undertaken to describe and document the dental school dental delivery system using an integrated systems approach. In late 1976 and early 1977, a team of systems analysts and dental consultants visited three dental schools to observe the delivery of dental services and patient flow and to interview administrative staff and faculty.…

  9. Importance of novel drug delivery systems in herbal medicines.

    PubMed

    Devi, V Kusum; Jain, Nimisha; Valli, Kusum S

    2010-01-01

    Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drug delivery system used for administering the herbal medicine to the patient is traditional and out-of-date, resulting in reduced efficacy of the drug. If the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems. However, modern phytopharmaceutical research can solve the scientific needs (such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required etc.) of herbal medicines to be incorporated in novel drug delivery system, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. This article summarizes various drug delivery technologies, which can be used for herbal actives together with some examples. PMID:22228938

  10. Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

    PubMed

    Masood, Farha

    2016-03-01

    A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. PMID:26706565

  11. 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

  12. 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

  13. 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

  14. SYNTHESIS AND CHARACTERIZATION OF POLYSIALIC ACID/CARBOXYMETHYL CHITOSAN HYDROGEL WITH POTENTIAL FOR DRUG DELIVERY.

    PubMed

    Wu, J R; Zhan, X B; Zheng, Z Y; Zhang, H T

    2015-01-01

    A novel hydrogel was prepared from polysialic acid (PSA) and carboxymethyl chitosan (CMCS) using glutaraldehyde as the cross-linking agent. The resulting PSA-CMCS hydrogel exhibited pH sensitivity, in which the swelling ratio under acidic conditions was higher than those under neutral or alkaline conditions. The swelling ratio of PSA-CMCS hydrogel at equilibrium depended on the medium pH, the cross-linking agent concentration, and the ratio of PSA to CMCS (w/w). Bovine serum albumin (BSA) and 5-fluorouracil (5-FU) were used as model drugs to prepare hydrogel delivery systems. The loading efficiencies of the hydrogel for BSA and 5-FU were 26.25 and 36.74%, respectively. Release behaviors of BSA and 5-FU were influenced by the pH. MTT assays confirmed that PSA-CMCS hydrogel has no cytotoxicity toward the NIH-3T3 cell line; in fact, the 100% aqueous extract of the PSA-CMCS hydrogel enhanced cell growth. These results suggest that PSA-CMCS hydrogel may be a promising pH-sensitive delivery system, especially for hydrophobic chemicals. PMID:26762102

  15. Ariadne: The Next Generation of Electronic Document Delivery Systems.

    ERIC Educational Resources Information Center

    Roes, Hans; Dijkstra, Joost

    1994-01-01

    Describes an approach to electronic document delivery which has evolved at Tilburg University (Netherlands), leading to the development of a system called Ariadne. Highlights include various generations of electronic document delivery systems; standards, including the work of the Group on Electronic Document Interchange; and a description of the…

  16. 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…

  17. 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…

  18. Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

    PubMed Central

    Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.

    2011-01-01

    From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

  19. Advanced drug delivery systems of curcumin for cancer chemoprevention.

    PubMed

    Bansal, Shyam S; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V; Gupta, Ramesh C

    2011-08-01

    Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. PMID:21546540

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

    PubMed

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

    2015-12-28

    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

  1. 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. PMID:24564350

  2. Bioavailability of phytochemicals and its enhancement by drug delivery systems

    PubMed Central

    Aqil, Farrukh; Munagala, Radha; Jeyabalan, Jeyaprakash; Vadhanam, Manicka V.

    2013-01-01

    Issues of poor oral bioavailability of cancer chemopreventives have hindered progress in cancer prevention. Novel delivery systems that modulate the pharmacokinetics of existing drugs, such as nanoparticles, cyclodextrins, niosomes, liposomes and implants, could be used to enhance the delivery of chemopreventive agents to target sites. The development of new approaches in prevention and treatment of cancer could encompass new delivery systems for approved and newly investigated compounds. In this review, we discuss some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many fold. PMID:23435377

  3. 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.

  4. The Controlled Drug Delivery Systems: Past Forward and Future Back

    PubMed Central

    Park, Kinam

    2014-01-01

    The controlled drug delivery technology has progressed over the last six decades. It began in 1952 with the introduction of the first sustained release formulation. The 1st generation (1950-1980) of drug delivery was focused on developing oral and transdermal sustained release systems and establishing the controlled drug release mechanisms. Attention of the 2nd generation (1980-2010) was dedicated to development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was consumed mostly for studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role during the 2nd generation of drug delivery technologies, and it will continue playing a leading role for the next generation. Taking the right path towards the productive 3rd generation of drug delivery technologies requires honest open dialogues without any preconceived ideas of the past. The drug delivery field needs to take a bold approach of designing the future drug delivery formulations first, based on today’s necessities, and produce necessary innovations. The JCR will provide the forum for sharing the new ideas that will shape the 3rd generation of drug delivery technologies. PMID:24794901

  5. 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

  6. Fluorescent graphene quantum dots as traceable, pH-sensitive drug delivery systems

    PubMed Central

    Qiu, Jichuan; Zhang, Ruibin; Li, Jianhua; Sang, Yuanhua; Tang, Wei; Rivera Gil, Pilar; Liu, Hong

    2015-01-01

    Graphene quantum dots (GQDs) were rationally fabricated as a traceable drug delivery system for the targeted, pH-sensitive delivery of a chemotherapeutic drug into cancer cells. The GQDs served as fluorescent carriers for a well-known anticancer drug, doxorubicin (Dox). The whole system has the capacity for simultaneous tracking of the carrier and of drug release. Dox release is triggered upon acidification of the intracellular vesicles, where the carriers are located after their uptake by cancer cells. Further functionalization of the loaded carriers with targeting moieties such as arginine-glycine-aspartic acid (RGD) peptides enhanced their uptake by cancer cells. DU-145 and PC-3 human prostate cancer cell lines were used to evaluate the anticancer ability of Dox-loaded RGD-modified GQDs (Dox-RGD-GQDs). The results demonstrated the feasibility of using GQDs as traceable drug delivery systems with the ability for the pH-triggered delivery of drugs into target cells. PMID:26604747

  7. Hybrid PET/CT for noninvasive pharmacokinetic evaluation of dynamic PolyConjugates, a synthetic siRNA delivery system.

    PubMed

    Mudd, Sarah R; Trubetskoy, Vladimir S; Blokhin, Andrei V; Weichert, Jamey P; Wolff, Jon A

    2010-07-21

    Positron emission tomography/computed tomography (PET/CT) hybrid imaging can be used to gain insights into a synthetic siRNA delivery system targeted to the liver. Either siRNA or the delivery vehicle was labeled with (64)Cu via 1, 4, 7, 10- tetraazacyclododecane- 1, 4, 7, 10- tetraacetic acid (DOTA) chelation. This study confirmed that the siRNA delivery system was successfully targeted to the liver. Incorporation of the siRNA into the delivery system protected the siRNA from renal filtration long enough so that the siRNA could be delivered to the liver. PET/CT imaging was important for confirming biodistribution and for determining differences in the distribution of labeled siRNA, siRNA incorporated into the delivery system, and the delivery system without siRNA. PMID:20552976

  8. 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.

  9. A new family of folate-decorated and carbon nanotube-mediated drug delivery system: synthesis and drug delivery response.

    PubMed

    Huang, H; Yuan, Q; Shah, J S; Misra, R D K

    2011-11-01

    We describe here a new family of folate-decorated and carbon nanotube (CNT)-mediated drug delivery system that involves uniquely combining carbon nanotubes with anticancer drug (doxorubicin) for controlled drug release, which is gaining significant attention. The synthesis of nanocarrier involved attachment of doxorubicin (DOX) to CNT surface via π-π stacking interaction, followed by encapsulation of CNTs with folic acid-conjugated chitosan. The π-π stacking interaction, ascribed as a non-covalent type of functionalization, allows controlled release of drug. Furthermore, encapsulation of CNTs enhances the stability of the nanocarrier in aqueous medium because of the hydrophilicity and cationic charge of chitosan. The unique integration of drug targeting and visualization has high potential to address the current challenges in cancer therapy. Thus, it is attractive to consider the possibility of investigating a drug delivery system that combines the biodegradable chitosan and carbon nanotubes (CNTs). PMID:21514336

  10. Marine Origin Polysaccharides in Drug Delivery Systems.

    PubMed

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

    2016-02-01

    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

  11. 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

  12. 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

  13. Recent Challenges in Insulin Delivery Systems: A Review

    PubMed Central

    Al-Tabakha, M. M.; Arida, A. I.

    2008-01-01

    Relatively, a large percentage of world population is affected by diabetes mellitus, out of which approximately 5-10% with type 1 diabetes while the remaining 90% with type 2. Insulin administration is essential for type 1 patients while it is required at later stage by the patients of type 2. Current insulin delivery systems are available as transdermal injections which may be considered as invasive. Several non-invasive approaches for insulin delivery are being pursued by pharmaceutical companies to reduce the pain, and hypoglycemic incidences associated with injections in order to improve patient compliance. While any new insulin delivery system requires health authorities' approval, to provide long term safety profile and insuring patients' acceptance. The inhalation delivery system Exubera® has already become clinically available in the United States and Europe for patients with diabetes as non-invasive delivery system. PMID:20046733

  14. 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. PMID:12944135

  15. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    PubMed

    Caramella, Carla M; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria Cristina; Sandri, Giuseppina

    2015-09-15

    This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. PMID:25683694

  16. Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.

    PubMed

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

    2015-01-01

    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 (NPs) 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 NP 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 the NP 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 NP 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 NPs 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 NP transport across the BBB does not necessarily yield proportional pharmacological effects. PMID:26453169

  17. 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

  18. 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

  19. [Recent trends on clinical development of oral insulin delivery systems].

    PubMed

    Takeda-Morishita, Mariko

    2015-12-01

    Great effort for developing effective needle-free insulin delivery technology, especially oral delivery, has been continued in worldwide, indeed, from the era of insulin discovered. Oral administration of insulin would offer not only the potential for improved patient compliance but also improved safety/efficacy in certain instances. Much effort for developing noninvasive delivery systems of insulin has been done, and recently, several promising insulin oral formulations are entered into clinical trials. Delivering insulin in orally was major challenge, but its realization is surely approaching. This review provides an update on recent approaches that have shown promise in insulin oral delivery systems. In addition, the progress of basic research in noninvasive delivery system research for biopharmaceuticals is discussed. PMID:26666165

  20. 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.

  1. pH-sensitive drug-delivery systems for tumor targeting.

    PubMed

    He, Xi; Li, Jianfeng; An, Sai; Jiang, Chen

    2013-12-01

    Drug-delivery system responses to stimuli have been well investigated recently. As pH decrease is observed in most solid tumors, drug-delivery systems responsive to the slightly acidic extracellular pH environment of solid tumors have been developed as a general strategy for tumor targeting. Drug vehicles that are sensitive to acidic endosome/lysosome pH have been constructed for efficient drug release in tumor cells. This review explains the mechanisms of acidic pH in the tumor microenvironment and endocytic-related organelles, endosomes and lysosomes. Nanoparticle responses to acidic extracellular pH are discussed, along with approaches for improving tumor-specific therapy. Endosome/lysosome pH-triggered vehicles are reviewed, which achieve rapid drug release in tumor cells and overcome multidrug resistance. PMID:24304248

  2. 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. PMID:26645149

  3. 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. PMID:19209604

  4. Auto-associative amphiphilic polysaccharides as drug delivery systems.

    PubMed

    Hassani, Leila N; Hendra, Frédéric; Bouchemal, Kawthar

    2012-06-01

    Self-assembly of amphiphilic polysaccharides provides a positive outlook for drug delivery systems without the need for solvents or surfactants. Various polymeric amphiphilic polysaccharides undergo intramolecular or intermolecular associations in water. This type of association, promoted by hydrophobic segments, led to the formation of various drug delivery systems such as micelles, nanoparticles, liposomes and hydrogels. Here, we review a selection of the most important amphiphilic polysaccharides used as drug delivery systems and their pharmaceutical applications. Attention focuses on amphiphilic chitosan owing to its unique properties such as excellent biocompatibility, non-toxicity and antimicrobial and bioadhesive properties. PMID:22305936

  5. 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.

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

    PubMed Central

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

    2013-01-01

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

  7. Ocular biocompatibility of carbodiimide cross-linked hyaluronic acid hydrogels for cell sheet delivery carriers.

    PubMed

    Lai, Jui-Yang; Ma, David Hui-Kang; Cheng, Hsiao-Yun; Sun, Chi-Chin; Huang, Shu-Jung; Li, Ya-Ting; Hsiue, Ging-Ho

    2010-01-01

    Due to its innocuous nature, hyaluronic acid (HA) is one of the most commonly used biopolymers for ophthalmic applications. We recently developed a cell sheet delivery system using carbodiimide cross-linked HA carriers. Chemical cross-linking provides an improvement in stability of polymer gels, but probably causes toxic side-effects. The aim of this study was to investigate the ocular biocompatibility of HA hydrogels cross-linked by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC). HA discs without cross-linking and glutaraldehyde (GTA) cross-linked HA samples were used for comparison. The disc implants were inserted in the anterior chamber of rabbit eyes for 24 weeks and characterized by slit-lamp biomicroscopy, histology and scanning electron microscopy. The ophthalmic parameters obtained from biomicroscopic examinations were also scored to provide a quantitative grading system. Results of this study showed that the HA discs cross-linked with EDC had better ocular biocompatibility than those with GTA. The continued residence of GTA cross-linked HA implants in the intraocular cavity elicited severe tissue responses and significant foreign body reactions, whereas no adverse inflammatory reaction was observed after contact with non-cross-linked HA or EDC cross-linked HA samples. It is concluded that the cross-linking agent type gives influence on ocular biocompatibility of cell carriers and the EDC-HA hydrogel is an ideal candidate for use as an implantable material in cell sheet delivery applications. PMID:20178691

  8. 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. PMID:25479058

  9. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26423010

  11. 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...

  12. 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

  13. 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.

  14. High Density Lipoproteins for the Systemic Delivery of short interfering RNA

    PubMed Central

    McMahon, Kaylin M.; Thaxton, C. Shad

    2014-01-01

    Introduction RNA interference (RNAi) is a powerful mechanism for gene silencing with the potential to greatly impact the development of new therapies for many human diseases. Short interfering RNAs (siRNAs) may be the ideal molecules for therapeutic RNAi. However, therapeutic siRNAs face significant challenges that must be overcome prior to widespread clinical use. Many efforts have been made to overcome the hurdles associated with systemic administration of siRNA; however, current approaches are still limited. As such, there is an urgent need to develop new strategies for siRNA delivery that have the potential to impact a broad spectrum of systemic diseases. Areas covered This review focuses on the promise of siRNA therapies and highlights current siRNA delivery methods. With an eye toward new strategies, this review first introduces high density lipoproteins (HDL) and their natural functions, and then transitions into how HDLs may provide significant opportunities as next generation siRNA delivery vehicles. Importantly, this review describes how synthetic HDLs leverage the natural ability of HDL to stabilize and deliver siRNAs. Expert Opinion HDLs are natural nanoparticles that are critical to understanding the systemic delivery of therapeutic nucleic acids, like siRNA. Methods to synthesize biomimetic HDLs are being explored and data demonstrate that this type of delivery vehicle may be highly beneficial for targeted and efficacious systemic delivery of siRNAs. PMID:24313310

  15. Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery.

    PubMed

    Jang, Yeon Lim; Ku, Sook Hee; Jin, So; Park, Jae Hyung; Kim, Won Jong; Kwon, Ick Chan; Kim, Sun Hwa; Jeong, Ji Hoon

    2014-10-01

    The clinical applications of therapeutic siRNA remain as a challenge due to the lack of efficient delivery system. In the present study, hyaluronic acid-siRNA conjugate (HA-SS-siRNA)/reducible polyethylenimine (BPEI1.2k-SS) complexes were developed to efficiently deliver the siRNA to HA receptor abundant region with the improved siRNA stability. HA and siRNA were conjugated with disulfide bonds, which are cleavable in cytoplasm. The synthesized HA-SS-siRNA was further complexed with BPEI1.2k-SS, resulting in the formation of spherical nanostructures with approximately 190 nm of size and neutral surface charge. HA-SS-siRNA/BPEI1.2k-SS complexes exhibited the improved stability against serum proteins or polyanions. These complexes were successfully translocated into intracellular region via HA receptor-mediated endocytosis, and silenced target gene expression. PMID:25942799

  16. Micro- and nano-fabricated implantable drug-delivery systems

    PubMed Central

    Meng, Ellis; Hoang, Tuan

    2013-01-01

    Implantable drug-delivery systems provide new means for achieving therapeutic drug concentrations over entire treatment durations in order to optimize drug action. This article focuses on new drug administration modalities achieved using implantable drug-delivery systems that are enabled by micro- and nano-fabrication technologies, and microfluidics. Recent advances in drug administration technologies are discussed and remaining challenges are highlighted. PMID:23323562

  17. 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

  18. A polymer-Triton X-100 conjugate capable of PH-dependent red blood cell lysis: a model system illustrating the possibility of drug delivery within acidic intracellular compartments.

    PubMed

    Duncan, R; Ferruti, P; Sgouras, D; Tuboku-Metzger, A; Ranucci, E; Bignotti, F

    1994-01-01

    Poly(amidoamines) are soluble polymers containing tertiary amino and amido groups regularly arranged along the macromolecular chain, and their net average charge alters considerably as pH changes from neutral to acidic leading to a change in conformation. This property provides the possibility to design polymer-drug conjugates that are, following intravenous administration, relatively compacted and thus protect a drug payload in the circulation, but following pinocytic internalisation into acidic intracellular compartments unfold permitting pH-triggered intracellular drug delivery. To study the feasibility of this approach, a covalent conjugate of a poly(amidoamine) (MBI) was prepared to contain the membrane lytic non-ionic detergent Triton X-100 (as a model), and its ability to lyse red blood cells in vitro was used as an indicator of conjugate conformation at at different pHs. Although Triton X-100 was highly lytic at pH 5.5, 7.4 and 8.0, and the parent polymer MBI was not lytic under any conditions, the conjugate only showed concentration-dependent red blood cell lysis at pH 5.5. Moreover, incubation of human leukaemic cells (CCRF) with these substrates showed conjugate to be more toxic than MBI (IC50 values of 100 micrograms/ml and 650 micrograms/ml respectively) and less toxic than Triton X-100 (IC50 of 1 microgram/ml). PMID:7858959

  19. Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B.

    PubMed

    Serafim, Cláudia; Ferreira, Inês; Rijo, Patrícia; Pinheiro, Lídia; Faustino, Célia; Calado, António; Garcia-Rio, Luis

    2016-01-30

    Lipoamino acid-based micelles have been developed as delivery vehicles for the hydrophobic drug amphotericin B (AmB). The micellar solubilisation of AmB by a gemini lipoamino acid (LAA) derived from cysteine and its equimolar mixtures with the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC), as well as the aggregation sate of the drug in the micellar systems, was studied under biomimetic conditions (phosphate buffered-saline, pH 7.4) using UV-vis spectroscopy. Pure surfactant systems and equimolar mixtures were characterized by tensiometry and important parameters were determined, such as critical micelle concentration (CMC), surface tension at the CMC (γCMC), maximum surface excess concentration (Γmax), and minimum area occupied per molecule at the water/air interface (Amin). Rheological behaviour from viscosity measurements at different shear rates was also addressed. Solubilisation capacity was quantified in terms of molar solubilisation ratio (χ), micelle-water partition coefficient (KM) and Gibbs energy of solubilisation (ΔGs°). Formulations of AmB in micellar media were compared in terms of drug loading, encapsulation efficiency, aggregation state of AmB and in vitro antifungal activity against Candida albicans. The LAA-containing micellar systems solubilise AmB in its monomeric and less toxic form and exhibit in vitro antifungal activity comparable to that of the commercial formulation Fungizone. PMID:26617315

  20. Silk-based delivery systems of bioactive molecules

    PubMed Central

    Numata, Keiji; Kaplan, David L

    2010-01-01

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

  1. 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. PMID:27433600

  2. Intrapulmonary delivery of ethyl pyruvate attenuates lipopolysaccharide- and lipoteichoic acid-induced lung inflammation in vivo.

    PubMed

    van Zoelen, Marieke A D; de Vos, Alex F; Larosa, Gregory J; Draing, Christian; von Aulock, Sonja; van der Poll, Tom

    2007-11-01

    Ethyl pyruvate (EP) is a stable pyruvate derivative that has been shown to exert anti-inflammatory effects in various models of systemic inflammation including endotoxemia. We here sought to determine the local effects of EP, after intrapulmonary delivery, in models of lung inflammation induced by instillation via the airways of either lipopolysaccharide (LPS, a constituent of the gram-negative bacterial cell wall) or lipoteichoic acid (LTA, a component of the gram-positive bacterial cell wall). For this, we first established that EP dose dependently reduced the responsiveness of mouse MH-S alveolar macrophages and mouse MLE-15 and MLE-12 respiratory epithelial cells to stimulation with LPS or LTA in vitro. We then showed that intranasal administration of EP dose dependently inhibited tumor necrosis factor alpha release in bronchoalveolar lavage fluid of mice challenged with either LPS or LTA via the airways. Moreover, EP reduced the recruitment of neutrophils into the bronchoalveolar space after either LPS or LTA administration. These data suggest that intrapulmonary delivery of EP diminishes lung inflammation induced by LPS or LTA, at least in part by targeting alveolar macrophages and respiratory epithelial cells. PMID:17577142

  3. 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

  4. Interactions of hyaluronic Acid with the skin and implications for the dermal delivery of biomacromolecules.

    PubMed

    Witting, Madeleine; Boreham, Alexander; Brodwolf, Robert; Vávrová, Kateřina; Alexiev, Ulrike; Friess, Wolfgang; Hedtrich, Sarah

    2015-05-01

    Hyaluronic acid (HA) hydrogels are interesting delivery systems for topical applications. Besides moisturizing the skin and improving wound healing, HA facilitates topical drug absorption and is highly compatible with labile biomacromolecules. Hence, in this study we investigated the influence of HA hydrogels with different molecular weights (5 kDa, 100 kDa, 1 MDa) on the skin absorption of the model protein bovine serum albumin (BSA) using fluorescence lifetime imaging microscopy (FLIM). To elucidate the interactions of HA with the stratum corneum and the skin absorption of HA itself, we combined FLIM and Fourier-transform infrared (FTIR) spectroscopy. Our results revealed distinct formulation and skin-dependent effects. In barrier deficient (tape-stripped) skin, BSA alone penetrated into dermal layers. When BSA and HA were applied together, however, penetration was restricted to the epidermis. In normal skin, penetration enhancement of BSA into the epidermis was observed when applying low molecular weight HA (5 kDa). Fluorescence resonance energy transfer analysis indicated close interactions between HA and BSA under these conditions. FTIR spectroscopic analysis of HA interactions with stratum corneum constituents showed an α-helix to β-sheet interconversion of keratin in the stratum corneum, increased skin hydration, and intense interactions between 100 kDa HA and the skin lipids resulting in a more disordered arrangement of the latter. In conclusion, HA hydrogels restricted the delivery of biomacromolecules to the stratum corneum and viable epidermis in barrier deficient skin, and therefore seem to be potential topical drug vehicles. In contrast, HA acted as an enhancer for delivery in normal skin, probably mediated by a combination of cotransport, increased skin hydration, and modifications of the stratum corneum properties. PMID:25871518

  5. 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. PMID:27343846

  6. Delivery of nucleic acids for cancer gene therapy: overcoming extra- and intra-cellular barriers.

    PubMed

    McErlean, Emma M; McCrudden, Cian M; McCarthy, Helen O

    2016-09-01

    The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective nonviral delivery systems can be applied successfully in oncology. Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration. PMID:27582234

  7. Mucoadhesive microparticulates based on polysaccharide for target dual drug delivery of 5-aminosalicylic acid and curcumin to inflamed colon.

    PubMed

    Duan, Haogang; Lü, Shaoyu; Gao, Chunmei; Bai, Xiao; Qin, Hongyan; Wei, Yuhui; Wu, Xin'an; Liu, Mingzhu

    2016-09-01

    In this work, thiolated chitosan/alginate composite microparticulates (CMPs) coated by Eudragit S-100 were developed for colon-specific delivery of 5-aminosalicylic acid (5-ASA) and curcumin (CUR), and the use of it as a multi drug delivery system for the treatment of colitis. The physicochemical properties of the CMPs were evaluated. In vitro release was performed in gradually pH-changing medium simulating the conditions of different parts of GIT, and the results showed that the Eudragit S-100 coating has a pH-sensitive release property, which can avoid drug being released at a pH lower than 7. An everted sac method was used to evaluate the mucoadhesion of CMPs. Ex vivo mucoadhesive tests showed CMPs have excellent mucosa adhesion for the colonic mucosa of rats. In vivo treatment effect of enteric microparticulates systems was evaluated in colitis rats. The results showed superior therapeutic efficiency of this drug delivery system for the colitis rats induced by TNBS. Therefore, the enteric microparticulates systems combined the properties of pH dependent delivery, mucoadhesive, and control release, and could be an available tool for the treatment of human inflammatory bowel disease. PMID:27239905

  8. Enhanced hepatic delivery of siRNA and microRNA using oleic acid based lipid nanoparticle formulations

    PubMed Central

    Wang, Xinmei; Yu, Bo; Ren, Wei; Mo, Xiaokui; Zhou, Chenguang; He, Hongyan; Jia, HuLiang; Wang, Lu; Jacob, Samson T.; Lee, Robert J.; Ghoshal, Kalpana; Lee, L. James

    2015-01-01

    Many cationic lipids have been developed for lipid-based nanoparticles (LNPs) for delivery of siRNA and microRNA (miRNA). However, less attention has been paid to “helper lipids”. Here, we investigated several “helper lipids” and examined their effects on the physicochemical properties such as particle size and zeta potential, as well as cellular uptake and transfection efficiency. We found that inclusion of oleic acid (OA), an unsaturated fatty acid; into the LNP formulation significantly enhanced the delivery efficacy for siRNA and miRNA. For proof-of-concept, miR-122, a liver-specific microRNA associated with many liver diseases, was used as a model agent to demonstrate the hepatic delivery efficacy both in tumor cells and in animals. Compared to Lipofectamine 2000, a commercial transfection agent, OA containing LNPs delivered microRNA-122 in a more efficient manner with a 1.8-fold increase in mature miR-122 expression and a 20% decrease in Bcl-w, a target of microRNA-122. In comparison with Invivofectamine, a commercial transfection agent specifically designed for hepatic delivery, OA containing LNPs showed comparable liver accumulation and in vivo delivery efficiency. These findings demonstrated the importance of “helper lipid” components of the LNP formulation on the cellular uptake and transfection activity of siRNA and miRNA. OA containing LNPs are a promising nanocarrier system for the delivery of RNA-based therapeutics in liver diseases. PMID:24121065

  9. 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

  10. Colloidal drug delivery systems: current status and future directions.

    PubMed

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

    2015-01-01

    In this paper, we provide an overview an extensive range of colloidal drug delivery systems with special focus on vesicular and particulates systems that are being used in research or might be potentially useful as carriers systems for drug or active biomolecules or as cell carriers with application in the therapeutic field. We present some important examples of commercially available drug delivery systems with applications in research or in clinical fields. This class of systems is widely used due to excellent drug targeting, sustained and controlled release behavior, higher entrapment efficiency of drug molecules, prevention of drug hydrolysis or enzymatic degradation, and improvement of therapeutic efficacy. These characteristics help in the selection of suitable carrier systems for drug, cell, and gene delivery in different fields. PMID:25955882

  11. pH-responsive targeted and controlled doxorubicin delivery using hyaluronic acid nanocarriers.

    PubMed

    Gurav, Deepanjali D; Kulkarni, Anuja S; Khan, Ayesha; Shinde, Vaishali S

    2016-07-01

    Biocompatible nanogels were prepared using thiol modified hyaluronic acid and diacrylated pluronic F127 polymer. A simple Michael type addition reaction of activated thiol groups on acrylate moiety lead to the formation of these nanogels, which were further effectively fabricated with an anticancer drug for evaluating sustained drug release approach. Nanogels prepared were of 150nm in diameter with a narrow size distribution pattern. DOX released from these nanogels showed a slow and sustained release at acidic pH 5.0 as compared to minimal release at physiological pH 7.4. Cytotoxicity data revealed the higher efficiency of DOX loaded nanogels as compared to free DOX in Hela cell lines. Cellular uptake images supported the cytotoxicity data and displayed DOX intercalation at nuclear level of cells. The sustained drug delivery system showed DOX release after 24h and continued thereafter without affecting normal cells. Based on these findings, such nanogel system may be useful for delivering anticancer drug without hampering their toxicity value over longer durations and reducing the total dose amount in anticancer therapy. PMID:27022876

  12. 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. PMID:24818769

  13. 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

  14. 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

  15. Vaporization as a smokeless cannabis delivery system: a pilot study.

    PubMed

    Abrams, D I; Vizoso, H P; Shade, S B; Jay, C; Kelly, M E; Benowitz, N L

    2007-11-01

    Although cannabis may have potential therapeutic value, inhalation of a combustion product is an undesirable delivery system. The aim of the study was to investigate vaporization using the Volcano((R)) device as an alternative means of delivery of inhaled Cannabis sativa. Eighteen healthy inpatient subjects enrolled to compare the delivery of cannabinoids by vaporization to marijuana smoked in a standard cigarette. One strength (1.7, 3.4, or 6.8% tetrahydrocannabinol (THC)) and delivery system was randomly assigned for each of the 6 study days. Plasma concentrations of Delta-9-THC, expired carbon monoxide (CO), physiologic and neuropsychologic effects were the main outcome measures. Peak plasma concentrations and 6-h area under the plasma concentration-time curve of THC were similar. CO levels were reduced with vaporization. No adverse events occurred. Vaporization of cannabis is a safe and effective mode of delivery of THC. Further trials of clinical effectiveness of cannabis could utilize vaporization as a smokeless delivery system. PMID:17429350

  16. Training Delivery Systems for Adult Learners. A Bibliography.

    ERIC Educational Resources Information Center

    Florida State Univ., Tallahassee. Center for Instructional Development and Services.

    This bibliography focuses on the training needs of adults and the incorporation of the most effective training delivery systems for adults into job training programs. It includes citations exploring current training practices, methods, and philosophies in both the private sector and the educational system; how each system can learn from the…

  17. A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels

    PubMed Central

    Murthy, Niren; Xu, Mingcheng; Schuck, Stephany; Kunisawa, Jun; Shastri, Nilabh; Fréchet, Jean M. J.

    2003-01-01

    The development of protein-based vaccines remains a major challenge in the fields of immunology and drug delivery. Although numerous protein antigens have been identified that can generate immunity to infectious pathogens, the development of vaccines based on protein antigens has had limited success because of delivery issues. In this article, an acid-sensitive microgel material is synthesized for the development of protein-based vaccines. The chemical design of these microgels is such that they degrade under the mildly acidic conditions found in the phagosomes of antigen-presenting cells (APCs). The rapid cleavage of the microgels leads to phagosomal disruption through a colloid osmotic mechanism, releasing protein antigens into the APC cytoplasm for class I antigen presentation. Ovalbumin was encapsulated in microgel particles, 200–500 nm in diameter, prepared by inverse emulsion polymerization with a synthesized acid-degradable crosslinker. Ovalbumin is released from the acid-degradable microgels in a pH-dependent manner; for example, microgels containing ovalbumin release 80% of their encapsulated proteins after 5 h at pH 5.0, but release only 10% at pH 7.4. APCs that phagocytosed the acid-degradable microgels containing ovalbumin were capable of activating ovalbumin-specific cytoxic T lymphocytes. The acid-degradable microgels developed in this article should therefore find applications as delivery vehicles for vaccines targeted against viruses and tumors, where the activation of cytoxic T lymphocytes is required for the development of immunity. PMID:12704236

  18. 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.

  19. 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.

  20. Improving vaccine delivery using novel adjuvant systems.

    PubMed

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  1. Dendrimeric systems and their applications in ocular drug delivery.

    PubMed

    Yavuz, Burçin; Pehlivan, Sibel Bozdağ; Unlü, 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

  2. 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

  3. Osmotically controlled drug delivery system with associated drugs.

    PubMed

    Gupta, Brahma Prakash; Thakur, Navneet; Jain, Nishi P; Banweer, Jitendra; Jain, Surendra

    2010-01-01

    Conventional drug delivery systems have slight control over their drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the controlled or modified release drug delivery systems. They include dosage forms for oral and transdermal administration as well as injectable and implantable systems. For most of drugs, oral route remains as the most acceptable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Development of an extended release dosage form also requires reasonable absorption throughout the gastro-intestinal tract (GIT). Among the available techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most appropriate one. Osmotic drug delivery systems release the drug with the zero order kinetics which does not depend on the initial concentration and the physiological factors of GIT. This review brings out new technologies, fabrication and recent clinical research in osmotic drug delivery. PMID:21486532

  4. Nanoporous multilayer poly(L-glutamic acid)/chitosan microcapsules for drug delivery.

    PubMed

    Yan, Shifeng; Rao, Shuiqin; Zhu, Jie; Wang, Zhichun; Zhang, Ying; Duan, Yourong; Chen, Xuesi; Yin, Jingbo

    2012-05-10

    Nanoporous poly(L-glutamic acid)/chitosan (PLGA/CS) multilayer microcapsules were fabricated by layer-by-layer (LbL) assembly using the porous silica particles as sacrificial templates. The LbL assembled nanoporous PLGA/CS microcapsules were characterized by Zeta-potential analyzer, FTIR, TGA, SEM, TEM and CLSM. 5-Fluorouracil (5-FU) was chosen as model drug. The drug loading content of PLGA/CS microcapsules depends on loading time, loading temperature, pH value and NaCl concentration. High loading capacity of microcapsules can be achieved by simply adjusting pH value and salt concentration. Moreover, 5-Fu loaded microcapsules take on a sustained release behavior, especially in an acid solution, in contrast to burst release of bare 5-Fu. The kinetics of 5-Fu release from PLGA/CS microcapsules conforms to Korsmeyer-Peppas and Baker-Lonsdale models, the mechanism of which can be ascribed to priority of drug diffusion and subordination of polymer degradation. The MTT cytotoxicity assay in vitro reveals the satisfactory anticancer activity of the drug-loaded PLGA/CS microcapsules. Therefore, the novel nanoporous PLGA/CS microcapsules is expected to find application in drug delivery systems. PMID:22301425

  5. 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

  6. 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

  7. 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

  8. 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. PMID:21719996

  9. Local arterial wall drug delivery using balloon catheter system.

    PubMed

    Tesfamariam, Belay

    2016-09-28

    Balloon-based drug delivery systems allow localized application of drugs to a vascular segment to reduce neointimal hyperplasia and restenosis. Drugs are coated onto balloons using excipients as drug carriers to facilitate adherence and release of drug during balloon inflation. Drug-coated balloon delivery system is characterized by a rapid drug transfer that achieves high drug concentration along the vessel wall surface, intended to correspond to the balloon dilation-induced vascular injury and healing processes. The balloon catheter system allows homogenous drug delivery to the vessel wall, such that the drug release per unit surface area is kept constant along balloons of different lengths. Optimization of the balloon coating matrix is essential for efficient drug transfer and tissue retention until the artery remodels to a normal set point. Challenges in the development of balloon-based drug delivery to the arterial wall include finding suitable excipients for drug formulation to enable drug release to a targeted lesion site effectively, maintain coating integrity during transit, prolong tissue retention and reduce particulate generation. This review highlights various factors involved in the successful design of balloon-based delivery systems, including drug release kinetics, matrix coating transfer, transmural drug partitioning, dissolution rate and release of unbound active drug. PMID:27473765

  10. Formulation and evaluation of ondansetron nasal delivery systems.

    PubMed

    Cho, Eunsook; Gwak, Hyesun; Chun, Inkoo

    2008-02-12

    This study aimed to formulate and evaluate nasal delivery systems containing ondansetron hydrochloride. In the in vitro study, the permeation rate with the addition of 10% polyethylene glycol 300 (PEG 300) to aqueous solution containing 0.01% benzalkonium chloride (BC) and 10% sulfobutylether beta-cyclodextrin sodium salt (SBCD) was somewhat more rapid up to 1.5h compared to the addition of 10% PG. The permeation flux increased as the drug concentration increased regardless of the vehicles used. The addition of nicotinamide or chitosan to aqueous drug solution (40 mg/ml) with 10% PEG 300 and 0.01% BC rather decreased permeation rate and delayed lag time. Even though cyclodextrins including SBCD or dimethyl-ss-cyclodextrin failed to show permeation enhancing effects of ondansetron hydrochloride, the addition of 10% SBCD to aqueous solution containing 10% PEG 300 and 0.01% BC could be a good candidate for ondansetron nasal delivery systems because of its safety profile, stable storage in refrigerator and solubilizing effect. With the above formulation, the nasal delivery system increased AUC0-2h and Cmax by 2.1 and 1.7 times compared to those of oral delivery, respectively while there was no difference found in AUC0-2h with intravenous administration. Therefore, the nasal delivery system of ondansetron hydrochloride formulated in this study was feasible for nasal administration. PMID:17822864

  11. 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

  12. Design of Educational Delivery Systems for Lifelong Learning.

    ERIC Educational Resources Information Center

    Gibson, R. Oliver; Gilbert, Randall L.

    To clarify delivery system concepts, several topics will be addressed: educational needs of lower-income older people, formulation of a design concept, specification of the system's concrete aspects, and research/development implications. As the proportion of persons over age sixty-four grows and sensitivity to unmet lifelong learning needs rises,…

  13. 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…

  14. 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

  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. PMID:27191059

  16. 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. PMID:26805518

  17. Biologically erodable microspheres as potential oral drug delivery systems

    NASA Astrophysics Data System (ADS)

    Mathiowitz, Edith; Jacob, Jules S.; Jong, Yong S.; Carino, Gerardo P.; Chickering, Donald E.; Chaturvedi, Pravin; Santos, Camilla A.; Vijayaraghavan, Kavita; Montgomery, Sean; Bassett, Michael; Morrell, Craig

    1997-03-01

    Biologically adhesive delivery systems offer important advantages1-5 over conventional drug delivery systems6. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA.

  18. 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

  19. Delivery systems for biopharmaceuticals. Part II: Liposomes, Micelles, Microemulsions and Dendrimers.

    PubMed

    Silva, Ana C; Lopes, Carla M; Lobo, José M S; Amaral, Maria H

    2015-01-01

    Biopharmaceuticals are a generation of drugs that include peptides, proteins, nucleic acids and cell products. According to their particular molecular characteristics (e.g. high molecular size, susceptibility to enzymatic activity), these products present some limitations for administration and usually parenteral routes are the only option. To avoid these limitations, different colloidal carriers (e.g. liposomes, micelles, microemulsions and dendrimers) have been proposed to improve biopharmaceuticals delivery. Liposomes are promising drug delivery systems, despite some limitations have been reported (e.g. in vivo failure, poor long-term stability and low transfection efficiency), and only a limited number of formulations have reached the market. Micelles and microemulsions require more studies to exclude some of the observed drawbacks and guarantee their potential for use in clinic. According to their peculiar structures, dendrimers have been showing good results for nucleic acids delivery and a great development of these systems during next years is expected. This is the Part II of two review articles, which provides the state of the art of biopharmaceuticals delivery systems. Part II deals with liposomes, micelles, microemulsions and dendrimers. PMID:26278524

  20. Engineering Stent Based Delivery System for Esophageal Cancer Using Docetaxel.

    PubMed

    Shaikh, Mohsin; Choudhury, Namita Roy; Knott, Robert; Garg, Sanjay

    2015-07-01

    Esophageal cancer patients are often diagnosed as "advanced" cases. These patients are subjected to palliative stenting using self-expanding metallic stents (SEMS) to maintain oral alimentation. Unfortunately, SEMS get reoccluded due to tumor growth, in and over the stent struts. To investigate potential solutions to this problem, docetaxel (DTX) delivery films were prepared using PurSil AL 20 (PUS), which can be used as a covering material for the SEMS. Drug-polymer miscibility and interactions were studied. Bilayer films were prepared by adhering the blank film to the DTX loaded film in order to maintain the unidirectional delivery to the esophagus. In vitro release and the local DTX delivery were studied using in vitro permeation experiments. It was found that DTX and PUS were physically and chemically compatible. The bilayer films exhibited sustained release (>30 days) and minimal DTX permeation through esophageal tissues in vitro. The rate-determining step for the DTX delivery was calculated. It was found that >0.9 fraction of rate control lies with the esophageal tissues, suggesting that DTX delivery can be sustained for longer periods compared to the in vitro release observed. Thus, the bilayer films can be developed as a localized sustained delivery system in combination with the stent. PMID:25936529

  1. Gastric retentive drug-delivery systems.

    PubMed

    Hwang, S J; Park, H; Park, K

    1998-01-01

    The development of a long-term oral controlled-release dosage form has been difficult mainly because of the transit of the dosage form through the gastrointestinal (GI) tract. Several approaches to extend gastric residence time have been tried. The most commonly used systems are (1) intragastric floating systems, (2) high-density systems, (3) mucoadhesive systems, (4) magnetic systems, (5) unfoldable, extendible, or swellable systems, and (6) superporous hydrogel systems. The concept of each approach is examined, and improvements that are needed for further development are discussed. Background materials in the GI physiology that are necessary for understanding the concept and usefulness of each approach are also provided. PMID:9699081

  2. Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery.

    PubMed

    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

  3. 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

  4. Coating nanocarriers with hyaluronic acid facilitates intravitreal drug delivery for retinal gene therapy.

    PubMed

    Martens, Thomas F; Remaut, Katrien; Deschout, Hendrik; Engbersen, Johan F J; Hennink, Wim E; van Steenbergen, Mies J; Demeester, Jo; De Smedt, Stefaan C; Braeckmans, Kevin

    2015-03-28

    Retinal gene therapy could potentially affect the lives of millions of people suffering from blinding disorders. Yet, one of the major hurdles remains the delivery of therapeutic nucleic acids to the retinal target cells. Due to the different barriers that need to be overcome in case of topical or systemic administration, intravitreal injection is an attractive alternative administration route for large macromolecular therapeutics. Here it is essential that the therapeutics do not aggregate and remain mobile in the vitreous humor in order to reach the retina. In this study, we have evaluated the use of hyaluronic acid (HA) as an electrostatic coating for nonviral polymeric gene nanomedicines, p(CBA-ABOL)/pDNA complexes, to provide them with an anionic hydrophilic surface for improved intravitreal mobility. Uncoated polyplexes had a Z-averaged diameter of 108nm and a zeta potential of +29mV. We evaluated polyplexes coated with HA of different molecular weights (22kDa, 137kDa and 2700kDa) in terms of size, surface charge and complexation efficiency and noticed their zeta potentials became anionic at 4-fold molar excess of HA-monomers compared to cationic monomers, resulting in submicron ternary polyplexes. Next, we used a previously optimized ex vivo model based on excised bovine eyes and fluorescence single particle tracking (fSPT) microscopy to evaluate mobility in intact vitreous humor. It was confirmed that HA-coated polyplexes had good mobility in bovine vitreous humor, similar to polyplexes functionalized with polyethylene glycol (PEG), except for those coated with high molecular weight HA (2700kDa). However, contrary to PEGylated polyplexes, HA-coated polyplexes were efficiently taken up in vitro in ARPE-19 cells, despite their negative charge, indicating uptake via CD44-receptor mediated endocytosis. Furthermore, the HA-polyplexes were able to induce GFP expression in this in vitro cell line without apparent cytotoxicity, where coating with low molecular

  5. 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.

  6. The Vacuum-Operated Nutrient Delivery System: hydroponics for microgravity.

    PubMed

    Brown, C S; Cox, W M; Dreschel, T W; Chetirkin, P V

    1992-11-01

    A nutrient delivery system that may have applicability for growing plants in microgravity is described. The Vacuum-Operated Nutrient Delivery System (VONDS) draws nutrient solution across roots that are under a partial vacuum at approximately 91 kPa. Bean (Phaseolus vulgaris L. cv. Blue Lake 274) plants grown on the VONDS had consistently greater leaf area and higher root, stem, leaf, and pod dry weights than plants grown under nonvacuum control conditions. This study demonstrates the potential applicability of the VONDS for growing plants in microgravity for space biology experimentation and/or crop production. PMID:11537607

  7. Delivery of siRNA Using Cationic Liposomes Incorporating Stearic Acid-modified Octa-Arginine.

    PubMed

    Yang, Dongsheng; Li, Yuhuan; Qi, Yuhang; Chen, Yongzhen; Yang, Xuewei; Li, Yujing; Liu, Songcai; Lee, Robert J

    2016-07-01

    Cationic liposomes incorporating stearic acid-modified octa-arginine (StA-R8) were evaluated for survivin small interfering RNA (siRNA) delivery. StA-R8 was synthesized and incorporated into liposomes. The composition of liposomes was optimized. Physicochemical properties, cytotoxicity, cellular uptake and gene silencing activity of the liposomes complexed to survivin siRNA were investigated. The results showed that StA-R8-containing liposomes had reduced cytotoxicity and improved delivery efficiency of siRNA into cancer cells compared with StA-R8 by itself. PMID:27354583

  8. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

    PubMed Central

    Makadia, Hirenkumar K.; Siegel, Steven J.

    2011-01-01

    In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release. PMID:22577513

  9. 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

  10. Vaccinia virus as a vaccine delivery system for marsupial wildlife.

    PubMed

    Cross, Martin L; Fleming, Stephen B; Cowan, Phil E; Scobie, Susie; Whelan, Ellena; Prada, Diana; Mercer, Andrew A; Duckworth, Janine A

    2011-06-20

    Vaccines based on recombinant poxviruses have proved successful in controlling diseases such as rabies and plague in wild eutherian mammals. They have also been trialled experimentally as delivery agents for fertility-control vaccines in rodents and foxes. In some countries, marsupial mammals represent a wildlife disease reservoir or a threat to conservation values but, as yet there has been no bespoke study of efficacy or immunogenicity of a poxvirus-based vaccine delivery system in a marsupial. Here, we report a study of the potential for vaccination using vaccinia virus in the Australian brushtail possum Trichosurus vulpecula, an introduced pest species in New Zealand. Parent-strain vaccinia virus (Lister) infected 8/8 possums following delivery of virus to the oral cavity and outer nares surfaces (oronasal immunisation), and persisted in the mucosal epithelium around the palatine tonsils for up to 2 weeks post-exposure. A recombinant vaccinia virus construct (VV399, which expresses the Eg95 antigen of the hydatid disease parasite Echinococcus granulosus) was shown to infect 10/15 possums after a single-dose oronasal delivery and to also persist. Both parent vaccinia virus and the VV399 construct virus induced peripheral blood lymphocyte reactivity against viral antigens in possums, first apparent at 4 weeks post-exposure and still detectable at 4 months post-exposure. Serum antibody reactivity to Eg95 was recorded in 7/8 possums which received a single dose of the VV399 construct and 7/7 animals which received triple-dose delivery, with titre end-points in the latter case exceeding 1/4000 dilution. This study demonstrates that vaccinia virus will readily infect possums via a delivery means used to deploy wildlife vaccines, and in doing is capable of generating immune reactivity against viral and heterologous antigens. This highlights the future potential of recombinant vaccinia virus as a vaccine delivery system in marsupial wildlife. PMID:21570435

  11. 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

  12. Micro and nanoparticle drug delivery systems for preventing allotransplant rejection.

    PubMed

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

    2015-09-01

    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

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

    PubMed

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

    2016-07-01

    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. PMID:27297745

  14. 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. PMID:24922130

  15. Electrosprayed nanoparticle delivery system for controlled release.

    PubMed

    Eltayeb, Megdi; Stride, Eleanor; Edirisinghe, Mohan; Harker, Anthony

    2016-09-01

    This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70nm at the rate of 1.37×10(9) nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈21% and the encapsulation efficiency ≈70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. PMID:27207047

  16. 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. PMID:26820107

  17. Assessment of Alternative Student and Delivery Systems: Assessment of the Current Delivery System. Supplement I to the Final Report.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    The effects of the current student financial aid delivery system on five major participant groups are examined: federal government, states/guarantee agencies, postsecondary institutions, lenders and secondary markets, and applicants and families. Attention is directed to effects of the current system, including: administrative costs, fund…

  18. Industrial beam delivery system for ultra-short pulsed laser

    NASA Astrophysics Data System (ADS)

    Funck, Max C.; Wedel, Björn; Kayander, Ilya; Niemeyer, Jörg

    2015-03-01

    Beam delivery systems are an integral part of industrial laser equipment. Separating laser source and application fiber optic beam delivery is employed wherever great flexibility is required. And today, fiber optic beam delivery of several kW average power is available for continuous wave operation using multimode step index fibers with core diameters of several 100 μm. However, during short-pulse or even ultra-short pulse laser operation step index fibers fail due to high power density levels and nonlinear effects such as self-focusing and induced scattering. Hollow core photonic crystal fibers (HC-PCF) are an alternative to traditional fibers featuring light propagation mostly inside a hollow core, enabling high power handling and drastically reduced nonlinear effects. These fibers have become available during the past decade and are used in research but also for fiber laser systems and exhibit a growing popularity. We report on using HC-PCF fibers and their integration into an industrial beam delivery package comparable to today's fiber optic standards and will discuss power handling, beam quality and efficiency as well as future prospects of this technology. In a preliminary industrial beam delivery setup 300 fs pulses at 100 W average power could be delivered.

  19. 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

  20. Hyaluronic acid based micelle for articular delivery of triamcinolone, preparation, in vitro and in vivo evaluation.

    PubMed

    Saadat, Ebrahim; Shakor, Naeeme; Gholami, Mehdi; Dorkoosh, Farid A

    2015-07-15

    A novel triamcinolone loaded polymeric micelle was synthesized based on hyaluronic acid and phospholipid for articular delivery. The newly developed micelle was characterized for physicochemical properties including size, zeta potential, differential scanning calorimetry (DSC) analysis and also morphology by means of transmission electron microscopy. The biocompatibility of micelle was explored by histopathological experiment in rat model. Also biological fate of micelle was investigated in rat by means of real time in vivo imaging system. Triamcinolone loaded micelle was in the size range of 186 nm with negative zeta potential charge. Micelles were spherical in shape with core shell like structure. Triamcinolone was released from micelle during 76 h with almost low burst effect. DSC analysis showed the conversion of crystalline triamcinolone from its crystalline state. Histopathological analysis showed no evidence of tissue damage or phagocytic accumulation in knee joint of rat. The real time in vivo imaging analysis suggested at least three days retention time of micellar system in knee joint post injection. PMID:25956051

  1. Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin.

    PubMed

    Kong, Bong Ju; Kim, Ayoung; Park, Soo Nam

    2016-08-20

    In the present study, the properties of hydrogel systems based on hyaluronic acid (HA)-hydroxyethyl cellulose (HEC) were investigated for effective transdermal delivery of isoliquiritigenin (ILTG). Hydrogels were synthesized by chemical cross-linking, and network structures were characterised using scanning electron microscopy (SEM) and surface area analyser. Texture properties and swelling of HA-HEC hydrogels were found to be closely linked to cross-linker concentration and swelling medium. Water in HA-HEC hydrogels was found to exist mostly in the form of free water. The viscoelasticity and the network stabilization of the hydrogels were analysed via rheological studies. The release kinetics of the hydrogel followed Fickian diffusion mechanism. In an in vitro skin penetration study, the system substantially improved the delivery of ILTG into the skin. These results indicate that the hydrogel system composed of HA and HEC has potential as a transdermal delivery system, with cross-linking density and the swelling medium influencing the properties. PMID:27178954

  2. 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

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

    PubMed

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

    2011-07-01

    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

  4. The Targeted-liposome Delivery System of Antitumor Drugs.

    PubMed

    Wu, Wei-dang; Yi, Xiu-lin; Jiang, Li-xin; Li, Ya-zhuo; Gao, Jing; Zeng, Yong; Yi, Rong-da; Dai, Li-peng; Li, Wei; Ci, Xiao-yan; Si, Duan-yun; Liu, Chang-xiao

    2015-01-01

    The liposome delivery system has been intensively explored as novel drug delivery system (DDS) for antitumor drugs, due to its safety, selective cytotoxicity, long circulation and slow elimination in blood, which is favorable for cancer therapy. The liposome-based chemotherapeutics are used to treat a variety of cancers to enhance the therapeutic index of antitumor drugs. Here, the author reviewed the important targets for cancer therapy and the pharmacokinetic behavior of liposomal drugs in vivo, as well as the application of the targeting liposomal system in cancer therapy. Considering further application for clinical use, the great challenges of the liposome-based delivery system were also proposed as follows: 1) prepare stealth liposome with steric stabilization and further enhance the therapeutic effects and safety; 2) explore more safe clinical targets and complementary or different types of targeting liposome; 3) thirdly, more investment is needed on the research of pharmacokinetics of the elements such as the ligands (antibody), PEG and lipids of liposome delivery system as well as safety evaluation. Considering the complex process of the liposomal encapsulation drugs in vivo, the author inferred that there are maybe different forms of the encapsulation drug to be internalized by the tumor tissues at the same time and space, although there are little reports on it. PMID:26652257

  5. Anti-inflammatory drug delivery from hyaluronic acid hydrogels.

    PubMed

    Hahn, Sei K; Jelacic, Sandra; Maier, Ronald V; Stayton, Patrick S; Hoffman, Allan S

    2004-01-01

    Two different types of hyaluronic acid (HA) hydrogels were synthesized by crosslinking HA with divinyl sulfone (DVS) and poly(ethylene glycol)-divinyl sulfone (VS-PEG-VS). Vitamin E succinate (VES), an anti-inflammatory drug, and bovine serum albumin (BSA), a model of anti-inflammatory protein drugs, were loaded into the gels and their release kinetics were measured in vitro. VES and BSA released with a burst from both HA hydrogels during the first few hours, and release continued gradually for several days. The rate of release from HA-VS-PEG-VS-HA hydrogels was faster than that from HA-DVS-HA hydrogels, presumably due to the lower crosslink density in the former. The anti-inflammatory action of released VES was tested by incubating peripheral blood mononuclear cells (PBMC) on HA hydrogels with and without VES in the gel. The number of cells adhering on HA hydrogels was very low compared to that on tissue culture polystyrene (TCPS), which might be one of the important advantages of using HA hydrogels for implant coatings or tissue engineering applications. ELISA test results showed that the tumor necrosis factor-alpha (TNF-alpha) concentration was very low in the supernatant of the wells containing the HA hydrogel with VES in contact with the activated macrophages compared to that without VES. This is probably the effect of the released VES reducing the production of anti-inflammatory cytokine, TNF-alpha. HA hydrogels containing anti-inflammatory drugs may have potential for use in tissue engineering and also as biocompatible coatings of implants. PMID:15503629

  6. Nanostructured Delivery Systems: Augmenting the Delivery of Antiretroviral Drugs for Better Management of HIV/AIDS.

    PubMed

    Singh, Gurinder; Pai, Roopa S; Mustafa, Sanaul

    2015-01-01

    In the last two decades, HIV-1, the retrovirus associated with acquired immunodeficiency syndrome (AIDS), is globally one of the primary causes of morbidity and mortality. Unfortunately, existing approaches for interventions are not able to suppress the progression of infection due to this virus. Of the many obstacles, viral entry into the mono-nuclear phagocyte system encompassing monocytes/macrophages and dendritic cells is a major concern. Viral infection is also responsible for the subsequent distribution of the virus into various tissues throughout the organism. Tremendous progress has been made during the past few years to diagnose and treat patients with HIV/AIDS infection, yet much remains to be done. Recommended treatment involves long-term and multiple drug therapy that causes severe side effects. With almost 12% of the world population suffering from HIV/AIDS, better management of this global threat is highly desired. Nanostructured delivery systems hold promise for improving the situation. Such systems can facilitate the uptake of antiretroviral drugs, causing a considerable improvement in HIV/AIDS therapy. Nanoscale systems have intriguing potential to drastically improve existing HIV/AIDS diagnosis and treatment platforms. Nanosystems constitute a wide range of systems varying from polymeric nanoparticles, to solid-lipid nanoparticles, liposomes, micro- and nanoemulsions, dendrimers, and self-nanoemulsifying systems. Improved bioavailability, solubility, stability, and biocompatibility make them an ideal choice for delivery of antiretroviral drugs. The present review initially describes an updated bird's-eye view account of the literature. Then, we provide a relatively sententious overview on updated patents of recent nanostructured delivery systems for antiretroviral drugs. Finally, we discuss low-cost therapy (such as antioxidants and immune modulators) for the treatment and prevention of HIV/AIDS. PMID:26559551

  7. Promoting quality of program delivery via an internet message delivery system.

    PubMed

    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 the impact of dosage of the message system by comparing results among three groups of teachers: non-users, low users, and high users. Results for norm setting were marginally significant, such that teachers within the agencies assigned to the intervention condition scored higher on their understanding of norm setting at posttest compared to teachers within comparison agencies, after controlling for pretest knowledge scores and demographic items. In the model examining impact of dosage, high users of the intervention scored significantly higher on self-reported understanding of their program, quality of delivery, and program effectiveness compared to non-users. Low users of the intervention reported significantly higher quality of delivery compared to non-users. PMID:25445506

  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. PMID:27062215

  9. 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

  10. 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.

  11. NANOPARTICLE DELIVERY SYSTEMS IN CANCER VACCINES

    PubMed Central

    Krishnamachari, Yogita; Geary, Sean M.; Lemke, Caitlin D.; Salem, Aliasger K.

    2013-01-01

    Therapeutic strategies that involve the manipulation of the host’s immune system are gaining momentum in cancer research. Antigen-loaded nanocarriers are capable of being actively taken up by antigen presenting cells (APCs) and have shown promising potential in cancer immunotherapy by initiating a strong immunostimulatory cascade that results in potent antigen-specific immune responses against the cancer. Such carrier systems offer versatility in that they can simultaneously co-deliver adjuvants with the antigens to enhance APC activation and maturation. Furthermore, modifying the surface properties of these nanocarriers affords active targeting properties to APCs and/or enhanced accumulation in solid tumors. Here we review some recent advances in these colloidal and particulate nanoscale systems designed for cancer immunotherapy and the potential for these systems to translate into clinical cancer vaccines. PMID:20721603

  12. Strategies for Instructors Using Electronic Instruction Delivery Systems.

    ERIC Educational Resources Information Center

    Hutchinson, Michelle

    2000-01-01

    Presents strategies needed by instructors changing to electronic instruction delivery systems in higher education. Topics include developing pedagogical goals, including interactive learning; organization and hierarchy of course content; communications skills; making students feel welcome; fostering student-to-student collaboration; providing…

  13. Coordination polymer particles as potential drug delivery systems.

    PubMed

    Imaz, Inhar; Rubio-Martínez, Marta; García-Fernández, Lorena; García, Francisca; Ruiz-Molina, Daniel; Hernando, Jordi; Puntes, Victor; Maspoch, Daniel

    2010-07-14

    Micro- and nanoscale coordination polymer particles can be used for encapsulating and delivering drugs. In vitro cancer cell cytotoxicity assays showed that these capsules readily release doxorubicin, which shows anticancer efficacy. The results from this work open up new avenues for metal-organic capsules to be used as potential drug delivery systems. PMID:20485835

  14. Are E-Readers Viable Instructional Delivery Systems?

    ERIC Educational Resources Information Center

    Schcolnik, Miriam

    2002-01-01

    Reports on a study of e-readers, or electronic book readers, that investigated strategies adult users applied to reading in the new medium, kinds of texts users read, and text characteristics for e-reading. Discusses the process of reading, purposes of reading, and whether e-readers are viable instructional delivery systems. (Contains 63…

  15. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... property, making false claims, and obstruction of justice. The State agency may add other types of... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2010-01-01 2010-01-01 false Food delivery systems. 246.12 Section...

  16. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... property, making false claims, and obstruction of justice. The State agency may add other types of... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2011-01-01 2011-01-01 false Food delivery systems. 246.12 Section...

  17. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., receiving stolen property, making false claims, and obstruction of justice. The State agency may add other... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2012-01-01 2012-01-01 false Food delivery systems. 246.12 Section...

  18. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., receiving stolen property, making false claims, and obstruction of justice. The State agency may add other... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2013-01-01 2013-01-01 false Food delivery systems. 246.12 Section...

  19. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., receiving stolen property, making false claims, and obstruction of justice. The State agency may add other... agency or its local agencies. (xx) Criminal penalties. A vendor who commits fraud or abuse in the Program... 7 Agriculture 4 2014-01-01 2014-01-01 false Food delivery systems. 246.12 Section...

  20. 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. PMID:10146127

  1. Vocational Education Distance Learning Delivery System. Final Report.

    ERIC Educational Resources Information Center

    Hardy, Darcy Walsh

    A project was conducted to identify criteria and procedures for using a distance learning delivery system at the University of Texas TeleLearning Center to teach Health Occupations II to high school seniors. Another objective was expanding the current distance learning program for health occupations to include between 15 and 20 school districts.…

  2. Aerosolization of lipoplexes using AERx Pulmonary Delivery System.

    PubMed

    Deshpande, Deepa; Blanchard, James; Srinivasan, Sudarshan; Fairbanks, Dallas; Fujimoto, Jun; Sawa, Teiji; Wiener-Kronish, Jeanine; Schreier, Hans; Gonda, Igor

    2002-01-01

    The lung represents an attractive target for delivering gene therapy to achieve local and potentially systemic delivery of gene products. The objective of this study was to evaluate the feasibility of the AERx Pulmonary Delivery System for delivering nonviral gene therapy formulations to the lung. We found that "naked" DNA undergoes degradation following aerosolization through the AERx nozzle system. However, DNA formulated with a molar excess of cationic lipids (lipoplexes) showed no loss of integrity. In addition, the lipoplexes showed no significant change in particle size, zeta (zeta) potential, or degree of complexation following extrusion. The data suggest that complexation with cationic lipids had a protective effect on the formulation following extrusion. In addition, there was no significant change in the potency of the formulation as determined by a transfection study in A-549 cells in culture. We also found that DNA formulations prepared in lactose were aerosolized poorly. Significant improvements in aerosolization efficiency were seen when electrolytes such as NaCl were added to the formulation. In conclusion, the data suggest that delivery of lipoplexes using the AERx Pulmonary Delivery System may be a viable approach for pulmonary gene therapy. PMID:12423062

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... State that elects to obtain health benefits coverage through a separate child health program must include in its State plan a description of the child health assistance provided under the plan for... control systems. A State must— (a) Describe the methods of delivery of child health assistance...

  4. 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…

  5. 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

  6. Drug delivery systems and combination therapy by using vinca alkaloids.

    PubMed

    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

  7. The new organization of the health care delivery system.

    PubMed

    Shortell, S M; Hull, K E

    1996-01-01

    The U.S. health care system is restructuring at a dizzying pace. In many parts of the country, managed care has moved into third-generation models emphasizing capitated payment for enrolled lives and, in the process, turning most providers and institutions into cost centers to be managed rather than generators of revenue. While the full impact of the new managed care models remains to be seen, most evidence to date suggests that it tends to reduce inpatient use, may be associated with greater use of physician services and preventive care, and appears to result in no net differences either positive or negative with regard to quality or outcomes of care in comparison with fee-for-service plans. Some patients, however, tend to be somewhat less satisfied with scheduling of appointments and the amount of time spent with providers. There is no persuasive evidence that managed care lowers the rate of growth in overall health care costs within a given market. Further, managed care performance varies considerably across the country, and the factors influencing managed care performance are not well understood. Organized delivery systems are a somewhat more recent phenomenon representing various forms of ownership and strategic alliances among hospitals, physicians, and insurers designed to provide more cost-effective care to defined populations by achieving desired levels of functional, physician-system, and clinical integration. Early evidence suggests that organized delivery systems that are more integrated have the potential to provide more accessible coordinated care across the continuum, and appear to be associated with higher levels of inpatient productivity, greater total system revenue, greater total system cash flow, and greater total system operating margin than less integrated delivery forms. Some key success factors for developing organized delivery systems have been identified. Important roles are played by organizational culture, information systems, internal

  8. 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

  9. 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

  10. 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. PMID:26027573

  11. Unsteady jet in designing innovative drug delivery system

    NASA Astrophysics Data System (ADS)

    Wang, Cong; Mazur, Paul; Cosse, Julia; Rider, Stephanie; Gharib, Morteza

    2014-11-01

    Micro-needle injections, a promising pain-free drug delivery method, is constrained by its limited penetration depth. This deficiency can be overcome by implementing fast unsteady jet that can penetrate sub-dermally. The development of a faster liquid jet would increase the penetration depth and delivery volume of micro-needles. In this preliminary work, the nonlinear transient behavior of an elastic tube balloon in providing fast discharge is analyzed. A physical model that combines the Mooney Rivlin Material model and Young-Lapalce's Law was developed and used to investigate the fast discharging dynamic phenomenon. A proof of concept prototype was constructed to demonstrate the feasibility of a simple thumb-sized delivery system to generate liquid jet with desired speed in the range of 5-10 m/s. This work is supported by ZCUBE Corporation.

  12. RaPToRS Sample Delivery System

    NASA Astrophysics Data System (ADS)

    Henchen, Robert; Shibata, Kye; Krieger, Michael; Pogozelski, Edward; Padalino, Stephen; Glebov, Vladimir; Sangster, Craig

    2010-11-01

    At various labs (NIF, LLE, NRL), activated material samples are used to measure reaction properties. The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system quickly and safely moves these radioactive samples through a closed PVC tube via airflow. The carrier travels from the reaction chamber to the control and analysis station, pneumatically braking at the outlet. A reversible multiplexer routes samples from various locations near the shot chamber to the analysis station. Also, the multiplexer allows users to remotely load unactivated samples without manually approaching the reaction chamber. All elements of the system (pneumatic drivers, flow control valves, optical position sensors, multiplexers, Geiger counters, and release gates at the analysis station) can be controlled manually or automatically using a custom LabVIEW interface. A prototype is currently operating at NRL in Washington DC. Prospective facilities for Raptors systems include LLE and NIF.

  13. Delivery Systems for Distance Education. ERIC Digest.

    ERIC Educational Resources Information Center

    Schamber, Linda

    This ERIC digest provides a brief overview of the video, audio, and computer technologies that are currently used to deliver instruction for distance education programs. The video systems described include videoconferencing, low-power television (LPTV), closed-circuit television (CCTV), instructional fixed television service (ITFS), and cable…

  14. Electronic Document Delivery: OCLC's Prototype System.

    ERIC Educational Resources Information Center

    Hickey, Thomas B.; Calabrese, Andrew M.

    1986-01-01

    Describes development of system for retrieval of documents from magnetic storage that uses stored font definition codes to control an inexpensive laser printer in the production of copies that closely resemble original document. Trends in information equipment and printing industries that will govern future application of this technology are…

  15. RESIDENCE-TO-GARDEN GREYWATER DELIVERY SYSTEM

    EPA Science Inventory

    Results will include a prototype of the system and garden, a summary of water and soil quality, and survey results. The website and educational materials will describe the project and water-consumption awareness. In addition, this project will deepen the university’s relation...

  16. Enhancing intestinal drug solubilisation using lipid-based delivery systems.

    PubMed

    Porter, Christopher J H; Pouton, Colin W; Cuine, Jean F; Charman, William N

    2008-03-17

    Lipid-based delivery systems are finding increasing application in the oral delivery of poorly water-soluble, lipophilic drugs. Whilst lipidic dose forms may improve oral bioavailability via several mechanisms, enhancement of gastrointestinal solubilisation remains argueably the most important method of absorption enhancement. This review firstly describes the mechanistic rationale which underpins the use of lipid-based delivery systems to enhance drug solubilisation and briefly reviews the available literature describing increases in oral bioavailability after the administration of lipid solution, suspension and self-emulsifying formulations. The use of in vitro methods including dispersion tests and more complex models of in vitro lipolysis as indicators of potential in vivo performance are subsequently described, with particular focus on recent data which suggests that the digestion of surfactants present in lipid-based formulations may impact on formulation performance. Finally, a series of seven guiding principles for formulation design of lipid-based delivery systems are suggested based on an analysis of recent data generated in our laboratories and elsewhere. PMID:18155801

  17. 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. PMID:25335929

  18. 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

  19. Self-Emulsifying Drug Delivery System for Enhancing Bioavailability and Lymphatic Delivery of Tacrolimus.

    PubMed

    Cho, Hea-Young; Choi, Ji-Hoon; Oh, In-Joon; Lee, Yong-Bok

    2015-02-01

    A self-emulsifying drug delivery system (SEDDS) containing tacrolimus has been developed to enhance the bioavailability and lymphatic delivery of tacrolimus. Solubility tests, combination tests, and phase diagrams were constructed for different sorts and ratios of oils, surfactants, and cosurfactants to identify optimal formulation. Optimized SEDDS was assessed for droplet size, zeta potential, stability in various media, and in vitro release. The tacrolimus-loaded SEDDS and commercial capsule (Prograf®) were orally administered (5 mg/kg) to rats. Whole blood, and mesenteric and axillary lymph node samples were taken and the concentrations of tacrolimus were measured to evaluate pharmacokinetic characteristics and the lymphatic delivery effects. The optimized SEDDS droplets were approximately 40 nm in size and stable enough to endure gastric pH environments. The release rate of tacrolimus from SEDDS was significantly higher than that from the commercial capsule. The bioavailability of tacrolimus in SEDDS after oral administration was significantly improved versus that of Prograf®. The lymphatic targeting efficiency of the prepared SEDDS formulation showed significantly greater than that of Prograf®. Our research indicates that prepared SEDDS can be an alternative to the conventional oral formulation of tacrolimus. Furthermore, SEDDS should be explored as a potential drug carrier for other lipophilic drugs. PMID:26353739

  20. Cost analysis of two implantable narcotic delivery systems.

    PubMed

    Bedder, M D; Burchiel, K; Larson, A

    1991-08-01

    This survey compares costs of two commonly utilized implantable narcotic delivery systems. The systems are classified into type-I (exteriorized system using the DuPen epidural catheter) and type-II (implanted system using the Synchromed pump). Costs were analyzed by reviewing actual patient hospital financial service records and Homecare vendor quotations. From the perspective of cost analysis alone, we conclude that savings accrue when patients requiring treatment beyond 3 months duration are managed with a type-II implanted system compared with a type-I system with an external pump. PMID:1908884

  1. 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.

  2. 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.

  3. 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. PMID:27468799

  4. Enhanced Mucosal Delivery of Antigen with Cell Wall Mutants of Lactic Acid Bacteria

    PubMed Central

    Grangette, Corinne; Müller-Alouf, Heide; Hols, Pascal; Goudercourt, Denise; Delcour, Jean; Turneer, Mireille; Mercenier, Annick

    2004-01-01

    The potential of recombinant lactic acid bacteria (LAB) to deliver heterologous antigens to the immune system and to induce protective immunity has been best demonstrated by using the C subunit of tetanus toxin (TTFC) as a model antigen. Two types of LAB carriers have mainly been used, Lactobacillus plantarum and Lactococcus lactis, which differ substantially in their abilities to resist passage through the stomach and to persist in the mouse gastrointestinal tract. Here we analyzed the effect of a deficiency in alanine racemase, an enzyme that participates in cell wall synthesis, in each of these bacterial carriers. Recombinant wild-type and mutant strains of L. plantarum NCIMB8826 and L. lactis MG1363 producing TTFC intracellularly were constructed and used in mouse immunization experiments. Remarkably, we observed that the two cell wall mutant strains were far more immunogenic than their wild-type counterparts when the intragastric route was used. However, intestinal TTFC-specific immunoglobulin A was induced only after immunization with the recombinant L. plantarum mutant strain. Moreover, the alanine racemase mutant of either LAB strain allowed induction of a much stronger serum TTFC-specific immune response after immunization via the vagina, which is a quite different ecosystem than the gastrointestinal tract. The design and use of these mutants thus resulted in a major improvement in the mucosal delivery of antigens exhibiting vaccine properties. PMID:15102782

  5. Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.

    PubMed

    Morçöl, T; Nagappan, P; Nerenbaum, L; Mitchell, A; Bell, S J D

    2004-06-11

    An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules. PMID:15158972

  6. System modeling speeds clamshell unloader delivery

    SciTech Connect

    Schuster, J.W.; Zirkler, A.H.; Duke, G.

    1995-04-01

    This article describes how enhanced dust control concepts and design studies found best method to ensure quick, safe clamshell unloader transport and assembly. A new facility, US Generating Co.`s Logan Generating Station, was built in New Jersey, along the Delaware River and four miles from Chester, Pa. At the outset, concerns arose over possible unusual regulatory issues because the plant`s coal barge unloading system extends into the river where it falls under the jurisdiction of the State of Delaware. However, the project contract with the equipment supplier avoided complications by calling for a turnkey project, including erection, start-up, commissioning and training. The supplier responded by using a modeling technique to ensure environmental compatibility. The contract called for one stationary-clamshell bucket grab unloader, complete with a dust control system, barge haul and barge breasting systems, and auxiliary cranes for handling the barge haul lines. Bucket coal capacity is 10 tons at 50 pounds per cubic foot density. When operating on a 40-second duty cycle, the unloader is rated at 910 tons per hour free digging capacity. Under dry, high dust conditions, the duty cycle is extended to 50 seconds to allow for pause time after the bucket closes and while over the hopper prior to bucket discharge.

  7. Synthetic Microbes As Drug Delivery Systems

    PubMed Central

    2015-01-01

    Synthetic cell therapy is a field that has broad potential for future applications in human disease treatment. Next generation therapies will consist of engineered bacterial strains capable of diagnosing disease, producing and delivering therapeutics, and controlling their numbers to meet containment and safety concerns. A thorough understanding of the microbial ecology of the human body and the interaction of the microbes with the immune system will benefit the choice of an appropriate chassis that engrafts stably and interacts productively with the resident community in specific body niches. PMID:25079685

  8. 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.

  9. Aerosol delivery of programmed cell death protein 4 using polysorbitol-based gene delivery system for lung cancer therapy.

    PubMed

    Kim, You-Kyoung; Xing, Lei; Chen, Bao-An; Xu, Fengguo; Jiang, Hu-Lin; Zhang, Can

    2014-11-01

    The development of a safe and effective gene delivery system is the most challenging obstacle to the broad application of gene therapy in the clinic. In this study, we report the development of a polysorbitol-based gene delivery system as an alternative gene carrier for lung cancer therapy. The copolymer was prepared by a Michael addition reaction between sorbitol diacrylate (SD) and spermine (SPE); the SD-SPE copolymer effectively condenses with DNA on the nanoscale and protects it from nucleases. SD-SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo, and aerosol delivery of SD-SPE complexes with programmed cell death protein 4 DNA significantly suppressed lung tumorigenesis in K-ras(LA1) lung cancer model mice. These results demonstrate that SD-SPE has great potential as a gene delivery system based on its excellent biocompatibility and high gene delivery efficiency for lung cancer gene therapy. PMID:24983766

  10. Vorinostat-polymer conjugate nanoparticles for Acid-responsive delivery and passive tumor targeting.

    PubMed

    Denis, Iza; El Bahhaj, Fatima; Collette, Floraine; Delatouche, Régis; Gueugnon, Fabien; Pouliquen, Daniel; Pichavant, Loic; Héroguez, Valérie; Grégoire, Marc; Bertrand, Philippe; Blanquart, Christophe

    2014-12-01

    In vivo histone deacetylase (HDAC) inhibition by vorinostat under clinically acceptable dosing is limited by its poor pharmacokinetics properties. A new type of nontoxic pH-responsive delivery system has been synthesized by ring-opening metathesis polymerization, allowing for the selective distribution of vorinostat in mesothelioma tumors in vivo and subsequent histone reacetylation. The delivery system is synthesized by generic click chemistry, possesses native stealth properties for passive tumor targeting, and does not need additional chemistry for cellular internalization. Although vorinostat alone at 50 mg/kg in mice showed no effect, our new delivery system with 2 mg/kg vorinostat promoted histone reacetylation in tumors without side effects, demonstrating that our strategy improves the activity of this HDAC inihibitor in vivo. PMID:25333409

  11. Encapsulation of paclitaxel into lauric acid-O-carboxymethyl chitosan-transferrin micelles for hydrophobic drug delivery and site-specific targeted delivery.

    PubMed

    Nam, Joung-Pyo; Park, Seong-Cheol; Kim, Tae-Hun; Jang, Jae-Yeang; Choi, Changyong; Jang, Mi-Kyeong; Nah, Jae-Woon

    2013-11-30

    Transferrin/PEG/O-carboxymethyl chitosan/fatty acid/paclitaxel (TPOCFP) micelles were tested for suitability as a drug carrier characterized by low cytotoxicity, sustained release, high cellular uptake, and site-specific targeted delivery of hydrophobic drugs. Characterization, drug content, encapsulation efficiency, and in vitro drug release were investigated. When the feeding amount of paclitaxel (PTX) was increased, the drug content increased, but loading efficiency decreased. TPOCFP micelles had a spherical shape, with a particle size of approximately 140-649 nm. In vitro cell cytotoxicity and hemolysis assays were conducted to confirm the safety of the micelles. Anticancer activity and confocal laser scanning microscopy (CLSM) were used to confirm the targeting efficiency of target ligand-modified TPOCFP micelles. Anticancer activity and CLSM results clearly demonstrated that transferrin-modified TPOCFP micelles were quickly taken up by the cell. The endocytic pathway of TPOCFP micelles was analyzed by flow cytometry, revealing transfection via receptor-mediated endocytosis. These results suggest that PTX-encapsulated TPOCFP micelles may be used as an effective cancer-targeting drug delivery system for chemotherapy. PMID:24076228

  12. 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.

  13. 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. PMID:24394377

  14. 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.

  15. Assessment of Alternative Student Aid Delivery Systems: Preliminary Specification of the Current System with Program Antecedents.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    Specifications of the current delivery systems of the Pell Grant program, the Guaranteed Student Loan (GSL) program, and campus-based aid programs are provided. The relationship between features of the programs and delivery systems is also examined. The campus-based programs include the Supplemental Educational Opportunity Grant (SEOG) Program,…

  16. 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

  17. Current status of central concentrate delivery system for hemodialysis in Korea.

    PubMed

    Han, Sang-Woong; Yi, Joo-Hark; Kim, Ho-Jung

    2009-01-01

    So far, less than 10% of hemodialysis (HD) facilities in Korea have adopted a kind of central delivery system (CDS) for dialysates, the so-called Korean central concentrate delivery system (CCDS). In our CCDS, all concentrate solutions of the acid and bicarbonate dry powder mixed with the treated reverse osmosis (RO) water in the mixing tank and stored in the holding tank are centrally delivered to individual HD machines via two streams along with a one further stream for dilution RO water. This mode of Korean CCDS is different from the central dialysate delivery system (CDDS), which uses already fully proportioned acid and bicarbonate concentrates with dilution RO water delivering it via a single stream. At present, the most popular CCDS in Korea is NephroMix Premium, which is an all-in-one system that combines the mixing tank, the holding tank, and the control functions into one unified case. Moreover, all CCDS data can be monitored in real-time through a user-friendly touch-screen panel, and stored on a desktop PC linked to the manufacturer's main office. For the disinfection and sterility of NephroMix Premium, ozone is used besides a three-step filtering system for removing endotoxin and microbials. Compared to the conventional system in Korea with individual concentrate delivery to single-patient dialysis machines, the Korean-style CCDS seems to be superb in the way of convenience, environmental friendliness, and economy, and also needs less space in the dialysis unit. However, full proof of its safety and effectiveness is required for further verification in the future. PMID:19556767

  18. Novel delivery systems for postoperative analgesia.

    PubMed

    Palmer, Pamela P; Royal, Mike A; Miller, Ronald D

    2014-03-01

    Moderate-to-severe postoperative pain is usually controlled using a multimodal approach, including opioids. Intravenously administered patient-controlled analgesia (IV PCA) with opioids, popular for over 40 years, enables patients to control their level of analgesia and has advantages over a nurse-administered approach, including more satisfied patients and improved pain relief. Unfortunately, IV PCA has drawbacks such as device programming errors, medication prescribing errors, pump malfunction, limitations on patient mobility, IV patency issues, and transmission of infection. Furthermore, the setup of an infusion pump is often complex, time-consuming, and requires witnessed confirmation. Complicating IV PCA is the problem of commonly used compounds, morphine and hydromorphone, having significantly reduced brain/effector-site permeability and active metabolites, both of which create the risk of delayed adverse events. Novel patient-controlled modalities that incorporate rapid effector site-permeating opioids and non-invasive routes of administration offer great promise to enhance both patient and caregiver experiences with postoperative analgesia systems. PMID:24815968

  19. Fatty acid modified octa-arginine for delivery of siRNA.

    PubMed

    Li, Yuhuan; Li, Yujing; Wang, Xinmei; Lee, Robert J; Teng, Lesheng

    2015-11-10

    Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Four fatty acids derivatives of octa-arginine (R8) were synthesized and evaluated for the delivery of siRNA into hepatocellular carcinoma Hep G2 and human lung adenocarcinoma A549 cells. The results showed that the long chain acid oleic acid or stearic acid derivatives of R8, OA-R8 and StA-R8, were more efficient in siRNA complexation and form nanoparticles with greater stability compared to the native R8. Cellular uptake of fluorescence-labeled siRNA delivered by OA-R8 and StA-R8 in Hep G2 and A549 cells was substantially 40-50 times higher than unmodified R8. A significant reduction in siRNA cellular uptake was observed in the presence of sucrose and cytochalasin D, indicating endocytosis as a primary mechanism of cellular entry. A survivin siRNA was used to prepare nanoparticles with OA-R8 or StA-R8 and evaluated for silencing of survivin mRNA and protein in A549 cells, and the inhibition efficiencies of survivin protein reached to 50.3% and 54.6%, respectively. The results showed greater effectiveness with the derivatized R8. Taken together, these findings showed that long chain fatty acid derivatives of R8 are efficient delivery agents for siRNA and may facilitate its therapeutic application. PMID:26386137

  20. Design, synthesis, and pharmacokinetic evaluation of a chemical delivery system for drug targeting to lung tissue.

    PubMed

    Saah, M; Wu, W M; Eberst, K; Marvanyos, E; Bodor, N

    1996-05-01

    We espouse the application of a novel chemical delivery system (CDS) approach to a delivery mechanism for drug targeting to lung tissue using the 1,2-dithiolane-3-pentyl moiety of lipoic acid as the "targetor moiety". The synthesis and the physicochemical and pharmacokinetic evaluation of a CDS modeling the lipoyl and other ester derivatives of chlorambucil (an antineoplastic agent) and cromolyn (a bischromone used in antiasthma prophylaxis) as compared with their respective parent drugs are described. The chlorambucil CDS was synthesized by esterifying the alcohol derivative of lipoic acid with chlorambucil using dicyclohexylcarbodiimide as the coupling agent. The cromolyn CDS was prepared by a multistep synthetic procedure culminating in the reaction of the alkyl bromide derivative of lipoic acid with the disodium salt of the bischromone compound. All the esters were highly lipophilic unlike the parent compounds. The in-vitro kinetic and in-vivo pharmacokinetic studies showed that the respective CDSs were sufficiently stable in buffer and biological media, hydrolyzed rapidly into the respective active parent drugs, and significantly enhanced delivery and retention of the active compound to lung tissue in comparison with the underivatized parent compounds used in conventional therapy. PMID:8742941

  1. Yeast retrotransposon particles as antigen delivery systems.

    PubMed

    Kingsman, A J; Burns, N R; Layton, G T; Adams, S E

    1995-05-31

    The development of technologies to produce recombinant proteins for use in the pharmaceutical industry has made substantial advances, in particular in the area of generating antigens containing multiple copies of important immunological regions. One such antigen-carrier system is based on the ability of a protein encoded by the yeast retrotransposon, Ty, to self-assemble into virus-like particles. Ty-fusion proteins retain this ability to form particles, and a range of hybrid VLPs carrying a variety of heterologous antigens have been produced and shown to induce potent immune responses. In particular, hybrid VLPs carrying the core protein p24 of HIV (p24-VLPs) have been shown to induce antibody and T-cell proliferative responses in both experimental animals and human volunteers, and immunization of rabbits with VLPs carrying the principal neutralizing determinant of HIV (V3-VLPs) resulted in the induction of neutralizing antibody responses and T-cell proliferation. Further studies with V3-VLPs have shown that this particulate antigen stimulates enhanced V3-specific lymphoproliferative responses as compared to whole recombinant gp120 or to V3 peptide conjugated to albumin. The V3-VLPs also induce potent CTL responses following immunization of mice in the absence of adjuvant. These responses are MHC class I restricted and are mediated by CD8-positive cells. These observations therefore demonstrate that hybrid Ty-VLPs induce both humoral and cellular immune responses against HIV and suggest that these immunogens may be important in combatting AIDS and other infections. PMID:7625653

  2. 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.

  3. Quality measurement and system change of cancer care delivery.

    PubMed

    Haggstrom, David A; Doebbeling, Bradley N

    2011-12-01

    Cancer care quality measurement and system change may serve as a case example for larger possibilities in the health care system related to other diseases. Cancer care quality gaps and variation exist across both technical and patient-centered cancer quality measures, especially among vulnerable populations. There is a need to develop measures that address the following dimensions of quality and its context: disparities, overuse, patient-centeredness, and uncertainty. Developments that may promote system change in cancer care delivery include changes in the information market, organizational accountability, and consumer empowerment. Information market changes include public cancer care quality reporting, enabled by health information exchange, and incentivized by pay-for-performance. Moving organizational accountability, reimbursement, and quality measurement from individual episodes of care to multiple providers providing coordinated cancer care may address quality gaps associated with the fragmentation of care delivery. Consumer empowerment through new technologies, such as personal health records, may lead to the collection of patient-centered quality measures and promote patient self-management. Across all of these developments, leadership and ongoing research to guide informed system changes will be necessary to transform the cancer care delivery system. PMID:20940654

  4. 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

  5. The Cleveland Health Network: a new integrated delivery system.

    PubMed

    Roman, L K

    1997-01-01

    CHN and its subsidiary CHN MCO have significantly impacted the Cleveland market place in the two years since their inception. CHN will continue to expand geographically with hospital and physician partners who are committed to providing quality care in the most cost-effective manner. Medical management will continue to be the central focus and over-riding success of the CHN MCO, making this organization extremely attractive to the payer market. The integrated CHN and its medical management focus could become a model for other integrated delivery systems. As the market place continues to experience an increase in managed care and more consolidation of healthcare providers (and in some cases, mergers with payers), more integrated delivery systems will emerge. Senior- and mid-level administrators and managers with operational responsibilities need to take into consideration how their patient access systems will need to be modified to meet the demands of managed care through the formation of integrated delivery systems. How patients access the systems is of critical importance in ensuring financial success, ease of access for the patient, and tracking of appropriate medical care. PMID:10166776

  6. 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

  7. 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

  8. 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

  9. Intracellular Delivery System for Antibody–Peptide Drug Conjugates

    PubMed Central

    Berguig, Geoffrey Y; Convertine, Anthony J; Frayo, Shani; Kern, Hanna B; Procko, Erik; Roy, Debashish; Srinivasan, Selvi; Margineantu, Daciana H; Booth, Garrett; Palanca-Wessels, Maria Corinna; Baker, David; Hockenbery, David; Press, Oliver W; Stayton, Patrick S

    2015-01-01

    Antibodies armed with biologic drugs could greatly expand the therapeutic potential of antibody–drug conjugates for cancer therapy, broadening their application to disease targets currently limited by intracellular delivery barriers. Additional selectivity and new therapeutic approaches could be realized with intracellular protein drugs that more specifically target dysregulated pathways in hematologic cancers and other malignancies. A multifunctional polymeric delivery system for enhanced cytosolic delivery of protein drugs has been developed that incorporates endosomal-releasing activity, antibody targeting, and a biocompatible long-chain ethylene glycol component for optimized safety, pharmacokinetics, and tumor biodistribution. The pH-responsive polymeric micelle carrier, with an internalizing anti-CD22 monoclonal targeting antibody, effectively delivered a proapoptotic Bcl-2 interacting mediator (BIM) peptide drug that suppressed tumor growth for the duration of treatment and prolonged survival in a xenograft mouse model of human B-cell lymphoma. Antitumor drug activity was correlated with a mechanistic induction of the Bcl-2 pathway biomarker cleaved caspase-3 and a marked decrease in the Ki-67 proliferation biomarker. Broadening the intracellular target space by more effective delivery of protein/peptide drugs could expand the repertoire of antibody–drug conjugates to currently undruggable disease-specific targets and permit tailored drug strategies to stratified subpopulations and personalized medicines. PMID:25669432

  10. 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.

  11. Porous Tube Plant Nutrient Delivery System development: a device for nutrient delivery in microgravity.

    PubMed

    Dreschel, T W; Brown, C S; Piastuch, W C; Hinkle, C R; Knott, W M

    1994-11-01

    The Porous Tube Plant Nutrient Delivery System 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 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. PMID:11540217

  12. Development and characterization of chronomodulated drug delivery system of captopril

    PubMed Central

    Patil, Archana S; Dandagi, Panchaxari M; Masthiholimath, Vinayak S; Gadad, Anand P; Najwade, Basavaraj K

    2011-01-01

    Background: Hypertension shows circadian rhythm that there is a rise in pressure from the time of waking or before (about 4 to 8 a.m.), in most people. Conventional drug delivery system of captopril is inappropriate for the delivery of drug, as they cannot be administered just before the symptoms are worsened, because during this time the patients are asleep, bedtime dosing of captopril will not provide a therapeutic plasma drug concentration at the early hours of morning because of poor pharmacokinetic profile and shorter half-life of 1.9 hours. Thus, this study attempts to design and evaluate a chronomodulated pulsatile drug delivery system of captopril which was aimed to release the drug after a lag time of 6 hours. Materials and Methods: Present delivery system was prepared by rupturable coating method. The core containing captopril as a bioactive compound were prepared by direct compression method and then coated sequentially with an inner swelling layer containing hydrocolloid HPMC E5 and an outer rupturable layer consisted of Eudragit RL/RS (1 : 1). Total 12 formulations with different levels of inner swelling layer and outer polymeric layer were prepared and subjected to various processing and formulative parameters like the effect of core composition, level of swelling layer, and rupturable coating on lag time was investigated. In vitro drug release and rupture tests were performed using United States Pharmacopoeia paddle method at 50 rpm in 0.1N HCl and phosphate buffer of pH 6.8. Results: The results showed that as the amount of inner swelling layer increases, the lag time decreases and as the Eudragit coating level increases, the lag time increases and percent water uptake of time-dependent pulsatile release system decreases. The presence of an osmotic agent and effervescent agent helped in shortening of lag time. Conclusion: The system was found to be satisfactory in terms of release of the drug after the lag time of 6 hours. PMID:23071948

  13. 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

  14. 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)

  15. Secure and effective gene delivery system of plasmid DNA coated by polynucleotide.

    PubMed

    Kodama, Yukinobu; Ohkubo, Chikako; Kurosaki, Tomoaki; Egashira, Kanoko; Sato, Kayoko; Fumoto, Shintaro; Nishida, Koyo; Higuchi, Norihide; Kitahara, Takashi; Nakamura, Tadahiro; Sasaki, Hitoshi

    2015-01-01

    Polynucleotides are anionic macromolecules which are expected to transfer into the targeted cells through specific uptake mechanisms. So, we developed polynucleotides coating complexes of plasmid DNA (pDNA) and polyethylenimine (PEI) for a secure and efficient gene delivery system and evaluated their usefulness. Polyadenylic acid (polyA), polyuridylic acid (polyU), polycytidylic acid (polyC), and polyguanylic acid (polyG) were examined as the coating materials. pDNA/PEI/polyA, pDNA/PEI/polyU, and pDNA/PEI/polyC complexes formed nanoparticles with a negative surface charge although pDNA/PEI/polyG was aggregated. The pDNA/PEI/polyC complex showed high transgene efficiency in B16-F10 cells although there was little efficiency in pDNA/PEI/polyA and pDNA/PEI/polyU complexes. An inhibition study strongly indicated the specific uptake mechanism of pDNA/PEI/polyC complex. Polynucleotide coating complexes had lower cytotoxicity than pDNA/PEI complex. The pDNA/PEI/polyC complex showed high gene expression selectively in the spleen after intravenous injection into mice. The pDNA/PEI/polyC complex showed no agglutination with erythrocytes and no acute toxicity although these were observed in pDNA/PEI complex. Thus, we developed polynucleotide coating complexes as novel vectors for clinical gene therapy, and the pDNA/PEI/polyC complex as a useful candidate for a gene delivery system. PMID:25148610

  16. Formulation and in vitro characterization of a novel solid lipid-based drug delivery system.

    PubMed

    Ma, Hongxing; Chu, Mingjuan; Itagaki, Kiyoshi; Xin, Ping; Zhou, Xuegang; Zhang, Dawei; Wang, Youzhi; Fu, Jia; Sun, Shiqin

    2014-01-01

    The liquid self-emulsifying drug delivery system (L-SEDDS), commonly used to deliver effective but poorly water-soluble oleanolic acid (OA), has many limitations such as high manufacturing costs, few choices of dosage forms, risk of leakage from hard gelatin capsules, low stability, limited portability, incompatibility with capsule materials, and relatively restricted storage conditions. Thus the main purpose of our study was to develop a promising solid lipid-based drug delivery system (S-SEDDS) for OA. The S-SEDDS, prepared from wet granulation with an optimized L-SEDDS formulation and mannitol, was characterized by particle size analysis, scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction. Finally, the solubility of the OA-loaded S-SEDDS was compared with that of OA powder in the dissolution assay. Our new S-SEDDS for OA was developed from the optimum L-SEDDS with ethyl oleate (oil phase), Labrasol (surfactant), and Transcutol P (cosurfactant) at a volume ratio of 15:71:14 with 1.5% w/v OA and mannitol. The dissolution of OA was improved by 60% compared with that of the pure OA powder. All the problems associated with the L-SEDDS were resolved. The methodologies we developed for OA delivery could also be utilized for the delivery of other drugs with the S-SEDDS. PMID:25450625

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

    PubMed

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

    2013-09-27

    Liquid crystalline systems with a lamellar structure have been extensively studied as dermal delivery systems. Ascorbyl palmitate (AP) is one of the most studied and used ascorbic acid derivatives and is employed as an antioxidant to prevent skin aging. The aim of this study was to develop and characterize skin-compliant dermal delivery systems with a liquid crystalline structure for AP. First, a pseudoternary phase diagram was constructed using Tween 80/lecithin/isopropyl myristate/water at a Tween 80/lecithin mass ratio of 1/1, and the region of lamellar liquid crystals was identified. Second, selected unloaded and AP-loaded lamellar liquid crystal systems were physicochemically characterized with polarizing optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology techniques. The interlayer spacing and rheological parameters differ regarding quantitative composition, whereas the microstructure of the lamellar phase was affected by the AP incorporation, resulting either in additional micellar structures (at 25 and 32 °C) or being completely destroyed at higher temperature (37°C). After this, the study was oriented towards in vitro cytotoxicity evaluation of lamellar liquid crystal systems on a keratinocyte cell line. The results suggest that the lamellar liquid crystals that were developed could be used as a physiologically acceptable dermal delivery system. PMID:23643736

  18. 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.

  19. Delivery systems for the treatment of degenerated intervertebral discs.

    PubMed

    Blanquer, S B G; Grijpma, D W; Poot, A A

    2015-04-01

    The intervertebral disc (IVD) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production, abnormal enzyme activities and production of pro-inflammatory substances like cytokines. The established treatment strategy for IVD degeneration consists of physiotherapy, pain medication by drug therapy and if necessary surgery. This approach, however, has shown limited success. Alternative strategies to increase and prolong the effects of bioactive agents and to reverse the process of IVD degeneration include the use of delivery systems for drugs, proteins, cells and genes. In view of the specific anatomy and physiology of the IVD and depending on the strategy of the therapy, different delivery systems have been developed which are reviewed in this article. PMID:25451138

  20. Microsponges: A novel strategy for drug delivery system

    PubMed Central

    Kaity, Santanu; Maiti, Sabyasachi; Ghosh, Ashoke Kumar; Pal, Dilipkumar; Ghosh, Animesh; Banerjee, Subham

    2010-01-01

    Microsponges are polymeric delivery systems composed of porous microspheres. They are tiny sponge-like spherical particles with a large porous surface. Moreover, they may enhance stability, reduce side effects and modify drug release favorably. Microsponge technology has many favorable characteristics, which make it a versatile drug delivery vehicle. Microsponge Systems are based on microscopic, polymer-based microspheres that can suspend or entrap a wide variety of substances, and can then be incorporated into a formulated product such as a gel, cream, liquid or powder. The outer surface is typically porous, allowing a sustained flow of substances out of the sphere. Microsponges are porous, polymeric microspheres that are used mostly for topical use and have recently been used for oral administration. Microsponges are designed to deliver a pharmaceutical active ingredient efficiently at the minimum dose and also to enhance stability, reduce side effects, and modify drug release. PMID:22247859

  1. 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'. PMID:25451137

  2. Magnetic nanoparticle drug delivery systems for targeting tumor

    NASA Astrophysics Data System (ADS)

    Mody, Vicky V.; Cox, Arthur; Shah, Samit; Singh, Ajay; Bevins, Wesley; Parihar, Harish

    2014-04-01

    Tumor hypoxia, or low oxygen concentration, is a result of disordered vasculature that lead to distinctive hypoxic microenvironments not found in normal tissues. Many traditional anti-cancer agents are not able to penetrate into these hypoxic zones, whereas, conventional cancer therapies that work by blocking cell division are not effective to treat tumors within hypoxic zones. Under these circumstances the use of magnetic nanoparticles as a drug delivering agent system under the influence of external magnetic field has received much attention, based on their simplicity, ease of preparation, and ability to tailor their properties for specific biological applications. Hence in this review article we have reviewed current magnetic drug delivery systems, along with their application and clinical status in the field of magnetic drug delivery.

  3. The ILC Beam Delivery System - Conceptual Design and RD Plans

    SciTech Connect

    Seryi, Andrei; /SLAC

    2005-05-27

    The Beam Delivery System of the ILC has many stringent and sometimes conflicting requirements. To produce luminosity, the beams must be focused to nanometer size. To provide acceptable detector backgrounds, particles far from the beam core must be collimated. Unique beam diagnostics and instrumentation are required to monitor parameters of the colliding beams such as the energy spectrum and polarization. The detector and beamline components must be protected against errant beams. After collision, the beams must also be transported to the beam dumps safely and with acceptable losses. An international team is actively working on the design of the ILC Beam Delivery System in close collaboration. Details of the design, recent progress and remaining challenges will be summarized in this paper.

  4. Experimental Shock Chemistry of Aqueous Amino Acid Solutions and the Cometary Delivery of Prebiotic Compounds

    NASA Astrophysics Data System (ADS)

    Blank, Jennifer G.; Miller, Gregory H.; Ahrens, Michael J.; Winans, Randall E.

    2001-02-01

    A series of shock experiments were conducted to assess the feasibility of the delivery of organic compounds to the Earth via cometary impacts. Aqueous solutions containing near-saturation levels of amino acids (lysine, norvaline, aminobutyric acid, proline, and phenylalanine) were sealed inside stainless steel capsules and shocked by ballistic impact with a steel projectile plate accelerated along a 12-m-long gun barrel to velocities of 0.5-1.9 km sec^-1. Pressure-temperature-time histories of the shocked fluids were calculated using 1D hydrodynamical simulations. Maximum conditions experienced by the solutions lasted 0.85-2.7 μs and ranged from 5.1-21 GPa and 412-870 K. Recovered sample capsules were milled open and liquid was extracted. Samples were analyzed using high performance liquid chromatography (HPLC) and mass spectrometry (MS). In all experiments, a large fraction of the amino acids survived. We observed differences in kinetic behavior and the degree of survivability among the amino acids. Aminobutyric acid appeared to be the least reactive, and phenylalanine appeared to be the most reactive of the amino acids. The impact process resulted in the formation of peptide bonds; new compounds included amino acid dimers and cyclic diketopiperazines. In our experiments, and in certain naturally occurring impacts, pressure has a greater influence than temperature in determining reaction pathways. Our results support the hypothesis that significant concentrations of organic material could survive a natural impact process.

  5. Experimental shock chemistry of aqueous amino acid solutions and the cometary delivery of prebiotic compounds.

    PubMed

    Blank, J G; Miller, G H; Ahrens, M J; Winans, R E

    2001-01-01

    A series of shock experiments were conducted to assess the feasibility of the delivery of organic compounds to the Earth via cometary impacts. Aqueous solutions containing near-saturation levels of amino acids (lysine, norvaline, aminobutyric acid, proline, and phenylalanine) were sealed inside stainless steel capsules and shocked by ballistic impact with a steel projectile plate accelerated along a 12-m-long gun barrel to velocities of 0.5-1.9 km sec-1. Pressure-temperature-time histories of the shocked fluids were calculated using 1D hydrodynamical simulations. Maximum conditions experienced by the solutions lasted 0.85-2.7 microseconds and ranged from 5.1-21 GPa and 412-870 K. Recovered sample capsules were milled open and liquid was extracted. Samples were analyzed using high performance liquid chromatography (HPLC) and mass spectrometry (MS). In all experiments, a large fraction of the amino acids survived. We observed differences in kinetic behavior and the degree of survivability among the amino acids. Aminobutyric acid appeared to be the least reactive, and phenylalanine appeared to be the most reactive of the amino acids. The impact process resulted in the formation of peptide bonds; new compounds included amino acid dimers and cyclic diketopiperazines. In our experiments, and in certain naturally occurring impacts, pressure has a greater influence than temperature in determining reaction pathways. Our results support the hypothesis that significant concentrations of organic material could survive a natural impact process. PMID:11296518

  6. Design and evaluation of an innovative floating and bioadhesive multiparticulate drug delivery system based on hollow structure.

    PubMed

    Zhang, Chungang; Tang, Jingya; Liu, Dechun; Li, Xuetao; Cheng, Lan; Tang, Xing

    2016-04-30

    In this study a gastric-retentive delivery system was prepared by a novel method which is reported here for the first time. An innovative floating and bioadhesive drug delivery system with a hollow structure was designed and prepared. The floating and bioadhesive drug delivery system was composed of a hollow spherical shell, a waterproof layer (Stearic acid), a drug layer (Ofloxacin), a release retarding film (the novel blended coating materials) and a bioadhesive layer (Carbomer 934P) prepared by using a liquid multi-layering process. A novel blended coating material was designed and investigated to solve the problem of the initial burst release of the formulation and the release mechanism of the novel material was analyzed in this study. The optimized formulation provided the sustained release characteristic and was able to float for 24h. The SEM cross-section images showed that the particulates were hollow with a spherical shell. X-ray images and pharmacokinetic studies (Frel = 124.1 ± 28.9%) in vivo showed that the gastric-retentive delivery system can be retained in the stomach for more than 6h. The floating and bioadhesive particulate drug delivery system based on a hollow structure with a dual function presented here is a viable alternative to other for gastroretentive drug delivery system. PMID:26943975

  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. 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

  9. 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.

  10. A look at emerging delivery systems for topical drug products.

    PubMed

    Fireman, Sharon; Toledano, Ofer; Neimann, Karine; Loboda, Natalia; Dayan, Nava

    2011-01-01

    The introduction of new topical drugs based on new chemical entities has become a rare event. Instead, pharmaceutical companies have been focused on reformulating existing drugs resulting in an ever-growing number of topical drug products for every approved drug substance. In light of this trend, soon reformulations may not be as rewarding to their sponsors as they are today unless they offer a substantial improvement over other formulations of the same drug substance and the same indication, namely improved efficacy over existing drugs, reduced side effects, unique drug combinations, or applicability for new indications. This article reviews and compares topical drug delivery systems currently under active research that are designed to offer such advantages in the coming years. The reviewed delivery systems are: liposomes, niosomes, transferosomes, ethosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrin, and sol-gel microcapsules. Among all the topical drug delivery systems currently undergoing active research, only the sol-gel microencapsulation is at clinical stages. PMID:22353154

  11. 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

  12. Peptide/protein vaccine delivery system based on PLGA particles.

    PubMed

    Allahyari, Mojgan; Mohit, Elham

    2016-03-01

    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

  13. Plasmid DNA delivery by arginine-rich cell-penetrating peptides containing unnatural amino acids.

    PubMed

    Kato, Takuma; Yamashita, Hiroko; Misawa, Takashi; Nishida, Koyo; Kurihara, Masaaki; Tanaka, Masakazu; Demizu, Yosuke; Oba, Makoto

    2016-06-15

    Cell-penetrating peptides (CPPs) have been developed as drug, protein, and gene delivery tools. In the present study, arginine (Arg)-rich CPPs containing unnatural amino acids were designed to deliver plasmid DNA (pDNA). The transfection ability of one of the Arg-rich CPPs examined here was more effective than that of the Arg nonapeptide, which is the most frequently used CPP. The transfection efficiencies of Arg-rich CPPs increased with longer post-incubation times and were significantly higher at 48-h and 72-h post-incubation than that of the commercially available transfection reagent TurboFect. These Arg-rich CPPs were complexed with pDNA for a long time in cells and effectively escaped from the late endosomes/lysosomes into the cytoplasm. These results will be helpful for designing novel CPPs for pDNA delivery. PMID:27132868

  14. 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.

  15. 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. PMID:27173823

  16. Liposomal drug delivery system from laboratory to clinic.

    PubMed

    Kshirsagar, N A; Pandya, S K; Kirodian, G B; Sanath, S

    2005-01-01

    The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B) remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, Fungisome) drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India. We have therefore

  17. Gelucire-stabilized nanoparticles as a potential DNA delivery system.

    PubMed

    Oyewumi, Moses O; Wehrung, Daniel; Sadana, Prabodh

    2016-09-01

    Clinical viability of gene delivery systems has been greatly impacted by potential toxicity of the delivery systems. Recently, we reported the nanoparticle (NP) preparation process that employs biocompatible materials such as Gelucire® 44/14 and cetyl alcohol as matrix materials. In the current study, the NP preparation was modified for pDNA loading through: (i) inclusion of cationic lipids (DOTAP or DDAB) with NP matrix materials; or (ii) application of cationic surfactants (CTAB) to generate NPs with desired surface charges for pDNA complexation. Colloidal stability and efficiency of loading pGL3-DR4X2-luciferase plasmid DNA in NPs were verified by gel permeation chromatography. Compared to pDNA alone, all the NPs were effective in preserving pDNA from digestion by DNase. While pDNA loading using CTAB-NPs involved fewer steps compared to DOTAP-NPs and DDAB-NPs, CTAB-NPs were greatly impacted by elevated cytotoxicity level which could be ascribed to the concentrations of CTAB in NP formulations. In vitro transfection studies (in HepG2 cells) based on luciferase expression showed the ranking of cell transfection efficiency as DOTAP-NPs > DDAB-NPs > CTAB-NPs. The overall work provided an initial assessment of gelucire-stabilized NPs as a potential platform for gene delivery. PMID:25915179

  18. 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

  19. Applications of novel drug delivery system for herbal formulations.

    PubMed

    Ajazuddin; Saraf, S

    2010-10-01

    Over the past several years, great advances have been made on development of novel drug delivery systems (NDDS) for plant actives and extracts. The variety of novel herbal formulations like polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes has been reported using bioactive and plant extracts. The novel formulations are reported to have remarkable advantages over conventional formulations of plant actives and extracts which include enhancement of solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation. The present review highlights the current status of the development of novel herbal formulations and summarizes their method of preparation, type of active ingredients, size, entrapment efficiency, route of administration, biological activity and applications of novel formulations. PMID:20471457

  20. 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.

  1. Filamentous Bacteriophage Fd as an Antigen Delivery System in Vaccination

    PubMed Central

    Prisco, Antonella; De Berardinis, Piergiuseppe

    2012-01-01

    Peptides displayed on the surface of filamentous bacteriophage fd are able to induce humoral as well as cell-mediated immune responses, which makes phage particles an attractive antigen delivery system to design new vaccines. The immune response induced by phage-displayed peptides can be enhanced by targeting phage particles to the professional antigen presenting cells, utilizing a single-chain antibody fragment that binds dendritic cell receptor DEC-205. Here, we review recent advances in the use of filamentous phage fd as a platform for peptide vaccines, with a special focus on the use of phage fd as an antigen delivery platform for peptide vaccines in Alzheimer’s Disease and cancer. PMID:22606037

  2. Creating a high-value delivery system for health care.

    PubMed

    Teisberg, Elizabeth O; Wallace, Scott

    2009-01-01

    Health care reform that focuses on improving value enhances both the well-being of patients and the professional satisfaction of physicians. Value in health care is the improvement in health outcomes achieved for patients relative to the money spent. Dramatic and ongoing improvement in the value of health care delivered will require fundamental restructuring of the system. Current efforts to improve safety and reduce waste are truly important but not sufficient. The following three structural changes will drive simultaneous improvement in outcomes and efficiency: (1) reorganizing care delivery into clinically integrated teams defined by patient needs over the full cycle of care; (2) measuring and reporting patient outcomes by clinical teams, across the cycle of care and for identified clusters of medical circumstances; and (3) enabling reimbursement tied to value rather than to quantity of services. Many of these changes require physician leadership. We discuss steps on the journey to value-based care delivery. PMID:19632561

  3. Numerical simulation of iontophoresis in the drug delivery system.

    PubMed

    Filipovic, Nenad; Zivanovic, Marko; Savic, Andrej; Bijelic, Goran

    2016-01-01

    The architecture and composition of stratum corneum act as barriers and limit the diffusion of most drug molecules and ions. Much effort has been made to overcome this barrier and it can be seen that iontophoresis has shown a good effect. Iontophoresis represents the application of low electrical potential to increase the transport of drugs into and across the skin or tissue. Iontophoresis is a noninvasive drug delivery system, and therefore, it is a useful alternative to drug transportation by injection. In this study, we present a numerical model and effects of electrical potential on the drug diffusion in the buccal tissue and the stratum corneum. The initial numerical results are in good comparison with experimental observation. We demonstrate that the application of an applied voltage can greatly improve the efficacy of localized drug delivery as compared to diffusion alone. PMID:26592537

  4. 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

  5. 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. PMID:23506535

  6. Mesostructured silica and aluminosilicate carriers for oxytetracycline delivery systems.

    PubMed

    Berger, D; Nastase, S; Mitran, R A; Petrescu, M; Vasile, E; Matei, C; Negreanu-Pirjol, T

    2016-08-30

    Oxytetracycline delivery systems containing various MCM-type silica and aluminosilicate with different antibiotic content were developed in order to establish the influence of the support structural and textural properties and aluminum content on the drug release profile. The antibiotic molecules were loaded into the support mesochannels by incipient wetness impregnation method using a drug concentrated aqueous solution. The carriers and drug-loaded materials were investigated by small- and wide-angle XRD, FTIR spectroscopy, TEM and N2 adsorption-desorption isotherms. Faster release kinetics of oxytetracycline from uncalcined silica and aluminosilicate supports was observed, whereas higher drug content led to lower delivery rate. The presence of aluminum into the silica network also slowed down the release rate. The antimicrobial assays performed on Staphylococcus aureus clinical isolates showed that the oxytetracycline-loaded materials containing MCM-41-type mesoporous silica or aluminosilicate carriers inhibited the bacterial development. PMID:26861688

  7. Potential and problems in ultrasound-responsive drug delivery systems.

    PubMed

    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

  8. 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

  9. pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin

    PubMed Central

    Wu, Jing-Liang; Tian, Gui-Xiang; Yu, Wen-Jing; Jia, Guang-Tao; Sun, Tong-Yi; Gao, Zhi-Qin

    2016-01-01

    The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid–glycyrrhetinic acid conjugate and a hyaluronic acid-l-histidine conjugate (HA–GA/HA–His) were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via 1H-NMR, particle size, and ζ potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA–GA/HA–His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA–GA/HA–His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA–GA/HA–His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma. PMID:27043540

  10. 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. PMID:26704543

  11. 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

  12. Dose error analysis for a scanned proton beam delivery system.

    PubMed

    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 cm(3) 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. PMID:21076200

  13. 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

  14. Targeted delivery of salicylic acid from acne treatment products into and through skin: role of solution and ingredient properties and relationships to irritation.

    PubMed

    Rhein, Linda; Chaudhuri, Bhaskar; Jivani, Nur; Fares, Hani; Davis, Adrian

    2004-01-01

    Salicylic acid (SA) is a beta hydroxy acid and has multifunctional uses in the treatment of various diseases in skin such as acne, psoriasis, and photoaging. One problem often cited as associated with salicylic acid is that it can be quite irritating at pH 3-4, where it exhibits the highest activity in the treatment of skin diseases. We have identified strategies to control the irritation potential of salicylic acid formulations and have focused on hydroalcoholic solutions used in acne wipes. One strategy is to control the penetration of SA into the skin. Penetration of the drug into various layers of skin, i.e., epidermis, dermis, and receptor fluid, was measured using a modified Franz in vitro diffusion method after various exposure times up to 24 hours. A polyurethane polymer (polyolprepolymer-15) was found to be an effective agent in controlling delivery of SA. In a dose-dependent fashion it targeted delivery of more SA to the epidermis as compared to penetration through the skin into the receptor fluid. It also reduced the rapid rate of permeation of a large dose of SA through the skin in the first few hours of exposure. A second strategy that proved successful was incorporation of known mild nonionic surfactants like isoceteth-20. These surfactants cleanse the skin, yet due to their inherent mildness (because of their reduced critical micelle concentration and monomer concentration), keep the barrier intact. Also, they reduce the rate of salicylic acid penetration, presumably through micellar entrapment (either in solution or on the skin surface after the alcohol evaporates). Cumulative irritation studies showed that targeting delivery of SA to the epidermis and reducing the rapid early rate of penetration of large amounts of drug through the skin resulted in a reduced irritation potential. In vivo irritation studies also showed that the surfactant system is the most important factor controlling irritancy. SA delivery is secondary, as formulations with less

  15. Anti-angiogenic therapy via cationic liposome-mediated systemic siRNA delivery.

    PubMed

    Tagami, Tatsuaki; Suzuki, Takuya; Matsunaga, Mariko; Nakamura, Kazuya; Moriyoshi, Naoto; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2012-01-17

    siRNA has been touted as a therapeutic molecule against genetic diseases, which include cancers. But several challenging issues remain in order to achieve efficient systemic siRNA delivery and a sufficient therapeutic effect for siRNA in vivo. Cationic liposome shows promise as a carrier for nucleic acids, as it can selectively bind to angiogenic tumor blood vessels. In this way, anti-angiogenic therapy via cationic liposome-mediated systemic siRNA delivery could be achieved in cancer therapy. In the present study, we proved our assumption by preparing various kinds of polyethylene glycol (PEG)-coated siRNA/cationic liposome complexes (siRNA-lipoplexes) and screening the avidity of these siRNA-lipoplexes upon angiogenic tumor blood vessels by means of a murine dorsal air sac (DAS) model. The lipoplex, having a lipid composition of DC-6-14/POPC/CHOL/DOPE/mPEG(2000)-DSPE=20/30/30/20/5 (molar ratio) and a charge ratio of cationic liposome and siRNA=3.81 (+/-), showed a higher binding index to newly formed blood vessels. Systemic injection with the lipoplex containing siRNA for the Argonaute2 gene (apoptosis-inducible siRNA) resulted in significant anti-tumor effect without severe side effects in mice with Lewis lung carcinoma. Our results indicate that the PEGylated cationic liposome-mediated systemic delivery of cytotoxic siRNA achieves anti-angiogenesis, resulting in the suppression of tumor growth. PMID:22101286

  16. The strategic role of health informatics in integrated delivery systems.

    PubMed

    Currie, G A

    1998-01-01

    Having accurate measures and high-quality health information is critically important for all providers today. Integrated delivery systems are faced with increasing demands for numerous redundant, sometimes conflicting, performance measurement and reporting data from managed care customers, regulators, and accreditors. When implemented independently within each organizational subunit, these measurement systems are costly and difficult to manage. Centralization of all measurement services can maximize the productivity of the costly resources required to deliver them and can achieve efficiencies, cost savings, and a better balance between internal and external resources while collecting information that is of a higher quality for managerial and clinical decision making. PMID:10185721

  17. A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin.

    PubMed

    Li, Lei; Jiang, Guohua; Yu, Weijiang; Liu, Depeng; Chen, Hua; Liu, Yongkun; Huang, Qin; Tong, Zaizai; Yao, Juming; Kong, Xiangdong

    2016-12-01

    Development of an oral delivery strategy for insulin therapeutics has drawn much attention in recent years. In this study, a glucose-responsive nanocarriers for loading of insulin has been prepared firstly. The resultant nanocarriers exhibited relative low cytotoxicity against Caco-2 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. In order to enhance the oral bioavailability of insulin, the insulin-loaded glucose-responsive nanocarriers were further encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel environment for overcoming multiple barriers and providing multi-protection for insulin during the transport process. The hypoglycemic effect for oral delivery of insulin was studied in vivo. After oral administration to the diabetic rats, the released insulin from hydrogel systems containing insulin-loaded glucose-responsive nanocarriers exhibited an effective hypoglycemic effect for longer time compared with insulin-loaded nanocarriers. PMID:27612686

  18. 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. PMID:27022867

  19. 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. PMID:8242586

  20. Computational modeling of environmentally responsive hydrogels (ERH) for drug delivery system.

    PubMed

    Namboori, P K Krishnan; Ranjini, U P; Manakadan, Asha A; Jose, Anila; Silvipriya, K S; Belzik, N; Deepak, O M

    2013-03-01

    The present work aims at computational analysis of environmentally responsive hydrogels with enormous prospective in the formulation aspect of drug delivery systems. The drug delivery potential of hydrogels to the targets is owing to the specific stimuli responsive nature of the hydrogels. The environmental factors looked upon in the study are changes in pH, alteration of temperature and glucose concentration rise originated in the body as a result of various disease conditions. Polymers, synthetic polypeptides and dendrimers have been used in the present work to study the feasibility of drug delivery. The computational methods have been used to formulate polymer properties, pharmacokinetics and toxicity studies. Diverse interactions approximating electrostatic, hydrophobic and hydrogen bond interactions acquire place during incorporation of drugs within the polymer and dendrimers. The covalent and electrostatic interactions between a drug and the surface of polymer and dendrimer have been analyzed. The docking interaction studies have been performed and the best polymer and dendrimer complex have been selected based on the docking score, binding energy and interaction energy with the drugs. G5 generation of poly amidoamine dendrimers and poly N-Ndiethyl acrylamide (PDEAAM) have been identified as most suitable stimuli-responsive effective drug carriers for anti diabetic drugs and diuretics. Favorable results have been obtained while using poly acrylic acid (PAA) for corticosteroids and polylysine for diabetic drugs. ConA protein along with poly aspartic acid also showed good results. PMID:23106779

  1. A patchless dissolving microneedle delivery system enabling rapid and efficient transdermal drug delivery

    PubMed Central

    Lahiji, Shayan F.; Dangol, Manita; Jung, Hyungil

    2015-01-01

    Dissolving microneedles (DMNs) are polymeric, microscopic needles that deliver encapsulated drugs in a minimally invasive manner. Currently, DMN arrays are superimposed onto patches that facilitate their insertion into skin. However, due to wide variations in skin elasticity and the amount of hair on the skin, the arrays fabricated on the patch are often not completely inserted and large amount of loaded materials are not delivered. Here, we report “Microlancer”, a novel micropillar based system by which patients can self-administer DMNs and which would also be capable of achieving 97 ± 2% delivery efficiency of the loaded drugs regardless of skin type or the amount of hair on the skin in less than a second. PMID:25604728

  2. EGF-coated nano-dendriplexes for tumor-targeted nucleic acid delivery in vivo.

    PubMed

    Li, Jun; Chen, Lei; Liu, Nan; Li, Shengnan; Hao, Yanli; Zhang, Xiaoning

    2016-06-01

    The clinical success of therapeutic DNA is still hindered due to the lack of effective delivery carriers. Here, we designed a tumor-targeted gene nano delivery system based on EGFR targeting strategy. Epidermal growth factor (EGF) was introduced to nano-complexes of PAMAM dendrimer and DNA via electrostatic interactions to form self-assembled PAMAM/DNA/EGF nano-complexes. The properties of self-assembled complexes were characterized by gel retardation assay and particle size and zeta potential analysis. Meanwhile, the toxicity of EGF-dendriplexes was evaluated by the MTT assay, which indicated that the complexes exhibited decreased cytotoxicity with the incorporation of EGF. We labeled polyamidoamine (PAMAM) dendrimers with FITC or a near-infrared (NIR) dye Lss670 and tested the cellular uptake in vitro and biodistribution in xenograft mouse tumor models. As compared to dendriplexes, the ternary EGF-dendriplexes showed a significantly higher cellular uptake into HepG2 cells due to the specific binding between EGF and EGF receptor (EGFR) over expressed on HepG2 cells, which resulted in the enhanced gene transfection efficiency. The biodistribution of EGF-dendriplexes in vivo was monitored with in vivo imaging technique, which indicated that EGF-dendriplexes enhanced EGFR-positive tumor-targeted biodistribution. These findings indicate that this novel nano-vector realized efficiently tumor-targeting gene delivery and high efficient gene expression in vivo, and it may possess a potential targeting gene delivery system in cancer therapy. PMID:25693638

  3. Local sustained delivery of acetylsalicylic acid via hybrid stent with biodegradable nanofibers reduces adhesion of blood cells and promotes reendothelialization of the denuded artery

    PubMed Central

    Lee, Cheng-Hung; Lin, Yu-Huang; Chang, Shang-Hung; Tai, Chun-Der; Liu, Shih-Jung; Chu, Yen; Wang, Chao-Jan; Hsu, Ming-Yi; Chang, Hung; Chang, Gwo-Jyh; Hung, Kuo-Chun; Hsieh, Ming-Jer; Lin, Fen-Chiung; Hsieh, I-Chang; Wen, Ming-Shien; Huang, Yenlin

    2014-01-01

    Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a highperformance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses. PMID:24421640

  4. 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

  5. BNNTs under the influence of external electric field as potential new drug delivery vehicle of Glu, Lys, Gly and Ser amino acids: A first-principles study

    NASA Astrophysics Data System (ADS)

    Farmanzadeh, Davood; Ghazanfary, Samereh

    2014-11-01

    The interaction of Glu (Glutamic acid), Lys (Lysine), Gly (Glycine) and Ser (Serine) amino acids with different polarities and (9, 0) zigzag single-wall boron nitride nanotubes (BNNTs) with various lengths in the presence and absence of external electric field (EF) in gas and solvent phases, are studied using density functional theory. It is found that interaction of Glu, Lys, Gly and Ser amino acids with BNNTs in both phases is energetically favorable. From solvation energy calculations, it can be seen that the BNNTs/amino acid complex dissolution in water is spontaneous. The adsorption energies and quantum molecular descriptors changed in the presence of external EF. Therefore, the study of BNNTs/amino acid complex under influence of external electric field is very important in proposing or designing new drug delivery systems in the presence of external EF. Results indicate that Glu, Lys, Gly and Ser amino acids can be adsorbed considerably on the BNNTs in the existence of external electric field. Our results showed that the BNNTs can act as a suitable drug delivery vehicle of Glu, Lys, Gly and Ser amino acids within biological systems and strength of adsorption and rate of drug release can be controlled by the external EF.

  6. Packaged Au-PPy valves for drug delivery systems

    NASA Astrophysics Data System (ADS)

    Tsai, Han-Kuan A.; Ma, Kuo-Sheng; Zoval, Jim; Kulinsky, Lawrence; Madou, Marc

    2006-03-01

    The most common methods for the drug delivery are swallowing pills or receiving injections. However, formulations that control the rate and period of medicine (i.e., time-release medications) are still problematic. The proposed implantable devices which include batteries, sensors, telemetry, valves, and drug storage reservoirs provide an alternative method for the responsive drug delivery system [1]. Using this device, drug concentration can be precisely controlled which enhances drug efficiency and decreases the side effects. In order to achieve responsive drug delivery, a reliable release valve has to be developed. Biocompatibility, low energy consumption, and minimized leakage are the main requirements for such release method. A bilayer structure composed of Au/PPy film is fabricated as a flap to control the release valve. Optimized potentiostatic control to synthesize polypyrrole (PPy) is presented. The release of miniaturize valve is tested and showed in this paper. A novel idea to simultaneously fabricate the device reservoirs as well as protective packaging is proposed in this paper. The solution of PDMS permeability problem is also mentioned in this article.

  7. Lung-targeted delivery system of curcumin loaded gelatin microspheres.

    PubMed

    Cao, Fengliang; Ding, Buyun; Sun, Min; Guo, Chenyu; Zhang, Lin; Zhai, Guangxi

    2011-11-01

    The purpose of the study is to design and evaluate curcumin loaded gelatin microspheres (C-GMS) for effective drug delivery to the lung. C-GMS was prepared by the emulsification-linkage technique and the formulation was optimized by orthogonal design. The mean encapsulation efficiency and drug loading of the optimal C-GMS were 75.5 ± 3.82 % and 6.15 ± 0.44%, respectively. The C-GMS presented a spherical shape and smooth surface with a mean particle diameter of 18.9 μm. The in vitro drug release behavior of C-GMS followed the first-order kinetics. The tissue distribution showed that the drug concentrations at lung tissue for the C-GMS suspension were significantly higher than those for the curcumin solution, and the Ce for lung was 36.19. Histopathological studies proved C-GMS was efficient and safe to be used as a passive targeted drug delivery system to the lung. Hence, C-GMS has a great potential for the targeted delivery of curcumin to the lung. PMID:21812751

  8. 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

  9. Lactic acid bacteria: reviewing the potential of a promising delivery live vector for biomedical purposes.

    PubMed

    Cano-Garrido, Olivia; Seras-Franzoso, Joaquin; Garcia-Fruitós, Elena

    2015-01-01

    Lactic acid bacteria (LAB) have a long history of safe exploitation by humans, being used for centuries in food production and preservation and as probiotic agents to promote human health. Interestingly, some species of these Gram-positive bacteria, which are generally recognized as safe organisms by the US Food and Drug Administration (FDA), are able to survive through the gastrointestinal tract (GIT), being capable to reach and colonize the intestine, where they play an important role. Besides, during the last decades, an important effort has been done for the development of tools to use LAB as microbial cell factories for the production of proteins of interest. Given the need to develop effective strategies for the delivery of prophylactic and therapeutic molecules, LAB have appeared as an appealing option for the oral, intranasal and vaginal delivery of such molecules. So far, these genetically modified organisms have been successfully used as vehicles for delivering functional proteins to mucosal tissues in the treatment of many different pathologies including GIT related pathologies, diabetes, cancer and viral infections, among others. Interestingly, the administration of such microorganisms would suppose a significant decrease in the production cost of the treatments agents since being live organisms, such vectors would be able to autonomously amplify and produce and deliver the protein of interest. In this context, this review aims to provide an overview of the use of LAB engineered as a promising alternative as well as a safety delivery platform of recombinant proteins for the treatment of a wide range of diseases. PMID:26377321

  10. Poly(propylacrylic acid) enhances cationic lipid mediated delivery of antisense oligonucleotides

    PubMed Central

    Lee, Li Kim; Williams, Charity L.; Devore, David; Roth, Charles M.

    2008-01-01

    The use of antisense oligodeoxynucleotides (ODNs) to inhibit the expression of specific mRNA targets represents a powerful technology for control of gene expression. Cationic lipids and polymers are frequently used to improve the delivery of ODNs to cells, but the resulting complexes often aggregate, bind to serum components, and are trafficked poorly within cells. We show that the addition of a synthetic, pH-sensitive, membrane-disrupting polyanion, poly(propylacrylic acid) (PPAA), improves the in vitro efficiency of the cationic lipid, DOTAP, with regard to oligonucleotide delivery and antisense activity. In characterization studies, ODN complexation with DOTAP/ODN was maintained even when substantial amounts of PPAA were added. The formulation also exhibited partial protection of phosphodiester oligonucleotides against enzymatic digestion. In Chinese hamster ovary (CHO) cells, incorporation of PPAA in DOTAP/ODN complexes improved two- to threefold the cellular uptake of fluorescently tagged oligonucleotides. DOTAP/ODN complexes containing PPAA also maintained high levels of uptake into cells upon exposure to serum. Addition of PPAA to DOTAP/ODN complexes enhanced the antisense activity (using GFP as the target) over a range of PPAA concentrations in both serum-free, and to a lesser extent, serum-containing media. Thus, PPAA is a useful adjunct that improves the lipid-mediated delivery of oligonucleotides. PMID:16677032

  11. Iontophoretic transdermal delivery of salicylic acid dissolved in ethanol-water mixture in rats.

    PubMed

    Murakami, T; Ihara, C; Kiyonaka, G; Yumoto, R; Shigeki, S; Ikuta, Y; Yata, N

    1999-01-01

    The usefulness of iontophoresis is restricted to highly water-soluble compounds, since drugs are generally applied as an aqueous solution in a drug electrode. In the present study, salicylic acid (SA) dissolved in ethanol-water mixture was loaded in a drug electrode, and the effect of ethanol on the iontophoretic transdermal delivery of SA was evaluated. Ethanol at a concentration of 10 or 30% showed no significant effect on the iontophoretic transdermal delivery of SA compared to that in the absence of ethanol, but 40 or 70% ethanol increased it significantly. The current density passing through in vivo during iontophoretic treatment decreased with increase in ethanol concentrations. These results suggested that the enhanced transdermal absorption of SA iontophoretically by the presence of ethanol in a drug solution is not due to the increased current density in vivo, but probably due to the direct action of ethanol on the stratum corneum. In conclusion, addition of ethanol to a drug solution at an appropriate concentration was proved to enhance the iontophoretic transdermal delivery of SA. A mixture of ethanol and water can dissolve many poorly water-soluble drugs, and therefore it would be able to expand the application of iontophoresis to include many drugs that are poorly soluble in water. PMID:10420142

  12. Pyrolysis of simple amino acids and nucleobases: survivability limits and implications for extraterrestrial delivery

    NASA Astrophysics Data System (ADS)

    Basiuk, V. A.; Douda, J.

    1999-04-01

    The idea of extraterrestrial delivery of organic matter to the early Earth is strongly supported by the detection of a large variety of organic compounds in the interstellar medium, comets, and carbonaceous chondrites. Whether organic compounds essential for the emergence and evolution of life, particularly amino acids and nucleic acid bases found in the meteorites, can be efficiently delivered by other space bodies is unclear and depends primarily on capability of the biomolecules to survive high temperatures during atmospheric deceleration and impacts to the terrestrial surface. In the present study we estimated survivability of simple amino acids (glycine, Lalanine, α-aminoisobutyric acid, L-valine and L-leucine), purines (adenine and guanine) and pyrimidines (uracil and cytosine) under rapid heating to temperatures of 400-1000°C under N2 or CO2 atmosphere. We have found that most of the compounds studied cannot survive the temperatures substantially higher than 700°C however at 500600°C, the recovery can be at a percent level (or even 10%-level for adenine, uracil, alanine, and valine). The final fate of amino acids and nucleobases during the atmospheric deceleration and surface impacts is discussed depending on such factors as size of the space body, nature and altitude of the heating, chemical composition of the space body and of the atmosphere.

  13. A slow release calcium delivery system for the study of reparative dentine formation.

    PubMed

    Hunter, A R; Kirk, E E; Robinson, D H; Kardos, T B

    1998-06-01

    Several liquid, semi-solid and solid delivery systems were formulated and tested to devise a method of reproducibly administering accurate micro-doses of calcium into a 700 microns diameter cavity in a rat maxillary incisor tooth, in the absence of hydroxyl ions. Development of this delivery system was necessary to facilitate studies of the mechanisms of pulpal repair and odontoblast differentiation. The principal requirements for the delivery system were that it should be easily administered into a small pulp exposure in the rat incisor and that a greater than 1000-fold range in calcium ion concentrations could be incorporated and delivered for a period of 2-3 days, preferably in an acidic environment to minimize the effect of non-specific nucleation under alkaline conditions. Poly- (ethylene) glycol microspheres were found to be an ideal vehicle. Under the in vitro dissolution conditions used, complete release of all calcium salts occurred within 12-15 hours, except for the very water-insoluble calcium stearate. It was anticipated that the release of calcium ions would be significantly more prolonged in vivo because of the physical constraints of the prepared cavity as well as the restricted access to fluid flow. PMID:9863419

  14. 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.

  15. Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems

    NASA Astrophysics Data System (ADS)

    Hwang, Tae Heon; Kim, Jin Bum; Som Yang, Da; Park, Yong-il; Ryu, WonHyoung

    2013-03-01

    Microfluidic drug delivery systems consisting of a drug reservoir and microfluidic channels have shown the possibility of simple and robust modulation of drug release rate. However, the difficulty of loading a small quantity of drug into drug reservoirs at a micro-scale limited further development of such systems. Electrohydrodynamic (EHD) printing was employed to fill micro-reservoirs with controlled amount of drugs in the range of a few hundreds of picograms to tens of micrograms with spatial resolution of as small as 20 µm. Unlike most EHD systems, this system was configured in combination with an inverted microscope that allows in situ targeting of drug loading at micrometer scale accuracy. Methylene blue and rhodamine B were used as model drugs in distilled water, isopropanol and a polymer solution of a biodegradable polymer and dimethyl sulfoxide (DMSO). Also tetracycline-HCl/DI water was used as actual drug ink. The optimal parameters of EHD printing to load an extremely small quantity of drug into microscale drug reservoirs were investigated by changing pumping rates, the strength of an electric field and drug concentration. This targeted EHD technique was used to load drugs into the microreservoirs of PDMS microfluidic drug delivery devices and their drug release performance was demonstrated in vitro.

  16. Effect of oleic acid modified polymeric bilayered nanoparticles on percutaneous delivery of spantide II and ketoprofen

    PubMed Central

    Shah, Punit; Desai, Pinaki; Singh, Mandip

    2011-01-01

    The objective of present study was to evaluate the effect of oleic acid modified polymeric bilayered nanoparticles (NPS) on combined delivery of two anti-inflammatory drugs, spantide II (SP) and ketoprofen (KP) on the skin permeation. NPS were prepared using poly(lactic-co-glycolic acid) (PLGA) and chitosan. SP and KP were encapsulated in different layers alone or/and in combination (KP-NPS, SP-NPS and SP+KP-NPS). The surface of NPS was modified with oleic acid (OA) (`Nanoease' technology) using an established procedure in the laboratory (KP-NPS-OA, SP-NPS-OA and SP+KP-NPS-OA). Fluorescent dyes (DiO and DID) containing surface modified (DiO-NPS-OA and DID-NPS-OA) and unmodified NPS (DiO-NPS and DID-NPS) were visualized in lateral rat skin sections using confocal microscopy and Raman confocal spectroscopy after skin permeation. In vitro skin permeation was performed in dermatomed human skin and HPLC was used to analyze the drug levels in different skin layers. Further, allergic contact dermatitis (ACD) model was used to evaluate the response of KP-NPS, SP-NPS, SP+KP-NPS, KP-NPS-OA, SP-NPS-OA and SP+KP-NPS-OA treatment in C57BL/6 mice. The fluorescence from OA modified NPS was observed upto depth of 240 μm and was significantly higher as compared to non-modified NPS. The amount of SP and KP retained in skin layers from OA modified NPS increased by several folds compare to unmodified NPS and control solution. In addition, the combination index value calculated from ACD response for solution suggested additive effect and moderate synergism for NPS-OA. Our results strongly suggest that surface modification of bilayered nanoparticles with oleic acid improved drug delivery to the deeper skin layers. PMID:22134117

  17. Oral delivery of shRNA based on amino acid modified chitosan for improved antitumor efficacy.

    PubMed

    Zheng, Hao; Tang, Cui; Yin, Chunhua

    2015-11-01

    In this investigation, chitosan-histidine-cysteine (CHC) was engineered for oral delivery of Survivin short hairpin RNA (shRNA)-expressing plasmid DNA (shSur-pDNA) to promote hepatoma regression through integrating the advantages of histidine and cysteine to conquer serial cellular and systemic barriers. CHC could effectively encapsulate shSur-pDNA to form compact nanocomplexes (NC) at adequate weight ratios. Sequential modification with histidine and cysteine conferred CHC NC with the beneficial attributes for shRNA delivery including improved stability, facilitated internalization, promoted endosomal escape, increased nuclear localization, and GSH-responsive release, which contributed to their superior performance in terms of apoptosis promotion, proliferation inhibition, and Survivin down-regulation of tumor cells. More importantly, in hepatoma-bearing mice, orally delivered CHC NC overweighed chitosan counterparts with respect to suppressed Survivin expression, retarded tumor growth, and prolonged surviving time, owing to their above-mentioned merits in combination with enhanced intestinal permeation. Especially, rapid intracellular release of CHC NC with lower molecular weight of 30 kDa (CHC30 NC) might be responsible for the most satisfactory antitumor efficacy with tumor inhibition ratio (TIR) of 92.5%, which rendered CHC30 NC a promising vehicle for oral delivery of shRNA. This investigation would shed light on the deliberate design of oral shRNA delivery vehicles to mediate effective antitumor efficacy. PMID:26310108

  18. Polypeptide Point Modifications with Fatty Acid and Amphiphilic Block Copolymers for Enhanced Brain Delivery

    PubMed Central

    Batrakova, Elena V.; Vinogradov, Serguei V.; Robinson, Sandra M.; Niehoff, Michael L.; Banks, William A.; Kabanov, Alexander V.

    2009-01-01

    There is a tremendous need to enhance delivery of therapeutic polypeptides to the brain to treat disorders of the central nervous system (CNS). The brain delivery of many polypeptides is severely restricted by the blood—brain barrier (BBB). The present study demonstrates that point modifications of a BBB-impermeable polypeptide, horseradish peroxidase (HRP), with lipophilic (stearoyl) or amphiphilic (Pluronic block copolymer) moieties considerably enhance the transport of this polypeptide across the BBB and accumulation of the polypeptide in the brain in vitro and in vivo. The enzymatic activity of the HRP was preserved after the transport. The modifications of the HRP with amphiphilic block copolymer moieties through degradable disulfide links resulted in the most effective transport of the HRP across in vitro brain microvessel endothelial cell monolayers and efficient delivery of HRP to the brain. Stearoyl modification of HRP improved its penetration by about 60% but also increased the clearance from blood. Pluronic modification using increased penetration of the BBB and had no significant effect on clearance so that uptake by brain was almost doubled. These results show that point modification can improve delivery of even highly impermeable polypeptides to the brain. PMID:16029020

  19. 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

  20. Paclitaxel Nano-Delivery Systems: A Comprehensive Review.

    PubMed

    Ma, Ping; Mumper, Russell J

    2013-02-18

    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