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Sample records for antigen delivery system

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

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    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.

  2. A Review of Intra- and Extracellular Antigen Delivery Systems for Virus Vaccines of Finfish.

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    Munang'andu, Hetron Mweemba; Evensen, Øystein

    2015-01-01

    Vaccine efficacy in aquaculture has for a long time depended on evaluating relative percent survival and antibody responses after vaccination. However, current advances in vaccine immunology show that the route in which antigens are delivered into cells is deterministic of the type of adaptive immune response evoked by vaccination. Antigens delivered by the intracellular route induce MHC-I restricted CD8+ responses while antigens presented through the extracellular route activate MHC-II restricted CD4+ responses implying that the route of antigen delivery is a conduit to induction of B- or T-cell immune responses. In finfish, different antigen delivery systems have been explored that include live, DNA, inactivated whole virus, fusion protein, virus-like particles, and subunit vaccines although mechanisms linking these delivery systems to protective immunity have not been studied in detail. Hence, in this review we provide a synopsis of different strategies used to administer viral antigens via the intra- or extracellular compartments. Further, we highlight the differences in immune responses induced by antigens processed by the endogenous route compared to exogenously processed antigens. Overall, we anticipate that the synopsis put together in this review will shed insights into limitations and successes of the current vaccination strategies used in finfish vaccinology.

  3. A Review of Intra- and Extracellular Antigen Delivery Systems for Virus Vaccines of Finfish

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    Hetron Mweemba Munang’andu

    2015-01-01

    Full Text Available Vaccine efficacy in aquaculture has for a long time depended on evaluating relative percent survival and antibody responses after vaccination. However, current advances in vaccine immunology show that the route in which antigens are delivered into cells is deterministic of the type of adaptive immune response evoked by vaccination. Antigens delivered by the intracellular route induce MHC-I restricted CD8+ responses while antigens presented through the extracellular route activate MHC-II restricted CD4+ responses implying that the route of antigen delivery is a conduit to induction of B- or T-cell immune responses. In finfish, different antigen delivery systems have been explored that include live, DNA, inactivated whole virus, fusion protein, virus-like particles, and subunit vaccines although mechanisms linking these delivery systems to protective immunity have not been studied in detail. Hence, in this review we provide a synopsis of different strategies used to administer viral antigens via the intra- or extracellular compartments. Further, we highlight the differences in immune responses induced by antigens processed by the endogenous route compared to exogenously processed antigens. Overall, we anticipate that the synopsis put together in this review will shed insights into limitations and successes of the current vaccination strategies used in finfish vaccinology.

  4. Cancer Immunotherapy Utilized Bubble Liposomes and Ultrasound as Antigen Delivery System

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    Oda, Yusuke; Otake, Shota; Suzuki, Ryo; Otake, Shota; Nishiie, Norihito; Hirata, Keiichi; Taira, Yuichiro; Utoguchi, Naoki; Maruyama, Kazuo

    2010-03-01

    In dendritic cells (DCs)-based cancer immunotherapy, it is important to present the epitope peptide derived from tumor associated antigens (TAAs) on MHC class I in order to induce tumor specific cytotoxic T lymphocytes (CTLs). However, MHC class I molecules generally present the epitope peptides derived from endogenous antigens for DCs but not exogenous ones such as TAAs. Recently, we developed the novel liposomal bubbles (Bubble liposomes) encapsulating perfluoropropane nanobubbles. In this study, we attempted to establish the novel antigen delivery system to induce MHC class I presentation using the combination of ultrasound and Bubble liposomes. Using ovalbumin (OVA) as model antigen, the combination of Bubble liposomes and ultrasound exposure for the DC could induce MHC class I presentation. In addition, the viability of DCs was more than 80%. These results suggest that Bubble liposomes might be a novel ultrasound enhanced antigen delivery tool in DC-based cancer immunotherapy.

  5. Chitosan-based delivery systems for protein therapeutics and antigens

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    Amidi, M.; Mastrobattista, E.; Jiskoot, W.; Hennink, W.E.

    2010-01-01

    Therapeutic peptides/proteins and protein-based antigens are chemically and structurally labile compounds, which are almost exclusively administered by parenteral injections. Recently, non-invasive mucosal routes have attracted interest for administration of these biotherapeutics. Chitosan-based del

  6. Heterologous protein secretion in Lactococcus lactis: a novel antigen delivery system

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    Langella P.

    1999-01-01

    Full Text Available Lactic acid bacteria (LAB are Gram-positive bacteria and are generally regarded as safe (GRAS organisms. Therefore, LAB could be used for heterologous protein secretion and they are good potential candidates as antigen delivery vehicles. To develop such live vaccines, a better control of protein secretion is required. We developed an efficient secretion system in the model LAB, Lactococcus lactis. Staphylococcal nuclease (Nuc was used as the reporter protein. We first observed that the quantity of secreted Nuc correlated with the copy number of the cloning vector. The nuc gene was cloned on a high-copy number cloning vector and no perturbation of the metabolism of the secreting strain was observed. Replacement of nuc native promoter by a strong lactococcal one led to a significant increase of nuc expression. Secretion efficiency (SE of Nuc in L. lactis was low, i.e., only 60% of the synthesized Nuc was secreted. Insertion of a synthetic propeptide between the signal peptide and the mature moiety of Nuc increased the SE of Nuc. On the basis of these results, we developed a secretion system and we applied it to the construction of an L. lactis strain which secretes a bovine coronavirus (BCV epitope-protein fusion (BCV-Nuc. BCV-Nuc was recognized by both anti-BCV and anti-Nuc antibodies. Secretion of this antigenic fusion is the first step towards the development of a novel antigen delivery system based on LAB-secreting strains.

  7. Preparing and Characterizing Chitosan Nanoparticles Containing Hemiscorpius lepturus Scorpion Venom as an Antigen Delivery System

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    Mohammadpour Dounighi, N.

    2012-11-01

    Full Text Available In recent years, chitosan nanoparticles have been studied widely for protein delivery. In this study, Hemiscorpius lepturus (HL venom was encapsulated in chitosan nanoparticles. The aim of the present work was to carry out a systematic study for preparing biocompatible and biodegradable nanoparticles for loading HL scorpion venom and to evaluate their potential as an antigen delivery system. In this study, HL venom loaded chitosan nanoparticles fabricated by ionic gelation of chitosan and tripolyphosphate and the factors which may be influenced in the preparation of nanoparticles were analyzed. Also, their physicochemical properties and in vitro release behavior were studied. The optimum encapsulation efficiency and capacity were observed when the chitosan concentration and HL venom were 2mg/ml and 500µg/ml, respectively. The HL venom loaded nanoparticles were in the size range of 130-160nm (polydispersity index values of 0.423 and exhibited the positive zeta potential. Transmission electron microscope imaging showed spherical and smooth surface of nanoparticles. The profiles of the release exhibited a burst releases about 50% in the first 4 hr and then slowed down at a constant rate. The obtained results suggested that the chitosan nanoparticles prepared in this work had the potential for antigen delivery.

  8. Vaccine potential of plasma bead-based dual antigen delivery system against experimental murine candidiasis.

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    Ahmad, Ejaj; Zia, Qamar; Fatima, Munazza Tamkeen; Owais, Mohammad; Saleemuddin, Mohammed

    2015-11-01

    The development of prophylactic anti-candidal vaccine comprising the Candida albicans cytosolic proteins (Cp) as antigen and plasma beads (PB) prepared from plasma as sustained delivery system, is described. The immune-prophylactic potential of various PBs-based dual antigen delivery systems, co-entrapping Cp pre-entrapped in PLGA microspheres were tested in the murine model. Induction of cell mediated immunity was measured by assaying DTH and NO production as well as in vitro proliferation of lymphocytes derived from the immunized animals. Expression of surface markers on APCs (CD80, CD86) and T-cells (CD4+, CD8+) was also evaluated. Humoral immune response was studied by measuring circulating anti-Cp antibodies and their subclasses. When the prophylactic efficacy of the vaccines was tested in mice challenged with virulent C. albicans, the PB-based formulation (PB-PLGA-Cp vaccine) was found to be most effective in the generation of desirable immune response, in terms of suppression of fungal load and facilitating the survival of the immunized animals.

  9. From Antigen Delivery System to Adjuvanticy: The Board Application of Nanoparticles in Vaccinology

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    Boraschi, Diana; Italiani, Paola

    2015-01-01

    In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems). The use of nanoparticles in medicine has brought about the issue of their interaction with the immune system for two main reasons: first, understanding how long nanomedicines could persist in the organism and exert their beneficial effects before being recognized and eliminated by our defensive systems; second, understanding how the immune responses can be modulated by nanoparticles in order to obtain optimal effects. This issue is crucial in vaccine formulations based on the use of nanoparticles, which can operate both as a delivery system to enhance antigen processing and as an immunostimulatory adjuvant to induce and amplify protective immunity, in part because of their ability to activate the inflammasome and induce the maturation of interleukin 1β. Nanoparticles can be excellent adjuvants due to their biocompatibility and their physicochemical properties (e.g., size, shape, and surface charge), which can be tailored to obtain different immunological effects. This review provides an overview of recent strategies for the use of nanoparticles as promising/attractive adjuvants for novel prophylactic and therapeutic vaccines. The use of nanovaccines, with their practically infinite possibilities of specific design, could open the way to precision vaccinology, i.e., vaccine formulations tailored on the individual immune reactivity status. PMID:26556378

  10. From Antigen Delivery System to Adjuvanticy: The Board Application of Nanoparticles in Vaccinology

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    Diana Boraschi

    2015-11-01

    Full Text Available In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems. The use of nanoparticles in medicine has brought about the issue of their interaction with the immune system for two main reasons: first, understanding how long nanomedicines could persist in the organism and exert their beneficial effects before being recognized and eliminated by our defensive systems; second, understanding how the immune responses can be modulated by nanoparticles in order to obtain optimal effects. This issue is crucial in vaccine formulations based on the use of nanoparticles, which can operate both as a delivery system to enhance antigen processing and as an immunostimulatory adjuvant to induce and amplify protective immunity, in part because of their ability to activate the inflammasome and induce the maturation of interleukin 1β. Nanoparticles can be excellent adjuvants due to their biocompatibility and their physicochemical properties (e.g., size, shape, and surface charge, which can be tailored to obtain different immunological effects. This review provides an overview of recent strategies for the use of nanoparticles as promising/attractive adjuvants for novel prophylactic and therapeutic vaccines. The use of nanovaccines, with their practically infinite possibilities of specific design, could open the way to precision vaccinology, i.e., vaccine formulations tailored on the individual immune reactivity status.

  11. Oxidized multiwalled carbon nanotubes as antigen delivery system to promote superior CD8(+) T cell response and protection against cancer.

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    de Faria, Paula Cristina Batista; dos Santos, Luara Isabela; Coelho, João Paulo; Ribeiro, Henrique Bücker; Pimenta, Marcos Assunção; Ladeira, Luiz Orlando; Gomes, Dawidson Assis; Furtado, Clascídia Aparecida; Gazzinelli, Ricardo Tostes

    2014-09-10

    Properties like high interfacial area with cellular membranes, unique ability to incorporate multiple functionalization, as well as compatibility and transport in biological fluids make carbon nanotubes (CNTs) useful for a variety of therapeutic and drug-delivery applications. Here we used a totally synthetic hybrid supramolecule as an anticancer vaccine formulation. This complex structure comprises CNTs as delivery system for the Cancer Testis Antigen named NY-ESO-1, allied to a synthetic Toll-Like Receptor agonist. The CNT constructs were rapidly internalized into dendritic cells, both in vitro and in vivo, and served as an intracellular antigen depot. This property favored the induction of strong CD4(+) T as well as CD8(+) T cell-mediated immune responses against the NY-ESO-1. Importantly, the vaccination significantly delayed the tumor development and prolonged the mice survival, highlighting the potential application of CNTs as a vaccine delivery system to provide superior immunogenicity and strong protection against cancer.

  12. Whole Pichia pastoris yeast expressing measles virus nucleoprotein as a production and delivery system to multimerize Plasmodium antigens.

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    Daria Jacob

    Full Text Available Yeasts are largely used as bioreactors for vaccine production. Usually, antigens are produced in yeast then purified and mixed with adjuvants before immunization. However, the purification costs and the safety concerns recently raised by the use of new adjuvants argue for alternative strategies. To this end, the use of whole yeast as both production and delivery system appears attractive. Here, we evaluated Pichia pastoris yeast as an alternative vaccine production and delivery system for the circumsporozoite protein (CS of Plasmodium, the etiologic agent of malaria. The CS protein from Plasmodium berghei (Pb was selected given the availability of the stringent C57Bl/6 mouse model of infection by Pb sporozoites, allowing the evaluation of vaccine efficacy in vivo. PbCS was multimerized by fusion to the measles virus (MV nucleoprotein (N known to auto-assemble in yeast in large-size ribonucleoprotein rods (RNPs. Expressed in P. pastoris, the N-PbCS protein generated highly multimeric and heterogenic RNPs bearing PbCS on their surface. Electron microscopy and immunofluorescence analyses revealed the shape of these RNPs and their localization in peripheral cytoplasmic inclusions. Subcutaneous immunization of C57Bl/6 mice with heat-inactivated whole P. pastoris expressing N-PbCS RNPs provided significant reduction of parasitemia after intradermal challenge with a high dose of parasites. Thus, in the absence of accessory adjuvants, a very low amount of PbCS expressed in whole yeast significantly decreased clinical damages associated with Pb infection in a highly stringent challenge model, providing a proof of concept of the intrinsic adjuvancy of this vaccine strategy. In addition to PbCS multimerization, the N protein contributed by itself to parasitemia delay and long-term mice survival. In the future, mixtures of whole recombinant yeasts expressing relevant Plasmodium antigens would provide a multivalent formulation applicable for antigen

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

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

    2016-12-13

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

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

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

    2016-01-01

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

  15. Virosomes for antigen and DNA delivery

    NARCIS (Netherlands)

    Daemen, T; de Mare, A; Bungener, L; de Jonge, J; Huckriede, A; Wilschut, J

    2005-01-01

    Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination agains

  16. Tumor Antigen-Derived Peptides Delivery for Cancer Immunotherapy.

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    Wenxue, Ma

    2014-02-05

    Tumor antigenic peptides therapeutics is a promising field for cancer immunotherapy. Benefits include the ease and rapid synthesis of antigenic peptides and capacity for modifications. In the past years, many peptide-based cancer vaccines have been tested in clinical trials with a limited success because of the difficulties associated with peptide stability and delivery approaches, consequently, resulting in inefficient antigen presentation and low response rates in patients with cancer. The development of suitable and efficient vaccine carrier systems still remains a major challenge. This article aims to describe a new delivery approach for tumor antigenic peptides and rationales of dendritic cells (DCs)-based vaccination. In order to elicit enhanced immune responses, poly(DL-lactide-co-glycolide) (PLGA), which has been approved by the US Food and Drug Administration (FDA) for the use of drug delivery, diagnostics and other applications of clinical and basic science research were employed for the formulation of making nanoparticles (NPs) while delivering tumor antigenic peptides.

  17. Immunoliposomes containing Soluble Leishmania Antigens (SLA) as a novel antigen delivery system in murine model of leishmaniasis.

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    Eskandari, Faeze; Talesh, Ghazal Alipour; Parooie, Maryam; Jaafari, Mahmoud Reza; Khamesipour, Ali; Saberi, Zahra; Abbasi, Azam; Badiee, Ali

    2014-11-01

    Development of new generation of vaccines against leishmaniasis requires adjuvants to elicit the type and intensity of immune response needed for protection. The coupling of target-specific antibodies to the liposomal surface to create immunoliposomes has appeared as a promising way in achieving a liposome active targeting. In this study, immunoliposomes were prepared by grafting non-immune mouse IgG onto the liposomal surface. The influence of active targeted immunoliposomes on the type and intensity of generated immune response against Leishmania was then investigated and compared with that of liposomes and control groups which received either SLA or HEPES buffer alone. All formulations contained SLA and were used to immunize the mice in the left hind footpad three times in 3-week intervals. Evaluation of lesion development and parasite burden in the foot and spleen after challenge with Leishmania major, evaluation of Th1 cytokine (IFN-γ), and titration of IgG isotypes were carried out to assess the type of generated immune response and the extent of protection. The results indicated that liposomes might be effective adjuvant systems to induce protection against L. major challenge in BALB/c mice, but stronger cell mediated immune responses were induced when immunoliposomes were utilized. Thus, immune modulation using immunoliposomes might be a practical approach to improve the immunization against L. major.

  18. Preparation and in vitro characterization of chitosan nanoparticles containing Mesobuthus eupeus scorpion venom as an antigen delivery system

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    N Mohammadpour Dounighi

    2012-01-01

    Full Text Available Hydrophilic nanoparticles have been widely investigated in recent years as delivery systems for therapeutic macromolecules such as antigens. In the present study Mesobuthus eupeus venom-loaded chitosan nanoparticles were prepared via ionic gelation of tripolyphosphate (TPP and chitosan. The optimum encapsulation efficiency (91.1% and loading capacity (76.3% were obtained by a chitosan concentration of 2 mg/mL, chitosan-to-TPP mass ratio of 2 and M. eupeus venom concentration of 500 µg/mL. The average nanoparticle size at optimum conditions was determined by Zetasizer (Malvern Instruments, UK. The nanoparticle size was about 370 nm (polydispersity index: 0.429 while the zeta potential was positive. Transmission electron microscope (TEM imaging showed a spherical, smooth and almost homogenous structure for nanoparticles. Fourier transform infrared (FTIR spectroscopy confirmed tripolyphosphoric groups of TPP linked with ammonium groups of chitosan in the nanoparticles. The in vitro release of nanoparticles showed an initial burst release of approximately 60% in the first ten hours, followed by a slow and much reduced additional release for about 60 hours. It is suggested that the chitosan nanoparticles fabricated in our study may provide a suitable alternative to traditional adjuvant systems.

  19. Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice.

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    Guo Chen

    2011-09-01

    Full Text Available BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice. METHODOLOGY/PRINCIPAL FINDINGS: Promoters (nirB or pagC were used to express the antigen (Sj23LHDGST and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104-Sj23LHD-GST efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69. CONCLUSION/SIGNIFICANCE: Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.

  20. Colloidal drug delivery systems in vaccine delivery.

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

    2013-01-01

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

  1. Comparison of vaccine efficacy for different antigen delivery systems for infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L.) in a cohabitation challenge model.

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    Munang'andu, Hetron M; Fredriksen, Børge N; Mutoloki, Stephen; Brudeseth, Bjørn; Kuo, Tsun-Yung; Marjara, Inderjit S; Dalmo, Roy A; Evensen, Øystein

    2012-06-01

    Two strains of IPNV made by reverse genetics on the Norwegian Sp strain NVI-015 (GenBank AY379740) backbone encoding the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs were used to prepare inactivated whole virus (IWV), nanoparticle vaccines with whole virus, Escherichia coli subunit encoding truncated VP2-TA and VP2-PT, VP2-TA and VP2-PT fusion antigens with putative translocating domains of Pseudomonas aeruginosa exotoxin, and plasmid DNA encoding segment A of the TA strain. Post challenge survival percentages (PCSP) showed that IWV vaccines conferred highest protection (PCSP=42-53) while nanoparticle, sub-unit recombinant and DNA vaccines fell short of the IWV vaccines in Atlantic salmon (Salmo salar L.) postsmolts challenged with the highly virulent Sp strain NVI-015 (TA strain) of IPNV after 560 degree days post vaccination. Antibody levels induced by these vaccines did not show antigenic differences between the virulent and avirulent motifs for vaccines made with the same antigen dose and delivery system after 8 weeks post vaccination. Our findings show that fish vaccinated with less potent vaccines comprising of nanoparticle, DNA and recombinant vaccines got infected much earlier and yielded to higher infection rates than fish vaccinated with IWV vaccines that were highly potent. Ability of the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs to limit establishment of infection showed equal protection for vaccines made of the same antigen dose and delivery systems. Prevention of tissue damage linked to viral infection was eminent in the more potent vaccines than the less protective ones. Hence, there still remains the challenge of developing highly efficacious vaccines with the ability to eliminate the post challenge carrier state in IPNV vaccinology.

  2. Administration routes affect the quality of immune responses: A cross-sectional evaluation of particulate antigen-delivery systems.

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    Mohanan, Deepa; Slütter, Bram; Henriksen-Lacey, Malou; Jiskoot, Wim; Bouwstra, Joke A; Perrie, Yvonne; Kündig, Thomas M; Gander, Bruno; Johansen, Pål

    2010-11-01

    Particulate delivery systems such as liposomes and polymeric nano- and microparticles are attracting great interest for developing new vaccines. Materials and formulation properties essential for this purpose have been extensively studied, but relatively little is known about the influence of the administration route of such delivery systems on the type and strength of immune response elicited. Thus, the present study aimed at elucidating the influence on the immune response when of immunising mice by different routes, such as the subcutaneous, intradermal, intramuscular, and intralymphatic routes with ovalbumin-loaded liposomes, N-trimethyl chitosan (TMC) nanoparticles, and poly(lactide-co-glycolide) (PLGA) microparticles, all with and without specifically selected immune-response modifiers. The results showed that the route of administration caused only minor differences in inducing an antibody response of the IgG1 subclass, and any such differences were abolished upon booster immunisation with the various adjuvanted and non-adjuvanted delivery systems. In contrast, the administration route strongly affected both the kinetics and magnitude of the IgG2a response. A single intralymphatic administration of all evaluated delivery systems induced a robust IgG2a response, whereas subcutaneous administration failed to elicit a substantial IgG2a response even after boosting, except with the adjuvanted nanoparticles. The intradermal and intramuscular routes generated intermediate IgG2a titers. The benefit of the intralymphatic administration route for eliciting a Th1-type response was confirmed in terms of IFN-gamma production of isolated and re-stimulated splenocytes from animals previously immunised with adjuvanted and non-adjuvanted liposomes as well as with adjuvanted microparticles. Altogether the results show that the IgG2a associated with Th1-type immune responses are sensitive to the route of administration, whereas IgG1 response associated with Th2-type immune

  3. A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8(+) T Cells.

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    Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md; Bhattacharya, Pradyot; Ali, Nahid

    2016-06-02

    The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8(+) cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4(+) and CD8(+) T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4(+) and CD8(+) T cells. Furthermore, lymphoid CD8(+) T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8(+) T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8(+) T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

  4. A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

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    Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md.; Bhattacharya, Pradyot; Ali, Nahid

    2016-06-01

    The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+ cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

  5. Potent Antigen-Adjuvant Delivery System by Conjugation of Mycobacterium tuberculosis Ag85B-HspX Fusion Protein with Arabinogalactan-Poly(I:C) Conjugate.

    Science.gov (United States)

    Huang, Qingrui; Yu, Weili; Hu, Tao

    2016-04-20

    Protein-based vaccine is promising to improve or replace Mycobacterium bovis BCG vaccine for its specificity, safety, and easy production. However, protein-based vaccine calls for potent adjuvants and improved delivery systems to protect against Mycobacterium tuberculosis. Poly(I:C) is one of the most potent pathogen-associated molecular patterns that signals primarily via TLR3. Arabinogalactan (AG) is a biocompatible polysaccharide that can increase splenocyte proliferation and stimulate macrophages. The AG-poly(I:C) conjugate (AG-P) showed an adjuvant potency through a synergistic interaction of AG and poly(I:C). Ag85B and HspX are two important virulent protein antigens of Mycobacterium tuberculosis and Ag85B-HspX fusion protein (AH) was prepared. An antigen-adjuvant delivery system (AH-AG-P) was developed by conjugation of AH with AG-P to ensure that both AH and AG-P reach the APCs simultaneously. AH-AG-P elicited high AH-specific IgG titers and stimulated lymphocyte proliferation. AH-AG-P provoked the secretion of Th1-type cytokines (TNF-α, IFN-γ, and IL-2) and Th2-type cytokines (IL-4 and IL-10). Pharmacokinetics revealed that conjugation with AG-P could prolong the serum exposure of AH to the immune system. Pharmacodynamics suggested that conjugation with AG-P led to a rapid and intense production of AH-specific IgG. Accordingly, conjugation with AG-P could promote a robust cellular and humoral immune response to AH. Thus, conjugation of AH with a potent adjuvant AG-P is an effective strategy to develop an efficacious protein-based vaccine against Mycobacterium tuberculosis.

  6. Protein antigen delivery by gene gun-mediated epidermal antigen incorporation (EAI).

    Science.gov (United States)

    Scheiblhofer, Sandra; Ritter, Uwe; Thalhamer, Josef; Weiss, Richard

    2013-01-01

    The gene gun technology can not only be employed for efficient transfer of gene vaccines into upper layers of the skin, but also for application of protein antigens. As a tissue rich in professional antigen presenting cells, the skin represents an attractive target for immunizations. In this chapter we present a method for delivery of the model antigen ovalbumin into the skin of mice termed epidermal antigen incorporation and describe in detail how antigen-specific proliferation in draining lymph nodes can be followed by flow cytometry.

  7. Oral Delivery of a Novel Recombinant Streptococcus mitis Vector Elicits Robust Vaccine Antigen-Specific Oral Mucosal and Systemic Antibody Responses and T Cell Tolerance.

    Directory of Open Access Journals (Sweden)

    Emily Xie

    Full Text Available The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases.

  8. Protective effect of antigen delivery using monoolein-based liposomes in experimental hematogenously disseminated candidiasis

    OpenAIRE

    Carneiro, Catarina; Correia, Alexandra; Lima, Tanea; Vilanova, Manuel; Pais, Célia; Gomes, Andreia; Real Oliveira, M. Elisabete C.D.; Sampaio, Paula

    2016-01-01

    We evaluated the potential of a liposomal antigen delivery system (ADS) containing Candida albicans cell wall surface proteins (CWSP) in mediating protection against systemic candidiasis. Treatment of bonemarrow- derived dendritic cells with CWSP-loaded dioctadecyldimethylammonium bromide:monoolein (DODAB:MO) liposomes enhanced and prolonged their activation comparatively to free antigen, indicating that liposome-entrapped CWSP were released more sustainable. Therefore, we immuniz...

  9. Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

    Science.gov (United States)

    Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

    2015-04-10

    Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination.

  10. Trypanosoma cruzi as an effective cancer antigen delivery vector.

    Science.gov (United States)

    Junqueira, Caroline; Santos, Luara I; Galvão-Filho, Bruno; Teixeira, Santuza M; Rodrigues, Flávia G; DaRocha, Wanderson D; Chiari, Egler; Jungbluth, Achim A; Ritter, Gerd; Gnjatic, Sacha; Old, Lloyd J; Gazzinelli, Ricardo T

    2011-12-06

    One of the main challenges in cancer research is the development of vaccines that induce effective and long-lived protective immunity against tumors. Significant progress has been made in identifying members of the cancer testis antigen family as potential vaccine candidates. However, an ideal form for antigen delivery that induces robust and sustainable antigen-specific T-cell responses, and in particular of CD8(+) T lymphocytes, remains to be developed. Here we report the use of a recombinant nonpathogenic clone of Trypanosoma cruzi as a vaccine vector to induce vigorous and long-term T cell-mediated immunity. The rationale for using the highly attenuated T. cruzi clone was (i) the ability of the parasite to persist in host tissues and therefore to induce a long-term antigen-specific immune response; (ii) the existence of intrinsic parasite agonists for Toll-like receptors and consequent induction of highly polarized T helper cell type 1 responses; and (iii) the parasite replication in the host cell cytoplasm, leading to direct antigen presentation through the endogenous pathway and consequent induction of antigen-specific CD8(+) T cells. Importantly, we found that parasites expressing a cancer testis antigen (NY-ESO-1) were able to elicit human antigen-specific T-cell responses in vitro and solid protection against melanoma in a mouse model. Furthermore, in a therapeutic protocol, the parasites expressing NY-ESO-1 delayed the rate of tumor development in mice. We conclude that the T. cruzi vector is highly efficient in inducing T cell-mediated immunity and protection against cancer cells. More broadly, this strategy could be used to elicit a long-term T cell-mediated immunity and used for prophylaxis or therapy of chronic infectious diseases.

  11. Project delivery system (PDS)

    CERN Document Server

    2001-01-01

    As business environments become increasingly competitive, companies seek more comprehensive solutions to the delivery of their projects. "Project Delivery System: Fourth Edition" describes the process-driven project delivery systems which incorporates the best practices from Total Quality and is aligned with the Project Management Institute and ISO Quality Standards is the means by which projects are consistently and efficiently planned, executed and completed to the satisfaction of clients and customers.

  12. Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery.

    Science.gov (United States)

    Farhadian, Asma; Dounighi, Naser Mohammadpour; Avadi, Mohammadreza

    2015-01-01

    Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pH-sensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 µg/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine.

  13. Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery

    Science.gov (United States)

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

    2013-05-01

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

  14. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  15. Mucoadhesive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Rahamatullah Shaikh

    2011-01-01

    Full Text Available 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.

  16. MEMS: Enabled Drug Delivery Systems.

    Science.gov (United States)

    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.

  17. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

    NARCIS (Netherlands)

    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is par

  18. Virosomes as an antigen delivery system

    NARCIS (Netherlands)

    Daemen, T; Bungener, L; Huckriede, A; Wilschut, J

    2000-01-01

    Live, replicating, vaccines have the advantage that they closely mimick the actual infection and therefore induce a broad and physiologically relevant immune response, involving both a humoral immune response (antibody: production) and cell-mediated immunity (cytotoxic T-lymphocytes). However, there

  19. Metal based nanoparticles as cancer antigen delivery vehicles for macrophage based antitumor vaccine.

    Science.gov (United States)

    Chattopadhyay, Sourav; Dash, Sandeep Kumar; Mandal, Debasis; Das, Balaram; Tripathy, Satyajit; Dey, Aditi; Pramanik, Panchanan; Roy, Somenath

    2016-02-10

    In the present study, we would like to evaluate the efficacy of modified metal oxide nanoparticles (NPs) as cancer antigen delivery vehicles for macrophage (MФs) based antitumor vaccine. The cobalt oxide nanoparticles (CoO NPs) were promising tools for delivery of antigens to antigen presenting cells and have induced an antitumor immune response. Synthesized CoO NPs were modified by N-phosphonomethyliminodiacetic acid (PMIDA), facilitated the conjugation of lysate antigen, i.e. cancer antigen derived from lysis of cancer cells. The cancer cell lysate antigen conjugated PMIDA-CoO NPs (Ag-PMIDA-CoO NPs) successfully activated macrophage (MФ) evident by the increasing the serum IFN-γ and TNF-α level. Immunization of mice with the Ag-PMIDA-CoO NPs constructed an efficient immunological adjuvant induced anticancer IgG responses, and increased the antibody dependent cellular cytotoxicity (ADCC) response than only lysate antigen treated group to combat the cancer cell. The nanocomplexes enhanced the anticancer CD4(+)T cell response in mice. The result showed that Ag-PMIDA-CoO NPs can stimulate the immune responses over only lysate antigens, which are the most important findings in this study. These NP-mediated Ag deliveries may significantly improve the anticancer immune response by activating MФs and may act as adjuvant and will balance the pro-inflammatory and anti-inflammatory immunoresponse. The crosstalk between the activated MФ with other immune competent cells will be monitored by measuring the cytokines which illustrate the total immunological network setups.

  20. Self-nanoemulsifying drug delivery systems for oral insulin delivery

    DEFF Research Database (Denmark)

    Li, Ping; Tan, Angel; Prestidge, Clive A

    2014-01-01

    This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w...

  1. Novel central nervous system drug delivery systems.

    Science.gov (United States)

    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.

  2. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

    Directory of Open Access Journals (Sweden)

    Martin Kreutz

    Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

  3. Exosome-based tumor antigens-adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA.

    Science.gov (United States)

    Morishita, Masaki; Takahashi, Yuki; Matsumoto, Akihiro; Nishikawa, Makiya; Takakura, Yoshinobu

    2016-12-01

    For cancer immunotherapy via tumor antigen vaccination in combination with an adjuvant, major challenges include the identification of a particular tumor antigen and efficient delivery of the antigen as well as adjuvant to antigen-presenting cells. In this study, we proposed an efficient exosome-based tumor antigens-adjuvant co-delivery system using genetically engineered tumor cell-derived exosomes containing endogenous tumor antigens and immunostimulatory CpG DNA. Murine melanoma B16BL6 cells were transfected with a plasmid vector encoding a fusion streptavidin (SAV; a protein that binds to biotin with high affinity)-lactadherin (LA; an exosome-tropic protein) protein, yielding genetically engineered SAV-LA-expressing exosomes (SAV-exo). SAV-exo were combined with biotinylated CpG DNA to prepare CpG DNA-modified exosomes (CpG-SAV-exo). Fluorescent microscopic observation revealed the successful modification of exosomes with CpG DNA by SAV-biotin interaction. CpG-SAV-exo showed efficient and simultaneous delivery of exosomes with CpG DNA to murine dendritic DC2.4 cells in culture. Treatment with CpG-SAV-exo effectively activated DC2.4 cells and enhanced tumor antigen presentation capacity. Immunization with CpG-SAV-exo exhibited stronger in vivo antitumor effects in B16BL6 tumor-bearing mice than simple co-administration of exosomes and CpG DNA. Thus, genetically engineered CpG-SAV-exo is an effective exosome-based tumor antigens-adjuvant co-delivery system that will be useful for cancer immunotherapy.

  4. Polymer nanomicelles for efficient mucus delivery and antigen-specific high mucosal immunity.

    Science.gov (United States)

    Noh, Young-Woock; Hong, Ji Hyun; Shim, Sang-Mu; Park, Hye Sun; Bae, Hee Ho; Ryu, Eun Kyoung; Hwang, Jung Hwan; Lee, Chul-Ho; Cho, Seong Hun; Sung, Moon-Hee; Poo, Haryoung; Lim, Yong Taik

    2013-07-22

    Micelles for mucosal immunity: A mucosal vaccine system based on γ-PGA nanomicelles and viral antigens was synthesized. The intranasal administration of the vaccine system induces a high immune response both in the humoral and cellular immunity (see picture).

  5. Software Build and Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Robey, Robert W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-07-10

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

  6. Optimizing Consulting Delivery Systems.

    Science.gov (United States)

    Spottswood, Curran

    1980-01-01

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

  7. Cancer antigen 125 after delivery in women with a normal pregnancy

    DEFF Research Database (Denmark)

    Szecsi, Pal B; Andersen, Malene R; Bjørngaard, Brian;

    2014-01-01

    OBJECTIVE: To establish reference intervals for cancer antigen 125 (CA-125) in women with expected normal pregnancy, delivery, and early postpartum period. DESIGN: Prospective observational study. SETTING: Department of Clinical Biochemistry and Obstetrics, Copenhagen University Hospital, Gentofte......, Denmark. POPULATION: Eight hundred and one women with expected normal pregnancies were investigated. Of these, 640 delivered vaginally, 82 by emergency cesarean section, and 79 by elective cesarean section; 720 women had uncomplicated pregnancies. METHODS: Samples were collected at gestational weeks 13...

  8. Attenuated Bordetella pertussis BPZE1 as a live vehicle for heterologous vaccine antigens delivery through the nasal route.

    Science.gov (United States)

    Li, Rui; Lim, Annabelle; Alonso, Sylvie

    2011-01-01

    Whereas the great majority of the current vaccines are delivered through the parenteral route, mucosal administration has been increasingly considered for controlling infection and preventing disease. Mucosal vaccination can trigger both humoral and cell-mediated protection, not only at the targeted mucosal surface, but also systemically. In this regard, nasal vaccination has shown great potential. The live attenuated strain of Bordetella pertussis, BPZE1, is particularly attractive and promising as a nasal vaccine delivery vector of heterologous antigen vaccine candidates. BPZE1 was originally developed as a live nasal pertussis vaccine candidate, and is currently undergoing phase I clinical trial in human (http://www.child-innovac.org). Highly adapted to the human respiratory tract and offering several potential protein carriers for presentation of the heterologous antigen vaccine candidates, BPZE1 represents an appealing platform for the development of live recombinant vaccines delivered via the nasal route that would confer simultaneous protection against pertussis and the targeted infectious disease(s).

  9. Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation

    Science.gov (United States)

    Kawasaki, Norihito; Vela, Jose Luis; Nycholat, Corwin M.; Rademacher, Christoph; Khurana, Archana; van Rooijen, Nico; Crocker, Paul R.; Kronenberg, Mitchell; Paulson, James C.

    2013-01-01

    Invariant natural killer T (iNKT) cells induce a protective immune response triggered by foreign glycolipid antigens bound to CD1d on antigen-presenting cells (APCs). A limitation of using glycolipid antigens to stimulate immune responses in human patients has been the inability to target them to the most effective APCs. Recent studies have implicated phagocytic CD169+ macrophages as major APCs in lymph nodes for priming iNKT cells in mice immunized with glycolipid antigen in particulate form. CD169 is known as sialoadhesin (Sn), a macrophage-specific adhesion and endocytic receptor of the siglec family that recognizes sialic acid containing glycans as ligands. We have recently developed liposomes decorated with glycan ligands for CD169/Sn suitable for targeted delivery to macrophages via CD169/Sn-mediated endocytosis. Here we show that targeted delivery of a lipid antigen to CD169+ macrophages in vivo results in robust iNKT cell activation in liver and spleen using nanogram amounts of antigen. Activation of iNKT cells is abrogated in Cd169−/− mice and is macrophage-dependent, demonstrating that targeting CD169+ macrophages is sufficient for systemic activation of iNKT cells. When pulsed with targeted liposomes, human monocyte–derived dendritic cells expressing CD169/Sn activated human iNKT cells, demonstrating the conservation of the CD169/Sn endocytic pathway capable of presenting lipid antigens to iNKT cells. PMID:23610394

  10. Engineered Human Ferritin Nanoparticles for Direct Delivery of Tumor Antigens to Lymph Node and Cancer Immunotherapy

    Science.gov (United States)

    Lee, Bo-Ram; Ko, Ho Kyung; Ryu, Ju Hee; Ahn, Keum Young; Lee, Young-Ho; Oh, Se Jin; Na, Jin Hee; Kim, Tae Woo; Byun, Youngro; Kwon, Ick Chan; Kim, Kwangmeyung; Lee, Jeewon

    2016-01-01

    Efficient delivery of tumor-specific antigens (TSAs) to lymph nodes (LNs) is essential to eliciting robust immune response for cancer immunotherapy but still remains unsolved. Herein, we evaluated the direct LN-targeting performance of four different protein nanoparticles with different size, shape, and origin [Escherichia coli DNA binding protein (DPS), Thermoplasma acidophilum proteasome (PTS), hepatitis B virus capsid (HBVC), and human ferritin heavy chain (hFTN)] in live mice, using an optical fluorescence imaging system. Based on the imaging results, hFTN that shows rapid LN targeting and prolonged retention in LNs was chosen as a carrier of the model TSA [red fluorescence protein (RFP)], and the flexible surface architecture of hFTN was engineered to densely present RFPs on the hFTN surface through genetic modification of subunit protein of hFTN. The RFP-modified hFTN rapidly targeted LNs, sufficiently exposed RFPs to LN immune cells during prolonged period of retention in LNs, induced strong RFP-specific cytotoxic CD8+ T cell response, and notably inhibited RFP-expressing melanoma tumor growth in live mice. This suggests that the strategy using protein nanoparticles as both TSA-carrying scaffold and anti-cancer vaccine holds promise for clinically effective immunotherapy of cancer. PMID:27725782

  11. Electronic Nicotine Delivery Systems Key Facts Infographic

    Data.gov (United States)

    U.S. Department of Health & Human Services — Explore the Electronic Nicotine Delivery Systems Key Facts Infographic which outlines key facts related to electronic nicotine delivery systems (ENDS), including...

  12. A REVIEW ON OSMOTIC DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Harnish Patel

    2012-04-01

    Full Text Available Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and 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 process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable controlled drug delivery systems and could be employed as oral drug delivery systems. Various patents available for osmotic drug delivery system like Rose-Nelson pump, Higuchi leeper pump, Higuchi Theeuwes pump, Elementary Osmotic pump etc. ODDS are useful for poorly soluble drug, for pulsatile drug release, zero order release. Various techniques available for preparation of ODDS include push pull osmotic Pump, osmotic Brusting osmotic pump, liquid oral osmotic system, sandwiched osmotic tablets , delayed delivery osmotic device, monolithic osmotic System and controlled porosity osmotic Pump. Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active agents. These systems can be utilized for systemic as well as targeted delivery of drugs. The release of drugs from osmotic systems is governed by various formulation factors such as solubility and osmotic pressure of the core components, size of the delivery orifice, and nature of the rate-controlling membrane. In this Paper mainly focused on the Osmotic System with example, the basic component of osmotic system and evaluation parameter of the osmotic drug delivery system.

  13. Mucosal vaccine delivery of antigens tightly bound to an adjuvant particle made from food-grade bacteria

    NARCIS (Netherlands)

    van Roosmalen, ML; Kanninga, R; El Khattabi, M; Neef, J; Audouy, S; Bosma, T; Kuipers, A; Post, E; Steen, A; Kok, J; Buist, G; Kuipers, OP; Robillard, G; Leenhouts, K

    2006-01-01

    Mucosal immunization with subunit vaccines requires new types of antigen delivery vehicles and adjuvants for optimal immune responses. We have developed a non-living and non-genetically modified gram-positive bacterial delivery particle (GEM) that has built-in adjuvant activity and a high loading ca

  14. UNIQUE ORAL DRUG DELIVERY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Raphael M. Ottenbrite; ZHAO Ruifeng; Sam Milstein

    1995-01-01

    An oral drug delivery system using proteinoid microspheres is discussed with respect to its unique dependence on pH. It has been found that certain drugs such as insulin and heparin can be encapsulated in proteinoid spheres at stomach pH's (1-3). These spheres also dissemble at intestinal pH's (6-7) releasing the drug for absorption. Using this technique low molecular weight heparin and human growth hormone have been orally delivered successfully to several animal species. Future work has been proposed to study the interaction and binding of the specific drugs with synthesized oligopeptides.

  15. TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

    Directory of Open Access Journals (Sweden)

    Virendra Yadav

    2012-01-01

    Full Text Available Transdermal drug delivery system (TDDS are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. By this constant concentration of drug remain in blood for long time. Polymer matrix, drug, permeation enhancers are the main components of TDDS; polymers includes Zein, Shellac (as a natural to synthetic ones (Polybutadiene, Polysiloxane, Polyvinyl chloride, Polyvinyl alcohol etc.. TDDS are of many types varying from single layer drug in adhesive to multi layer drug in adhesive and others are reservoir and the matrix systems. The market value of TDDS products are increasing with rapid rate, more than 35 products have now been approved for sale in US, and approximately 16 active ingredients are approved globally for use as a TDDS. Transdermal drug delivery is a recent technology which promises a great future it has a potential to limit the use of needles for administering wide variety of drugs but cost factor is a important thing to consider since developing nations like INDIA have second highest population, but due to higher cost TDDS are the hidden part of therapy used in general population.

  16. Chemically modified inulin microparticles serving dual function as a protein antigen delivery vehicle and immunostimulatory adjuvant.

    Science.gov (United States)

    Gallovic, Matthew D; Montjoy, Douglas G; Collier, Michael A; Do, Clement; Wyslouzil, Barbara E; Bachelder, Eric M; Ainslie, Kristy M

    2016-03-01

    To develop a new subunit vaccine adjuvant, we chemically modified a naturally-occurring, immunostimulatory inulin polysaccharide to produce an acid-sensitive biopolymer (acetalated inulin, Ace-IN). Various hydrophobic Ace-IN polymers were formed into microparticles (MPs) by oil-in-water emulsions followed by solvent evaporation These Ace-IN MPs possessed tunable degradation characteristics that, unlike polyesters used in FDA-approved microparticulate formulations, had only pH-neutral hydrolytic byproducts. Macrophages were passively targeted with cytocompatible Ace-IN MPs. TNF-α production by macrophages treated with Ace-IN MPs could be altered by adjusting the polymers' chemistry. Mice immunized with Ace-IN MPs encapsulating a model ovalbumin (OVA) antigen showed higher production of anti-OVA IgG antibody levels relative to soluble antigen. The antibody titers were also comparable to an alum-based formulation. This proof-of-concept establishes the potential for chemically-modified inulin MPs to simultaneously enable dual functionality as a stimuli-controlled antigen delivery vehicle and immunostimulatory adjuvant.

  17. Cell Delivery System for Traumatic Brain Injury

    Science.gov (United States)

    2008-03-21

    REPORT Cell Delivery System for Traumatic Brain Injury 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: We have met all of the milestones outlined in this...COVERED (From - To) 18-Sep-2006 Standard Form 298 (Rev 8/98) Prescribed by ANSI Std. Z39.18 - 17-Mar-2008 Cell Delivery System for Traumatic Brain Injury Report...Manassero*, Justin Kim*, Maureen St Georges*, Nicole Esclamado* and Elizabeth Orwin. “Development of a Cell Delivery System for Traumatic Brain Injury Using

  18. Integrated delivery systems. Evolving oligopolies.

    Science.gov (United States)

    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.

  19. Gene gun delivery systems for cancer vaccine approaches.

    Science.gov (United States)

    Aravindaram, Kandan; Yang, Ning Sun

    2009-01-01

    Gene-based immunization with transgenic DNA vectors expressing tumor-associated antigens (TAA), cytokines, or chemokines, alone or in combination, provides an attractive approach to increase the cytotoxic T cell immunity against various cancer diseases. With this consideration, particle-mediated or gene gun technology has been developed as a nonviral method for gene transfer into various mammalian tissues. It has been shown to induce both humoral and cell-mediated immune responses in both small and large experimental animals. A broad range of somatic cell types, including primary cultures and established cell lines, has been successfully transfected ex vivo or in vitro by gene gun technology, either as suspension or adherent cultures. Here, we show that protocols and techniques for use in gene gun-mediated transgene delivery system for skin vaccination against melanoma using tumor-associated antigen (TAA) human gpl00 and reporter gene assays as experimental systems.

  20. Starch Applications for Delivery Systems

    Science.gov (United States)

    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

  1. Organoclays for drug delivery Systems

    OpenAIRE

    Canovas Creus, Alba

    2008-01-01

    Modified clays can be used as carriers of drugs due to their suitable properties and structure in order to achieve improvements in drug delivery. The study of this thesis starts with an introduction to mineral clays and its classification, properties and characterization, then deepens into modified clays (properties, comparison with mineral clays, applications and procedure of modification). Another chapter is focused in drug delivery: definition, its difficulties nowadays and the different w...

  2. Antigen presentation for priming T cells in central system.

    Science.gov (United States)

    Dasgupta, Shaoni; Dasgupta, Subhajit

    2017-01-01

    Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system. The recent approach towards circulating B-lymphocytes is an important area in the context. Here, we analyze the existing findings on antigen presentation in the central nervous system. The aim is to visualize signaling events of myelin antigen presentation to T cells and lead to the strategy of future goals on immunotherapy research.

  3. Intradermal delivery of Shigella IpaB and IpaD type III secretion proteins: kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity, and protection across serotypes.

    Science.gov (United States)

    Heine, Shannon J; Diaz-McNair, Jovita; Andar, Abhay U; Drachenberg, Cinthia B; van de Verg, Lillian; Walker, Richard; Picking, Wendy L; Pasetti, Marcela F

    2014-02-15

    Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25-40 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.

  4. Engineered nanoscaled polyplex gene delivery systems.

    Science.gov (United States)

    Fernandez, Christian A; Rice, Kevin G

    2009-01-01

    Improving the transfection efficiencies of nonviral gene delivery requires properly engineered nanoscaled delivery carriers that can overcome the multiple barriers associated with the delivery of oligonucleotides from the site of administration to the nucleus or cytoplasm of the target cell. This article reviews the current advantages and limitation of polyplex nonviral delivery systems, including the apparent barriers that limit gene expression efficiency compared to physical methods such as hydrodynamic dosing and electroporation. An emphasis is placed on engineered nanoscaled polyplexes (NSPs) of modular design that both self-assemble and systematically disassemble at the desired stage of delivery. It is suggested that NSPs of increasingly sophisticated designs are necessary to improve the efficiency of the rate limiting steps in gene delivery.

  5. Multi-channel gas-delivery system

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-13

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

  6. Fiber laser coupled optical spark delivery system

    Science.gov (United States)

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

    2008-03-04

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

  7. Preparing and evaluating delivery systems for proteins

    DEFF Research Database (Denmark)

    Jorgensen, L; Moeller, E H; van de Weert, M

    2006-01-01

    From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping...

  8. Lipid Based Vesicular Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Shikha Jain

    2014-01-01

    Full Text Available Vesicular drug delivery system can be defined as highly ordered assemblies consisting of one or more concentric bilayers formed as a result of self-assembling of amphiphilic building blocks in presence of water. Vesicular drug delivery systems are particularly important for targeted delivery of drugs because of their ability to localize the activity of drug at the site or organ of action thereby lowering its concentration at the other sites in body. Vesicular drug delivery system sustains drug action at a predetermined rate, relatively constant (zero order kinetics, efficient drug level in the body, and simultaneously minimizes the undesirable side effects. It can also localize drug action in the diseased tissue or organ by targeted drug delivery using carriers or chemical derivatization. Different types of pharmaceutical carriers such as polymeric micelles, particulate systems, and macro- and micromolecules are presented in the form of novel drug delivery system for targeted delivery of drugs. Particulate type carrier also known as colloidal carrier system, includes lipid particles, micro- and nanoparticles, micro- and nanospheres, polymeric micelles and vesicular systems like liposomes, sphingosomes, niosomes, transfersomes, aquasomes, ufasomes, and so forth.

  9. New Delivery Systems and Propellants

    Directory of Open Access Journals (Sweden)

    Myrna Dolovich

    1999-01-01

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

  10. Identification of protective antigens for vaccination against systemic salmonellosis

    Directory of Open Access Journals (Sweden)

    Dirk eBumann

    2014-08-01

    Full Text Available There is an urgent medical need for improved vaccines with broad serovar coverage and high efficacy against systemic salmonellosis. Subunit vaccines offer excellent safety profiles but require identification of protective antigens, which remains a challenging task. Here, I review crucial properties of Salmonella antigens that might help to narrow down the number of potential candidates from more than 4000 proteins encoded in Salmonella genomes, to a more manageable number of 50-200 most promising antigens. I also discuss complementary approaches for antigen identification and potential limitations of current pre-clinical vaccine testing.

  11. Drug delivery systems from nose to brain.

    Science.gov (United States)

    Misra, Ambikanandan; Kher, Gitanjali

    2012-09-01

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

  12. Radiation sterilization of new drug delivery systems.

    Science.gov (United States)

    Abuhanoğlu, Gürhan; Ozer, A Yekta

    2014-06-01

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

  13. Hydrogen storage and delivery system development

    Energy Technology Data Exchange (ETDEWEB)

    Handrock, J.L.; Wally, K.; Raber, T.N. [Sandia National Labs., Livermore, CA (United States)

    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.

  14. Cyclodextrins in delivery systems: Applications

    Directory of Open Access Journals (Sweden)

    Gaurav Tiwari

    2010-01-01

    Full Text Available 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.

  15. Delivery of Echinococcus granulosus antigen EG95 to mice and sheep using recombinant vaccinia virus.

    Science.gov (United States)

    Dutton, S; Fleming, S B; Ueda, N; Heath, D D; Hibma, M H; Mercer, A A

    2012-06-01

    The tapeworm Echinococcus granulosus is the causative agent of hydatid disease and affects sheep, cattle, dogs and humans worldwide. It has a two-stage life cycle existing as worms in the gut of infected dogs (definitive host) and as cysts in herbivores and humans (intermediate host). The disease is debilitating and can be life threatening where the cysts interfere with organ function. Interruption of the hydatid life cycle in the intermediate host by vaccination may be a way to control the disease, and a protective oncosphere antigen EG95 has been shown to protect animals against challenge with E. granulosus eggs. We explored the use of recombinant vaccinia virus as a delivery vehicle for EG95. Mice and sheep were immunized with the recombinant vector, and the result monitored at the circulating antibody level. In addition, sera from immunized mice were assayed for the ability to kill E. granulosus oncospheres in vitro. Mice immunized once intranasally developed effective oncosphere-killing antibody by day 42 post-infection. Antibody responses and oncosphere killing were correlated and were significantly enhanced by boosting mice with either EG95 protein or recombinant vector. Sheep antibody responses to the recombinant vector or to EG95 protein mirrored those in mice.

  16. Intranasal delivery of cholera toxin induces th17-dominated T-cell response to bystander antigens.

    Directory of Open Access Journals (Sweden)

    Jee-Boong Lee

    Full Text Available Cholera toxin (CT is a potent vaccine adjuvant, which promotes mucosal immunity to protein antigen given by nasal route. It has been suggested that CT promotes T helper type 2 (Th2 response and suppresses Th1 response. We here report the induction of Th17-dominated responses in mice by intranasal delivery of CT. This dramatic Th17-driving effect of CT, which was dependent on the B subunit, was observed even in Th1 or Th2-favored conditions of respiratory virus infection. These dominating Th17 responses resulted in the significant neutrophil accumulation in the lungs of mice given CT. Both in vitro and in vivo treatment of CT induced strongly augmented IL-6 production, and Th17-driving ability of CT was completely abolished in IL-6 knockout mice, indicating a role of this cytokine in the Th17-dominated T-cell responses by CT. These data demonstrate a novel Th17-driving activity of CT, and help understand the mechanisms of CT adjuvanticity to demarcate T helper responses.

  17. AN OVERVIEW ON VARIOUS APPROACHES TO ORAL CONTROLLED DRUG DELIVERY SYSTEM VIA GASTRORETENTIVE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Bhalla.Neetika

    2012-04-01

    Full Text Available In recent years scientific and technological advancements have been made in the research and development of oral drug delivery system. Oral sustained drug delivery system is complicated by limited gastric residence times (GRTs. In order to understand various physiological difficulties to achieve gastric retention, we have summarized important factors controlling gastric retention. To overcome these limitations, various approaches have been proposed to increase gastric residence of drug delivery systems in the upper part of the gastrointestinal tract includes floating drug dosage systems (FDDS, swelling or expanding systems , mucoadhesive systems , magnetic systems, modified-shape systems, high density system and other delayed gastric emptying devices.

  18. STRATEGIES AND PROSPECTS OF NASAL DRUG DELIVERY SYSTEMS

    OpenAIRE

    Gannu Praveen Kumar

    2012-01-01

    The recent advancement of nasal drug delivery systems has increased enormously and is gaining significant importance. Intranasal therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. The non-invasive delivery of nasal drug delivery systems made to exploit for the development of successful treatment. The advantages, disadvantages, mechanism of action and application of nasal drug delivery system in local delivery, systematic delivery, nasal vaccines and CNS...

  19. Emulsomes: An emerging vesicular drug delivery system

    Directory of Open Access Journals (Sweden)

    Bhawandeep Gill

    2012-01-01

    Full Text Available The oral route is the easiest, cost effective, and most vital method for drug administration. Therefore, improvement of dosage forms mainly for the prolonged release purpose has been a challenge for scientists. Vesicular drug delivery systems are developed with a purpose to overcome problems coupled with the drugs such a poor bioavailability, protection from harsh gastric environment, and from gastric enzymes, which degrade the drug. Vesicular drug delivery systems such as liposomes, emulsions, niosomes, proniosomes, solid lipid-nano particles, ethosomes, nanoparticles, and pharmacosomes, etc have gained much attention, but emulsomes have rouse as system, which bypasses many disadvantages associated with other systems, developed as novel lipoidal vesicular system with internal solid fat core surrounded by phospholipid bilayer. This technology is designed to act as vehicle for poorly soluble drugs. The drug is enclosed in the emulsomes and provide prolong existence of drug in systemic circulation. Furthermore, emulsomal-based formulations of genetic drugs such as antisense oligonucleotides and plasmids for gene therapy that have clear potential for systemic utility are increasingly available. This review addresses the concept of emulsomal drug delivery system, summarizes the success of emulsomes for the delivery of small molecules, and special attention has been paid to its formulation design, advantages, biopharmaceutical aspects, stability aspects, and various aspects related to drug delivery including future aspects.

  20. Structure-Function Assessment of Mannosylated Poly(β-amino esters) upon Targeted Antigen Presenting Cell Gene Delivery.

    Science.gov (United States)

    Jones, Charles H; Chen, Mingfu; Gollakota, Akhila; Ravikrishnan, Anitha; Zhang, Guojian; Lin, Sharon; Tan, Myles; Cheng, Chong; Lin, Haiqing; Pfeifer, Blaine A

    2015-05-11

    Antigen presenting cell (APC) gene delivery is a promising avenue for modulating immunological outcomes toward a desired state. Recently, our group developed a delivery methodology to elicit targeted and elevated levels of APC-mediated gene delivery. During these initial studies, we observed APC-specific structure-function relationships with the vectors used during gene delivery that differ from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector-associated parameters in the context of APC gene transfer. Thus, we describe the synthesis and characterization of a second-generation mannosylated poly(β-amino ester) library stratified by molecular weight. To better understand the APC-specific structure-function relationships governing polymeric gene delivery, the library was systematically characterized by (1) polymer molecular weight, (2) relative mannose content, (3) polyplex biophysical properties, and (4) gene delivery efficacy. In this library, polymers with the lowest molecular weight and highest relative mannose content possessed gene delivery transfection efficiencies as good as or better than commercial controls. Among this group, the most effective polymers formed the smallest polymer-plasmid DNA complexes (∼300 nm) with moderate charge densities (structure and polyplex biophysical properties suggests a unique mode of action and provides a framework within which future APC-targeting polymers can be designed.

  1. Goals for Postsecondary Instructional Delivery Systems.

    Science.gov (United States)

    Knapp, Stuart E.; Valentine, Carol A.

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

  2. CURRENT TRENDS IN PULSATILE DRUG DELIVERY SYSTEMS

    Directory of Open Access Journals (Sweden)

    S. R. Tajane et al.

    2012-01-01

    Full Text Available The purpose for this review on pulsatile drug delivery systems (PDDS is to compile the recent literatures with special focus on the different types and approaches involved in the development of the formulation. Pulsatile drug delivery system is the most interesting time and site-specific system. This system is designed for chronopharmacotherapy. Thus, to mimic the function of living systems and in view of emerging chronotherapeutic approaches, pulsatile delivery, which is meant to release a drug following programmed lag phase, has increasing interest in the recent years. Diseases wherein PDDS are promising include asthma, peptic ulcer, cardiovascular diseases, arthritis, and attention deficit syndrome in children, cancer, diabetes, and hypercholesterolemia. Pulsatile drug delivery system divided into 2 types’ preplanned systems and stimulus induced system, preplanned systems based on osmosis, rupturable layers, and erodible barrier coatings. Stimuli induced system based on electrical, temperature and chemically induced systems. This review also summarizes some current PDDS already available in the market. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form.

  3. RECENT TRENDS IN DENTAL DRUG DELIVERY SYSTEMS

    Directory of Open Access Journals (Sweden)

    Sharma Nishu

    2013-07-01

    Full Text Available Controlled release local drug delivery systems offer advantages compared to systemic dosage forms for many dental diseases like gingivitis, periodontitis. The objective of this literature survey was to gain knowledge about various dental drug delivery systems for targeted delivery of the drug. The polymer ethyl cellulose was used in the formulation of dental films. The dental film was then evaluated for various parameters like thickness, folding endurance and weight variation and content uniformity, in vitro and in vivo study. There has been a great attention in using iontophoretic technique for the transdermal drug delivery of medications, both ionic and non ionic. This technique of facilitated movement of ions across a membrane under the influence of an externally applied electric potential difference is one of the most promising physical skin penetrations enhancing method. Another novel approach is the use of lasers in dentistry. Lasers can be used in both hard and soft tissue applications including laser bleaching, frenectomy, gingivectomy, caries removal etc. Drugs delivery via the buccal routs using bio adhesive dosage forms offers such a novel route of drugs administration. This route has been used successfully for the systematic delivery of number of drugs candidates. Problems such as high first pass metabolisms and drugs degradation in the gastrointestinal tract can be circumvented by administrating the drug buccal routes.

  4. Microemulsion: As Excellent Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Pathan Maksud

    2012-09-01

    Full Text Available Today though the oral drug delivery system is dominant still it is found to be need of ideal transdermal drug delivery system. “A micro emulsion is a system of water, oil and an amphiphile which is a single optically isotropic and thermodynamically stable liquid solution”. Microemulsions offer several advantages as drug delivery systems as these are thermodynamically stable and stability allows for self emulsification of the system with microemulsion acting as supersolvent of the drugs which are poorly or insoluble in water. They are preferred more as compared to conventional emulsions due stability. The dispersed phase mainly acts as the solvent for the water insoluble drug. Microemulsions have been proved to increase the cutaneous absorption of both lipophilic and hydrophilic API’s when compared to conventional vehicles.

  5. Pulsatile drug delivery systems: An approach for controlled drug delivery

    Directory of Open Access Journals (Sweden)

    Arora Shweta

    2006-01-01

    Full Text Available Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. These systems are designed according to the circadian rhythm of the body. The principle rationale for the use of pulsatile release is for the drugs where a constant drug release, i.e., a zero-order release is not desired. The release of the drug as a pulse after a lag time has to be designed in such a way that a complete and rapid drug release follows the lag time. Various systems like capsular systems, osmotic systems, single- and multiple-unit systems based on the use of soluble or erodible polymer coating and use of rupturable membranes have been dealt with in the article. It summarizes the latest technological developments, formulation parameters, and release profiles of these systems. Products available as once-a-daily formulation based on Pulsatile release like Pulsincap ®, Ritalin ®, and Pulsys ® are also covered in the review. These systems are beneficial for the drugs having chronopharmacological behaviour where night time dosing is required and for the drugs having high first-pass effect and having specific site of absorption in GIT. Drugs used in asthmatic patients and patients suffering from rheumatoid arthritis are also discussed along with many other examples.

  6. Delivery systems for gene therapy

    Directory of Open Access Journals (Sweden)

    Shrikant Mali

    2013-01-01

    Full Text Available The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

  7. PULSATILE DRUG DELIVERY SYSTEMS: RECENT TECHNOLOGY

    Directory of Open Access Journals (Sweden)

    Abdul Sayeed*, Md. M. Hamed , Mohd. Rafiq and Nahid Ali

    2013-03-01

    Full Text Available ABSTRACT: Pulsatile Drug Delivery Systems are gaining a lot of interest as they deliver the drug at the right place at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. These systems are designed according to the circadian rhythm of the body. The principle rationale for the use of pulsatile release of the drugs is where a constant drug release is not desired. A pulse has to be designed in such a way that a complete and rapid drug release is achieved after the lag time. Various systems like capsular systems, osmotic systems, single- and multiple-unit systems based on the use of soluble or erodible polymer coating and use of rupturable membranes have been dealt with in the article. It summarizes the latest technological developments, formulation parameters, and release profiles of these systems. These systems are beneficial for the drugs having chronopharmacological behavior where night time dosing is required, such as anti-arhythmic and anti-asthmatic. Current review article discussed the reasons for development of pulsatile drug delivery system, types of the disease in which pulsatile release is required, classification, advantages, limitation, and future aspects of pulsatile drug delivery system.

  8. Aerial Delivery Systems and Technologies (Review Paper

    Directory of Open Access Journals (Sweden)

    Balraj Gupta

    2010-03-01

    Full Text Available Aerial Delivery Research & Development Establishment (ADRDE was started at Kanpur during latter part of 1950's consisting of two Aerial Delivery Sections primarily for the indigenisation of Parachutes and related equipment for Para-dropping of men and materials. Today, the charter of ADRDE includes design & development of parachutes, Aerostat Systems, Aircraft Arrester Barrier Systems and Heavy-Drop Systems for both military and civilian applications. The technological competence built in Aeronautical, Textile, Mechanical and Electronics engineering has imparted ADRDE, a unique combination of know-how and capabilities to evolve new solutions in these fields, with emphasis on quality assurance. This paper highlights the design and development of technologies developed by ADRDE to stengthen the India's aerial delivery system and its future plans.Defence Science Journal, 2010, 60(2, pp.124-136, DOI:http://dx.doi.org/10.14429/dsj.60.326

  9. Vaccine delivery system for tuberculosis based on nano-sized hepatitis B virus core protein particles

    Directory of Open Access Journals (Sweden)

    Dhanasooraj D

    2013-02-01

    Full Text Available Dhananjayan Dhanasooraj, R Ajay Kumar, Sathish MundayoorMycobacterium Research Group, Rajiv Gandhi Centre for Biotechnology, Kerala, IndiaAbstract: Nano-sized hepatitis B virus core virus-like particles (HBc-VLP are suitable for uptake by antigen-presenting cells. Mycobacterium tuberculosis antigen culture filtrate protein 10 (CFP-10 is an important vaccine candidate against tuberculosis. The purified antigen shows low immune response without adjuvant and tends to have low protective efficacy. The present study is based on the assumption that expression of these proteins on HBc nanoparticles would provide higher protection when compared to the native antigen alone. The cfp-10 gene was expressed as a fusion on the major immunodominant region of HBc-VLP, and the immune response in Balb/c mice was studied and compared to pure proteins, a mixture of antigens, and fusion protein-VLP, all without using any adjuvant. The humoral, cytokine, and splenocyte cell proliferation responses suggested that the HBc-VLP bearing CFP-10 generated an antigen-specific immune response in a Th1-dependent manner. By virtue of its self-adjuvant nature and ability to form nano-sized particles, HBc-VLPs are an excellent vaccine delivery system for use with subunit protein antigens identified in the course of recent vaccine research.Keywords: Mycobacterium tuberculosis, VLP, hepatitis B virus core particle, CFP-10, self-adjuvant, vaccine delivery

  10. Pharmacosomes: A Potential Vesicular Drug Delivery System

    Directory of Open Access Journals (Sweden)

    D. Nagasamy Venkatesh

    2014-04-01

    Full Text Available Lipid based drug delivery systems have been examined in various studies and exhibited their potential in controlled and targeted drug delivery. Pharmacosomes, a novel vesicular drug delivery system, offering a unique advantage over liposomes and niosomes, and serve as potential alternative to these conventional vesicles. They constitute an amphiphilic phospholipid complex with drug bearing an active hydrogen atom covalently that bind to phospholipids. They provide an efficient delivery of drug required at the site of action, which ultimately reduces the drug toxicity with reduced adverse effects and also reduces the cost of therapy by imparting better biopharmaceutical properties to the drug, resulting in increases bioavailability, especially in case of poorly soluble drugs. As the system is formed by binding the drug (pharmakon to carrier (soma, they are termed as pharmacosomes. Depending upon the chemical structure of the drug lipid complex they may exist as ultrafine vesicular, micellar and hexagonal aggregate. Drug having active hydrogen group such as carboxyl, hydroxyl group can be esterified to lipids, resulting in amphiphilic compound. Pharmacosomes are widely used as carriers for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular and antineoplastic drugs. The release of drug from pharmacosomes is generally governed by the process of enzymatic reaction and acid hydrolysis. Here, in the present review paper we have discussed the potential of pharmacosomes as a controlled and targeted drug delivery system and highlighted the method of preparation and characterization.

  11. Expression, Purification and Characterization of Ricin vectors used for exogenous antigen delivery into the MHC Class I presentation pathway

    Directory of Open Access Journals (Sweden)

    Smith Daniel C.

    2003-01-01

    Full Text Available Disarmed versions of the cytotoxin ricin can deliver fused peptides into target cells leading to MHC class I-restricted antigen presentation [Smith et al. J Immunol 2002; 169:99-107]. The ricin delivery vector must contain an attenuated catalytic domain to prevent target cell death, and the fused peptide epitope must remain intact for delivery and functional loading to MHC class I molecules. Expression in E. coli and purification by cation exchange chromatography of the fusion protein is described. Before used for delivery, the activity of the vector must be characterized in vitro, via an N-glycosidase assay, and in vivo, by a cytotoxicity assay. The presence of an intact epitope must be confirmed using mass spectrometry by comparing the actual mass with the predicted mass.

  12. FLOATING DRUG DELIVERY SYSTEM - CHRONOTHERAPEUTIC APPROACH

    Directory of Open Access Journals (Sweden)

    Vishal Kalal

    2011-04-01

    Full Text Available The purpose of writing this review on the floating drug delivery systems (FDDS was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. FDDS is one of the approaches in chronotherapeutic drug delivery. In the past reviews of FDDS the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, their classification and formulation aspects have been covered. This review summarizes the special focus on chronotherapeutics, diseases affected by biological rhythm, its importance, advantages, various approaches in Chronotherapeutic drug delivery and applications of FDDS. These systems are useful for several problems encountered during the development of a pharmaceutical dosage forms.

  13. Nanotechnology-based drug delivery systems

    Directory of Open Access Journals (Sweden)

    Singh Baljit

    2007-12-01

    Full Text Available Abstract Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression.

  14. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy.

    Science.gov (United States)

    Fan, Yuchen; Moon, James J

    2015-01-01

    Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens) and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy.

  15. Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Yuchen Fan

    2015-08-01

    Full Text Available Recent studies have demonstrated great therapeutic potential of educating and unleashing our own immune system for cancer treatment. However, there are still major challenges in cancer immunotherapy, including poor immunogenicity of cancer vaccines, off-target side effects of immunotherapeutics, as well as suboptimal outcomes of adoptive T cell transfer-based therapies. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges facing cancer vaccines and immunotherapy. Nanoparticle systems have been shown to improve targeted delivery of tumor antigens and therapeutics against immune checkpoint molecules, amplify immune activation via the use of new stimuli-responsive or immunostimulatory materials, and augment the efficacy of adoptive cell therapies. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to potentiate cancer immunotherapies, including cancer vaccines with subunit antigens (e.g., oncoproteins, mutated neo-antigens, DNA and mRNA antigens and whole-cell tumor antigens, dendritic cell-based vaccines, artificial antigen-presenting cells, and immunotherapeutics based on immunogenic cell death, immune checkpoint blockade, and adoptive T-cell therapy.

  16. Thermo-sensitive hydrogel PLGA-PEG-PLGA as a vaccine delivery system for intramuscular immunization.

    Science.gov (United States)

    Wang, Xiaoyan; Zhang, Yu; Xue, Wei; Wang, Hong; Qiu, Xiaozhong; Liu, Zonghua

    2016-11-25

    In this work, we explored the potential of thermo-sensitive PLGA-PEG-PLGA with sol-gel transition temperature around 32℃ as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. First, in vitro release test showed that the PLGA-PEG-PLGA-deriving hydrogels could release ovalbumin in vitro in a more sustainable way. From fluorescence living imaging, 50-200 mg/mL of PLGA-PEG-PLGA formulations could release antigen in a sustainable manner in vivo, suggesting that the PLGA-PEG-PLGA hydrogel worked as an antigen-depot. Further, the sustainable antigen release from the PLGA-PEG-PLGA hydrogels increased antigen availability in the spleens of the immunized mice. The intramuscular immunization results showed that 50-200 mg/mL of PLGA-PEG-PLGA formulations promoted significantly more potent antigen-specific IgG immune response. In addition, 200 mg/mL of PLGA-PEG-PLGA formulation significantly enhanced the secretion of both Th1 and Th2 cytokines. From in vitro splenocyte proliferation assay, 50-200 mg/mL of PLGA-PEG-PLGA formulations all initiated significantly higher splenocyte activation. These results indicate that the thermo-sensitive and injectable PLGA-PEG-PLGA hydrogels (particularly, 200 mg/mL of PLGA-PEG-PLGA-based hydrogel) own promising potential as an intramuscular vaccine delivery system.

  17. RECENT ADVANCES IN NOVEL DRUG DELIVERY SYSTEMS

    Directory of Open Access Journals (Sweden)

    Manivannan Rangasamy

    2010-12-01

    Full Text Available Drug delivered can have significant effect on its efficacy. Some drugs have an optimum concentration range with in which maximum benefit is derived and concentrations above (or below the range can be toxic or produce no therapeutic effect. Various drug delivery and drug targeting systems are currently under development. The main goal for developing such delivery systems is to minimize drug degradation and loss, to prevent harmful side effects and to increase bioavailability. Targeting is the ability to direct the drug loaded system to the site of interest. Among drug carrier one can name soluble polymers, microparticles made of insoluble (or biodegradable natural and synthetic polymers, microcapsules, cells, cell ghosts, lipoproteins, liposomes and micelles. Two major mechanisms can be distinguished for addressing the desired sites for drug release, (a Passive and (b Active targeting. Controlled drug carrier systems such as micellar solutions, vescicles and liquid crystal dispersions, as well as nanoparticle dispersions consisting of small particles of 10 – 400 nm show great promise as drug delivery systems. Hydrogels are three dimensional, hydrophilic, polymer networks capable of imbibing large amounts of water or biological fluids. Buckyballs, a novel delivery system with 60 carbon atoms formed in the shape of hollow ball. They are other type’s namely bucky babies, fuzzy balls, gadofullereness, and giant fullerenes. Nanoparticles can be classified as nano tubes, nano wires, nano cantilever, nanoshells, quantum dots, nano pores. Researchers at north western university using gold particles to develop ultra sensitive detection systems for DNA and protein markers associated with many forms of cancer, including breast and prostrate cancer. Drug loaded erythrocytes is one of the growing and potential systems for delivery of drugs and enzymes.

  18. Targeted antigen delivery to dendritic cells elicits robust antiviral T cell-mediated immunity in the liver

    Science.gov (United States)

    Volckmar, Julia; Gereke, Marcus; Ebensen, Thomas; Riese, Peggy; Philipsen, Lars; Lienenklaus, Stefan; Wohlleber, Dirk; Klopfleisch, Robert; Stegemann-Koniszewski, Sabine; Müller, Andreas J.; Gruber, Achim D.; Knolle, Percy; Guzman, Carlos A.; Bruder, Dunja

    2017-01-01

    Hepatotropic viruses such as hepatitis C virus cause life-threatening chronic liver infections in millions of people worldwide. Targeted in vivo antigen-delivery to cross-presenting dendritic cells (DCs) has proven to be extraordinarily efficient in stimulating antigen-specific T cell responses. To determine whether this approach would as well be suitable to induce local antiviral effector T cells in the liver we compared different vaccine formulations based on either the targeting of DEC-205 or TLR2/6 on cross-presenting DCs or formulations not involving in vivo DC targeting. As read-outs we used in vivo hepatotropic adenovirus challenge, histology and automated multidimensional fluorescence microscopy (MELC). We show that targeted in vivo antigen delivery to cross-presenting DCs is highly effective in inducing antiviral CTLs capable of eliminating virus-infected hepatocytes, while control vaccine formulation not involving DC targeting failed to induce immunity against hepatotropic virus. Moreover, we observed distinct patterns of CD8+ T cell interaction with virus-infected and apoptotic hepatocytes in the two DC-targeting groups suggesting that the different vaccine formulations may stimulate distinct types of effector functions. Our findings represent an important step toward the future development of vaccines against hepatotropic viruses and the treatment of patients with hepatic virus infection after liver transplantation to avoid reinfection. PMID:28266658

  19. Waste Feed Delivery Transfer System Analysis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Status of the CLIC Beam Delivery System

    CERN Document Server

    Tomás, R; Resta López, J; Rumolo, G; Schulte, D; Schuler, P; Bolzon, B; Brunetti, L; Brunetti, L; Geffroy, N; Jeremie, A; Seryi, A; Angal-Kalinin, D; Jackson, F

    2010-01-01

    The CLIC Beam Delivery System (BDS) is experiencing the careful revision from a large number of world wide experts. This was particularly enhanced by the successful CLIC’08 workshop held at CERN. Numerous new ideas, improvements and critical points are arising, establishing the path towards the Conceptual Design Report by 2010.

  1. Liposomes as a gene delivery system

    Directory of Open Access Journals (Sweden)

    C. Ropert

    1999-02-01

    Full Text Available Gene therapy is an active field that has progressed rapidly into clinical trials in a relatively short time. The key to success for any gene therapy strategy is to design a vector able to serve as a safe and efficient gene delivery vehicle. This has encouraged the development of nonviral DNA-mediated gene transfer techniques such as liposomes. Many liposome-based DNA delivery systems have been described, including molecular components for targeting given cell surface receptors or for escaping from the lysosomal compartment. Another recent technology using cationic lipids has been evaluated and has generated substantial interest in this approach to gene transfer.

  2. Auditing Information System : Delivery Product Service

    Directory of Open Access Journals (Sweden)

    Purwoko Purwoko

    2011-05-01

    Full Text Available Purpose of the research is to ensure the securities of information system asset and to ensure if informa-tion system support the operational and data collected was valid. Research method that used in this research were library studies and field studies. Field studies such an observation, questioner, and inter-view. the expected result are founding the weakness of security management control, operational man-agement control, input control, and output control of risk happened in the company. Conclusion of this research are the system on the company work good and there’s no potential risk happened and make an impact to the delivery process of information system.Index Terms - Auditing Information system, Delivery product process.

  3. Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection.

    Science.gov (United States)

    Choi, Bongseo; Moon, Hyojin; Hong, Sung Joon; Shin, Changsik; Do, Yoonkyung; Ryu, Seongho; Kang, Sebyung

    2016-08-23

    In cancer immunotherapy, robust and efficient activation of cytotoxic CD8(+) T cell immune responses is a promising, but challenging task. Dendritic cells (DCs) are well-known professional antigen presenting cells that initiate and regulate antigen-specific cytotoxic CD8(+) T cells that kill their target cells directly as well as secrete IFN-γ, a cytokine critical in tumor rejection. Here, we employed recently established protein cage nanoparticles, encapsulin (Encap), as antigenic peptide nanocarriers by genetically incorporating the OT-1 peptide of ovalbumin (OVA) protein to the three different positions of the Encap subunit. With them, we evaluated their efficacy in activating DC-mediated antigen-specific T cell cytotoxicity and consequent melanoma tumor rejection in vivo. DCs efficiently engulfed Encap and its variants (OT-1-Encaps), which carry antigenic peptides at different positions, and properly processed them within phagosomes. Delivered OT-1 peptides were effectively presented by DCs to naïve CD8(+) T cells successfully, resulting in the proliferation of antigen-specific cytotoxic CD8(+) T cells. OT-1-Encap vaccinations in B16-OVA melanoma tumor bearing mice effectively activated OT-1 peptide specific cytotoxic CD8(+) T cells before or even after tumor generation, resulting in significant suppression of tumor growth in prophylactic as well as therapeutic treatments. A large number of cytotoxic CD8(+) T cells that actively produce both intracellular and secretory IFN-γ were observed in tumor-infiltrating lymphocytes collected from B16-OVA tumor masses originally vaccinated with OT-1-Encap-C upon tumor challenges. The approaches we describe herein may provide opportunities to develop epitope-dependent vaccination systems that stimulate and/or modulate efficient and epitope-specific cytotoxic T cell immune responses in nonpathogenic diseases.

  4. NOVEL PARADIGMS IN MUCOADHESIVE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Deepak Sharma et al

    2012-08-01

    Full Text Available Mucoadhesion is a field of current interest in the design of drug delivery systems. Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Mucoadhesive drug delivery system may be designed to enable prolonged residence time of the dosage form at the site of application or absorption and facilitate an intimate contact of the dosage form with the underline absorption surface. Extending the residence time of a dosage form at a particular site and controlling the release of drug from the dosage form are useful especially for achieving controlled plasma level of the drug as well as improving bioavailability. Application of these 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 present review describes mucoadhesion, mucoadhesive polymers and use of these polymers in designing different types of mucoadhesive gastrointestinal, nasal, ocular, vaginal and rectal drug delivery systems. The research on mucoadhesives, however, is still in its early stage, and further advances need to be made for the successful translation of the concept into practical application in controlled drug delivery.

  5. Liposomal drug delivery systems--clinical applications.

    Science.gov (United States)

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

    2005-03-01

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

  6. Hydrogen storage and delivery system development: Fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Handrock, J.L.; Malinowski, M.E.; Wally, K. [Sandia National Lab., Livermore, CA (United States)

    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.

  7. Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells.

    Science.gov (United States)

    Sherman, Alexandra; Su, Jin; Lin, Shina; Wang, Xiaomei; Herzog, Roland W; Daniell, Henry

    2014-09-04

    Hemophilia A is the X-linked bleeding disorder caused by deficiency of coagulation factor VIII (FVIII). To address serious complications of inhibitory antibody formation in current replacement therapy, we created tobacco transplastomic lines expressing FVIII antigens, heavy chain (HC) and C2, fused with the transmucosal carrier, cholera toxin B subunit. Cholera toxin B-HC and cholera toxin B-C2 fusion proteins expressed up to 80 or 370 µg/g in fresh leaves, assembled into pentameric forms, and bound to GM1 receptors. Protection of FVIII antigen through bioencapsulation in plant cells and oral delivery to the gut immune system was confirmed by immunostaining. Feeding of HC/C2 mixture substantially suppressed T helper cell responses and inhibitor formation against FVIII in mice of 2 different strain backgrounds with hemophilia A. Prolonged oral delivery was required to control inhibitor formation long-term. Substantial reduction of inhibitor titers in preimmune mice demonstrated that the protocol could also reverse inhibitor formation. Gene expression and flow cytometry analyses showed upregulation of immune suppressive cytokines (transforming growth factor β and interleukin 10). Adoptive transfer experiments confirmed an active suppression mechanism and revealed induction of CD4(+)CD25(+) and CD4(+)CD25(-) T cells that potently suppressed anti-FVIII formation. In sum, these data support plant cell-based oral tolerance for suppression of inhibitor formation against FVIII.

  8. Evaluation of Salmonella enterica type III secretion system effector proteins as carriers for heterologous vaccine antigens.

    Science.gov (United States)

    Hegazy, Wael Abdel Halim; Xu, Xin; Metelitsa, Leonid; Hensel, Michael

    2012-03-01

    Live attenuated strains of Salmonella enterica have a high potential as carriers of recombinant vaccines. The type III secretion system (T3SS)-dependent translocation of S. enterica can be deployed for delivery of heterologous antigens to antigen-presenting cells. Here we investigated the efficacy of various effector proteins of the Salmonella pathogenicity island (SPI2)-encoded T3SS for the translocation of model antigens and elicitation of immune responses. The SPI2 T3SS effector proteins SifA, SteC, SseL, SseJ, and SseF share an endosomal membrane-associated subcellular localization after translocation. We observed that all effector proteins could be used to translocate fusion proteins with the model antigens ovalbumin and listeriolysin into the cytosol of host cells. Under in vitro conditions, fusion proteins with SseJ and SteC stimulated T-cell responses that were superior to those triggered by fusion proteins with SseF. However, in mice vaccinated with Salmonella carrier strains, only fusion proteins based on SseJ or SifA elicited potent T-cell responses. These data demonstrate that the selection of an optimal SPI2 effector protein for T3SS-mediated translocation is a critical parameter for the rational design of effective Salmonella-based recombinant vaccines.

  9. Hydrogen storage and delivery system development: Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Handrock, J.L. [Sandia National Labs., Livermore, CA (United States)

    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.

  10. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ

    1996-01-01

    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative co

  11. ORGANOGELS: ADVANCED AND NOVEL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Garg Tarun

    2011-12-01

    Full Text Available Organogel, is a non crystalline, non-glassy thermoreversible (thermoplastic solid material and viscoelastic system, can be regarded as a semi-solid preparation which has an immobilized external apolar phase. The apolar phase gets immobilized within spaces of the three-dimensional networked structure formed due to the physical interactions amongst the self assembled structures of compounds regarded as gelators. Often, these systems are based on self-assembly of the structurant molecules. In general, organogels are thermodynamically stable in nature and have been explored as matrices for the delivery of bioactive agents. Organogels have potential for use in a number of applications, such as in pharmaceuticals, cosmetics, art conservation, and food. An example of formation of an undesired thermoreversible network is the occurrence of wax crystallization in petroleum. In the current manuscript, attempts have been made to understand the properties of organogels, various types of organogelators and some applications of the organogels in controlled delivery.

  12. Chitosan magnetic nanoparticles for drug delivery systems.

    Science.gov (United States)

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

    2016-06-01

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

  13. Recent Advances in Ocular Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Shinobu Fujii

    2011-01-01

    Full Text Available Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient’s and doctor’s convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed.

  14. Drug delivery system and breast cancer cells

    Science.gov (United States)

    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.

  15. TRANSCUTANEOUS DRUG DELIVERY SYSTEM: A COMPREHENSIVE REVIEW

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    Sandhu Premjeet

    2011-12-01

    Full Text Available Conventional drug delivery systems are often not suitable for new protein based and other Therapeutic compounds produced by modern technology. Therefore an alternative Approach to deliver these drugs can be achieved through the skin in the form of transcutaneous drug delivery system. Modern medicine has responded with the development of methods to deliver drug transcutanously (through the skin for therapeutic use as an alternative to traditional route including oral, intravascular, intramuscular, subcutaneous, and sublingual. Transcutaneous drug delivery has many theoretic and practical advantage and disadvantages, and such issues are often a concern for both clinicians and patients. Transcutaneous patches are flexible pharmaceutical preparations of varying sizes, containing one or more active ingredient, intended to be applied to the unbroken skin in order to deliver the active ingredient to the systemic circulation after passing through the skin barriers. A Transcutaneous patch or skin patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Often, this promotes healing to an injured area of the body. In this method, the drug enters the bloodstream directly through skin and it avoid first pass effect. Characterization of Transcutaneous patch are necessary because check it’s quality, size, time of onset & duration, adhesive property, thickness, weight of patch, moisture of content, uniformity & cutaneous toxicological studies. Their requirements for evaluation are HPLC, U.V. spectrophotometer, screw gauge, digital balance, desiccators, thin layer chromatography & K.C. Cell used.

  16. 42 CFR 457.490 - Delivery and utilization control systems.

    Science.gov (United States)

    2010-10-01

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

  17. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

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    Shyamal Kumar Kundu

    2014-01-01

    Full Text Available 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.

  18. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    Science.gov (United States)

    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.

  19. Transdermal drug delivery system: An overview

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    Vaibhav Rastogi

    2012-01-01

    Full Text Available Transdermal drug delivery system (TDDS is one of the systems lying under the category of controlled drug delivery, in which the aim is to deliver the drug through the skin in a predetermined and controlled rate. It has various advantages, like prolonged therapeutic effect, reduced side-effects, improved bioavailability, better patient compliance and easy termination of drug therapy. The stratum corneum is considered as the rate limiting barrier in transdermal permeation of most molecules. There are three main routes of drug penetration, which include the appendageal, transcellular and intercellular routes. Skin age, condition, physicochemical factors and environmental factors are some factors that are to be considered while delivering drug through this route. Basic components of TDDS include polymer matrix, membrane, drug, penetration enhancers, pressure-sensitive adhesives, backing laminates, release liner, etc. Transdermal patches can be divided into various systems like reservoir system, matrix system and micro-reservoir system, which are used to incorporate the active ingredients into the circulatory system via the skin. After preparation of transdermal patches, consistent methodology are adopted to test the adhesion properties, physicochemical properties, in vitro drug release studies, in vitro skin permeation studies, skin irritation studies and stability studies. According to the duration of therapy, various drugs are commercially available in the form of transdermal patches.

  20. Ultrasound-mediated nail drug delivery system.

    Science.gov (United States)

    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 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.

  1. Advanced drug delivery systems: Nanotechnology of health design A review

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    Javad Safari

    2014-04-01

    Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.

  2. Systemic and mucosal immune responses to sublingual or intramuscular human papilloma virus antigens in healthy female volunteers.

    Directory of Open Access Journals (Sweden)

    Zhiming Huo

    Full Text Available The sublingual route has been proposed as a needle-free option to induce systemic and mucosal immune protection against viral infections. In a translational study of systemic and mucosal humoral immune responses to sublingual or systemically administered viral antigens, eighteen healthy female volunteers aged 19-31 years received three immunizations with a quadravalent Human Papilloma Virus vaccine at 0, 4 and 16 weeks as sublingual drops (SL, n = 12 or intramuscular injection (IM, n = 6. IM antigen delivery induced or boosted HPV-specific serum IgG and pseudovirus-neutralizing antibodies, HPV-specific cervical and vaginal IgG, and elicited circulating IgG and IgA antibody secreting cells. SL antigens induced ~38-fold lower serum and ~2-fold lower cervical/vaginal IgG than IM delivery, and induced or boosted serum virus neutralizing antibody in only 3/12 subjects. Neither route reproducibly induced HPV-specific mucosal IgA. Alternative delivery systems and adjuvants will be required to enhance and evaluate immune responses following sublingual immunization in humans.ClinicalTrials.govNCT00949572.

  3. A Review: Transdermal Drug Delivery System: A Tool For Novel Drug Delivery System

    Directory of Open Access Journals (Sweden)

    NIKHIL SHARMA

    2011-06-01

    Full Text Available The human skin is a readily accessible surface for drug delivery. Skin of an average adult body covers a surface of approximately 2 m2 and receives about one-third of the blood circulating through the body. Over the past decades, developing controlled drug delivery has become increasingly important in the pharmaceutical industry. The human skin surface is known to contain, on an average, 10- 70 hair follicles and 200-250 sweat ducts on every square centimeters of the skin area. It is one of the most readily accessible organs of the human body. There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, the skin, in particular the stratum corneum, poses a formidable barrier to drug penetration thereby limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drugs for which topical and transdermal delivery is a viable option. During the past decade, the number of drugs formulated in the patches has hardly increased, and there has been little change in the composition of the patch systems. Modifications have been mostly limited to refinements of the materials used. The present review article explores the overall study on transdermal drug delivery system (TDDS which leads to novel drug delivery system (NDDS.

  4. GLIMPS sensor and taggant delivery systems

    Science.gov (United States)

    Nunan, Scott C.; Coakley, Peter G.; Niederhaus, Gregory A.; Lum, Chris

    2001-02-01

    A system has been developed for delivering and attaching a sensor payload to a target using a standard 40-mm grenade launcher. The GLIMPS projectile is intended to be a general purpose delivery system for a variety of sensor payloads including visual, acoustic, and chemical sensors. The GLIMPS projectile flight characteristics are similar to existing 40-mm rounds, with a useful range of up to 300 m. The projectile incorporates an attachment mechanism, a shock mitigation system, a power source, and a telemetry system for transmission of sensor data at up to 1/4 mile range. A second design is also being considered. It is a small taggant projectile that uses an adhesive to attach a tracking transmitter or other small payload to a vehicle at up to 50 m range. While initially developed as a military system, both projectiles can be used to enhance law enforcement operations.

  5. Systemic and mucosal immune response induced by transcutaneous immunization using Hepatitis B surface antigen-loaded modified liposomes.

    Science.gov (United States)

    Mishra, Dinesh; Mishra, Pradyumna Kumar; Dubey, Vaibhav; Nahar, Manoj; Dabadghao, Sunil; Jain, N K

    2008-04-23

    We have evaluated the efficiency of novel modified liposomes (ethosomes) for transcutaneous immunization (TCI) against Hepatitis B. Antigen-loaded ethosomes were prepared and characterized for shape, lamellarity, fluidity, size distribution, and entrapment efficiency. Spectral bio-imaging and flow cytometric studies showed efficient uptake of Hepatitis B surface antigen (HBsAg)-loaded ethosomes by murine dendritic cells (DCs) in vitro, reaching a peak by 180 min. Transcutaneous delivery potential of the antigen-loaded system using human cadaver skin demonstrated a much higher skin permeation of the antigen in comparison to conventional liposomes and soluble antigen preparation. Topically applied HBsAg-loaded ethosomes in experimental mice showed a robust systemic and mucosal humoral immune response compared to intramuscularly administered alum-adsorbed HBsAg suspension, topically applied plain HBsAg solution and hydroethanolic (25%) HBsAg solution. The ability of the antigen-pulsed DCs to stimulate autologous peripheral blood lymphocytes was demonstrated by BrdU assay and a predominantly TH1 type of immune response was observed by multiplex cytometric bead array analysis. HBsAg-loaded ethosomes are able to generate a protective immune response and their ability to traverse and target the immunological milieu of the skin may find a potential application in the development of a transcutaneous vaccine against Hepatitis B virus (HBV).

  6. Self-assembled PEG-b-PDPA-b-PGEM copolymer nanoparticles as protein antigen delivery vehicles to dendritic cells: preparation, characterization and cellular uptake

    Science.gov (United States)

    Li, Pan; Zhou, Junhui; Huang, Pingsheng; Zhang, Chuangnian; Wang, Weiwei; Li, Chen; Kong, Deling

    2017-01-01

    Antigen uptake by dendritic cells (DCs) is a key step for initiating antigen-specific T cell immunity. In the present study, novel synthetic polymeric nanoparticles were prepared as antigen delivery vehicles to improve the antigen uptake by DCs. Well-defined cationic and acid-responsive copolymers, monomethoxy poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate)-block-poly(2-(guanidyl) ethyl methacrylate) (mPEG-b-PDPA-b-PGEM, PEDG) were synthesized by reversible addition-fragmentation chain transfer polymerization of 2-(diisopropylamino)ethyl methacrylate) and N-(tert-butoxycarbonyl) amino ethyl methacrylate monomers, followed by deprotection of tert-butyl protective groups and guanidinylation of obtained primary amines. 1H NMR, 13C NMR and GPC results indicated the successful synthesis of well-defined PEDG copolymers. PEDG copolymers could self-assemble into nanoparticles in aqueous solution, which were of cationic surface charges and showed acid-triggered disassembly contributed by PGEM and PDPA moieties, respectively. Significantly, PEDG nanoparticles could effectively condense with negatively charged model antigen ovalbumin (OVA) to form OVA/PEDG nanoparticle formulations with no influence on its secondary and tertiary structures demonstrating by far-UV circular dichroism and UV–vis spectra. In vitro antigen cellular uptake by bone marrow DCs (BMDCs) indicated using PEDG nanoparticles as antigen delivery vehicles could significantly improve the antigen uptake efficiency of OVA compared with free OVA or the commercialized Alum adjuvant. Moreover, as the surface cationic charges of OVA/PEDG nanoparticle formulations reduced, the uptake efficiency decreased correspondingly. Collectively, our work suggests that guanidinylated, cationic and acid-responsive PEDG nanoparticles represent a new kind of promising antigen delivery vehicle to DCs and hold great potential to serve as immunoadjuvants in the development of vaccines. PMID:28149525

  7. Multifunctional non-viral delivery systems based on conjugated polymers.

    Science.gov (United States)

    Yang, Gaomai; Lv, Fengting; Wang, Bing; Liu, Libing; Yang, Qiong; Wang, Shu

    2012-12-01

    Multifunctional nanomaterials with simultaneous therapeutic and imaging functions explore new strategies for the treatment of various diseases. Conjugated polymers (CPs) are considered as novel candidates to serve as multifunctional delivery systems due to their high fluorescence quantum yield, good photostability, and low cytotoxicity. Highly sensitive sensing and imaging properties of CPs are well reviewed, while the applications of CPs as delivery systems are rarely covered. This feature article mainly focuses on CP-based multifunctional non-viral delivery systems for drug, protein, gene, and cell delivery. Promising directions for the further development of CP-based delivery systems are also discussed.

  8. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy

    Science.gov (United States)

    Kranz, Lena M.; Diken, Mustafa; Haas, Heinrich; Kreiter, Sebastian; Loquai, Carmen; Reuter, Kerstin C.; Meng, Martin; Fritz, Daniel; Vascotto, Fulvia; Hefesha, Hossam; Grunwitz, Christian; Vormehr, Mathias; Hüsemann, Yves; Selmi, Abderraouf; Kuhn, Andreas N.; Buck, Janina; Derhovanessian, Evelyna; Rae, Richard; Attig, Sebastian; Diekmann, Jan; Jabulowsky, Robert A.; Heesch, Sandra; Hassel, Jessica; Langguth, Peter; Grabbe, Stephan; Huber, Christoph; Türeci, Özlem; Sahin, Ugur

    2016-06-01

    Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.

  9. P System antigenic determiners expression in Ascaris lumbricoides

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    Ponce De León Patricia

    2003-01-01

    Full Text Available The P System antigens have been detected in numerous parasites, bacterias and viruses, nevertheless the clinical significance is still unknown. The aim was to study the presence of P1 antigenic determiners in A. lumbricoides extracts by means of the use of 6 different monoclonal antibodies of well-known concentrations and Ig class. We worked with 14 A. lumbricoides extracts. Inhibition Agglutination Test was made in a bromelin enzymatic medium and 4 masculineC temperature. Titre, Score and Sensitivity Parameter were determined for each monoclonal antibody against red cells suspension used as revealing system. Ten extracts inhibited the agglutination of all anti P1 monoclonal antibodies. The 4 remaining extracts only inhibited the agglutination of some of them. It is demonstrated that the extracts have P1 activity. This activity is independent of titre, Score, Sensitivity Parameter, concentration and Ig class and it depends on the epitope at which the monoclonal antibody is directed.

  10. [Drug delivery systems for intraocular applications].

    Science.gov (United States)

    Bourges, J-L; Touchard, E; Kowalczuk, L; Berdugo, M; Thomas-Doyle, A; Bochot, A; Gomez, A; Azan, F; Gurny, R; Behar-Cohen, F

    2007-12-01

    Numerous drug delivery systems (DDSs) can be used as intraocular tools to provide a sustained and calibrated release for a specific drug. Great progress has been made on the design, biocompatibility, bioavailability, and efficacy of DDSs. Although several of them are undergoing clinical trials, a few are already on the market and could be of a routine use in clinical practice. Moreover, miniaturization of the implants makes them less and less traumatic for the eye tissues and some DDSs are now able to target certain cells or tissues specifically. An overview of ocular implants with therapeutic application potentials is provided.

  11. Mucoadhesive drug delivery system: An overview

    Directory of Open Access Journals (Sweden)

    Bindu M Boddupalli

    2010-01-01

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

  12. Intracellular chromobody delivery by mesoporous silica nanoparticles for antigen targeting and visualization in real time.

    Science.gov (United States)

    Chiu, Hsin-Yi; Deng, Wen; Engelke, Hanna; Helma, Jonas; Leonhardt, Heinrich; Bein, Thomas

    2016-05-13

    Chromobodies have recently drawn great attention as bioimaging nanotools. They offer high antigen binding specificity and affinity comparable to conventional antibodies, but much smaller size and higher stability. Chromobodies can be used in live cell imaging for specific spatio-temporal visualization of cellular processes. To date, functional application of chromobodies requires lengthy genetic manipulation of the target cell. Here, we develop multifunctional large-pore mesoporous silica nanoparticles (MSNs) as nanocarriers to directly transport chromobodies into living cells for antigen-visualization in real time. The multifunctional large-pore MSNs feature high loading capacity for chromobodies, and are efficiently taken up by cells. By functionalizing the internal MSN surface with nitrilotriacetic acid-metal ion complexes, we can control the release of His6-tagged chromobodies from MSNs in acidified endosomes and observe successful chromobody-antigen binding in the cytosol. Hence, by combining the two nanotools, chromobodies and MSNs, we establish a new powerful approach for chromobody applications in living cells.

  13. Superiority of needle-free transdermal plasmid delivery for the induction of antigen-specific IFNgamma T cell responses in the dog.

    Science.gov (United States)

    Goubier, A; Fuhrmann, L; Forest, L; Cachet, N; Evrad-Blanchard, M; Juillard, V; Fischer, L

    2008-04-24

    Although successful needle-free DNA vaccination has been described on several occasions, the true benefit of this delivery technology over needle-based injections for DNA vaccination of dogs has not yet been documented. We conducted a side-by-side comparison of needle-free transdermal plasmid delivery vs. intramuscular vs. intradermal needle-based delivery of the same plasmid in dogs. Our data confirmed the importance of the route of plasmid delivery and further established the unique potential of needle-free transdermal plasmid delivery to elicit strong antigen-specific, hTyr-specific IFNgamma T in the dog. Further, this study demonstrated that properly enabled DNA vaccination has the potential to trigger very significant cell-based immune responses in dogs, establishing needle-free transdermal plasmid delivery as a critical technology for successful immunotherapy of cancer and/or chronic infectious diseases in companion animal medicine.

  14. Comparison of polystyrene nanoparticles and UV-inactivated antigen-displaying adenovirus for vaccine delivery in mice

    Science.gov (United States)

    2013-01-01

    Background Inert nanoparticles are attracting attention as carriers for protein-based vaccines. Here we evaluate the immunogenicity of the model antigen ovalbumin delivered on polystyrene particles and directly compare particulate delivery with adenovirus-based immunization. Findings Mice were vaccinated with soluble ovalbumin, ovalbumin-coated polystyrene particles of different sizes, or an adenovirus-based expression-display vector that encodes and displays a pIX-ovalbumin fusion protein. Antibody responses were clearly higher when ovalbumin was administered on polystyrene particles compared to soluble protein administration, regardless of the particle size. Compared to adenovirus-based immunization, antibody levels were lower if an equivalent amount of protein was delivered, and no cellular immune response was detectable. Conclusions We demonstrate in a side-by-side comparison that inert nanoparticles allow for the reduction of the administered antigen amount compared to immunization with soluble protein and induce strongly enhanced antibody responses, but responses are lower compared to adenovirus-based immunization. PMID:23560981

  15. Antigen-displaying lipid-enveloped PLGA nanoparticles as delivery agents for a Plasmodium vivax malaria vaccine.

    Science.gov (United States)

    Moon, James J; Suh, Heikyung; Polhemus, Mark E; Ockenhouse, Christian F; Yadava, Anjali; Irvine, Darrell J

    2012-01-01

    The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) "enveloped" by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

  16. Antigen-displaying lipid-enveloped PLGA nanoparticles as delivery agents for a Plasmodium vivax malaria vaccine.

    Directory of Open Access Journals (Sweden)

    James J Moon

    Full Text Available The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide acid (PLGA "enveloped" by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA, was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs. Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

  17. Targeted delivery of an antigenic peptide to the endoplasmic reticulum: application for development of a peptide therapy for ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    Hui-Chun Yu

    Full Text Available The development of suitable methods to deliver peptides specifically to the endoplasmic reticulum (ER can provide some potential therapeutic applications of such peptides. Ankylosing spondylitis (AS is strongly associated with the expression of human leukocytic antigen-B27 (HLA-B27. HLA-B27 heavy chain (HC has a propensity to fold slowly resulting in the accumulation of misfolded HLA-B27 HC in the ER, triggering the unfolded protein response, and forming a homodimer, (B27-HC2. Natural killer cells and T-helper 17 cells are then activated, contributing to the major pathogenic potentials of AS. The HLA-B27 HC is thus an important target, and delivery of an HLA-B27-binding peptide to the ER capable of promoting HLA-B27 HC folding is a potential mechanism for AS therapy. Here, we demonstrate that a His6-ubiquitin-tagged Tat-derived peptide (THU can deliver an HLA-B27-binding peptide to the ER promoting HLA-B27 HC folding. The THU-HLA-B27-binding peptide fusion protein crossed the cell membrane to the cytosol through the Tat-derived peptide. The HLA-B27-binding peptide was specifically cleaved from THU by cytosolic ubiquitin C-terminal hydrolases and subsequently transported into the ER by the transporter associated with antigen processing. This approach has potential application in the development of peptide therapy for AS.

  18. Nanoemulsion: A new concept of delivery system

    Directory of Open Access Journals (Sweden)

    Nitin Sharma

    2010-01-01

    Full Text Available Nanoemulsion has been identified as a promising delivery system for various drugs including biopharmaceuticals. Nanoemulsion is a heterogeneous system composed of one immiscible liquid dispersed as droplets within another liquid. The droplets size of nano emulsion is between 20 to 500 nm. Diameter and surface properties of droplets of nanoemulsion plays an important role in the biological behavior of the formulation. Small droplet sizes lead to transparent emulsions so that product appearance is not altered by the addition of an oil phase. In this paper various aspects of nanoemulsion have been discussed including advantages, disadvantages and methods of preparation. Furthermore new approaches of stability of formulation, effect of types and concentration of surfactant, process variables and method are also discussed to improve the stability of nanoemulsion formulation

  19. An Insight into Ophthalmic Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Rathore K. S.

    2009-04-01

    Full Text Available Promising management of eye ailments take off effective concentration of drug at the eye for sufficient period of time. Dosage forms are administered directly to eye for localized ophthalmic therapy. Most of the treatments call for the topical administration of ophthalmic active drugs to the tissues around the ocular cavity. Conventional ophthalmic drug delivery systems including eye drops, ophthalmic ointments, are no longer sufficient to encounter eye diseases. This article reviews the constraints with conventional ocular therapy and explores various novel approaches like in-situ gel, ocular films or ocuserts, nanosuspension, collagen shields, latex systems, nanoparticles, liposomes, niosomes, iontophorosis, eye implants, etc to improve the ophthalmic bioavailability of drugs to the anterior chamber of the eye.

  20. A telemedicine health care delivery system

    Science.gov (United States)

    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.

  1. Ternary particles for effective vaccine delivery to the pulmonary system

    Science.gov (United States)

    Terry, Treniece La'shay

    Progress in the fields of molecular biology and genomics has provided great insight into the pathogenesis of disease and the defense mechanisms of the immune system. This knowledge has lead to the classification of an array of abnormal genes, for which, treatment relies on cellular expression of proteins. The utility of DNA-based vaccines hold great promise for the treatment of genetically based and infectious diseases, which ranges from hemophilia, cystic fibrosis, and HIV. Synthetic delivery systems consisting of cationic polymers, such as polyethylenimine (PEI), are capable of condensing DNA into compact structures, maximizing cellular uptake of DNA and yielding high levels of protein expression. To date, short term expression is a major obstacle in the development of gene therapies and has halted their expansion in clinical applications. This study intends to develop a sustained release vaccine delivery system using PLA-PEG block copolymers encapsulating PEI:DNA polyplexes. To enhance the effectiveness of such DNA-based vaccines, resident antigen presenting cells, macrophages and dendritic cells, will be targeted within the alveoli regions of the lungs. Porous microspheres will be engineered with aerodynamic properties capable of achieving deep lung deposition. A fabrication technique using concentric nozzles will be developed to produce porous microspheres. It was observed that modifications in the dispersed to continuous phase ratios have the largest influence on particle size distributions, release rates and encapsulation efficiency which ranged form 80--95% with fourteen days of release. Amphiphilic block copolymers were also used to fabricate porous microspheres. The confirmation of PEG within the biodegradable polymer backbone was found to have a tremendous impact on the microsphere morphology and encapsulation efficiency which varied from 50--90%. Porous microspheres were capable of providing sustained gene expression when tested in vitro using the

  2. Leadership Dynamics Promoting Systemic Reform for Inclusive Service Delivery

    Science.gov (United States)

    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…

  3. Transdermal Patches: A Complete Review on Transdermal Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Patel DS

    2012-03-01

    Full Text Available Today about 70% of drugs are taken orally and are found not to be as effective as desired. To improvesuch characters transdermal drug delivery system was emerged. Transdermal drug delivery system(TDDS provides a means to sustain drug release as well as reduce the intensity of action and thusreduce the side effects associated with its oral therapy and differs from traditional topical drug delivery.Transdermal Drug Delivery System is the system in which the delivery of the active ingredients of thedrug occurs by means of skin. Several important advantages of transdermal drug delivery are limitationof hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steadyplasma level of the drug. Various types of transdermal patches are used to incorporate the activeingredients into the circulatory system via skin. This review article covers a brief outline of theprinciples of transdermal permeation, various components of transdermal patch, approaches oftransdermal patch, evaluation of transdermal system, its application with its limitation.

  4. Near-infrared labeled, ovalbumin loaded polymeric nanoparticles based on a hydrophilic polyester as model vaccine : In vivo tracking and evaluation of antigen-specific CD8+ T cell immune response

    NARCIS (Netherlands)

    Rahimian, Sima; Kleinovink, Jan Willem; Fransen, Marieke F.; Mezzanotte, Laura; Gold, Henrik; Wisse, Patrick; Overkleeft, Hermen; Amidi, Maryam; Jiskoot, Wim; Lo¨wik, Clemens W.; Ossendorp, Ferry; Hennink, Wim E.

    2015-01-01

    Particulate antigen delivery systems aimed at the induction of antigen-specific T cells form a promising approach in immunotherapy to replace pharmacokinetically unfavorable soluble antigen formulations. In this study, we developed a delivery system using the model protein antigen ovalbumin (OVA) en

  5. The Future of North Korean Nuclear Delivery Systems

    Science.gov (United States)

    2015-01-01

    national security policy. NORTH KOREA’S NUCLEAR FUTURES SERIES US-KOREA INSTITUTE AT SAIS The Future of North Korean Nuclear Delivery Systems JOHN...NORTH KOREA’S NUCLEAR FUTURES SERIES US-KOREA INSTITUTE AT SAIS The Future of North Korean Nuclear Delivery Systems JOHN SCHILLING HENRY KAN...REPORT TYPE 3. DATES COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE The Future of North Korean Nuclear Delivery Systems 5a. CONTRACT

  6. Polymers for Pharmaceutical Packaging and Delivery Systems

    DEFF Research Database (Denmark)

    Fristrup, Charlotte Juel

    -bromoisobutyrate initiating sites. Each modification step of PEEK as well as grafting of poly(ethylene glycol) methacrylate (PEGMA) was followed and confirmed by Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy, water contact angle (WCA) measurements, and Thermal Gravimetric Analysis....... X-ray Photoelectron Spectroscopy also confirmed the presence of the poly(PEGMA) grafts on the PEEK surface by comparing the C/O ratio and the chemical composition after each modification step. The surface topography was evaluated by Atomic Force Microscopy. Polypropylene (PP) is one of the polymeric...... materials of interest for pharmaceutical packaging and delivery systems. Confocal fluorescence microscopy studies and stability studies with insulin aspart (AspB28 insulin) were conducted to evaluate the impact of modified PP compared to unmodified PP. In contrast to PEEK, PP did not contain any functional...

  7. Synthetic polyacrylate polymers as particulate intranasal vaccine delivery systems for the induction of mucosal immune response.

    Science.gov (United States)

    Zaman, Mehfuz; Simerska, Pavla; Toth, Istvan

    2010-04-01

    The nasal route as a site of vaccine delivery for both local and systemic effect is currently of considerable interest. The administration of vaccines to mucosal surfaces such as the nasopharynx associated lymphoid tissues confers many advantages since the nasal mucosa is a primary site through which most inhaled antigens are encountered. However, the success of intranasally delivered mucosal vaccines is limited by lack of effective vaccine formulations or delivery systems suitable for use in humans. This review provides a brief overview of the mucosal immune system at the nasal surface, enhancement techniques for induction of mucosal immune response after intranasal administration of particulate systems and an explanation of the inherent properties of polyacrylate polymer-based particulate systems that may facilitate mucosal immune responses.

  8. STRATEGIES AND PROSPECTS OF NASAL DRUG DELIVERY SYSTEMS

    Directory of Open Access Journals (Sweden)

    Gannu Praveen Kumar

    2012-03-01

    Full Text Available The recent advancement of nasal drug delivery systems has increased enormously and is gaining significant importance. Intranasal therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. The non-invasive delivery of nasal drug delivery systems made to exploit for the development of successful treatment. The advantages, disadvantages, mechanism of action and application of nasal drug delivery system in local delivery, systematic delivery, nasal vaccines and CNS delivery are explained lucidly. The relevant aspects of biological, physicochemical and pharmaceutical factors of nasal cavity that must be considered during the process of discovery and development of new drugs for nasal delivery as well as in their incorporation into appropriate nasal pharmaceutical formulations are also discussed. Nasal route is more suitable for those drugs which cannot be administered orally due to gastric degradation or hepatic first pass metabolism of the drug. Intranasal drug delivery is found much promising route for administration of peptides and protein drugs. Much has been investigated and much more are to be investigated for the recent advancement of nasal drug delivery systems.

  9. Dextran-based microspheres as controlled delivery systems for proteins

    NARCIS (Netherlands)

    Vlugt-Wensink, K.D.F.

    2007-01-01

    Dextran-based microspheres as controlled delivery systems for proteins Dextran based microspheres are investigated as controlled delivery system for proteins. Microspheres were prepared by polymerization of dex-HEMA in an aqueous two-phase system of dex-HEMA and PEG. Protein loaded microspheres are

  10. MICROENCAPSULATION: AN INDISPENSABLE TECHNOLOGY FOR DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Malakar Jadupati

    2012-04-01

    Full Text Available In this review, the various new and well established technologies relevant to the controlled and targeted drug delivery systems have been precisely discussed. A perfectly designed controlled drug delivery system can be of huge advantage towards solving problems concerning to the targeting of drug to a specific organ or tissue and controlling the rate of drug delivery at the target site. Novel drug delivery systems have various advantages over other conventional drug therapy. In which microencapsulation is one approach for achieving the novel drug delivery dosage forms such as sustained release and controlled release, though the development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and focus the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. Our objective is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to elucidate the application of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

  11. Advanced drug delivery systems: Nanotechnology of health design A review

    OpenAIRE

    Javad Safari; Zohre Zarnegar

    2014-01-01

    Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements ...

  12. Polymer hydrogels as optimized delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Batista, Jorge G.S.; Varca, Gustavo H.C.; Ferraz, Caroline C.; Garrido, Gabriela P.; Diniz, Bruna M.; Carvalho, Vinicius S.; Lugao, Ademar B., E-mail: jorgegabriel@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Hydrogels are formed by polymers capable of absorbing large quantities of water. They consist of one or more three-dimensionally structured polymer networks formed by macromolecular chains linked by covalent bonds-crosslinks - and physical interactions. The application of hydrogels, has been widely studied. Biodegradable synthetic or natural polymers such as chitosan, starch and poly-lactic-co-glycolic acid, have properties that allow the development of biodegradable systems for drug and nutraceutics delivery. This study aimed to develop polymeric hydrogels based on polyvinyl alcohol, polyacrylamide and polyvinylpyrrolidone using ionizing radiation in order to develop hydrogels for improved loading and release of compounds. Polymer solutions were solubilized in water and poured into thermoformed packages. After sealing, the material was subjected to γ-irradiation at 25kGy. The samples were assayed by means of mechanical properties, gel fraction and swelling degree. Nanostructure characterization was performed using Flory's equation to determine crosslinking density. The systems developed showed swelling degree and adequate mechanical resistance. The nanostructure evaluation showed different results for each system demonstrating the need of choosing the polymer based on the specific properties of each material. (author)

  13. REVIEW ON ADVANCES IN COLON TARGETED DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Sunena Sethi, SL Harikumar* and Nirmala

    2012-09-01

    Full Text Available The colon is the terminal part of the GIT which has gained in recent years as a potential site for delivery of various novel therapeutic drugs, i.e. peptides. However, colon is rich in microflora which can be used to target the drug release in the colon. Colon is a site where both local and systemic drug delivery can take place. Local delivery allows the topical treatment of inflammatory bowel disease. If drug can be targeted directly into the colon, treatment can become more effective and side effects can be minimized. These systemic side effects can be minimized by primary approaches for CDDS (Colon specific drug delivery namely prodrugs, pH and time dependent systems and microbially triggered system which gained limited success and have limitations as compared with recently new CDDS namely pressure controlled colon delivery capsules (PCDCS, CODESTM (Novel colon targeted delivery system osmotic controlled drug delivery system, Pulsincap system, time clock system, chronotropic system. This review is to understand the pharmaceutical approaches to colon targeted drug delivery systems for better therapeutic action without compromising on drug degradation (or its low bioavailability.

  14. NASAL IN SITU GEL: A NOVEL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Dhrupesh panchal

    2012-06-01

    Full Text Available Over the past few decades, advances in the in situ gel technologies have spurred development in manymedical and biomedical applications including controlled drug delivery. Many novel in situ gel baseddelivery matrices have been designed and fabricated to fulfill the ever increasing needs of thepharmaceutical and medical fields. In situ gelling systems are liquid at room temperature but undergogelation when in contact with body fluids or change in pH. In situ gel forming drug delivery is a type ofmucoadhesive drug delivery system. The formation of gel depends on factors like temperaturemodulation, pH change, presence of ions and ultraviolet irradiation from which the drug gets released ina sustained and controlled manner. Nasal delivery is a promising drug delivery option where commondrug administrations such as intravenous, intramuscular or oral are inapplicable. Recently, it has beenshown that many drugs have better bioavailability by nasal route than the oral route. This has beenattributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled withavoidance of hepatic first-pass elimination, gut wall metabolism and/or destruction in thegastrointestinal tract. The physiology of the nose presents obstacles but offers a promising route for noninvasivesystemic delivery of numerous therapies and debatably drug delivery route to the brain. Thusthis review focuses on nasal drug delivery, various aspects of nasal anatomy and physiology, nasal drugabsorption mechanisms, various nasal drug delivery systems and their applications in drug delivery.

  15. Tumor Destruction and In Situ Delivery of Antigen Presenting Cells Promote Anti-Neoplastic Immune Responses: Implications for the Immunotherapy of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Manfredi AA

    2004-07-01

    Full Text Available Antigen presenting cells (APCs activate helper and cytotoxic T cells specific for antigens expressed by tissue cells, including neoplastic cells. This event occurs after the antigen transfer from tissue cells to APC, and is referred to as "cross-presentation". The number and the state of activation of APC in the tumor control the outcome of cross-presentation, including the establishment of protective immune responses. Cell death favors cross-presentation. Cancer cells normally die, either spontaneously or as a consequence of targeted therapies. The transfer of tumor antigens from dying tumor cells to APCs in vivo, exploiting the cross-presentation pathway, has the potential of yielding novel immunotherapeutic strategies. Their success will depend on at least two factors: the induction of synchronized cell death in the tumor, and the recruitment of activated dendritic cells in the tumor. Under normal conditions, pancreatic cancer represents a privileged environment; its profound chemoresistance reflects limited apoptosis after chemotherapy. Moreover, it usually contains only a few cells endowed with APC function. Endoscopic ultrasonography offers attractive possibilities of circumventing this privilege, including the delivery of ultrasound, radiofrequency or radiation in order to destroy the tumor and the delivery in situ of autologous APC or appropriate chemotactic signals. In general, loco-regional approaches offer the possibility of using the tumor of each patient as a complex antigen source, thus limiting the risk of tumor escape and reducing the need for extensive ex vivo handling of the neoplasm and of the patient APCs.

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

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe...... biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral...... delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract...

  17. Guidelines for Psychological Practice in Health Care Delivery Systems

    Science.gov (United States)

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

    OpenAIRE

    Meng, Ellis; Hoang, Tuan

    2012-01-01

    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.

  19. siRNA delivery with lipid-based systems

    DEFF Research Database (Denmark)

    Foged, Camilla

    2012-01-01

    in vivo, toxicity and non-specific stimulation of the immune system. To optimally design and tailor the lipidic systems for siRNA delivery, better insight is needed into the mechanisms of cell delivery. More specifically, further clarification is need regarding the nature of cell surface interactions...

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

    Science.gov (United States)

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

    2013-06-28

    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.

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

    Science.gov (United States)

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

    2010-01-01

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

  2. Controlled drug delivery systems: past forward and future back.

    Science.gov (United States)

    Park, Kinam

    2014-09-28

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

  3. Employing Escherichia coli-derived outer membrane vesicles as an antigen delivery platform elicits protective immunity against Acinetobacter baumannii infection

    Science.gov (United States)

    Huang, Weiwei; Wang, Shijie; Yao, Yufeng; Xia, Ye; Yang, Xu; Li, Kui; Sun, Pengyan; Liu, Cunbao; Sun, Wenjia; Bai, Hongmei; Chu, Xiaojie; Li, Yang; Ma, Yanbing

    2016-11-01

    Outer membrane vesicles (OMVs) have proven to be highly immunogenic and induced an immune response against bacterial infection in human clinics and animal models. We sought to investigate whether engineered OMVs can be a feasible antigen-delivery platform for efficiently inducing specific antibody responses. In this study, Omp22 (an outer membrane protein of A. baumannii) was displayed on E. coli DH5α-derived OMVs (Omp22-OMVs) using recombinant gene technology. The morphological features of Omp22-OMVs were similar to those of wild-type OMVs (wtOMVs). Immunization with Omp22-OMVs induced high titers of Omp22-specific antibodies. In a murine sepsis model, Omp22-OMV immunization significantly protected mice from lethal challenge with a clinically isolated A. baumannii strain, which was evidenced by the increased survival rate of the mice, the reduced bacterial burdens in the lung, spleen, liver, kidney, and blood, and the suppressed serum levels of inflammatory cytokines. In vitro opsonophagocytosis assays showed that antiserum collected from Omp22-OMV-immunized mice had bactericidal activity against clinical isolates, which was partly specific antibody-dependent. These results strongly indicated that engineered OMVs could display a whole heterologous protein (~22 kDa) on the surface and effectively induce specific antibody responses, and thus OMVs have the potential to be a feasible vaccine platform.

  4. Prostate stem cell antigen antibody-conjugated multiwalled carbon nanotubes for targeted ultrasound imaging and drug delivery.

    Science.gov (United States)

    Wu, Huixia; Shi, Haili; Zhang, Hao; Wang, Xue; Yang, Yan; Yu, Chao; Hao, Caiqin; Du, Jing; Hu, He; Yang, Shiping

    2014-07-01

    Multiwalled carbon nanotubes (MWCNTs) are cut short and grafted with polyethylenimine (PEI) for further covalent conjugation to fluorescein isothiocyanate (FITC) and prostate stem cell antigen (PSCA) monoclonal antibody (mAb). The in vitro and in vivo toxicity data reveal that the as-prepared CNT-PEI(FITC)-mAb has good biocompatibility. Combined flow cytometry and confocal luminescence imaging experiments confirm that the CNT-PEI(FITC)-mAb can specifically target the cancer cells which overexpress PSCA. The results of in vitro and in vivo ultrasound (US) imaging indicate that CNT-PEI(FITC)-mAb has great potential to be used as a targeted US contrast agent. The in vivo anti-cancer efficacy testing using PC-3 tumor-bearing mice as animal models demonstrates that CNT-PEI(FITC)-mAb can targetedly deliver drug to the tumors and suppress tumor growth. Findings from this study suggest that the CNT-PEI(FITC)-mAb could be used as a multifunctional platform for simultaneous US imaging and drug delivery applications.

  5. Water delivery in the Early Solar System

    CERN Document Server

    Dvorak, Rudolf; Süli, Áron; Sándor, Zsolt; Galiazzo, Mattia; Pilat-Lohinger, Elke

    2015-01-01

    As part of the national scientific network 'Pathways to Habitable Worlds' the delivery of water onto terrestrial planets is a key question since water is essential for the development of life as we know it. After summarizing the state of the art we show some first results of the transport of water in the early Solar System for scattered main belt objects. Hereby we investigate the questions whether planetesimals and planetesimal fragments which have gained considerable inclination due to the strong dynamical interactions in the main belt region around 2 AU can be efficient water transporting vessels. The Hungaria asteroid group is the best example that such scenarios are realistic. Assuming that the gas giants and the terrestrial planets are already formed, we monitor the collisions of scattered small bodies containing water (in the order of a few percent) with the terrestrial planets. Thus we are able to give a first estimate concerning the respective contribution of such bodies to the actual water content i...

  6. Marine Origin Polysaccharides in Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Matias J. Cardoso

    2016-02-01

    Full Text Available 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.

  7. Pharmacokinetics of formulated tenoxicam transdermal delivery systems.

    Science.gov (United States)

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

    2008-01-01

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

  8. Controlled drug delivery systems towards new frontiers in patient care

    CERN Document Server

    Rossi, Filippo; Masi, Maurizio

    2016-01-01

    This book offers a state-of-the-art overview of controlled drug delivery systems, covering the most important innovative applications. The principles of controlled drug release and the mechanisms involved in controlled release are clearly explained. The various existing polymeric drug delivery systems are reviewed, and new frontiers in material design are examined in detail, covering a wide range of polymer modification techniques. The concluding chapter is a case study focusing on use of a drug-eluting stent. The book is designed to provide the reader with a complete understanding of the mechanisms and design of controlled drug delivery systems, and to this end includes numerous step-by-step tutorials. It illustrates how chemical engineers can advance medical care by designing polymeric delivery systems that achieve either temporal or spatial control of drug delivery and thus ensure more effective therapy that eliminates the potential for both under-and overdosing.

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

    Science.gov (United States)

    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.

  10. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    Science.gov (United States)

    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.

  11. Methods and metrics challenges of delivery-system research

    Directory of Open Access Journals (Sweden)

    Alexander Jeffrey A

    2012-03-01

    Full Text Available Abstract Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned. This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1 modeling intervention context; (2 measuring readiness for change; (3 assessing intervention fidelity and sustainability; (4 assessing complex, multicomponent interventions; and (5 incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ, US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on

  12. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and anti-tumor effects

    OpenAIRE

    Osada, Takuya; Berglund, Peter; Morse, Michael A; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R.; Clay, Timothy M.; Smith, Jonathan; Lyerly, H. Kim

    2012-01-01

    We recently demonstrated that Venezuelan equine encephalitis (VEE) virus-based replicon particles (VRP) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP expressing Interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and anti-tumor efficacy. Mice were immunized with VRP encoding the human tumor-associat...

  13. Optical diagnostics integrated with laser spark delivery system

    Science.gov (United States)

    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.

  14. An Overview on Osmotic Controlled Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Thummar A

    2013-06-01

    Full Text Available This paper reviews constructed drug delivery systems applying osmotic principles for controlled drugrelease from the formulation. Osmotic devices which are tablets coated with walls of controlled porosityare the most promising strategy based systems for controlled drug delivery. In contrast to commontablets, these pumps provide constant (zero order drug release rate. When these systems are exposed towater, low levels of water soluble additive is leached from polymeric material i.e. semipermeablemembrane and drug releases in a controlled manner over an extended period of time. The main clinicalbenefits of oral osmotic drug delivery system are their ability to improve treatment tolerability andpatient compliance. These advantages are mainly driven by the capacity to deliver drugs in a sustainedmanner, independent of the drug chemical properties, of the patient’s physiological factors or followingfood intake. This review brings out the theoretical concept of drug delivery, history, advantages anddisadvantages of the delivery systems, types of oral osmotic drug delivery systems, factors affecting thedrug delivery system and marketed products.

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

    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.

  17. Immunoliposome-PCR: a generic ultrasensitive quantitative antigen detection system

    Directory of Open Access Journals (Sweden)

    He Junkun

    2012-06-01

    Full Text Available Abstract Background The accurate quantification of antigens at low concentrations over a wide dynamic range is needed for identifying biomarkers associated with disease and detecting protein interactions in high-throughput microarrays used in proteomics. Here we report the development of an ultrasensitive quantitative assay format called immunoliposome polymerase chain reaction (ILPCR that fulfills these requirements. This method uses a liposome, with reporter DNA encapsulated inside and biotin-labeled polyethylene glycol (PEG phospholipid conjugates incorporated into the outer surface of the liposome, as a detection reagent. The antigenic target is immobilized in the well of a microplate by a capture antibody and the liposome detection reagent is then coupled to a biotin-labeled second antibody through a NeutrAvidin bridge. The liposome is ruptured to release the reporter DNA, which serves as a surrogate to quantify the protein target using real-time PCR. Results A liposome detection reagent was prepared, which consisted of a population of liposomes ~120 nm in diameter with each liposome possessing ~800 accessible biotin receptors and ~220 encapsulated reporters. This liposome detection reagent was used in an assay to quantify the concentration of carcinoembryonic antigen (CEA in human serum. This ILPCR assay exhibited a linear dose–response curve from 10-10 M to 10-16 M CEA. Within this range the assay coefficient of variance was Conclusions The ILPCR assay has several advantages over other immuno-PCR methods. The reporter DNA and biotin-labeled PEG phospholipids spontaneously incorporate into the liposomes as they form, simplifying preparation of the detection reagent. Encapsulation of the reporter inside the liposomes allows nonspecific DNA in the assay medium to be degraded with DNase I prior to quantification of the encapsulated reporter by PCR, which reduces false-positive results and improves quantitative accuracy. The ability to

  18. NIOSOMES: A ROLE IN TARGETED DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Soumya Singh

    2013-02-01

    Full Text Available Niosomes are non-ionic surfactant vesicles inclosing an aqueous phase and a wide range of molecules could be encapsulated within aqueous spaces of lipid membrane vesicles. They are microscopic lamellar structures formed on the admixture of a non-ionic surfactant, cholesterol and phosphate with subsequent hydration in aqueous media. Niosomes belongs to novel drug delivery system which offers a large number of advantages over other conventional and vesicular delivery systems. Namely they are the targeted drug delivery system which showing reduction of dose, stability and compatibility of non-ionic surfactants, easy modification, delayed clearance, suitability for a wide range of Active Pharmaceutical Agents.

  19. Mechanical valve assembly for xenon 133 gas delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Round, W.H. (Royal Brisbane Hospital, Herston (Australia))

    Some gas delivery systems used in pulmonary ventilation scanning are unable to satisfactorily supply /sup 133/Xe gas to bed-ridden patients. A mechanical gas valve assembly to control the flow of gas in such systems was constructed. A commercially produced /sup 133/Xe gas delivery system when fitted with the new assembly was able to ventilate almost all patients whereas previously this could be achieved with approximately only 50% of patients.

  20. 76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Science.gov (United States)

    2011-08-17

    ... Related Drug Delivery Systems; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice... entitled ``Residual Drug in Transdermal and Related Drug Delivery Systems.'' This guidance provides recommendations to developers and manufacturers of transdermal drug delivery systems (TDDS), transmucosal...

  1. Microneedles as a Delivery System for Gene Therapy

    Directory of Open Access Journals (Sweden)

    Wei eChen

    2016-05-01

    Full Text Available 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.

  2. A Novel Gene Delivery System Targeting Urokinase Receptor

    Institute of Scientific and Technical Information of China (English)

    Xing-Hui SUN; Li TAN; Chun-Yang LI; Chang TONG; Jin FAN; Ping LI; Yun-Song ZHU

    2004-01-01

    Recombinant proteins that combine different functions required for cell targeting and intracellular delivery of DNA present an attractive approach for the development of nonviral gene delivery vectors. Here, we described a novel protein termed ATF-lys10 which facilitated cell-specific gene transfer via receptor-mediated endocytosis. ATF-lys 10 was composed of the amino-terminal fragment of urokinase and ten lysines at the carboxyl terminus. Bacterially expressed ATF-lys 10 protein existed in soluble form, and had antigenicity of human urokinase. Purified ATF-lys 10 specifically bound to uPAR-expressing cells and formed protein-DNA complexes with plasmid pGL3-control. After neutralization of excess negative charge with poly-L-lysine, these complexes served as a specific gene delivery vector for uPAR-expressing cells. Lysosomotropic compounds, such as chloroquine, drastically increased the ATF-lysl0 mediated gene delivery efficiency. Our results suggest that the recombinant protein ATF-lys 10 with the properties of DNA binding and tumor cell targeting represents a promising method for gene transfer and expression in tumor cells.

  3. Elastin-like recombinamers as smart drug delivery systems.

    Science.gov (United States)

    Javier Arias, F; Santos, Mercedes; Ibáñez-Fonseca, Arturo; Piña, Maria Jesús; Serrano, Sofía

    2016-01-31

    Drug delivery systems that are able to control site and rate release of bioactive molecules are of particular interest for tissue therapy. Systems comprising biocompatible materials that can respond to environmental stimuli include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, which are especially useful as advanced drug delivery systems in the biomedical field. This review brings together information concerning different versions of ELR-based delivery systems that allow targeted delivery. ELR-drug systems in their monomeric form as well as drug encapsulation by nanoparticle-forming ELRs will be reviewed, focusing later on these drug carriers in which smart release is triggered by pH or temperature with a particular interest on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act both as a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed.

  4. Microcontainers as an oral delivery system for spray dried cubosomes containing ovalbumin

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Rades, Thomas; Boyd, Ben

    2016-01-01

    The purpose of this study was to prepare cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric...... microcontainers intended as an oral drug delivery system. The cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that cubosomes were formed after hydration of the spray dried precursor...... the cubosomes and microcontainers occurred at pH 6.8, releasing 44.1±5.6% of the OVA in 96h. Small-angle X-ray scattering (SAXS) revealed that the 'dry' particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after...

  5. MULTIPARTICULATE DRUG DELIVERY SYSTEM: PELLETIZATION THROUGH EXTRUSION AND SPHERONIZATION

    OpenAIRE

    Anshuli Sharma; Sandhya Chaurasia

    2013-01-01

    Pharmaceutical invention and research are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. Recent trends indicate that multiparticulate drug delivery systems are especially suitable for achieving controlled or delayed release oral formulations with low risk of dose dumping, flexibility of blending to attain different release patterns as well as reproducible and short gastric residence time. Pelletization is a technique use...

  6. Customer participation in service production and delivery system

    OpenAIRE

    Sridhar, M. S.

    1998-01-01

    Highlights significance of designing service delivery system, explains the integral role of customer in service production process, stresses the importance of customer-organisation interface, lists important ingredients of service package to be considered while designing customer interface, enumerates various dimensions of customer interface which can be positively made use of in design of service production and delivery system, discusses various ways and means of inducing and enhancing custo...

  7. Preparation and evaluation of alginate nanoparticles containing pertussis toxin as a particulate delivery system

    Directory of Open Access Journals (Sweden)

    Hamid Reza Goudarzi

    2016-04-01

    Full Text Available During the last decades, research on different kinds of nanoparticles (NPs has been increased to prepare various medical applications, for instance in vaccine and gene delivery and as new generation of adjuvant candidates. The aim of the present study was to prepare sodium alginate nanoparticles (Alg-NPs containing pertussis toxin (PTX as an candidate acellular vaccine. Formulation of antigen loaded Alg-NPs were assessed for immunological activities and their role as potential immunological adjuvant. Alg-Nps were prepared using mild ionic gelation method. Optimal formulation was obtained by concentration of 0.2%w/v sodium alginate, 0.1%w/v CaCl2 solution and magnetically homogenization condition of 45 min and rate of 2000 rpm. Obtained Alg-NPs showed average size of 88 nm and zeta potential of -32mV in blank and 72 nm and -29 mV in PTX entrapped nanoparticles, respectively. A Loading efficiency of more than 90% was determined for PTX. The antigen loaded nanoparticles showed 75.3% of release within 144 h in in vitro release studies. The immunological evaluation in female Balb/c mice groups revealed that the Alg-NPs formulation induced significantly higher serum antibody titers (p < 0.01 as compared with commercial acellular pertussis vaccine and conventional alum-adjuvanted antigen administered by subcutaneous route. The results showed the potential of Alg-NPS to be a simplex and efficient delivery system. This study also indicated the potential of Alg-NPs as new generation of immunostimulant adjuvant to boost the antigenecity of the antigens in a cellular pertussis vaccines.

  8. Model for determining and optimizing delivery performance in industrial systems

    Directory of Open Access Journals (Sweden)

    Fechete Flavia

    2017-01-01

    Full Text Available Performance means achieving organizational objectives regardless of their nature and variety, and even overcoming them. Improving performance is one of the major goals of any company. Achieving the global performance means not only obtaining the economic performance, it is a must to take into account other functions like: function of quality, delivery, costs and even the employees satisfaction. This paper aims to improve the delivery performance of an industrial system due to their very low results. The delivery performance took into account all categories of performance indicators, such as on time delivery, backlog efficiency or transport efficiency. The research was focused on optimizing the delivery performance of the industrial system, using linear programming. Modeling the delivery function using linear programming led to obtaining precise quantities to be produced and delivered each month by the industrial system in order to minimize their transport cost, satisfying their customers orders and to control their stock. The optimization led to a substantial improvement in all four performance indicators that concern deliveries.

  9. Biological studies of matrix metalloproteinase sensitive drug delivery systems

    DEFF Research Database (Denmark)

    Johansen, Pia Thermann

    due to severe side effects as a result of drug distribution to healthy tissues. To enhance ecacy of treatment and improve life quality of patients, tumor specific drug delivery strategies, such as liposome encapsulated drugs, which accumulate in tumor tissue, has gained increased attention. Several...... for delivery of drugs to specific tissues or cells utilizing biological knowledge of cancer tissue is getting increased attention. In this thesis a novel matrix metalloproteinase-2 (MMP-2) sensitive poly-ethylene glycol (PEG) coated liposomal drug delivery system for treatment of cancer was developed...... the use of MMP- 2 as a trigger for liposomal activation in tumor tissue. Thus, this new strategy provides a promising system for specific delivery of encapsulated drugs and controlled release in tumor tissues, resulting in enhanced drug bioavailability and decreased systemic side effects. In addition, we...

  10. An efficient fusion protein system for expression ofBacillus anthracis protective antigen as immunogenic and diagnostic antigen

    Institute of Scientific and Technical Information of China (English)

    Vahid Bagheri; Hossein Motamedi; Masoud Reza Seifiabad Shapouri

    2010-01-01

    Objective:To produce high quantities of recombinant protective antigen (rPA) for human vaccine and diagnosis.Methods: ThePAgene was amplified byPCR with pXO1 plasmid as template. ThePCR product was cloned into pMAL-c2X vector using theBamHI andSalI restriction enzymes. The recombinant plasmid was transformed intoEscherichia coliDH5α strain and then screened for transformation. The expression of protective antigen was analyzed bySDS-PAGE and Western blotting after isopropyl β-D-thiogalactopyranoside(IPTG) induction.Results:The full-length PA gene (2.2kb) was cloned into pMAL vector system. The recombinant vector was confirmed by restriction enzyme andPCRanalysis. The expression of cytoplasmic maltose-binding protein-protective (MBP-P) antigen fusion protein was detected bySDS-PAGE and Western blotting, and obtained a125 kDa protein band, which was similar to expected size of fusion protein.Conclusions: This expression system can be used in the high production of rPA. After purification and immunization studies, the purified rPA may be used in the development of the human recombinant anthrax vaccine and also in diagnosis of anthrax disease.

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

    Science.gov (United States)

    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.

  12. A REVIEW ON FLOATING TYPE GASTRORETENTIVE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Pallavi Pal

    2012-04-01

    Full Text Available Oral controlled release delivery systems are programmed to deliver the drug in predictable time frame that will increase the efficacy and minimize the adverse effects and increase the bioavailability of drugs. Oral route is considered mostnatural, uncomplicated, convenient and safe due to its ease of administration, patient acceptance, and cost-effective manufacturing process.Floating Drug delivery system are designed to prolong the gastric residence time after oral administration, at particular site and controlling the release of drug especially useful for achieving controlled plasma level a swell as improving bioavailability Several approaches are currently being used to prolong the GRT, including floating drug delivery systems (FDDS, also known as hydrodynamically balanced systems (HBS, swelling and expanding systems, high-density systems, and other delayed gastric emptying devices.

  13. A REVIEW ON PARENTERAL CONTROLLED DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Milan Agrawal et al

    2012-10-01

    Full Text Available The parenteral administration route is the most effective and common form of delivery for active drug substances with poor bioavailability and the drugs with a narrow therapeutic index. Drug delivery technology that can reduce the total number of injection throughout the drug therapy period will be truly advantageous not only in terms of compliance, but also to improve the quality of the therapy and also may reduce the dosage frequency. Such reduction in frequency of drug dosing is achieved by the use of specific formulation technologies that guarantee the release of the active drug substance in a slow and predictable manner. The development of new injectable drug delivery system has received considerable attention over the past few years. A number of technological advances have been made in the area of parenteral drug delivery leading to the development of sophisticated systems that allow drug targeting and the sustained or controlled release of parenteral medicines.

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

    Science.gov (United States)

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

    2010-11-01

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

  15. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.

    Science.gov (United States)

    Osada, Takuya; Berglund, Peter; Morse, Michael A; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Yang, Xiao Yi; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R; Clay, Timothy M; Smith, Jonathan; Kim Lyerly, H

    2012-11-01

    We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12, and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP-IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing antitumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than that of VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted.

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

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse;

    2015-01-01

    are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use......Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe...... biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    INTRODUCTION: In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism...... by which intestinal absorption of peptides and proteins is promoted. AREAS COVERED: The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two...... most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides...

  18. SOLID LIPID NANOPARTICLES: AN ADVANCED DRUG DELIVERY SYSTEM

    OpenAIRE

    Raghu Nandan Reddy* and Arshia Shariff

    2013-01-01

    Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, research and clinical medicine, as well as in other varied sciences. Solid lipid nanoparticle (SLN) dispersions have been proposed as a new type of colloidal drug carrier system suitable for intravenous administration. Solid lipid nanoparticles (SLNs) technology represents a promising new approach to lipophilic drug delivery. Solid lipid nanopa...

  19. PROBIOTIC DELIVERY SYSTEMS: APPLICATIONS, CHALLENGES AND PROSPECTIVE

    Directory of Open Access Journals (Sweden)

    Yadav Nisha R.

    2013-04-01

    Full Text Available Probiotic are bacteria that help to maintain the natural balance of the microorganism in the intestine. Probiotic is gaining its popularity as an alternate approach for the healthcare management and till now has proofed its therapeutic indication in many simple to complex diseases. Diverse mechanism of action and being a living organism are two main advantages. However there are several drawbacks also associated with this new emerging therapeutic area. Probiotic strain identification, characterization, screening, understanding its mechanism of action for particular disease which is seeking much attention. The primary aim associated with the probiotic delivery is maintaining bacteria viability during product manufacturing and during storage. Several approaches such as microencapsulation and use of suitable biocompatible material have been studied and still under continuous exploration. Along with the regulatory aspect associated with the probiotics in this review details on current research in the area of exploring indication and advancement in delivery technologies has been covered. Review concluded with rational recommendations of each aspect of probiotics.

  20. Recent trends in challenges and opportunities of Transdermal drug delivery system

    Directory of Open Access Journals (Sweden)

    P.M.Patil

    2012-03-01

    Full Text Available Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered very effectively to skin patch. There has been great progress in the Transdermal drug delivery system for the delivery of different forms and our aim is to collect the information about what progressed have done in Transdermal drug delivery system and developments in Transdermal drug delivery systems in theoretical form. Also, to collect the information about the advantages and application of the Transdermal drug delivery systems.

  1. Recent trends in protein and peptide drug delivery systems

    Directory of Open Access Journals (Sweden)

    Gupta Himanshu

    2009-01-01

    Full Text Available With the discovery of insulin in 1922, identification and commercialization of potential protein and peptide drugs have been increased. Since then, research and development to improve the means of delivering protein therapeutics to patients has begun. The research efforts have followed two basic pathways: One path focused on noninvasive means of delivering proteins to the body and the second path has been primarily aimed at increasing the biological half-life of the therapeutic molecules. The search for approaches that provide formulations that are stable, bioavailable, readily manufacturable, and acceptable to the patient, has led to major advances in the development of nasal and controlled release technology, applicable to every protein or peptide. In several limited cases, sustained delivery of peptides and proteins has employed the use of polymeric carriers. More successes have been achieved by chemical modification using amino acid substitutions, protein pegylation or glycosylation to improve the pharmacodynamic properties of certain macromolecules and various delivery systems have been developed like the prolease technology, nano-particulate and microparticulate delivery systems, and the mucoadhesive delivery of peptides. The needle and syringe remain the primary means of protein delivery. Major hurdles remain in order to overcome the combined natural barriers of drug permeability, drug stability, pharmacokinetics, and pharmacodynamics of protein therapeutics. In our present review we have tried to compile some recent advances in protein and peptide drug delivery systems.

  2. Formulation and Stability Aspects of Nanosized Solid Drug Delivery Systems.

    Science.gov (United States)

    Szabo, Peter; Zelko, Romana

    2015-01-01

    Nano drug delivery systems are considered as useful means to remedy the problems of drugs of poor solubility, permeability and bioavailability, which became one of the most troublesome questions of the pharmaceutical industry. Different types of nanosized drug delivery systems have been developed and investigated for oral administration, providing auspicious solutions for drug development. In this paper nanosized drug delivery systems intended for oral administration are discussed based on the chemical nature of the carrier of drug molecules. Lipid nanoparticles comprising solid lipid nanoparticles, improved nanostructured lipid carriers and nanostructured silica- lipid hybrid particles have become popular in the formulation of lipophilic drugs of poor oral bioavailability. Polymeric nanoparticles including nanospheres and nanocapsules and polymeric fibrous systems have also emerged as potential drug delivery systems owing to their unique structure. The feasibility of surface functionalization of mesoporous materials and gold nanoparticles enables high level of control over particle characteristics making inorganic nanoparticles an exceptional formulation approach. The authors paid particular attention to the functionality-related stability of the reviewed delivery systems.

  3. Hydrocolloid-based nutraceutical delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Janaswamy, Srinivas; Youngren, Susanne R. (Purdue)

    2012-07-11

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

  4. MAST Propellant and Delivery System Design Methods

    Science.gov (United States)

    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.

  5. Supramolecular hydrogels as drug delivery systems.

    Science.gov (United States)

    Saboktakin, Mohammad Reza; Tabatabaei, Roya Mahdavi

    2015-04-01

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

  6. Coacervate delivery systems for proteins and small molecule drugs.

    Science.gov (United States)

    Johnson, Noah R; Wang, Yadong

    2014-12-01

    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: i) elastin-like peptides for delivery of anticancer therapeutics; ii) heparin-based coacervates with synthetic polycations for controlled growth factor delivery; iii) carboxymethyl chitosan aggregates for oral drug delivery; iv) 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.

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

    Science.gov (United States)

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

    2016-03-01

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

  8. ORAL MULTIPARTICULATE PULSATILE DRUG DELIVERY SYSTEMS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Shaji Jessy

    2011-02-01

    Full Text Available Pulsatile drug delivery aims to release drugs in a planned pattern i.e. at appropriate time and/or at a suitable site of action. Pharmaceutical invention and research are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. However, in recent pharmaceutical applications involving pulsatile delivery, multiparticulate dosage forms are gaining much favour over single-unit dosage forms because of their potential benefits like predictable gastric emptying, no risk of dose dumping, flexible release patterns and increased bioavailability with less inter- and intra-subject variability. Based on these, the present review aims to study multiparticulate pulsatile delivery systems, for which the Reservoir systems with rupturable polymeric coatings and Reservoir systems with erodible polymer coatings are primarily involved in the control of release. Multiparticulate drug delivery systems provide tremendous opportunities for designing new controlled and delayed release oral formulations, thus extending the frontier of future pharmaceutical development. The development of low density floating multiparticulate pulsed-release dosage forms possessing gastric retention capabilities has also been addressed with increasing focus on the upcoming multiparticulate-pulsatile technologies being exploited on an industrial scale.

  9. A DETAILED REVIEW ON ORAL MUCOSAL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Radha Bhati

    2012-03-01

    Full Text Available Oral mucosal drug delivery system is widely applicable as novel site for administration of drug for immediate and controlled release action by preventing first pass metabolism and enzymatic degradation due to GI microbial flora. Oral mucosal drug delivery system provides local and systemic action. In this review, attention is focused to give regarding physiology of oral mucosal including tissue permeability, barriers to permeation and route of permeation, biopharmaceutics of buccal and sublingual absorption, factors affecting drug absorption, detailed information of penetration enhancers, design of oral mucosal drug delivery system and role of mucoadhesion and various theories of bioadhesion. Evaluation techniques and selection of animal model for in-vivo studies are also discussed.

  10. Delivery systems and cost recovery in Mectizan treatment for onchocerciasis.

    Science.gov (United States)

    Amazigo, U; Noma, M; Boatin, B A; Etya'alé, D E; Sékétéli, A; Dadzie, K Y

    1998-04-01

    The efficiency of on-going delivery systems and cost recovery in Mectizan (ivermectin, MSD) treatment for onchocerciasis are reviewed. The search is on for an effective system of Mectizan delivery, involving drug procurement, delivery from port to districts and distribution to eligible persons, which can be sustained by the endemic countries for many years. The mechanisms for procuring and clearing the drug at the ports, and the drug's integration into the existing delivery systems of each national health service, need to be improved. Although large-scale treatments by mobile teams or community-based methods evidently achieve high and satisfactory rates of coverage, they also incur high recurrent costs which have to be covered by external partners and are not sustainable by national health services. Cost-sharing is considered an important factor in a sustainable delivery system and community-directed treatment, in which the community shares the cost and ownership of local distribution and is empowered to design and implement it, is likely to be more cost-effective and sustainable.

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

    Science.gov (United States)

    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.

  12. Structure analysis and performance measurement of Chinese health delivery system

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: Although evidence has already demonstrated that the performance of Health Delivery System (HDS) varies widely across nations, relatively little is known about the factors that give rise to these variations and the key point to improve the performance besides adjusting system structure. By setup of HDS performance measurement system on the base of association of financial, social, and environmental characteristics, we construct system dynamic model of HDS to simulate the invention policies. Methods:Performance measures were collected from HDS in 31 regions of China and combined with secondary data sources. Multivariate, linear, nonlinear regression and factor analysis models were used to estimate associations between system characteristics and the performance. Results: Performance varied significantly with the size, financial resources and organizational structure of HDS. Performance measurement system of health delivery system was developed to give the rank of all Chinese regions. Conclusion: Performance measurement system of HDS is the basic of HDS modeling by system dynamic.

  13. An epitope delivery system for use with recombinant mycobacteria

    NARCIS (Netherlands)

    Hetzel, C.; Janssen, R.; Ely, S.J.; Kristensen, N.M.; Bunting, K.; Cooper, J.B.; Lamb, J.R.; Young, D.B.; Thole, J.E.R.

    1998-01-01

    We have developed a novel epitope delivery system based on the insertion of peptides within a permissive loop of a bacterial superoxide dismutase molecule. This system allowed high-level expression of heterologous peptides in two mycobacterial vaccine strains, Mycobacterium bovis bacille Calmette- G

  14. FORMATION OF POROUS MEMBRANES FOR DRUG DELIVERY SYSTEMS

    NARCIS (Netherlands)

    VANDEWITTE, P; ESSELBRUGGE, H; PETERS, AMP; DIJKSTRA, PJ; FEIJEN, J; GROENEWEGEN, RJJ; SMID, J; OLIJSLAGER, J; SCHAKENRAAD, JM; EENINK, MJD; SAM, AP

    1993-01-01

    Highly crystalline porous hollow poly (L-lactide) (PLLA) fibres suitable for the delivery of various drugs were obtained using a dry-wet spinning process. The pore structure of the fibres could be regulated by changing the spinning systems and spinning conditions. Using the spinning system PLLA-diox

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

    Science.gov (United States)

    Moseley, H; Johnston, S; Allen, A

    1990-03-01

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

  16. Safety design integrated in the Building Delivery System

    DEFF Research Database (Denmark)

    Jørgensen, Kirsten

    2012-01-01

    It is important to see safety and health in construction as an integrated part of the way in which designers, architects, constructors, engineers and others carry out their consulting services. The purpose of this article is to demonstrate how safety and health can be integrated in the design...... phases of the building delivery system by using the principle of the lean construction modelling. The method for the research was to go through the lean construction building delivery system step by step and create a normative description of what to do, when to do and how to do to fully integration...... and the consultants. The result is a concept and guideline including control schemes for how to integrate safety design in the lean construction building delivery system including what to do and when. The concept has been tested in an educational context and found useful by the designers. The practical value...

  17. Safety design integrated in the building delivery system

    DEFF Research Database (Denmark)

    Jørgensen, Kirsten

    2013-01-01

    In construction, it is important to view safety and health as an integrated part of the way that “designers” are working. The designers cowers architects, constructors, engineers and others who carry out their consulting services in the design phase of a construction project. The philosophy....... The purpose of this article is to demonstrate how safety and health can be integrated in the design phases integrated in the management delivery systems within construction, The method for the research was to go through the building delivery system step by step and create a normative description of what, when...... and how to fully integrate safety in each part of the process. The result is a concept and guideline including control forms for how to integrate safety design in the Building Delivery System plus what to do and when. The concept has been tested in an educational context. The practical value...

  18. MULTIPARTICULATE DRUG DELIVERY SYSTEM: PELLETIZATION THROUGH EXTRUSION AND SPHERONIZATION

    Directory of Open Access Journals (Sweden)

    Anshuli Sharma

    2013-02-01

    Full Text Available Pharmaceutical invention and research are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. Recent trends indicate that multiparticulate drug delivery systems are especially suitable for achieving controlled or delayed release oral formulations with low risk of dose dumping, flexibility of blending to attain different release patterns as well as reproducible and short gastric residence time. Pelletization is a technique used to prepare fine powders into pellets used as multiparticulate drug delivery systems. There are different pelletization techniques used to prepare pellets. Extrusion and spheronization is one of them used to prepare pellets drug loaded beads/pellets for extended release or sustained release oral formulations such as tablets and capsules.

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

    Science.gov (United States)

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

    2017-03-01

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

  20. Information Delivery System through Bluetooth in Ubiquitous Networks

    Directory of Open Access Journals (Sweden)

    D.Asha Devi

    2009-07-01

    Full Text Available Ubiquitous and pervasive computing (UPC is a popular paradigm whose purpose is to emerge computers into the real world, to serve humans where the ubiquitous network is the underneath infrastructure. In order to provide ubiquitous services (u-Service which deliver useful information to service users without human intervention, this paper implements a proactive information delivery system using Bluetooth technology. Bluetooth is a lowpowered networking service that supports several protocol profiles, most importantly file transfer.Combined together, ubiquitous computing and Bluetooth have the potential to furnish ubiquitous solutions (u-Solutions that are efficient, employ simplified design characteristics, and collaboratively perform functions they are otherwise not capable. Thus, this paper first addresses the current Bluetooth technology. Then, it suggests and develops the proactive information delivery system utilizing Bluetooth and ubiquitous computing network concepts. The proactive information delivery system can be used in many ubiquitous applications such as ubiquitous commerce (u-Commerce and ubiquitous education (u- Education.

  1. Information Delivery System through Bluetooth in Ubiquitous Networks

    CERN Document Server

    Devi, D Asha; Pavani, V L; Geethanjali, N

    2010-01-01

    computers into the real world, to serve humans where the ubiquitous network is the underneath infrastructure. In order to provide ubiquitous services (u-Service) which deliver useful information to service users without human intervention, this paper implements a proactive information delivery system using Bluetooth technology. Bluetooth is a lowpowered networking service that supports several protocol profiles, most importantly file transfer.Combined together, ubiquitous computing and Bluetooth ha e the potential to furnish ubiquitous solutions (u-Solutions) that are efficient, employ simplified design characteristics, and collaboratively perform functions they are otherwise not capable. Thus, this paper first addresses the current Bluetooth technology. Then, it suggests and develops the proactive information delivery system utilizing Bluetooth and ubiquitous computing network concepts. The proactive information delivery system can be used in many ubiquitous applications such as ubiquitous commerce (u-Commer...

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

    Science.gov (United States)

    Kompella, U B; Koushik, K

    2001-01-01

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

  3. Pulsatile Drug Delivery System Based on Electrohydrodynamic Method

    CERN Document Server

    Zheng, Yi; Hu, Junqiang; Gao, Wenle

    2012-01-01

    Electrohydrodynamic (EHD) generation, a commonly used method in BioMEMS, plays a significant role in the pulsatile drug delivery system for a decade. In this paper, an EHD based drug delivery system is well designed, which can be used to generate a single drug droplet as small as 2.83 nL in 8.5 ms with a total device of 2\\times2\\times3 mm^3, and an external supplied voltage of 1500 V. Theoretically, we derive the expressions for the size and the formation time of a droplet generated by EHD method, while taking into account the drug supply rate, properties of liquid, gap between two electrodes, nozzle size, and charged droplet neutralization. This work proves a repeatable, stable and controllable droplet generation and delivery system based on EHD method experimentally as well as theoretically.

  4. The systems biology of MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra

    2012-01-01

    Major histocompatibility class II molecules (MHC class II) are one of the key regulators of adaptive immunity because of their specific expression by professional antigen presenting cells (APC). They present peptides derived from endocytosed material to T helper lymphocytes. Consequently, MHC class

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

    Science.gov (United States)

    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.

  6. [Development of drug delivery systems for targeting to macrophages].

    Science.gov (United States)

    Chono, Sumio

    2007-09-01

    Drug delivery systems (DDS) using liposomes as drug carriers for targeting to macrophages have been developed for the treatment of diseases that macrophages are related to their progress. Initially, DDS for the treatment of atherosclerosis are described. The influence of particle size on the drug delivery to atherosclerotic lesions that macrophages are richly present and antiatherosclerotic effects following intravenous administration of liposomes containing dexamethasone (DXM-liposomes) was investigated in atherogenic mice. Both the drug delivery efficacy of DXM-liposomes (particle size, 200 nm) to atherosclerotic lesions and their antiatherosclerotic effects were greater than those of 70 and 500 nm. These results indicate that there is an optimal particle size for drug delivery to atherosclerotic lesions. DDS for the treatment of respiratory infections are then described. The influence of particle size and surface mannosylation on the drug delivery to alveolar macrophages (AMs) and antibacterial effects following pulmonary administration of liposomes containing ciprofloxacin (CPFX-liposomes) was investigated in rats. The drug delivery efficacy of CPFX-liposomes to AMs was particle size-dependent over the range 100-1000 nm and then became constant at over 1000 nm. These results indicate that the most effective size is 1000 nm. Both the drug delivery efficacy of mannosylated CPFX-liposomes (particle size, 1000 nm) to AMs and their antibacterial effects were significantly greater than those of unmodified CPFX-liposomes. These results indicate that the surface mannosylation is useful method for drug delivery to AMs. This review provides useful information to help in the development of novel pharmaceutical formulations aimed at drug targeting to macrophages.

  7. Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

    Directory of Open Access Journals (Sweden)

    Savannah E. Howe

    2016-10-01

    Full Text Available Nanoparticles (NPs are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n. priming followed by i.n. or subcutaneous (s.c. boosting immunization affects the humoral immune response to chicken ovalbumin (Ova and Ova conjugated to 20 nm NPs (NP-Ova. We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA. In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.

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

    Science.gov (United States)

    Allen, Theresa M; Cullis, Pieter R

    2013-01-01

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

  9. Novel therapeutic approaches for various cancer types using a modified sleeping beauty-based gene delivery system.

    Science.gov (United States)

    Hong, In-Sun; Lee, Hwa-Yong; Kim, Hyun-Pyo

    2014-01-01

    Successful gene therapy largely depends on the selective introduction of therapeutic genes into the appropriate target cancer cells. One of the most effective and promising approaches for targeting tumor tissue during gene delivery is the use of viral vectors, which allow for high efficiency gene delivery. However, the use of viral vectors is not without risks and safety concerns, such as toxicities, a host immune response towards the viral antigens or potential viral recombination into the host's chromosome; these risks limit the clinical application of viral vectors. The Sleeping Beauty (SB) transposon-based system is an attractive, non-viral alternative to viral delivery systems. SB may be less immunogenic than the viral vector system due to its lack of viral sequences. The SB-based gene delivery system can stably integrate into the host cell genome to produce the therapeutic gene product over the lifetime of a cell. However, when compared to viral vectors, the non-viral SB-based gene delivery system still has limited therapeutic efficacy due to the lack of long-lasting gene expression potential and tumor cell specific gene transfer ability. These limitations could be overcome by modifying the SB system through the introduction of the hTERT promoter and the SV40 enhancer. In this study, a modified SB delivery system, under control of the hTERT promoter in conjunction with the SV40 enhancer, was able to successfully transfer the suicide gene (HSV-TK) into multiple types of cancer cells. The modified SB transfected cancer cells exhibited a significantly increased cancer cell specific death rate. These data suggest that our modified SB-based gene delivery system can be used as a safe and efficient tool for cancer cell specific therapeutic gene transfer and stable long-term expression.

  10. A real-time virtual delivery system for photon radiotherapy delivery monitoring

    Directory of Open Access Journals (Sweden)

    Feng Shi

    2014-03-01

    Full Text Available Purpose: Treatment delivery monitoring is important for radiotherapy, which enables catching dosimetric error at the earliest possible opportunity. This project develops a virtual delivery system to monitor the dose delivery process of photon radiotherapy in real-time using GPU-based Monte Carlo (MC method.Methods: The simulation process consists of 3 parallel CPU threads. A thread T1 is responsible for communication with a linac, which acquires a set of linac status parameters, e.g. gantry angles, MLC configurations, and beam MUs every 20 ms. Since linac vendors currently do not offer interface to acquire data in real time, we mimic this process by fetching information from a linac dynalog file at the set frequency. Instantaneous beam fluence map (FM is calculated based. A FM buffer is also created in T1 and the instantaneous FM is accumulated to it. This process continues, until a ready signal is received from thread T2 on which an in-house developed MC dose engine executes on GPU. At that moment, the accumulated FM is transferred to T2 for dose calculations, and the FM buffer in T1 is cleared. Once the dose calculation finishes, the resulting 3D dose distribution is directed to thread T3, which displays it in three orthogonal planes in color wash overlaid on the CT image. This process continues to monitor the 3D dose distribution in real-time.Results: An IMRT and a VMAT cases used in our patient-specific QA are studied. Maximum dose differences between our system and treatment planning system are 0.98% and 1.58% for the IMRT and VMAT cases, respectively. The update frequency is >10Hz and the relative uncertainty level is 2%.Conclusion: By embedding a GPU-based MC code in a novel data/work flow, it is possible to achieve real-time MC dose calculations to monitor delivery process.------------------------------Cite this article as: Shi F, Gu X, Graves YJ, Jiang S, Jia X. A real-time virtual delivery system for photon radiotherapy delivery

  11. Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system

    Directory of Open Access Journals (Sweden)

    Hanagata N

    2012-04-01

    Full Text Available Nobutaka HanagataNanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Ibaraki, and Graduate School of Life Science, Hokkaido University, Kita-ku, Sapporo, JapanAbstract: Unmethylated cytosine-phosphate-guanosine (CpG oligodeoxynucleotides (ODNs are recognized by Toll-like receptor 9 (TLR9 found in antigen-presenting cells and B cells and can activate the immune system. Using CpG ODNs as an adjuvant has been found to be effective for treating infectious diseases, cancers, and allergies. Because natural ODNs with only a phosphodiester backbone are easily degraded by nuclease (deoxyribonuclease [DNase] in serum, CpG ODNs with a phosphorothioate backbone have been studied for clinical application. CpG ODNs with a phosphorothioate backbone have raised concern regarding undesirable side effects; however, several CpG ODNs with only a phosphodiester backbone have been reported to be stable in serum and to show an immunostimulatory effect. In recent years, research has been conducted on delivery systems for CpG ODNs using nanoparticles (NPs. The advantages of NP-based delivery of CpG ODN include (1 it can protect CpG ODN from DNase, (2 it can retain CpG ODN inside the body for a long period of time, (3 it can improve the cellular uptake efficiency of CpG ODN, and (4 it can deliver CpG ODN to the target tissues. Because the target cells of CpG ODN are cells of the immune system and TLR9, the receptor of CpG ODN is localized in endolysosomes, CpG ODN delivery systems are required to have qualities different from other nucleic acid drugs such as antisense DNA and small interfering RNA. Studies until now have reported various NPs as carriers for CpG ODN delivery. This review presents DNase-resistant CpG ODNs with various structures and their immunostimulatory effects and also focuses on delivery systems of CpG ODNs that utilize NPs. Because CpG ODNs interact with TLR9 and activate both the innate and the adaptive immune

  12. Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

    Science.gov (United States)

    Maity, Amit Ranjan; Stepensky, David

    2016-01-01

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

  13. Cell-Penetrating Peptides—Mechanisms of Cellular Uptake and Generation of Delivery Systems

    Directory of Open Access Journals (Sweden)

    Sara Trabulo

    2010-03-01

    Full Text Available The successful clinical application of nucleic acid-based therapeutic strategies has been limited by the poor delivery efficiency achieved by existing vectors. The development of alternative delivery systems for improved biological activity is, therefore, mandatory. Since the seminal observations two decades ago that the Tat protein, and derived peptides, can translocate across biological membranes, cell-penetrating peptides (CPPs have been considered one of the most promising tools to improve non-invasive cellular delivery of therapeutic molecules. Despite extensive research on the use of CPPs for this purpose, the exact mechanisms underlying their cellular uptake and that of peptide conjugates remain controversial. Over the last years, our research group has been focused on the S413-PV cell-penetrating peptide, a prototype of this class of peptides that results from the combination of 13-amino-acid cell penetrating sequence derived from the Dermaseptin S4 peptide with the SV40 large T antigen nuclear localization signal. By performing an extensive biophysical and biochemical characterization of this peptide and its analogs, we have gained important insights into the mechanisms governing the interaction of CPPs with cells and their translocation across biological membranes. More recently, we have started to explore this peptide for the intracellular delivery of nucleic acids (plasmid DNA, siRNA and oligonucleotides. In this review we discuss the current knowledge of the mechanisms responsible for the cellular uptake of cell-penetrating peptides, including the S413-PV peptide, and the potential of peptide-based formulations to mediate nucleic acid delivery.

  14. Advanced Drug Delivery Systems - a Synthetic and Biological Applied Evaluation

    DEFF Research Database (Denmark)

    Bjerg, Lise Nørkjær

    Specific delivery of drugs to diseased sites in the body is a major topic in the development of drug delivery system today. Especially, the field of cancer treatment needs improved drug delivery systems as the strong dose-limiting side effects of chemotherapy today often present a barrier...... unloading of the encapsulated drug have been tried optimized in a variety of ways. Many propose the use of small molecules, such as vitamins and peptides, for active targeting of the liposomes to overexpressed receptors on the cancerous tissue. Once located close to the diseased site a trigger mechanism...... for releasing the drug from the liposome interior is often needed. Several approaches have been suggested to work as release mechanisms such a pH changes, the presence of enzymes or external applied stimulus as heat or light. Chapter two deals with the synthesis of the functionalized phospholipids, which...

  15. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Science.gov (United States)

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

    2013-08-01

    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

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

    Science.gov (United States)

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

    2016-07-07

    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.

  17. A COMPREHENSIVE REVIEW OF PULSATILE DRUG DELIVERY SYSTEMS

    Directory of Open Access Journals (Sweden)

    Rompicharla Bhargavi

    2012-03-01

    Full Text Available Pulsatile drug delivery systems are gaining popularity in the field of pharmaceutical formulation, research and development. The prime advantage in this drug delivery is that the drug is released as per the pathophysiological need of the disease. As a result the change of development of drug resistance which is seen in conventional and sustained released formulations can be reduced. This therapy is mainly applicable where sustained action is not required and the drugs are toxic. Basic point of development of this formulation is to find out the circadian rhythms that is a suitable indicator that will trigger the release of drug from the device. Clock genes are the genes that control the circadian rhythms in human physiology. Pulsatile drug delivery systems are promising incase of asthma, cardiovascular diseases, peptic ulcers, arthritis, and hypercholesterolemic conditions.

  18. Antibodies to early EBV, CMV, and HHV6 antigens in systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Rasmussen, N S; Draborg, A H; Nielsen, C T

    2015-01-01

    OBJECTIVES: We investigated the antibody levels against early antigens of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology/biochemistry, serol......OBJECTIVES: We investigated the antibody levels against early antigens of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in systemic lupus erythematosus (SLE) patients and healthy controls, and further correlated these antibodies to haematology...

  19. Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles

    OpenAIRE

    Fujita, Yoshio; Taguchi, Hiroaki

    2011-01-01

    Many studies are currently investigating the development of safe and effective vaccines to prevent various infectious diseases. Multiple antigen-presenting peptide vaccine systems have been developed to avoid the adverse effects associated with conventional vaccines (i.e., live-attenuated, killed or inactivated pathogens), carrier proteins and cytotoxic adjuvants. Recently, two main approaches have been used to develop multiple antigen-presenting peptide vaccine systems: (1) the addition of f...

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

    Science.gov (United States)

    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

  1. New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs

    DEFF Research Database (Denmark)

    Müllertz, Anette; Ogbonna, Anayo; Ren, Shan;

    2010-01-01

    The aim of this review is to highlight relevant considerations when implementing a rational strategy for the development of lipid and surfactant based drug delivery system and to discuss shortcomings and challenges to the current classification of these delivery systems. We also aim to offer...

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

    Science.gov (United States)

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

    2012-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Reshmy Rajan

    2011-01-01

    Full Text Available 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.

  4. Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles

    Directory of Open Access Journals (Sweden)

    Taguchi Hiroaki

    2011-08-01

    Full Text Available Abstract Many studies are currently investigating the development of safe and effective vaccines to prevent various infectious diseases. Multiple antigen-presenting peptide vaccine systems have been developed to avoid the adverse effects associated with conventional vaccines (i.e., live-attenuated, killed or inactivated pathogens, carrier proteins and cytotoxic adjuvants. Recently, two main approaches have been used to develop multiple antigen-presenting peptide vaccine systems: (1 the addition of functional components, e.g., T-cell epitopes, cell-penetrating peptides, and lipophilic moieties; and (2 synthetic approaches using size-defined nanomaterials, e.g., self-assembling peptides, non-peptidic dendrimers, and gold nanoparticles, as antigen-displaying platforms. This review summarizes the recent experimental studies directed to the development of multiple antigen-presenting peptide vaccine systems.

  5. Evolution of implantable and insertable drug delivery systems.

    Science.gov (United States)

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

    2014-05-10

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

  6. Mercury sorbent delivery system for flue gas

    Science.gov (United States)

    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.

  7. Review of Innovative Sediment Delivery Systems

    Science.gov (United States)

    2013-04-01

    analyzing site-specific hydrodynamics. The system employs numerical wave, current, and morphology models to optimize an offshore stockpile...refraction, and many other wave behaviors. TRANSPOR2004 is a sed- iment morphology model used for computation of sand transport under current and...CON World Systems, http://www.all-con.com/ newsletter /newsletter1.html. ACRONYMS AND ABBREVIATIONS. Term Definition CAS Conveyor Application

  8. The NCI Delivery System for PDQ

    OpenAIRE

    1984-01-01

    The Physician Data Query System (PDQ) represents a major effort by the National Cancer Institute (NCI) to communicate advances in cancer treatment using computer technology. It utilizes a modern large scale computer mainframe to provide processing speed, a general purpose database management system to provide retrieval and display functions and flexibility, and commercial communications networks to provide access to an audience of physicians and other health care professionals seeking up-to-d...

  9. Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

    Directory of Open Access Journals (Sweden)

    Juliana De Souza Rebouças

    2012-01-01

    Full Text Available In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  10. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy.

    Science.gov (United States)

    De Souza Rebouças, Juliana; Esparza, Irene; Ferrer, Marta; Sanz, María Luisa; Irache, Juan Manuel; Gamazo, Carlos

    2012-01-01

    In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  11. Magnetic microspheres as magical novel drug delivery system: A review

    Directory of Open Access Journals (Sweden)

    Satinder Kakar

    2013-01-01

    Full Text Available Magnetic microspheres hold great promise for reaching the goal of controlled and site specific drug delivery. Magnetic microspheres as an alternative to traditional radiation methods which uses highly penetrating radiations that is absorbed throughout the body. Its use is limited by toxicity and side effects. Now days, several targeted treatment systems including magnetic field, electric field, ultrasound, temperature, UV light and mechanical force are being used in many disease treatments (e.g. cancer, nerve damage, heart and artery, anti-diabetic, eye and other medical treatments. Among them, the magnetic targeted drug delivery system is one of the most attractive and promising strategy for delivering the drug to the specified site. Magnetically controlled drug targeting is one of the various possible ways of drug targeting. This technology is based on binding establish anticancer drug with ferrofluid that concentrate the drug in the area of interest (tumor site by means of magnetic fields. There has been keen interest in the development of a magnetically target drug delivery system. These drug delivery systems aim to deliver the drug at a rate directed by the needs of the body during the period of treatment, and target the activity entity to the site of action. Magnetic microspheres were developed to overcome two major problems encountered in drug targeting namely: RES clearance and target site specificity.

  12. Orally disintegrating films: A modern expansion in drug delivery system

    Directory of Open Access Journals (Sweden)

    Muhammad Irfan

    2016-09-01

    Full Text Available Over the past few decades, tendency toward innovative drug delivery systems has majorly increased attempts to ensure efficacy, safety and patient acceptability. As discovery and development of new chemical agents is a complex, expensive and time consuming process, so recent trends are shifting toward designing and developing innovative drug delivery systems for existing drugs. Out of those, drug delivery system being very eminent among pediatrics and geriatrics is orally disintegrating films (ODFs. These fast disintegrating films have superiority over fast disintegrating tablets as the latter are associated with the risks of choking and friability. This drug delivery system has numerous advantages over conventional fast disintegrating tablets as they can be used for dysphasic and schizophrenic patients and are taken without water due to their ability to disintegrate within a few seconds releasing medication in mouth. Various approaches are employed for formulating ODFs and among which solvent casting and spraying methods are frequently used. Generally, hydrophilic polymers along with other excipients are used for preparing ODFs which allow films to disintegrate quickly releasing incorporated active pharmaceutical ingredient (API within seconds. Orally disintegrating films have potential for business and market exploitation because of their myriad of benefits over orally disintegrating tablets. This present review attempts to focus on benefits, composition, approaches for formulation and evaluation of ODFs. Additionally, the market prospect of this innovative dosage form is also targeted.

  13. Modification of microbial polyacids for drug delivery systems

    OpenAIRE

    Lanz Landázuri, Alberto

    2014-01-01

    Polymers are becoming preferred materials in biomedical applications because of their vast diversity of properties, functionalities and applications. Properties as mechanical strength, stability against degradation, biocompatibility and biodegradability, among others, have been attractive for different medical applications. One of the most interesting applications of these materials is drug delivery systems. Biodegradable polymers and copolymers are the preferred materials for the manufacture...

  14. Novel targeted bladder drug-delivery systems: a review

    Directory of Open Access Journals (Sweden)

    Zacchè MM

    2015-11-01

    Full Text Available Martino Maria Zacchè, Sushma Srikrishna, Linda Cardozo Department of Urogynaecology, King's College Hospital, London, UK Abstract: 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. Keywords: drug targeting, drug-delivery system, bladder disorders

  15. REVIEW ON FLOATING DRUG DELIVERY SYSTEMS: AN APPROACH TO ORAL CONTROLLED DRUG DELIVERY VIA GASTRIC RETENTION

    Directory of Open Access Journals (Sweden)

    Kadam Shashikant M

    2011-06-01

    Full Text Available Controlled release (CR dosage forms have been extensively used to improve therapy with many important drugs. Several approaches are currently utilized in prolongation of gastric residence time, including floating drug delivery system, swelling and expanding system, polymeric bioadhesive system, modified shape system, high density system and other delayed gastric emptying devices. However, the development processes are faced with several physiological difficulties such as the inability to restrain and localize the system within the desired region of the gastrointestinal tract and the highly variable nature of the gastric emptying process. On the other hand, incorporation of the drug in a controlled release gastroretentive dosage forms (CR-GRDF which can remain in the gastric region for several hours would significantly prolong the gastric residence time of drugs and improve bioavailability, reduce drug waste, and enhance the solubility of drugs that are less soluble in high pH environment. Gastroretention would also facilitate local drug delivery to the stomach and proximal small intestine. Thus, gastroretention could help to provide greater availability of new products and consequently improved therapeutic activity and substantial benefits to patients. The purpose of this paper is to review the recent literature and current technology used in the development of gastroretentive dosage forms.

  16. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    Directory of Open Access Journals (Sweden)

    Ravi Kant Upadhyay

    2014-01-01

    Full Text Available 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.

  17. Novel drug-delivery systems for patients with chronic rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Albu S

    2012-05-01

    Full Text Available Silviu AlbuDepartment of Otolaryngology, University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, RomaniaAbstract: Chronic rhinosinusitis, one of the most common chronic medical complaints in the United States, seems to be increasing in incidence and prevalence, and has a significant impact on quality of life. Topical forms of medical therapy represent an attractive alternative for drug delivery to the nasal cavity and paranasal sinuses. Topical drug delivery has the advantage of directly acting on the site of inflammation, producing a higher concentration at the target site while avoiding systemic side effects. Although considerable research has been undertaken into improving nasal formulations in order to enhance absorption, little attention has so far been directed to upgrading the delivery devices. The aim of this review is to present current knowledge on the novel drug-delivery devices in use in the management of chronic rhinosinusitis patients, and to present the current available knowledge on topical drug penetration into the sinuses using various delivery devices. Additionally, methods used to enhance fluid sinus deposition are presented and the published clinical studies on the results of nebulized antibiotics in the treatment of chronic rhinosinusitis patients are discussed.Keywords: paranasal sinuses, topical therapy, nebulized antibiotics, clinical trials

  18. Unsteady jet in designing innovative drug delivery system

    Science.gov (United States)

    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.

  19. Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

    Science.gov (United States)

    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.

  20. MICROEMULSIONS AS ANTIDIABETIC DRUG DELIVERY SYSTEMS

    Directory of Open Access Journals (Sweden)

    Omnia Sarhan, Mahmoud M. Ibrahim* and Mahmoud Mahdy

    2012-11-01

    Full Text Available Glibenclamide is practically insoluble in water and its gastrointestinal absorption is limited by its dissolution rate. Therefore, to enhance the drug dissolution and its hypoglycemic effects, the drug was formulated in different microemulsion systems and in vitro/in vivo evaluated. Microemulsion systems were prepared by Water titration method in which surfactants and cosurfactants (S/CoS were mixed at different weight ratios of 1:1, 2:1 and 3:1. They were subjected to transmission electron microscopical examination, pH determination and viscosity tests. The solubility of Glibenclamide in different microemulsion systems was determined. Forms 8, 9, 10, 11, 14 and 18 were found to have high Glibenclamide solubility using different oils. Form 11 and 9 showed the highest Glibenclamide release rates of 59.72% and 52.35%, respectively after 6 hours. In-vivo studies were tested using diabetic rats by application of form 11 with n-butanol as cosurfactant transdermally and form 8 with propylene glycol cosurfactant orally and transdermally. The results were compared to the drug suspension as a positive control. It was shown that microemulsion systems gave an effective tool of increasing drug dissolution probably due to enhanced wettability and reduced drug particle size, which in turn led to enhance its hypoglycemic effects.

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

    Science.gov (United States)

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

    2014-11-01

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

  2. Chitosan nanoparticle based delivery systems for sustainable agriculture.

    Science.gov (United States)

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

    2015-01-01

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

  3. Nanoparticle-based drug delivery systems: promising approaches against infections

    Energy Technology Data Exchange (ETDEWEB)

    Ranghar, Shweta; Sirohi, Parul [Department of Applied Mechanics, Motilal Nehru National Institute of Technology, Allahabad (India); Verma, Pritam; Agarwal, Vishnu, E-mail: vishnu_agarwal02@rediffmail.com [Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad (India)

    2014-03-15

    Despite the fact that many new drugs and technologies have been developed to combat the infectious diseases, these have continued to be global health challenges. The use of conventional antimicrobial agents against these infections is always associated with problems such as the development of multiple drug resistance and adverse side effects. In addition, the inefficient traditional drug delivery system results in inadequate therapeutic index, low bioavailability of drugs and many other limitations. In this regard, antimicrobial nanoparticles and nanosized drug delivery carriers have emerged as potent effective agents against the infections. Nanoparticles have unique properties owing to their ultra small and controllable size such as high surface area, enhanced reactivity, and functionalizable structure. This review focused on different classes of antimicrobial nanoparticles, including metal, metal oxide and others along with their mechanism of action and their potential use against the infections. The review also focused on the development of nanoparticle systems for antimicrobial drug delivery and use of these systems for delivery of various antimicrobial agents, giving an overview about modern nanoparticle based therapeutic strategies against the infections. (author)

  4. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Alka Lohani

    2014-01-01

    Full Text Available 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.

  5. Self emulsifying drug delivery system (SEDDS) for phytoconstituents: a review.

    Science.gov (United States)

    Chouhan, Neeraj; Mittal, Vineet; Kaushik, Deepak; Khatkar, Anurag; Raina, Mitali

    2015-01-01

    The self emulsifying drug delivery system (SEDDS) is considered to be the novel technique for the delivery of lipophillic plant actives. The self emulsifying (SE) formulation significantly enhance the solubility and bioavailability of poorly aqueous soluble phytoconstituents. The self emulsifying drug delivery system (SEDDS) can be developed for such plant actives to enhance the oral bioavailability using different excipients (lipid, surfactant, co solvent etc.) and their concentration is selected on the basis of pre formulation studies like phase equilibrium studies, solvent capacity of oil for drug and mutual miscibility of excipients. The present review focuses mainly on the development of SEDDS and effect of excipients on oral bioavailability and aqueous solubility of poorly water soluble phytoconstituents/ derived products. A recent list of patents issued for self emulsifying herbal formulation has also been included. The research data for various self emulsifying herbal formulation and patents issued were reviewed using different databases such as PubMed, Google Scholar, Google patents, Scopus and Web of Science. In a nutshell, we can say that SEDDS was established as a novel drug delivery system for herbals and with the advances in this technique, lots of patents on herbal SEDDS can be translated into the commercial products.

  6. Steerable/distance enhanced penetrometer delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Amini, A.; Boyd, G.M.

    1996-12-31

    Characterization, monitoring, and remediation of many of the nation`s highly contaminated sites are high priority at DOE. Penetrometers are often used for rapid characterization of underground contamination (plumes). Because of their heavy weight, use of penetrometer trucks over shallow buried storage tanks is restricted and risky. To close this gap, UTD developed a new position location device for penetrometers, called POLO (POsition LOcator), which provides real- time position location without blocking downhole access for environmental sensors. UTD also developed a system to make penetrometers steerable and capable of deeper penetration. Products of this work is a Steerable Vibratory System, which a relatively lightweight rig capable of greater penetration than traditional penetrometers of the same weight.

  7. Direct current power delivery system and method

    Science.gov (United States)

    Zhang, Di; Garces, Luis Jose; Dai, Jian; Lai, Rixin

    2016-09-06

    A power transmission system includes a first unit for carrying out the steps of receiving high voltage direct current (HVDC) power from an HVDC power line, generating an alternating current (AC) component indicative of a status of the first unit, and adding the AC component to the HVDC power line. Further, the power transmission system includes a second unit for carrying out the steps of generating a direct current (DC) voltage to transfer the HVDC power on the HVDC power line, wherein the HVDC power line is coupled between the first unit and the second unit, detecting a presence or an absence of the added AC component in the HVDC power line, and determining the status of the first unit based on the added AC component.

  8. Fluid delivery manifolds and microfluidic systems

    Energy Technology Data Exchange (ETDEWEB)

    Renzi, Ronald F.; Sommer, Gregory J.; Singh, Anup K.; Hatch, Anson V.; Claudnic, Mark R.; Wang, Ying-Chih; Van de Vreugde, James L.

    2017-02-28

    Embodiments of fluid distribution manifolds, cartridges, and microfluidic systems are described herein. Fluid distribution manifolds may include an insert member and a manifold base and may define a substantially closed channel within the manifold when the insert member is press-fit into the base. Cartridges described herein may allow for simultaneous electrical and fluidic interconnection with an electrical multiplex board and may be held in place using magnetic attraction.

  9. Comparative Evaluation of Native Antigens for the Development of Brucellosis Antibody Detection System

    Directory of Open Access Journals (Sweden)

    Yasmin Bano

    2015-09-01

    Full Text Available Brucellosis is a highly infectious zoonotic disease and an economically important infection of humans and livestock with a worldwide distribution. The main mode of transmission of this disease to humans is through the consumption of infected milk, milk products, and uncooked or raw meat. The present study was designed to prepare few native antigens, that is, sonicated antigen (SA, cell envelope (CE antigen, and freeze and thaw (FT antigen from Brucella abortus S99 culture and to test them in a highly sensitive and specific indirect enzyme-linked immunosorbent assay (I-ELISA in both a microtiter plate and a dot-blot format for the development of field-based diagnosis. All 50 suspected bovine samples were tested by plate as well as in dot ELISA formats for all the three antigens prepared. The CE antigen was found to be more suitable as it had the maximum agreement with the Rose Bengal plate agglutination test results followed by the SA and the least agreement was found with that of the FT antigen. This detection system in microtiter plates and a dot-blot format will be useful for the rapid screening of samples for the disease surveillance and routine diagnosis.

  10. Applications of polymers in intraocular drug delivery systems

    Science.gov (United States)

    Alhalafi, Ali Mohammed

    2017-01-01

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

  11. Applications of polymers in intraocular drug delivery systems

    Directory of Open Access Journals (Sweden)

    Ali Mohammed Alhalafi

    2017-01-01

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

  12. The Application Model of Moving Objects in Cargo Delivery System

    Institute of Scientific and Technical Information of China (English)

    ZHANG Feng-li; ZHOU Ming-tian; XU Bo

    2004-01-01

    The development of spatio-temporal database systems is primarily motivated by applications which track and present mobile objects. In this paper, solutions for establishing the moving object database based on GPS/GIS environment are presented, and a data modeling of moving object is given by using Temporal logical to extent the query language, finally the application model in cargo delivery system is shown.

  13. An emerging platform for drug delivery: aerogel based systems.

    Science.gov (United States)

    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.

  14. Emulsion forming drug delivery system for lipophilic drugs.

    Science.gov (United States)

    Wadhwa, Jyoti; Nair, Anroop; Kumria, Rachna

    2012-01-01

    In the recent years, there is a growing interest in the lipid-based formulations for delivery of lipophilic drugs. Due to their potential as therapeutic agents, preferably these lipid soluble drugs are incorporated into inert lipid carriers such as oils, surfactant dispersions, emulsions, liposomes etc. Among them, emulsion forming drug delivery systems appear to be a unique and industrially feasible approach to overcome the problem of low oral bioavailability associated with the BCS class II drugs. Self-emulsifying formulations are ideally isotropic mixtures of oils, surfactants and co-solvents that emulsify to form fine oil in water emulsions when introduced in aqueous media. Fine oil droplets would pass rapidly from stomach and promote wide distribution of drug throughout the GI tract, thereby overcome the slow dissolution step typically observed with solid dosage forms. Recent advances in drug carrier technologies have promulgated the development of novel drug carriers such as control release self-emulsifying pellets, microspheres, tablets, capsules etc. that have boosted the use of "self-emulsification" in drug delivery. This article reviews the different types of formulations and excipients used in emulsion forming drug delivery system to enhance the bioavailability of lipophilic drugs.

  15. A REVIEW ON ADVANCES OF SUSTAINED RELEASE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Sujit Bose

    2013-06-01

    Full Text Available Sustained release matrix tablets facilitate prolonged and continuous drug release and improve the bioavailability of drugs while avoiding unwanted side effects. Ofloxacin is a broad spectrum antibacterial agent used for treating wide range of gram positive and gram negative infections. The goal in designing sustained or controlled delivery systems is to reduce frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, providing uniform drug delivery. Sustained release drug administration means not only prolongation of duration of drug delivery, but the term also implies the predictability and reproducibility of drug release kinetics. The controlled release of drug substances and their effective transport to sites of action can be exploited to maximize the beneficial clinical response and to minimize the incidence of unbeneficial adverse reactions and side effects. Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for sustained release systems, oral route of administration has received most of the attention with respect to research on physiological and drug constraints as well as design and testing of products.

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

    Science.gov (United States)

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

    2012-01-01

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

  17. Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine.

    Science.gov (United States)

    Liu, Tzu-Yu; Hussein, Waleed M; Giddam, Ashwini Kumar; Jia, Zhongfan; Reiman, Jennifer M; Zaman, Mehfuz; McMillan, Nigel A J; Good, Michael F; Monteiro, Michael J; Toth, Istvan; Skwarczynski, Mariusz

    2015-01-22

    Vaccination can provide a safe alternative to chemotherapy by using the body's natural defense mechanisms to create a potent immune response against tumor cells. Peptide-based therapeutic vaccines against human papillomavirus (HPV)-related cancers are usually designed to elicit cytotoxic T cell responses by targeting the HPV-16 E7 oncoprotein. However, peptides alone lack immunogenicity, and an additional adjuvant or external delivery system is required. In this study, we developed new polymer-peptide conjugates to create an efficient self-adjuvanting system for peptide-based therapeutic vaccines. These conjugates reduced tumor growth and eradicated E7-positive TC-1 tumors in mice after a "single shot" immunization, without the help from an external adjuvant. The new conjugates had a significantly higher anticancer efficacy than the antigen formulated with a commercial adjuvant. Furthermore, the polymer-peptide conjugates were promptly taken up by antigen presenting cells, including dendritic cells and macrophages, and efficiently activated CD4(+) T-helper cells and CD8(+) cytotoxic T lymphocyte cells.

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

    Directory of Open Access Journals (Sweden)

    Kooijmans SAA

    2012-03-01

    Full Text Available Sander AA Kooijmans, Pieter Vader, Susan M van Dommelen, Wouter W van Solinge, Raymond M SchiffelersDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The NetherlandsAbstract: 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.Keywords: exosomes, extracellular vesicles, liposomes, drug delivery systems

  19. Targeted multidrug delivery system to overcome chemoresistance in breast cancer

    Directory of Open Access Journals (Sweden)

    Tang Y

    2017-01-01

    Full Text Available Yuan Tang,1 Fariborz Soroush,1 Zhaohui Tong,2 Mohammad F Kiani,1 Bin Wang1,3 1Department of Mechanical Engineering, Temple University, Philadelphia, PA, 2Department of Agricultural and Biological Engineering, University of Florida, Gainesville, FL, 3Department of Biomedical Engineering, Widener University, Chester, PA, USA Abstract: Chemotherapy has been widely used in breast cancer patients to reduce tumor size. However, most anticancer agents cannot differentiate between cancerous and normal cells, resulting in severe systemic toxicity. In addition, acquired drug resistance during the chemotherapy treatment further decreases treatment efficacy. With the proper treatment strategy, nanodrug carriers, such as liposomes/immunoliposomes, may be able to reduce undesired side effects of chemotherapy, to overcome the acquired multidrug resistance, and to further improve the treatment efficacy. In this study, a novel combinational targeted drug delivery system was developed by encapsulating antiangiogenesis drug bevacizumab into liposomes and encapsulating chemotherapy drug doxorubicin (DOX into immunoliposomes where the human epidermal growth factor receptor 2 (HER2 antibody was used as a targeting ligand. This novel combinational system was tested in vitro using a HER2 positive and multidrug resistant breast cancer cell line (BT-474/MDR, and in vivo using a xenograft mouse tumor model. In vitro cell culture experiments show that immunoliposome delivery led to a high cell nucleus accumulation of DOX, whereas free DOX was observed mostly near the cell membrane and in cytoplasm due to the action of P-gp. Combining liposomal bevacizumab with immunoliposomal DOX achieved the best tumor growth inhibition and the lowest toxicity. Tumor size decreased steadily within a 60-day observation period indicating a potential synergistic effect between DOX and bevacizumab through the targeted delivery. Our findings clearly indicate that tumor growth was significantly

  20. Highly efficient intracellular chromobody delivery by mesoporous silica nanoparticles for antigen targeting and visualization in real time

    CERN Document Server

    Chiu, Hsin-Yi; Engelke, Hanna; Helma, Jonas; Leonhardt, Heinrich; Bein, Thomas

    2015-01-01

    Chromobodies have recently drawn great attention as bioimaging nanotools. They offer antigen binding specificity and affinity comparable to conventional antibodies, but much smaller size and higher stability. Importantly, chromobodies can be used in live cell imaging for highly specific spatio-temporal visualization of cellular processes. To date, functional application of chromobodies requires lengthy genetic manipulation of the target cell. Here, we developed multifunctional large-pore mesoporous silica nanoparticles (MSNs) as nanocarriers to directly transport chromobodies into living cells for antigen-visualization in real time. The multifunctional large-pore MSNs feature high loading capacity for chromobodies, and are efficiently taken up by cells. By functionalizing the internal MSN surface with nitrilotriacetic acid-metal ion complexes, we could control the release of His6-tagged chromobodies from MSNs in acidified endosomes. When chromobodies escape from the endosomes through the proton sponge effect ...

  1. THE ROLE OF HOSPITAL IN OVERALL HEALTH DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    M. Nozadi

    1982-09-01

    Full Text Available Since hospitals are an important and integral part of the overall health delivery system, this study was carried out to measure the effectiveness of this institution within the system. The records of 633 hospitalized patients in the pediatrics ward of Ghaem Hospital in Mashhad during 1357 (21 March 1978-20 March 1979 has been consulted. More than half of the patients were hospitalized with the following diagnoses: Bronchopneumonia, Gastroentritis, Septicemia, and Malnutrition. Bronchopneumonia peaked in winter, whereas Gastroentritis and Malnutrition peaked in summer. Most of the hospitalized patients were male and the malnutrition was limited to the pre-school children of 1-6 years of age. The importance of these findings in development and utilization of the health delivery system has been discussed and considering the preventable nature of the above mentioned diseases, development and expansion of primary health care activities has been stressed.

  2. MICROSPONGE DELIVERY SYSTEM (MDS: A UNIQUE TECHNOLOGY FOR DELIVERY OF ACTIVE INGREDIENTS

    Directory of Open Access Journals (Sweden)

    Saurabh Kumar et al.

    2011-12-01

    Full Text Available In pharmaceutical industry, various controlled released dosage forms like solid formulation, semi solid formulation and topical preparation have more importance due to efficacy and patient compliance. Topical preparations have some disadvantages like unpleasant odour, greasiness and skin irritation and fail to reach the systemic circulation in sufficient amounts in few cases. This problem is overcome by microsponge delivery system. Microsponges are tiny sponge like spherical and highly porous micro-sized particles with a unique ability for entrapping actives. They offers programmable release active drug into the skin in order to reduce systemic exposure and minimize local cutaneous reactions to active. These MDS’s are closely related to microspheres, and used in the sun screens, creams, ointments, over- the-counter (OTC skin care preparations, recently used in oral drug as well as biopharmaceuticals (peptides, proteins and DNA-based therapeutics drug delivery. The present review introduces microsponge technology along with its synthesis, characterization, programmable parameters and release mechanism of MDS.

  3. Chitosan-based delivery systems for diclofenac delivery: preparation and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Dreve, Simina; Kacso, Irina; Bratu, Ioan; Indrea, Emil, E-mail: simina.dreve@itim-cj.r [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath, 400293 Cluj-Napoca (Romania)

    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{sup 0}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.

  4. Nanoscale drug delivery systems and the blood-brain barrier.

    Science.gov (United States)

    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.

  5. Food Delivery System with the Utilization of Vehicle Using Geographical Information System (GIS) and A Star Algorithm

    Science.gov (United States)

    Siregar, B.; Gunawan, D.; Andayani, U.; Sari Lubis, Elita; Fahmi, F.

    2017-01-01

    Food delivery system is one kind of geographical information systems (GIS) that can be applied through digitation process. The main case in food delivery system is the way to determine the shortest path and food delivery vehicle movement tracking. Therefore, to make sure that the digitation process of food delivery system can be applied efficiently, it is needed to add shortest path determination facility and food delivery vehicle tracking. This research uses A Star (A*) algorithm for determining shortest path and location-based system (LBS) programming for moving food delivery vehicle object tracking. According to this research, it is generated the integrated system that can be used by food delivery driver, customer, and administrator in terms of simplifying the food delivery system. Through the application of shortest path and the tracking of moving vehicle, thus the application of food delivery system in the scope of geographical information system (GIS) can be executed.

  6. LIPOSOME AS A POTENTIAL DRUG DELIVERY SYSTEM: A REVIEW

    Directory of Open Access Journals (Sweden)

    Dash Tapaswi Rani

    2013-01-01

    Full Text Available Liposomes are microscopic phospholipid vescicles made of lipid bilayer which are the drug carrier for improving the delivery of therapeutic agents. Research on liposome technology has progressed from conventional vesicles (“first-generation liposomes” to “second-generation liposomes”, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol (PEG in liposome composition. Due to advancement in liposomal technology a number of liposomal formulations are available in market for clinical use, with gene delivery and cancer therapy and some formulations are under clinical trial. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution. This review discusses the basic principles of liposome structures and preparations, evaluation parameters of liposomal formulation, pharmacokinetics of liposomes and liposome-encapsulated drugs, the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.

  7. Oral pulsatile delivery systems based on swellable hydrophilic polymers.

    Science.gov (United States)

    Gazzaniga, Andrea; Palugan, Luca; Foppoli, Anastasia; Sangalli, Maria Edvige

    2008-01-01

    Upon contact with aqueous fluids, swellable hydrophilic polymers undergo typical chain relaxation phenomena that coincide with a glassy-rubbery transition. In the rubbery phase, these polymers may be subject to swelling, dissolution and erosion processes or, alternatively, form an enduring gel barrier when cross-linked networks (hydrogels) are dealt with. Because of the peculiar hydration and biocompatibility properties, such materials are widely exploited in the pharmaceutical field, particularly as far as hydrophilic cellulose derivatives are concerned. In oral delivery, they have for long been employed in the manufacturing of prolonged release matrices and, more recently, for pulsatile (delayed) release devices as well. Pulsatile delivery, which is meant as the liberation of drugs following programmed lag phases, has drawn increasing interest especially in view of emerging chronotherapeutic approaches. In pursuit of pulsatile release, various design strategies have been proposed, chiefly including reservoir, capsular and osmotic formulations. In most cases, water-swellable polymers play a key role in the overall delivery mechanism after being activated by physiological media. Based on these premises, the aim of the present review is to survey the main oral pulsatile delivery systems, for which swelling, dissolution and/or erosion of hydrophilic polymers are primarily involved in the control of release.

  8. Use of liposomes as injectable-drug delivery systems.

    Science.gov (United States)

    Ostro, M J; Cullis, P R

    1989-08-01

    The formation of liposomes and their application as delivery systems for injectable drugs are described. Liposomes are microscopic vesicles composed of one or more lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid-soluble drugs within the membrane itself. Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis, lipid exchange, or fusion. Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes. Liposomes also accumulate preferentially at the sites of inflammation and infection and in some solid tumors; however, the reason for this accumulation is not clear. Four major factors influence liposomes' in vivo behavior and biodistribution: (1) liposomes tend to leak if cholesterol is not included in the vesicle membrane, (2) small liposomes are cleared more slowly than large liposomes, (3) the half-life of a liposome increases as the lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of liposome-based therapy is in the treatment of systemic fungal infections, especially with amphotericin B. Liposomes are also under investigation for treatment of neoplastic disorders. Liposomes' uses in cancer therapy include encapsulation of known antineoplastic agents such as doxorubicin and methotrexate, delivery of immune modulators such as N-acetylmuramyl-L-alanine-D-isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into lipid bilayers. Liposomal formulations of injectable antimicrobial agents and antineoplastic agents already are undergoing clinical testing, and most probably will receive

  9. Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

    Directory of Open Access Journals (Sweden)

    Pan L

    2014-12-01

    a double dose of Chi-Tre-Inactivated nanoparticles and animals immunized by intranasal route three times with Chi-Tre-Inactivated nanoparticles (P<0.05. FMDV-specific IgA antibodies in serum showed a similar pattern. All animals immunized by intranasal route developed low levels of detectable IgG in serum at 10 dpv. Following stimulation with FMDV, the highest levels of proliferation were observed in splenocytes harvested from Chi-PLGA-DNA-immunized animals, followed by proliferation of cells harvested from Chi-Tre-Inactivated nanoparticle-immunized animals (P<0.05. Higher protection rates were associated with the highest sIgA antibody responses induced in the Chi-PLGA-DNA nanoparticle-immunized group. Only one animal was clinically affected with mild signs after 7 days of contact challenge, after a delay of 2–3 days compared with the clinically affected negative-control group. Of the five animals directly challenged that were vaccinated by intranasal route with a double dose of Chi-Tre-Inactivated, four were clinically infected; however, the degree of severity of disease in this group was lower than in control cattle. The number of viral RNA copies in nasal swabs from the vaccinated, severely infected group was significantly higher than in swabs from the vaccinated, clinically protected group. These data suggested that intranasal delivery of Chi-PLGA-DNA nanoparticles resulted in higher levels of mucosal, systemic, and cell-mediated immunity than did of Chi-Tre-Inactivated nanoparticles. In conclusion, although intranasal delivery with FMDV antigen mediated by nanoparticles did not provide complete clinical protection, it reduced disease severity and virus excretion and delayed clinical symptoms. Chi-PLGA-DNA nanoparticle vaccines have potential as a nasal delivery system for vaccines. Keywords: FMDV, nanoparticles, chitosan, trehalose, poly(lactic-co-glycolic acid, PLGA

  10. Nanoengineered drug delivery systems for enhancing antibiotic therapy.

    Science.gov (United States)

    Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

    2015-03-01

    Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections.

  11. Receptor-Mediated Drug Delivery Systems Targeting to Glioma

    Directory of Open Access Journals (Sweden)

    Shanshan Wang

    2015-12-01

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

  12. Biopolymer-Based Delivery Systems: Challenges and Opportunities.

    Science.gov (United States)

    Joye, Iris J; McClements, D Julian

    2016-01-01

    Biopolymer-based nanostructures or microstructures can be fabricated with different compositions, structures, and properties so that colloidal delivery systems can be tailored for specific applications. These structures can be assembled using various approaches, including electrospinning, coacervation, nanoprecipitation, injection, layer-by-layer deposition, and/or gelation. A major application of biopolymer-based particles is to encapsulate, protect, and release active molecules in the agricultural, food, supplements, personal care, and pharmaceutical sectors. The inherent variability and complexity of biopolymers (proteins and polysaccharides) often makes it challenging to produce particles with well-defined physicochemical and functional attributes. In this review, we discuss the properties of biopolymers, common particle fabrication methods, and some of the major challenges and opportunities associated with developing biopolymer-based particles for application as food-grade delivery systems.

  13. Inhaled formulations and pulmonary drug delivery systems for respiratory infections.

    Science.gov (United States)

    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'.

  14. Printing technologies in fabrication of drug delivery systems

    DEFF Research Database (Denmark)

    Kolakovic, Ruzica; Viitala, Tapani; Ihalainen, Petri

    2013-01-01

    INTRODUCTION: There has been increased activity in the field recently regarding the development and research on various printing techniques in fabrication of dosage forms and drug delivery systems. These technologies may offer benefits and flexibility in manufacturing, potentially paving the way....... Challenges on different levels exist and include: i) technological development of printers and production lines; ii) printable formulations and carrier substrates; iii) quality control and characterization; and iv) regulatory perspectives....

  15. EXPLOITING NANOSCALE MATERIALS PROPERTIES FOR CONTROLLED DRUG DELIVERY SYSTEMS

    OpenAIRE

    Che Rose, Laili

    2013-01-01

    Abstract The main objective of this work was to develop a novel drug delivery system exploiting special opportunities afforded by synthesis of nanoscale materials to be applied inside the colon. It must be robust enough to cope with the adverse conditions in the gastrointestinal tract (GI) and be able to reach and release “on demand” at the colon area at the right time. In this work, an oral capsule formulation with iron oxide nanoparticles (IONs) containing coating was used...

  16. Feasibility Study: Ductless Hydronic Distribution Systems with Fan Coil Delivery

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. APPROACHES, TECHNIQUES AND EVALUATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEMS: AN OVERVIEW

    OpenAIRE

    Kumar D; Saini S; Seth N; Khullar R; Sharma R

    2011-01-01

    This review explains the recent advances in gastroretentive drug delivery systems with special focus on floating drug delivery systems. Oral route is the most convenient and painless technique of drug delivery. Gastroretentive drug delivery systems have been developed which overcome physiological conditions in gastrointestinal tract such as short gastric resident time (GRT) and unpredictable gastric emptying times (GET). Various approaches used for prolonging GRT are mucoadhesive systems (Bio...

  18. Leishmaniasis: focus on the design of nanoparticulate vaccine delivery systems.

    Science.gov (United States)

    Doroud, Delaram; Rafati, Sima

    2012-01-01

    Although mass vaccination of the entire population of an endemic area would be the most cost-effective tool to diminish Leishmania burden, an effective vaccine is not yet commercially available. Practically, vaccines have failed to achieve the required level of protection, possibly owing to the lack of an appropriate adjuvant and/or delivery system. Therefore, there is still an imperative demand for an improved, safe and efficient delivery system to enhance the immunogenicity of available vaccine candidates. Nanoparticles are proficient in boosting the quality and magnitude of immune responses in a predictable fashion. Herein, we discuss how nanoparticulate vaccine delivery systems can be used to induce appropriate immune responses against leishmaniasis by controlling physicochemical properties of the vaccine. Stability, production reproducibility, low cost per dose and low risk-benefit ratios are desirable characteristics of an ideal vaccine formulation and solid lipid nanoparticles may serve as one of the most promising practical strategies to help to achieve such a leishmanial vaccine, at least in canine species in the developing world.

  19. DESIGN OF GASTRO RETENTIVE DRUG DELIVERY SYSTEM OF DILTIAZEM HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    L. K. Omray

    2014-02-01

    Full Text Available Gastro retentive drug delivery system of diltiazem hydrochloride was designed and evaluated for its effectiveness for the management of mild to moderate hypertension. Gastro retentive drug delivery system were prepared using polyvinyl alcohol and sodium carboxy methyl cellulose as the polymers and sodium bicarbonate as a gas generating agent for the reduction of floating lag time. Gastro retentive drug delivery system tablets were prepared by wet granulation method by compression in tablet compression machine. Formulations DL1, DL2, DL3, DL4 and DL5 were developed which differed in the ratio of polyvinyl alcohol and sodium carboxy methyl cellulose polymers. All the formulations were evaluated for hardness, weight variation, friability, drug content, swelling index, buoyancy studies and in vitro drug release study. In vitro drug release study was performed using United State Pharmacopoeia 23 type 2 dissolution test apparatus employing paddle stirrer at 50 r/pm. Dissolution medium was 900 ml of 0.1N hydrochloric acid at 37ºC ± 3ºC. Formulations DL3 was found to be better as compared to other formulation.

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

    Science.gov (United States)

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

    2015-12-01

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

  1. Data delivery system for MAPPER using image compression

    Science.gov (United States)

    Yang, Jeehong; Savari, Serap A.

    2013-03-01

    The data delivery throughput of electron beam lithography systems can be improved by applying lossless image compression to the layout image and using an electron beam writer that can decode the compressed image on-the-fly. In earlier research we introduced the lossless layout image compression algorithm Corner2, which assumes a somewhat idealized writing strategy, namely row-by-row with a raster order. The MAPPER system has electron beam writers positioned in a lattice formation and each electron beam writer writes a designated block in a zig-zag order. We introduce Corner2-MEB, which redesigns Corner2 for MAPPER systems.

  2. Intelligent Drug Delivery System Using UML Diagrams Analysis

    Institute of Scientific and Technical Information of China (English)

    CUI Qi-feng; LIU Cheng-liang; ZHA Xuan F

    2008-01-01

    A novel intelligent drug delivery system potential for the more effective therapy of the diabeticswas proposed, and the composition of system was analyzed. Based on the design of micro-electro-mechanicalsystems (MEMS), an iterative modeling process was introduced. Unified modeling language (UML) was em-ployed to describe the function requirement, and different diagrams were built up to explore the static model,the dynamic model and the employment model. The mapping analysis of different diagrams can simply verifythe consistency and completeness of the system model.

  3. Overview on gastroretentive drug delivery systems for improving drug bioavailability.

    Science.gov (United States)

    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.

  4. 41 CFR 60-300.84 - Responsibilities of appropriate employment service delivery system.

    Science.gov (United States)

    2010-07-01

    ... appropriate employment service delivery system. 60-300.84 Section 60-300.84 Public Contracts and Property... of appropriate employment service delivery system. By statute, appropriate employment service... referrals. The employment service delivery systems shall provide OFCCP, upon request, information...

  5. Intrauterine levonorgestrel delivery with frameless fibrous delivery system: review of clinical experience

    Science.gov (United States)

    Wildemeersch, Dirk; Andrade, Amaury; Goldstuck, Norman D; Hasskamp, Thomas; Jackers, Geert

    2017-01-01

    The concept of using a frameless intrauterine device (IUD) instead of the conventional plastic framed IUD is not new. Frameless copper IUDs have been available since the late 1990s. They rely on an anchoring system to retain in the uterine cavity. The clinical experience with these IUDs suggests that frameless IUDs fit better as they are thin and, therefore, do not disturb or irritate the uterus. High tolerance and continuation rates have been achieved as complaints of pain are virtually nonexistent and the impact on menstrual blood loss is minimal. Conventional levonorgestrel-releasing intrauterine systems (LNG-IUSs) are very popular as they significantly reduce menstrual bleeding and provide highly effective contraception. However, continuation of use remains problematic, particularly in young users. Total or partial expulsion and displacement of the LNG-IUS also occur too often due to spatial incompatibility within a small uterine cavity, as strong uterine contractions originate, attempting to get rid of the bothersome IUD/IUS. If not expelled, embedment ensues, often leading to chronic pain and early removal of the IUD/IUS. Several studies conducted recently have requested attention to the relationship between the LNG-IUS and the endometrial cavity. Some authors have proposed to measure the cavity width prior to inserting an IUD, as many uterine cavities are much smaller than the currently existing LNG-IUSs. A frameless fibrous drug delivery system fits, in principle, in all uterine cavities and may therefore be preferable to framed drug delivery systems. This review examines the clinical performance, acceptability, and potential of the frameless LNG-IUS (FibroPlant®) when used for contraception, treatment of heavy menstrual bleeding, dysmenorrhea, and endometrial suppression in women using estrogen replacement therapy, endometrial hyperplasia, and other gynecological conditions. The review concludes that FibroPlant LNG-IUS offers unique advantages in reducing

  6. Liposomal drug delivery system from laboratory to clinic

    Directory of Open Access Journals (Sweden)

    Kshirsagar N

    2005-01-01

    Full Text Available 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, FungisomeTM 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

  7. New targets and delivery systems for antifungal therapy.

    Science.gov (United States)

    Walsh, T J; Viviani, M A; Arathoon, E; Chiou, C; Ghannoum, M; Groll, A H; Odds, F C

    2000-01-01

    Development of new approaches for treatment of invasive fungal infections encompasses new delivery systems for approved and investigational compounds, as well as exploiting the cell membrane, cell wall and virulence factors as putative antifungal targets. Novel delivery systems consisting of cyclodextrins, cochleates, nanoparticles/nanospheres and long circulating ('stealth') liposomes, substantially modulate the pharmacokinetics of existing compounds, and may also be useful to enhance the delivery of antifungal agents to sites of infection. Further insights into the structure-activity relationship of the antifungal triazoles that target the biosynthesis of ergosterol in the fungal cell membrane have led to the development of highly potent broad spectrum agents, including posaconazole, ravuconazole and voriconazole. Similarly, a novel generation of cell-wall active semisynthetic echinocandin 1,3 beta-glucan inhibitors (caspofungin, FK463, and VER-002) has entered clinical development. These agents have potent and broad-spectrum activity against Candida spp, and potentially useful activity against Aspergillus spp. and Pneumocystis carinii. The ongoing convergence of the fields of molecular pathogenesis, antifungal pharmacology and vaccine development will afford the opportunity to develop novel targets to complement the existing antifungal armamentarium.

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

    Science.gov (United States)

    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.

  9. An implantable thermoresponsive drug delivery system based on Peltier device.

    Science.gov (United States)

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

    2013-04-15

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

  10. A 400G optical wireless integration delivery system.

    Science.gov (United States)

    Li, Xinying; Yu, Jianjun; Zhang, Junwen; Dong, Ze; Li, Fan; Chi, Nan

    2013-08-12

    We experimentally demonstrate a record 400G optical wireless integration system simultaneously delivering 2 × 112 Gb/s two-channel polarization-division-multiplexing 16-ary quadrature amplitude modulation (PDM-16QAM) signal at 37.5 GHz wireless carrier and 2 × 108 Gb/s two-channel PDM quadrature phase shift keying (PDM-QPSK) signal at 100 GHz wireless carrier, adopting two millimeter-wave (mm-wave) frequency bands, two orthogonal antenna polarizations, multiple-input multiple-output (MIMO), photonic mm-wave generation and advanced digital signal processing (DSP). In the case of no fiber transmission, the bit error ratios (BERs) for both the 112 Gb/s PDM-16QAM signal after 1.5 m wireless delivery at 37.5 GHz and the 108 Gb/s PDM-QPSK signal after 0.7 m wireless delivery at 100 GHz are below the pre-forward-error-correction (pre-FEC) threshold of 3.8 × 10(-3). To our knowledge, this is the first demonstration of a 400G optical wireless integration system in mm-wave frequency bands and also a capacity record of wireless delivery.

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

    Science.gov (United States)

    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.

  12. Potential applications of boron nitride nanotubes as drug delivery systems.

    Science.gov (United States)

    Ciofani, Gianni

    2010-08-01

    In recent years, there has been an explosion of research in the 'bio-nano' field, with the discovery and introduction of ever more fascinating materials for applications as drug delivery systems, sensors, transducers, and so on. The author's group, for the first time in the literature, proposed boron nitride nanotubes as a valid alternative to carbon nanotubes and other kinds of inorganic materials, because of their improved chemical properties that theoretically guarantee better stability and compatibility in a biological context. In this paper, the bio-applications of boron nitride nanotubes that have emerged in the literature are summarized, with special attention given to their exploitation as safe drug delivery and targeting carriers. Finally, the possibility of combining their physical and chemical properties is approached, highlighting the features that render these innovative nanovectors unique and exceptional candidates for many bio-applications.

  13. Sustained Delivery of Chondroitinase ABC from Hydrogel System

    Directory of Open Access Journals (Sweden)

    Filippo Rossi

    2012-03-01

    Full Text Available In the injured spinal cord, chondroitin sulfate proteoglycans (CSPGs are the principal responsible of axon growth inhibition and they contribute to regenerative failure, promoting glial scar formation. Chondroitinase ABC (chABC is known for being able to digest proteoglycans, thus degrading glial scar and favoring axonal regrowth. However, its classic administration is invasive, infection-prone and clinically problematic. An agarose-carbomer (AC1 hydrogel, already used in SCI repair strategies, was here investigated as a delivery system capable of an effective chABC administration: the material ability to include chABC within its pores and the possibility to be injected into the target tissue were firstly proved. Subsequently, release kinetic and the maintenance of enzymatic activity were positively assessed: AC1 hydrogel was thus confirmed to be a feasible tool for chABC delivery and a promising device for spinal cord injury topic repair strategies.

  14. A REVIEW ARTICLE ON MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Jasvir Singh* and Pawan Deep

    2013-03-01

    Full Text Available ABSTRACT: As an alternative to injection pharmaceutical researcher and scientist are trying to explore transdermal and transmucosal route over the last few years. To overcome the deficiency associated with the other route of administration buccal region of oral cavity is an alternative target for the administration of choice of drug. The disadvantages relative with the oral drug delivery is the extensive presystemic metabolism, instability in acidic medium as a result inadequate absorption of the drugs. However parental route may overcome the drawback related with the oral route but these formulations have high cost, supervision is required and least patient compliance. By the buccal route the drug are directly pass through into systemic circulation, less hepatic metabolism and high bioavailability. The aim of the review article is an overview of buccal drug delivery, anatomy of oral mucosa, mechanism of drug penetration and their in-vitro and in-vivo mucoadhesion testing method.

  15. Use of microwave in processing of drug delivery systems.

    Science.gov (United States)

    Wong, T W

    2008-04-01

    Microwave has received a widespread application in pharmaceuticals and food processing, microbial sterilization, biomedical therapy, scientific and biomedical analysis, as well as, drug synthesis. This paper reviews the basis of application of microwave to prepare pharmaceutical dosage forms such as agglomerates, gel beads, microspheres, nanomatrix, solid dispersion, tablets and film coat. The microwave could induce drying, polymeric crosslinkages as well as drug-polymer interaction, and modify the structure of drug crystallites via its effects of heating and/or electromagnetic field on the dosage forms. The use of microwave opens a new approach to control the physicochemical properties and drug delivery profiles of pharmaceutical dosage forms without the need for excessive heat, lengthy process or toxic reactants. Alternatively, the microwave can be utilized to process excipients prior to their use in the formulation of drug delivery systems. The intended release characteristics of drugs in dosage forms can be met through modifying the physicochemical properties of excipients using the microwave.

  16. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  17. Naive T lymphocytes traffic to inflamed central nervous system, but require antigen recognition for activation

    DEFF Research Database (Denmark)

    Krakowski, M L; Owens, T

    2000-01-01

    Organ-specific autoimmune diseases may be induced by infiltration of the target tissue by CD4(+) T cells with specificity for self antigen(s). As disease progresses, T cells of other specificities appear in the tissue. Traffic of naive, antigen-inexperienced T cells to target tissues has not been...... shown, although many studies have shown extravasation of activated or memory T cells. We have used a novel experimental system to track naive T cells to the central nervous system (CNS) in TCR transgenic mice with adoptively transferred experimental autoimmune encephalomyelitis. Ovalbumin (OVA)-specific...... CD4(+) T cells were equivalent in number to disease-inducing myelin basic protein (MBP)-specific T cells at disease onset. Furthermore, OVA-specific T cells retained a naive phenotype and did not transcribe Th1 cytokines, in contrast to MBP-specific T cells. These findings demonstrate that the T cell...

  18. Relationship between systemic inflammation and delayed-type hypersensitivity response to Candida antigen in older adults.

    Directory of Open Access Journals (Sweden)

    Brandt D Pence

    Full Text Available Research has shown that aging is associated with increased systemic inflammation as well as a reduction in the strength of immune responses. However, little evidence exists linking the decrease in cell-mediated immunity in older adults with other health parameters. We sought to examine the relationship between cell-mediated immunity as measured in vivo by the delayed-type hypersensitivity (DTH response to candida antigen and demographic and physiological variables in older (65-80 y.o. adults. Candida antigen response was not related to gender or obesity, or to a number of other physiological variables including fitness and body composition. However, positive responders had significantly lower serum C-reactive protein levels (CRP, p4.75 mg•L(-1. Therefore, positive responses to candida antigen in older adults appears to be related to lower levels of systemic inflammation.

  19. Dielectric Collimators for Linear Collider Beam Delivery System

    CERN Document Server

    Kanareykin, A; Baturin, S; Tomás, R

    2011-01-01

    The current status of ILC and CLIC concepts require additional research on wakefield reduction in the collimator sections. New materials and new geometries have been considered recently*. Dielectric collimators for the CLIC Beam Delivery System have been discussed with a view to minimize the BDS collimation wakefields**. Dielectric collimator concepts for the linear collider are presented in this paper; cylindrical and planar collimators for the CLIC parameters have been considered, and simulations to minimize the beam impedance have been performed. The prototype collimator system is planned to be fabricated and experimentally tested at Facilities for Accelerator Science and Experimental Test Beams (FACET) at SLAC.

  20. Aperture and Delivery Precision of the LHC Injection System

    CERN Document Server

    Goddard, B; Jeanneret, J B; Kain, V; Lamont, M; Maire, V; Mertens, V; Wenninger, J

    2004-01-01

    The main LHC injection elements in interaction regions 2 and 8 comprise the injection septa (MSI), the injection kickers (MKI), together with three families of passive protection devices (TDI, TCDD and TCLI). The apertures of the two circulating beams are detailed for these elements, together with a summary of recent design modifications. The errors in the SPS, the transfer lines and the injection system are analysed, and the expected performance of the system derived, in terms of the expected delivery precision of the injected beam.

  1. A clinician-driven home care delivery system.

    Science.gov (United States)

    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.

  2. [A novel anticancer drug delivery system -DAC-70/CDDP].

    Science.gov (United States)

    Sugitachi, Akio; Otsuka, Koki; Fujisawa, Kentaro; Itabashi, Tetsuya; Akiyama, Yuji; Sasaki, Akira; Ikeda, Kenichiro; Yoshida, Yasuo; Takamori, Yoshimori; Kurozumi, Seiji; Mori, Takatoshi; Wakabayashi, Go

    2007-11-01

    We devised a muco-adhesive anticancer drug delivery system using 70% deacetylated chitin (DAC-70) and cisplatin (CDDP) and 5-fluorouracil (5-FU). The adhesive force between the system and human colonic mucosa was measured ex vivo, and a release profile of each drug was examined in vitro. Each system demonstrated a stronger muco-adhesive force at 37 degrees C than that of 25 degrees C. The CDDP-loaded system showed a sustained release of the drug while the 5-FU-loaded system exhibited an initial bursting of the agent. We presume that the release profile of CDDP and 5-FU is closely related to both degradability of the chitin and interactions between the chitin and each drug. The DAC-70/CDDP system would be clinically promising in loco-regional cancer chemotherapy.

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

    Science.gov (United States)

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

    2015-01-21

    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.

  4. Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo.

    Science.gov (United States)

    Xiang, Xi; Tang, Yuanjiao; Leng, Qianying; Zhang, Lingyan; Qiu, Li

    2016-02-01

    The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (Parthritis therapy.

  5. Systemically administered gp100 encoding DNA vaccine for melanoma using water-in-oil-in-water multiple emulsion delivery systems.

    Science.gov (United States)

    Kalariya, Mayurkumar; Amiji, Mansoor M

    2013-09-10

    The purpose of this study was to develop a water-in-oil-in-water (W/O/W) multiple emulsions-based vaccine delivery system for plasmid DNA encoding the gp100 peptide antigen for melanoma immunotherapy. The gp100 encoding plasmid DNA was encapsulated in the inner-most aqueous phase of squalane oil containing W/O/W multiple emulsions using a two-step emulsification method. In vitro transfection ability of the encapsulated plasmid DNA was investigated in murine dendritic cells by transgene expression analysis using fluorescence microscopy and ELISA methods. Prophylactic immunization using the W/O/W multiple emulsions encapsulated the gp100 encoding plasmid DNA vaccine significantly reduced tumor volume in C57BL/6 mice during subsequent B16-F10 tumor challenge. In addition, serum Th1 cytokine levels and immuno-histochemistry of excised tumor tissues indicated activation of cytotoxic T-lymphocytes mediated anti-tumor immunity causing tumor growth suppression. The W/O/W multiple emulsions-based vaccine delivery system efficiently delivers the gp100 plasmid DNA to induce cell-mediated anti-tumor immunity.

  6. New Delivery Systems for Local Anaesthetics—Part 2

    Directory of Open Access Journals (Sweden)

    Edward A. Shipton

    2012-01-01

    Full Text Available Part 2 of this paper deals with the techniques for drug delivery of topical and injectable local anaesthetics. The various routes of local anaesthetic delivery (epidural, peripheral, wound catheters, intra-nasal, intra-vesical, intra-articular, intra-osseous are explored. To enhance transdermal local anaesthetic permeation, additional methods to the use of an eutectic mixture of local anaesthetics and the use of controlled heat can be used. These methods include iontophoresis, electroporation, sonophoresis, and magnetophoresis. The potential clinical uses of topical local anaesthetics are elucidated. Iontophoresis, the active transportation of a drug into the skin using a constant low-voltage direct current is discussed. It is desirable to prolong local anaesthetic blockade by extending its sensory component only. The optimal release and safety of the encapsulated local anaesthetic agents still need to be determined. The use of different delivery systems should provide the clinician with both an extended range and choice in the degree of prolongation of action of each agent.

  7. Phenotype of Antigen Unexperienced TH Cells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Franck, Sophia; Paterka, Magdalena; Birkenstock, Jerome; Zipp, Frauke; Siffrin, Volker; Witsch, Esther

    2016-11-10

    Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes. By applying two-photon laser scanning microscopy we could show in vivo that antigen unexperienced T helper cells migrated into the deep parenchyma of the inflamed central nervous system in experimental autoimmune encephalomyelitis, independent of their antigen specificity. Using flow cytometric analyses of central nervous system-derived lymphocytes we found that only antigen-specific, formerly naive T helper cells became activated during inflammation of the central nervous system encountering their corresponding antigen.

  8. Nanoscale drug delivery systems and the blood–brain barrier

    Directory of Open Access Journals (Sweden)

    Alyautdin R

    2014-02-01

    Full Text Available Renad Alyautdin,1 Igor Khalin,2 Mohd Ismail Nafeeza,1 Muhammad Huzaimi Haron,1 Dmitry Kuznetsov31Faculty of Medicine, Universiti Teknologi MARA (UiTM, Sungai Buloh, Selangor, Malaysia; 2Faculty of Medicine and Defence Health, National Defence University of Malaysia (NDUM, Kuala Lumpur, Malaysia; 3Department of Medicinal Nanobiotechnologies, N. I. Pirogoff Russian State Medical University, Moscow, RussiaAbstract: 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

  9. Comparison of SAGS I vs. SAGS II delivery systems in emerging implantation technologies

    Science.gov (United States)

    Despres, Joseph; Sweeney, Joseph

    2012-11-01

    The International Fire Code has classified Subatmospheric Gas Delivery Systems (SAGS) technologies into two main categories: SAGS Type I and SAGS Type II systems. SAGS Type I delivery systems both store and deliver gases at subatmospheric pressures. An example of this technology is ATMI's Safe Delivery Source (SDS®) adsorbent based cylinder. SAGS Type II delivery systems store fluids at high pressure and utilize mechanical devices internal to the cylinder to deliver the gas at subatmospheric pressures. Typical mechanical devices used to enable subatmospheric delivery are either set point regulators or mechanical capillary based systems. This paper focuses on how these delivery systems perform against the unique requirements of traditional beam line ion implantation as well as solar and flat panel applications. Specifically, data are provided showing the capability of these systems with respect to flow rate, residual gas left within the cylinder, and cylinder end-point flow and delivery pressure dynamics.

  10. Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice.

    Science.gov (United States)

    Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Jung, Myunghwan; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

    2012-05-01

    A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC.

  11. Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A review

    OpenAIRE

    M. Abd Elgadir; Md.Salim Uddin; Sahena Ferdosh; Aishah Adam; Ahmed Jalal Khan Chowdhury; Md. Zaidul Islam Sarker

    2015-01-01

    Chitosan is a promising biopolymer for drug delivery systems. Because of its beneficial properties, chitosan is widely used in biomedical and pharmaceutical fields. In this review, we summarize the physicochemical and drug delivery properties of chitosan, selected studies on utilization of chitosan and chitosan-based nanoparticle composites in various drug delivery systems, and selected studies on the application of chitosan films in both drug delivery and wound healing. Chitosan is considere...

  12. Monitoring the degree of implementation of an integrated delivery system

    Directory of Open Access Journals (Sweden)

    Réjean Hébert

    2004-09-01

    Full Text Available Introduction: The aim of the study was to develop a method to measure the implementation of specific components of an Integrated Service Delivery system for the frail elderly. The system includes six mechanisms and tools: (1 coordination of all organizations involved in delivering health and social services, (2 a single entry point, (3 case management, (4 a single assessment tool with a case-mix classification system, (5 an individualized service plan, and (6 a computerized clinical chart. Method: Focus groups of researchers, clinicians, managers and policy-makers identified quantitative indicators for each component. The six components were weighted according to their relative importance in order to generate a total score. Data were collected every six months over 30 months to establish the implementation degree in the three experimental areas: Sherbrooke, Granit and Coaticook in the Province of Quebec, Canada. Results: After 30 months, coordination is the most developed component in the three experimental areas. Overall, in July 2003, the Integrated Service Delivery system was implemented at the rate of 73%, 71% and 70% in Sherbrooke, Granit and Coaticook, respectively. Discussion: This type of quantitative assessment provides data for managers and researchers to monitor the implementation. Moreover, when there is an outcome study, the results of the outcome study can be correlated with the degree of implementation, thus allowing for dose-response analyzes and helping to decrease the “black box” effect.

  13. G2 Autonomous Control for Cryogenic Delivery Systems

    Science.gov (United States)

    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.

  14. Characterisation of zinc delivery from a nipple shield delivery system using a breastfeeding simulation apparatus

    Science.gov (United States)

    Bruggraber, Sylvaine F. A.; Gerrard, Stephen E.; Kendall, Richard A.; Tuleu, Catherine; Slater, Nigel K. H.

    2017-01-01

    Zinc delivery from a nipple shield delivery system (NSDS), a novel platform for administering medicines to infants during breastfeeding, was characterised using a breastfeeding simulation apparatus. In this study, human milk at flow rates and pressures physiologically representative of breastfeeding passed through the NSDS loaded with zinc-containing rapidly disintegrating tablets, resulting in release of zinc into the milk. Inductively coupled plasma optical emission spectrometry was used to detect the zinc released, using a method that does not require prior digestion of the samples and that could be applied in other zinc analysis studies in breast milk. Four different types of zinc-containing tablets with equal zinc load but varying excipient compositions were tested in the NSDS in vitro. Zinc release measured over 20 minutes ranged from 32–51% of the loaded dose. Total zinc release for sets tablets of the same composition but differing hardness were not significantly different from one another with P = 0.3598 and P = 0.1270 for two tested pairs using unpaired t tests with Welch’s correction. By the same test total zinc release from two sets of tablets having similar hardness but differing composition were also not significantly significant with P = 0.2634. Future zinc tablet composition and formulation optimisation could lead to zinc supplements and therapeutics with faster drug release, which could be administered with the NSDS during breastfeeding. The use of the NSDS to deliver zinc could then lead to treatment and prevention of some of the leading causes of child mortality, including diarrheal disease and pneumonia. PMID:28158283

  15. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients

    DEFF Research Database (Denmark)

    Draborg, Anette Holck; Sandhu, Noreen; Larsen, Nanna

    2016-01-01

    We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired...

  16. Intrauterine levonorgestrel delivery with frameless fibrous delivery system: review of clinical experience

    Directory of Open Access Journals (Sweden)

    Wildemeersch D

    2017-01-01

    currently existing LNG-IUSs. A frameless fibrous drug delivery system fits, in principle, in all uterine cavities and may therefore be preferable to framed drug delivery systems. This review examines the clinical performance, acceptability, and potential of the frameless LNG-IUS (FibroPlant® when used for contraception, treatment of heavy menstrual bleeding, dysmenorrhea, and endometrial suppression in women using estrogen replacement therapy, endometrial hyperplasia, and other gynecological conditions. The review concludes that FibroPlant LNG-IUS offers unique advantages in reducing side effects. Keywords: LNG-IUS, frameless, efficacy, safety, acceptability

  17. Activity-based costing for integrated delivery systems.

    Science.gov (United States)

    Baker, J J

    1995-01-01

    The paradigm shift toward managed care is fueling new cost-finding demands. More sophisticated methods are emerging to meet these demands. Foremost among the new methods is activity-based costing (ABC). ABC is designed to eliminate cross-subsidies between products or services. Because costs are traced by activities across departments and cost centers, costs can also be traced by activities across integrated delivery systems (IDSs). The methodology makes ABC very applicable to combinations of providers including chains, affiliated groups, and IDS participants.

  18. Tuning of the Compact Linear Collider Beam Delivery System

    CERN Document Server

    Garcia, H; Inntjore Levinsen, Y; Latina, A; Tomas, R; Snuverink, J

    2014-01-01

    Tuning the Compact Linear Collider (CLIC) BeamDelivery System (BDS), and in particular the Final Focus (FF), is a challenging task. In simulations without misalignments, the goal is to reach 120%o f the nominal luminosity target, in order to allow for 10% loss due to static imperfections, and another 10% loss from dynamic imperfections. Various approaches have been considered to correct the magnet misalignments, including 1-1 correction, Dispersion Free Steering (DFS), and several minimization methods utilizing multipole movers. In this paper we report on the recent advancements towards a feasible tuning approach that reaches the required luminosity target.

  19. The Superconducting Magnets of the ILC Beam Delivery System

    Energy Technology Data Exchange (ETDEWEB)

    Parker, B.; Anerella, M.; Escallier, J.; He, P.; Jain, A.; Marone, A.; /Brookhaven; Nosochkov, Y.; Seryi, Andrei; /SLAC

    2007-09-28

    The ILC Beam Delivery System (BDS) uses a variety of superconducting magnets to maximize luminosity and minimize background. Compact final focus quadrupoles with multifunction correction coils focus incoming beams to few nanometer spot sizes while focusing outgoing disrupted beams into a separate extraction beam line. Anti-solenoids mitigate effects from overlapping focusing and the detector solenoid field. Far from the interaction point (IP) strong octupoles help minimize IP backgrounds. A low-field but very large aperture dipole is integrated with the detector solenoid to reduce backgrounds from beamstrahlung pairs generated at the IP. Physics requirements and magnetic design solutions for the BDS superconducting magnets are reviewed in this paper.

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

    OpenAIRE

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

    2011-01-01

    Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infections, with an oral bioavailability of only 10–20% [limiting absorption in gastrointestinal tract to duodenum and jejunum] and half-life of about 3 h, and is soluble only at acidic pH (pKa 2.27). Mucoadhesive polymeric nanodrug delivery systems of acyclovir have been designed and optimized using 23 full factorial design. Poly (lactic-co-glycolic acid) (PLGA) (50:50) was used as the polymer along with polycarbop...

  1. Delivery of Probiotics in the Space Food System

    Science.gov (United States)

    Castro, S. L.; Ott, C. M.; Douglas, G. L.

    2014-01-01

    The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers during spaceflight, counteracting the immune dysregulation that has been documented in spaceflight. Specifically, the probiotic Lactobacillus acidophilus has been shown to promote health benefits including antagonism towards and inhibition of virulence related gene expression in pathogens, mucosal stimulation of immune cells, and a reduction in the occurrence and duration of cold and flu-like symptoms. The optimum delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. This work proposes to determine whether L. acidophilus is more viable, and therefore more likely to confer immune benefit, when delivered in a capsule form or when delivered in nonfat dry milk powder with a resuscitation opportunity upon rehydration, following 0, 4, and 8 months of storage at -80degC, 4degC, and 22degC, and both prior to and after challenge with simulated gastric and intestinal juices. We hypothesize that the low moisture neutral dairy matrix provided by the nonfat dry milk, and the rehydration step prior to consumption, will extend probiotic viability and stress tolerance compared to a capsule during potential storage conditions in spaceflight and in simulated digestion conditions.

  2. Interactive mixture as a rapid drug delivery system.

    Science.gov (United States)

    Lee, Chin Chiat; Ong, Charlene Li Ching; Heng, Paul Wan Sia; Chan, Lai Wah; Wong, Tin Wui

    2008-02-01

    The effectiveness of an interactive mixture as a rapid drug delivery system is compared with that of a solid dispersion. The influences of drug load, particle size, and crystallinity of these test systems are investigated. The interactive mixtures and solid dispersions were prepared from polyethylene glycol (PEG) 3350 and hydrophobic nifedipine drug by means of physical mixing and melting methods, respectively. The formed products were subjected to drug particle size and crystallinity analyses, and dissolution tests. In comparison with the interactive mixtures, the solid dispersions with low drug load were more effective as a rapid drug delivery system, as the size of a given batch of drug particles was markedly reduced by the molten PEG 3350. The rate and extent of drug dissolution were mainly promoted by decreasing effective drug particle size. However, these were lower in the solid dispersions than in the interactive mixtures when a high load of fine drug particles was used as the starting material. This was attributed to drug coarsening during the preparation of the solid dispersion. Unlike solid dispersions, the interactive mixtures could accommodate a high load of fine drug particles without compromising its capacity to enhance the rate and extent of drug dissolution. The interactive mixture is appropriate for use to deliver a fine hydrophobic drug in a formulation requiring a high drug load.

  3. Epstein-Barr virus early antigen diffuse (EBV-EA/D)-directed immunoglobulin A antibodies in systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Draborg, A H; Jørgensen, J M; Müller, H

    2012-01-01

    We sought to determine whether the serological response towards lytic cycle antigens of Epstein-Barr virus (EBV) is altered in systemic lupus erythematosus (SLE) patients.......We sought to determine whether the serological response towards lytic cycle antigens of Epstein-Barr virus (EBV) is altered in systemic lupus erythematosus (SLE) patients....

  4. Versatile RNA interference nanoplatform for systemic delivery of RNAs.

    Science.gov (United States)

    Choi, Ki Young; Silvestre, Oscar F; Huang, Xinglu; Min, Kyung Hyun; Howard, Gregory P; Hida, Naoki; Jin, Albert J; Carvajal, Nicole; Lee, Sang Wook; Hong, Jong-In; Chen, Xiaoyuan

    2014-05-27

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

  5. Evaluation of bioadhesive polymers as delivery systems for nose to brain delivery: in vitro characterisation studies.

    Science.gov (United States)

    Charlton, S T; Davis, S S; Illum, L

    2007-04-01

    There is an increasing need for nasal drug delivery systems that could improve the efficiency of the direct nose to brain pathway especially for drugs for treatment of central nervous system disorders. Novel approaches that are able to combine active targeting of a formulation to the olfactory region with controlled release bioadhesive characteristics, for maintaining the drug on the absorption site are suggested. If necessary an absorption enhancer could be incorporated. Low methylated pectins have been shown to gel and be retained in the nasal cavity after deposition. Chitosan is known to be bioadhesive and also to work as an absorption enhancer. Consequently, two types of pectins, LM-5 and LM-12, together with chitosan G210, were selected for characterisation in terms of molecular weight, gelling ability and viscosity. Furthermore, studies on the in vitro release of model drugs from candidate formulations and the transport of drugs across MDCK1 cell monolayers in the presence of pectin and chitosan were also performed. Bioadhesive formulations providing controlled release with increased or decreased epithelial transport were developed. Due to their promising characteristics 3% LM-5, 1% LM-12 pectin and 1% chitosan G210 formulations were selected for further biological evaluation in animal models.

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

    Science.gov (United States)

    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.

  7. Aerosol assisted depositions of polymers using an atomiser delivery system.

    Science.gov (United States)

    Crick, Colin R; Clausen-Thue, Victoria; Parkin, Ivan P

    2011-09-01

    The hydrophobicity, robustness and anti-microbial properties of Sylgard 184 polymer films deposited via AACVD were optimised by using aerosol droplets from an atomiser delivery system, polymer coating substrates and the swell encapsulation of methylene blue. By using an atomiser deposition system (average droplet size 0.35 microm) rather than a misting aerosol system (45 microm) lead to a surface with smaller surface features, which improved hydrophobicity (water contact angle 165 degrees) in addition to increasing the films transparency from ca 10 to 65%. Pre-treating the substrates with the same Sylgard 184 elastomer lead to a highly consistent surface hydrophobicity and an increase in average water contact angle measured (169 degrees). This paper shows the first example of dye incorporation in a CVD derived polymer film-these films have potential as antimicrobial surfaces.

  8. Rapid assembly of customized TALENs into multiple delivery systems.

    Directory of Open Access Journals (Sweden)

    Zhengxing Zhang

    Full Text Available Transcriptional activator-like effector nucleases (TALENs have become a powerful tool for genome editing. Here we present an efficient TALEN assembly approach in which TALENs are assembled by direct Golden Gate ligation into Gateway(® Entry vectors from a repeat variable di-residue (RVD plasmid array. We constructed TALEN pairs targeted to mouse Ddx3 subfamily genes, and demonstrated that our modified TALEN assembly approach efficiently generates accurate TALEN moieties that effectively introduce mutations into target genes. We generated "user friendly" TALEN Entry vectors containing TALEN expression cassettes with fluorescent reporter genes that can be efficiently transferred via Gateway (LR recombination into different delivery systems. We demonstrated that the TALEN Entry vectors can be easily transferred to an adenoviral delivery system to expand application to cells that are difficult to transfect. Since TALENs work in pairs, we also generated a TALEN Entry vector set that combines a TALEN pair into one PiggyBac transposon-based destination vector. The approach described here can also be modified for construction of TALE transcriptional activators, repressors or other functional domains.

  9. Regulatory considerations on new adjuvants and delivery systems.

    Science.gov (United States)

    Sesardic, D

    2006-04-12

    New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

  10. Communication Between Devices in the Viola Document Delivery System

    Directory of Open Access Journals (Sweden)

    Theodor Tolstoy

    2015-01-01

    Full Text Available Viola is a newly developed document delivery system that handles incoming and outgoing requests for printed books, articles, sharing electronic resources, and other document delivery services on the local level in a library organisation. An important part of Viola is the stack fetching Android application that enables librarians to collect books in the open and closed stacks in an efficient manner using a smartphone and a Bluetooth connected portable printer. The aim of this article is to show how information is transferred between systems and devices in Viola. The article presents code examples from Viola that use current .NET technologies. The examples span from the creation of high-level REST-based JSON APIs to byte array communication with a Bluetooth connected printer and the reading of RFID tags. Please note that code examples in this article are for illustration purposes only. Null checking and other exception handling has been removed for clarity. Code that is separated in Viola for testability and other reasons has been brought together to make it more readable.

  11. Self-Assembling Multifunctional Peptide Dimers for Gene Delivery Systems

    Directory of Open Access Journals (Sweden)

    Kitae Ryu

    2015-01-01

    Full Text Available Self-assembling multifunctional peptide was designed for gene delivery systems. The multifunctional peptide (MP consists of cellular penetrating peptide moiety (R8, matrix metalloproteinase-2 (MMP-2 specific sequence (GPLGV, pH-responsive moiety (H5, and hydrophobic moiety (palmitic acid (CR8GPLGVH5-Pal. MP was oxidized to form multifunctional peptide dimer (MPD by DMSO oxidation of thiols in terminal cysteine residues. MPD could condense pDNA successfully at a weight ratio of 5. MPD itself could self-assemble into submicron micelle particles via hydrophobic interaction, of which critical micelle concentration is about 0.01 mM. MPD showed concentration-dependent but low cytotoxicity in comparison with PEI25k. MPD polyplexes showed low transfection efficiency in HEK293 cells expressing low level of MMP-2 but high transfection efficiency in A549 and C2C12 cells expressing high level of MMP-2, meaning the enhanced transfection efficiency probably due to MMP-induced structural change of polyplexes. Bafilomycin A1-treated transfection results suggest that the transfection of MPD is mediated via endosomal escape by endosome buffering ability. These results show the potential of MPD for MMP-2 targeted gene delivery systems due to its multifunctionality.

  12. The Smart Drug Delivery System and Its Clinical Potential.

    Science.gov (United States)

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications.

  13. Smart drug delivery systems: from fundamentals to the clinic.

    Science.gov (United States)

    Alvarez-Lorenzo, Carmen; Concheiro, Angel

    2014-07-25

    Forty years after the first reports on stimuli-responsive phase transitions in synthetic hydrogels, the first medicines based on responsive components are approaching the market. Sensitiveness to internal or external signals of the body can be achieved by means of materials (mostly polymers, but also lipids and metals) that modify their properties as a function of the intensity of the signal and that enable the transduction into changes in the delivery system that affect its ability to host/release a therapeutic substance. Integration of responsive materials into implantable depots, targetable nanocarriers and even insertable medical devices can endow them with activation-modulated and feedback-regulated control of drug release. This review offers a critical overview of therapeutically-interesting stimuli to trigger drug release and the evolution of responsive materials suitable as functional excipients, illustrated with recent examples of formulations in clinical trials or already commercially available, which can provide a perspective on the current state of the art on smart drug delivery systems.

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

  16. Intramuscular delivery of adenovirus serotype 5 vector expressing humanized protective antigen induces rapid protection against anthrax that may bypass intranasally originated preexisting adenovirus immunity.

    Science.gov (United States)

    Wu, Shipo; Zhang, Zhe; Yu, Rui; Zhang, Jun; Liu, Ying; Song, Xiaohong; Yi, Shaoqiong; Liu, Ju; Chen, Jianqin; Yin, Ying; Xu, Junjie; Hou, Lihua; Chen, Wei

    2014-02-01

    Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10⁸ infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD₅₀) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.

  17. Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety.

    Science.gov (United States)

    Donnelly, Ryan F; Raj Singh, Thakur Raghu; Woolfson, A David

    2010-05-01

    Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN.

  18. Formulation development and evaluation of controlled porosity osmotic pump delivery system for oral delivery of atenolol

    Directory of Open Access Journals (Sweden)

    Garvendra S Rathore

    2012-01-01

    Full Text Available In the present study, we developed and evaluated the controlled porosity osmotic pump (CPOP based drug delivery system of sparingly water soluble drug atenolol (ATL. We selected target release profile and optimized different variables to help us achieve this. Formulation variables, such as, the levels of solubility enhancer (0-15% w/w of drug, ratio of the drug to the osmogents, coat thickness of the semipermeable membrane (SPM and level of pore former (0-20% w/w of polymer were found to effect the drug release from the developed formulations. Cellulose acetate (CA 398-10 was used as the semipermeable membrane containing polyethylene glycol 400 as the Cplasticizer. ATL release was directly proportional to the level of the solubility enhancer, osmotic pressure generated by osmotic agent and level of pore former; however, was inversely proportional to the coat thickness of SPM. Drug release from developed formulations was independent of the pH and agitation intensities of release media. Burst strength of the exhausted shells decreased with increase in the level of pore former. The optimized formulations were subjected to stability studies as per International Conference on Harmonisation (ICH guidelines, and formulations were found to be stable after 3 months study. Steady-state plasma levels of drug were predicted by the method of superposition.

  19. Encapsulation, protection, and release of hydrophilic active components: potential and limitations of colloidal delivery systems.

    Science.gov (United States)

    McClements, David Julian

    2015-05-01

    There have been major advances in the development of edible colloidal delivery systems for hydrophobic bioactives in recent years. However, there are still many challenges associated with the development of effective delivery systems for hydrophilic bioactives. This review highlights the major challenges associated with developing colloidal delivery systems for hydrophilic bioactive components that can be utilized in foods, pharmaceuticals, and other products intended for oral ingestion. Special emphasis is given to the fundamental physicochemical phenomena associated with encapsulation, stabilization, and release of these bioactive components, such as solubility, partitioning, barriers, and mass transport processes. Delivery systems suitable for encapsulating hydrophilic bioactive components are then reviewed, including liposomes, multiple emulsions, solid fat particles, multiple emulsions, biopolymer particles, cubosomes, and biologically-derived systems. The advantages and limitations of each of these delivery systems are highlighted. This information should facilitate the rational selection of the most appropriate colloidal delivery systems for particular applications in the food and other industries.

  20. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

    Science.gov (United States)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release.

  1. Spatial service delivery system for smart licensing & enforcement management

    Science.gov (United States)

    Wahap, N. A.; Ismail, N. M.; Nor, N. M.; Ahmad, N.; Omar, M. F.; Termizi, A. A. A.; Zainal, D.; Noordin, N. M.; Mansor, S.

    2016-06-01

    Spatial information has introduced a new sense of urgency for a better understanding of the public needs in term of what, when and where they need services and through which devices, platform or physical locations they need them. The objective of this project is to value- add existing license management process for business premises which comes under the responsibility of Local Authority (PBT). Manipulation of geospatial and tracing technology via mobile platform allows enforcement officers to work in real-time, use a standardized system, improve service delivery, and optimize operation management. This paper will augment the scope and capabilities of proposed concept namely, Smart Licensing/Enforcement Management (SLEm). It will review the current licensing and enforcement practice of selected PBT in comparison to the enhanced method. As a result, the new enhanced system is expected to offer a total solution for licensing/enforcement management whilst increasing efficiency and transparency for smart city management and governance.

  2. Technical Evaluation Report 5: Classification of DE Delivery Systems

    Directory of Open Access Journals (Sweden)

    Diane Belyk

    2002-01-01

    Full Text Available For their optimal use in distance education (DE, online educational applications need to be integrated within a comprehensive course management system (CMS. Such systems are server-based software that supports the development, delivery, administration, and evaluation of online learning environments. The selection of an appropriate CMS should be considered from the multiple perspectives of the student, the course developer, the course instructor/ tutor, the technical support staff, and the DE institution’s administration. The current evaluation of CMS packages was conducted by a team of individuals with experience and contacts in relation to each of these DE user types. The report compares a series of CMS packages in terms of their range of features, and in relation to their satisfaction of international online education standards.

  3. Stateless and Delivery Guaranteed Geometric Routing on Virtual Coordinate System

    CERN Document Server

    Liu, Ke

    2008-01-01

    Stateless geographic routing provides relatively good performance at a fixed overhead, which is typically much lower than conventional routing protocols such as AODV. However, the performance of geographic routing is impacted by physical voids, and localization errors. Accordingly, virtual coordinate systems (VCS) were proposed as an alternative approach that is resilient to localization errors and that naturally routes around physical voids. However, VCS also faces virtual anomalies, causing their performance to trail geographic routing. In existing VCS routing protocols, there is a lack of an effective stateless and delivery guaranteed complementary routing algorithm that can be used to traverse voids. Most proposed solutions use variants of flooding or blind searching when a void is encountered. In this paper, we propose a spanning-path virtual coordinate system which can be used as a complete routing algorithm or as the complementary algorithm to greedy forwarding that is invoked when voids are encountere...

  4. Temperature-Sensitive Microemulsion Gel: An Effective Topical Delivery System for Simultaneous Delivery of Vitamins C and E

    OpenAIRE

    2009-01-01

    Microemulsions (ME)—nanostructured systems composed of water, oil, and surfactants—have frequently been used in attempts to increase cutaneous drug delivery. The primary objective addressed in this work has been the development of temperature-sensitive microemulsion gel (called gel-like ME), as an effective and safe delivery system suitable for simultaneous topical application of a hydrophilic vitamin C and a lipophilic vitamin E. By changing water content of liquid o/w ME (o/w ME), a gel-lik...

  5. Antigen capture ELISA system for henipaviruses using polyclonal antibodies obtained by DNA immunization.

    Science.gov (United States)

    Kaku, Yoshihiro; Noguchi, Akira; Marsh, Glenn A; Barr, Jennifer A; Okutani, Akiko; Hotta, Kozue; Bazartseren, Boldbaatar; Broder, Christopher C; Yamada, Akio; Inoue, Satoshi; Wang, Lin-Fa

    2012-08-01

    A novel antigen-capture sandwich ELISA system targeting the glycoproteins of the henipaviruses Nipah virus (NiV) and Hendra virus (HeV) was developed. Utilizing purified polyclonal antibodies derived from NiV glycoprotein-encoding DNA-immunized rabbits, we established a system that can detect the native antigenic structures of the henipavirus surface glycoproteins using simplified and inexpensive methods. The lowest detection limit against live viruses was achieved for NiV Bangladesh strain, 2.5 × 10(4) TCID(50). Considering the recent emergence of genetic variants of henipaviruses and the resultant problems that arise for PCR-based detection, this system could serve as an alternative rapid diagnostic and detection assay.

  6. Strategic workforce planning for a multihospital, integrated delivery system.

    Science.gov (United States)

    Datz, David; Hallberg, Colleen; Harris, Kathy; Harrison, Lisa; Samples, Patience

    2012-01-01

    Banner Health has long recognized the need to anticipate, beyond the immediate operational realities or even the annual budgeting projection exercises, the necessary workforce needs of the future. Thus, in 2011, Banner implemented a workforce planning model that included structures, processes, and tools for predicting workforce needs, with particular focus on identified critical systemwide practice areas. The model represents the incorporation of labor management tools and processes with more strategic, broad-view, long-term assessment and planning mechanisms. The sequential tying of the workforce planning lifecycle with the organization's strategy and financial planning process supports alignment of goals, objectives, and resource allocation. Collaboration among strategy, finance, human resources, and operations has provided us with the ability to identify critical position groups based on 3-year strategic priorities. By engaging leaders from across the organization, focusing on activities at facility, regional, and system levels, and building in mechanisms for accountability, we are now engaged in continuous evaluations of our delivery models, the competencies and preparations necessary for the staff to effectively function within those delivery models, and developing and implementing action plans designed to ensure adequate numbers of the staff whose competencies will be suited to the work expected of them.

  7. A novel gene delivery system for mammalian cells.

    Science.gov (United States)

    Gibson, Brian; Duffy, Angela M; Gould Fogerite, Susan; Krause-Elsmore, Sara; Lu, Ruying; Shang, Gaofeng; Chen, Zi-Wei; Mannino, Raphael J; Bouchier-Hayes, David J; Harmey, Judith H

    2004-01-01

    Although gene therapy holds great promise for the treatment of both acquired and genetic diseases, its development has been limited by practical considerations. Non-viral efficacy of delivery remains quite poor. We are investigating the feasibility of a novel lipid-based delivery system, cochleates, to deliver transgenes to mammalian cells. Rhodamine-labelled empty cochleates were incubated with two cell-lines (4T1 adenocarcinoma and H36.12 macrophage hybridoma) and primary macrophages in vitro and in vivo. Cochleates containing green fluorescent protein (GFP) expression plasmid were incubated with 4T1 adenocarcinoma cells. Cellular uptake of labelled cochleates or transgene GFP expression were visualised with fluorescence microscopy. 4T1 and H36.12 lines showed 39% and 23.1% uptake of rhodamine-cochleates, respectively. Human monocyte-derived macrophages and mouse peritoneal macrophages had 48+/-5.38% and 51.46+/-15.6% uptake of rhodamine-cochleates in vitro. In vivo 25.69+/-0.127% of peritoneal macrophages were rhodamine-positive after intra-peritoneal injection of rhodamine-cochleates. 19.49+/-10.12% of 4T1 cells expressed GFP. Cochleates may therefore be an effective, non-toxic and non-immunogenic method to introduce transgenes in vitro and in vivo.

  8. SOLID LIPID NANOPARTICLES: AN ADVANCED DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Raghu Nandan Reddy* and Arshia Shariff

    2013-01-01

    Full Text Available Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, research and clinical medicine, as well as in other varied sciences. Solid lipid nanoparticle (SLN dispersions have been proposed as a new type of colloidal drug carrier system suitable for intravenous administration. Solid lipid nanoparticles (SLNs technology represents a promising new approach to lipophilic drug delivery. Solid lipid nanoparticles are spherical lipid particles ranging in size from 1 to 1000 nm and are dispersed in water or in aqueous surfactant solution. It is identical to an oil-in-water emulsion, but the liquid lipid (oil of the emulsion has been replaced by a solid lipid, i.e., yielding Solid Lipid Nanoparticles. SLN are particles made from solid lipid or lipid blends produced by high pressure homogenization. The biodegradable and bioacceptable nature of SLNs makes them less toxic as compared to polymeric nanoparticles. SLNs can also be used to improve the bioavailability of drugs. In this present review this new approach is discussed in terms of their advantages, disadvantages, methods, characterization, pharmacokinetic studies, in-vivo studies, in-vitro studies, and special features

  9. Biologics: the role of delivery systems in improved therapy

    Directory of Open Access Journals (Sweden)

    Škalko-Basnet N

    2014-03-01

    Full Text Available Nataša Škalko-Basnet Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, Tromsø, Norway Abstract: The beginning of the 21st century saw numerous protein and peptide therapeuticals both on the market and entering the final stages of clinical studies. They represent a new category of biologically originated drugs termed biologics or biologicals. Their main advantages over conventional drugs can be summarized by their high selectivity and potent therapeutic efficacy coupled with limited side effects. In addition, they exhibit more predictable behavior under in vivo conditions. However, up to now most of the formulations of biologics are designed and destined for the parenteral route of administration. As a consequence, many suffer from short plasma half-lives, resulting in their frequent administration and ultimately poor patient compliance. This review represents an attempt to address some of the challenges and promises in the product development of biologics both for parenteral and noninvasive administration. Some of the products currently in the pipeline of pharmaceutical development and corresponding perspectives are discussed in more detail. Keywords: biologics, drug delivery systems, medical devices

  10. Absorption Enhancing Excipients in Systemic Nasal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Edward T. Maggio

    2014-06-01

    Full Text Available Intranasal drug delivery is becoming an increasingly important form of drug administration for chronic and chronic-intermittent diseases. Important new applications in development include drugs for diabetes, osteoporosis, obesity, certain types of convulsive disorders, migraine headaches, symptomatic pain relief, nausea, and anxiety, among others. Transmucosal absorption across the nasal mucosa is generally limited to molecules under 1,000 Da in size. Systemic delivery of molecules larger than this requires formulation with a suitable transmucosal absorption enhancer. More than one hundred potential transmucosal absorption enhancing excipients have been tested to date. Nearly all have failed to be practical due to poor effectiveness or unacceptable toxicity to mucosal tissue. Alkylsaccharides, cyclodextrins, and chitosan's have emerged as the leading candidates for potential broad clinical applications and are allowing development of convenient, patient-friendly, needle free formulations of small molecule drugs, as well as peptide and protein drugs that can be administered at home, at work, or in other public and private settings outside of the doctor’s office or hospital environment.

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

    Directory of Open Access Journals (Sweden)

    Zhao YZ

    2013-04-01

    Full Text Available Ying-Zheng Zhao,1,3 Li-Na Du,2 Cui-Tao Lu,1 Yi-Guang Jin,2 Shu-Ping Ge3 1Wenzhou Medical College, Wenzhou City, Zhejiang Province, 2Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3St Christopher’s Hospital for Children/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: 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. Keywords: ultrasound, targeted therapy, clinical application

  12. Delivery Systems for In Vivo use of Nucleic Acid Drugs

    Directory of Open Access Journals (Sweden)

    Resende R.R

    2007-01-01

    Full Text Available 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 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 affi nity 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.

  13. Multiparticulate system for colon targeted delivery of ondansetron

    Directory of Open Access Journals (Sweden)

    Jose S

    2010-01-01

    Full Text Available Targeted delivery of drugs to colon has the potential for local treatment of a variety of colonic diseases. The main objective of the study was to develop a multiparticulate system containing chitosan microspheres for the colon targeted delivery of ondansetron for the treatment of irritable bowel syndrome. This work combines pH-dependent solubility of eudragit S-100 polymers and microbial degradability of chitosan polymers. Chitosan microspheres containing ondansetron were prepared by emulsion cross linking method. The effect of process variables like chitosan concentration, drug-polymer ratio, emulsifier concentration and stirring speed were studied on particle size and entrapment efficiency of chitosan microspheres. In vitro drug release studies in simulated gastro intestinal fluids showed a burst drug release pattern in the initial hour necessitating microencapsulation around the chitosan microspheres. The optimized formulation was then subjected to microencapsulation with eudragit S-100 by solvent evaporation technique. The effect of different coat/core ratio on particle size, drug entrapment efficiency and in vitro drug release were studied. Formulation which contain 1:10 core/coat ratio released lesser amount of drug in the upper gastro intestinal conditions and so selected as best formulation and then subjected to in vitro drug release studies in presence of rat ceacal contents to assess biodegradability of chitosan microspheres in colon. In order to study the drug release mechanism in vitro drug release data was fitted into various kinetic models. Analysis of regression values suggested that the possible drug release mechanism was Peppas model.

  14. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Directory of Open Access Journals (Sweden)

    Maria Victoria Maliandi

    2011-01-01

    Full Text Available The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  15. Phyto-vesicles:conduit between conventional and novel drug delivery system

    Institute of Scientific and Technical Information of China (English)

    Nidhi Mishra; Narayan P Yadav; Jaya Gopal Meher; Priyam Sinha

    2012-01-01

    Objective: To discuss the preparation, characterization, targeting and formulation aspect of phospholipids based drug delivery system i.e. Phyto-vesicles. Methods: The methods of phyto-vesicles preparation on R & D scale and different analytical techniques to characterize them have been discussed. Result: Phyto-vesicles are the advanced form of herbal drug delivery systems as its structure includes water soluble head and two fat soluble tails which act as an effective emulsifier. Conclusion: It is concluded that phytovesicular delivery system has improved pharmacokinetic and pharmacodynamic parameter as compared to conventional system Therefore, phyto-vesicles are called as conduit between conventional and novel drug delivery system.

  16. Localization of organ-specific antigens in the nervous system of the rat.

    Science.gov (United States)

    Weinrauder, H; Lach, B

    1977-08-16

    Localization of organ-specific brain antigens in the central nervous system of the rat has been studied by means of indirect immunofluorescence. Rabbit antiserum against homogenate of rat brain, previously absorbed with normal serum and homogenates of rat organs (kidney, liver, spleen), reacted with the water-soluble antigens of rat brain prepared by extraction with phosphate buffer (pH 7.3) and ultracentrifugation at 50 000 X g to give one band in the immunodiffusion test and 2--3 precipitation arcs in immunoelectrophoresis. There was also a positive reaction with peripheral nerve. The antigen was detectable in all regions of the CNS. Cells with distinct cytoplasmic immunofluorescence were most frequently observed in cerebellar white matter, pons, cerebellar pedunculi, longitudinal tracts of the brain stem. Positive immunofluorecence reaction has appeared in the outer plexiform layer and granular layer of the retina, satelite cells of the spinal root ganglia and Schwann cells. A similar reaction was observed in human, mouse and guinea pig brain slices. Both the morphological and immunochemical reactions are indicative of glial localization of this antigen.

  17. Chronotherapeutic drug delivery systems: an approach to circadian rhythms diseases.

    Science.gov (United States)

    Sunil, S A; Srikanth, M V; Rao, N Sreenivasa; Uhumwangho, M U; Latha, K; Murthy, K V Ramana

    2011-11-01

    The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology. A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

  18. Progress in psoriasis therapy via novel drug delivery systems

    Directory of Open Access Journals (Sweden)

    Nitha Vincent

    2014-09-01

    Full Text Available Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment.

  19. Progress in non-viral gene delivery systems fabricated via supramolecular assembly

    Institute of Scientific and Technical Information of China (English)

    WANG Youxiang; SHEN Jiacong

    2005-01-01

    Gene delivery systems are one of key issues that limit the development of gene therapy. The novel non-viral gene delivery systems fabricated via supramolecular assembly have begun to show increasing promising and applications in gene therapy due to its suitable nanometric size, controllable structure and excellent biocompatibility. In this review, the fundamental and recent progress of non-viral gene supramolecular assembly is reviewed. Artificial viruses--the future direction of non-viral gene delivery systems are also described.

  20. Systemic gene delivery to the central nervous system using Adeno-associated virus

    Directory of Open Access Journals (Sweden)

    Mathieu eBOURDENX

    2014-06-01

    Full Text Available Adeno-associated virus (AAV-mediated gene delivery has emerged as an effective and safe tool for both preclinical and clinical studies of neurological disorders. The recent discovery that several serotypes are able to cross the blood-brain-barrier when administered systemically has been a real breakthrough in the field of neurodegenerative diseases. Widespread transgene expression after systemic injection could spark interest as a therapeutic approach. Such strategy will avoid invasive brain surgery and allow non-focal gene therapy promising for CNS diseases affecting large portion of the brain. Here, we will review the recent results achieved through different systemic routes of injection generated in the last decade using systemic AAV-mediated delivery and propose a brief assessment of their values. In particular, we emphasize how the methods used for virus engineering could improve brain transduction after peripheral delivery.

  1. Red blood cells as innovative antigen carrier to induce specific immune tolerance.

    Science.gov (United States)

    Cremel, Magali; Guérin, Nathalie; Horand, Françoise; Banz, Alice; Godfrin, Yann

    2013-02-25

    The route of administration, the dose of antigen as well as the type of antigen-presenting cells (APCs) targeted are important factors to induce immune tolerance. Despite encouraging results obtained in animal models, intravenous injection of soluble antigen is unsuccessful in human clinical trials on autoimmune disease due to inefficient antigen delivery. To improve antigen delivery, we used mouse red blood cells (RBCs) as antigen vehicles to specifically target APCs which are responsible for removal of senescent RBCs after phagocytosis. In this study, we demonstrated that antigen-delivery by RBCs induced a strong decrease in the humoral response compared with the ovalbumin (OVA) free form in mice. In addition, OVA-loaded RBC treated with [bis(sulphosuccinimidyl)] suberate (BS3), a chemical compound known to enhance RBC phagocytosis, induced an inhibition of antigen-specific T cell responses and an increase in the percentage of regulatory T cells. The state of tolerance induced is long lasting, antigen-specific and sufficiently robust to withstand immunization with antigen mixed with cholera toxin adjuvant. This RBC strategy, which does not abolish the immune system, constitutes an attractive approach for induction of tolerance compared to systemic immunosuppressant therapies already in use.

  2. Bioinspired silica as drug delivery systems and their biocompatibility

    DEFF Research Database (Denmark)

    Steven, Christopher R.; Busby, Grahame A.; Mather, Craig

    2014-01-01

    Silica nanoparticles have been shown to have great potential as drug delivery systems (DDS), however, their fabrication often involves harsh chemicals and energy intensive laborious methods. This work details the employment of a bioinspired "green" method for the controlled synthesis of silica, use...... allowing a one step and one pot method for simultaneous silica synthesis and drug loading. We established that the drug release profile can be modulated by synthetic parameters, which can allow design of tailored DDS. A systematic investigation using a two level factorial design was adopted in order...... of the products to entrap and release drug molecules and their cytotoxicity in order to develop novel DDS. Bioinspired silica synthesis occurs at pH 7, room temperature and in less than 5 minutes, resulting in a rapid, cheaper and greener route. Drugs were loaded into silica during the silica formation, thus...

  3. Enzymatically triggered multifunctional delivery system based on hyaluronic acid micelles

    KAUST Repository

    Deng, Lin

    2012-01-01

    Tumor targetability and stimuli responsivity of drug delivery systems (DDS) are key factors in cancer therapy. Implementation of multifunctional DDS can afford targetability and responsivity at the same time. Herein, cholesterol molecules (Ch) were coupled to hyaluronic acid (HA) backbones to afford amphiphilic conjugates that can self-assemble into stable micelles. Doxorubicin (DOX), an anticancer drug, and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), magnetic resonance imaging (MRI) contrast agents, were encapsulated by Ch-HA micelles and were selectively released in the presence of hyaluronidase (Hyals) enzyme. Cytotoxicity and cell uptake studies were done using three cancer cell lines (HeLa, HepG2 and MCF7) and one normal cell line (WI38). Higher Ch-HA micelles uptake was seen in cancer cells versus normal cells. Consequently, DOX release was elevated in cancer cells causing higher cytotoxicity and enhanced cell death. © 2012 The Royal Society of Chemistry.

  4. Evaluation of metal nanoparticles for drug delivery systems

    Institute of Scientific and Technical Information of China (English)

    Oluyomi S.Adeyemi; Faoziyat A.Sulaiman

    2015-01-01

    Diminazene aceturate is a trypanocide with unwanted toxicity and limited efficacy.It was reasoned that conjugating diminazene aceturate to functionalized nanoparticle would lower untoward toxicity while improving selectivity and therapeutic efficacy.Silver and gold nanoparticles were evaluated for their capacities to serve as carriers for diminazene aceturate.The silver and gold nanoparticles were synthesized,functionalized and coupled to diminazene aceturate following established protocols.The nanoparticle conjugates were characterized.The free diminazene aceturate and drug conjugated nanoparticles were subsequently evaluated for cytotoxicity in vitro.The characterizations by transmission electron microscopy or UV/Vis spectroscopy revealed that conjugation of diminazene aceturate to silver or gold nanoparticles was successful.Evaluation for cytotoxic actions in vitro demonstrated no significance difference between free diminazene aceturate and the conjugates.Our data suggest that surface modified metal nanoparticles could be optimized for drug delivery systems.

  5. Chewing gum and lozenges as delivery systems for noscapine

    DEFF Research Database (Denmark)

    Norgaard Jensen, L.; Christrup, Lona Louring; Menger, N.

    1991-01-01

    Chewing gum and lozenges were evaluated as delivery systems for noscapine with the aim of developing improved antitussive preparations. The formulations studied were prepared with both the water-soluble hydrochloride salt of noscapine and with the poorly soluble embonate salt and noscapine free...... base. The release characteristics of the preparations were evaluated both in vitro and in vivo, and their taste properties examined. Only the formulations containing noscapine base were without any appreciable taste. Chewing gum containing this compound showed, however, a low level of drug release both...... in vitro and in vivo and is therefore not a suitable dosage form. Only a lozenge formulation containing noscapine base fulfilled the requirements of taste acceptability and adequate release properties....

  6. Recent developments in retinal lasers and delivery systems

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Yadav

    2014-01-01

    Full Text Available Photocoagulation is the standard of care for several ocular disorders and in particular retinal conditions. Technology has offered us newer lasing mediums, wavelengths and delivery systems. Pattern scan laser in proliferative diabetic retinopathy and diabetic macular edema allows laser treatment that is less time consuming and less painful. Now, it is possible to deliver a subthreshold micropulse laser that is above the threshold of biochemical effect but below the threshold of a visible, destructive lesion thereby preventing collateral damage. The advent of solid-state diode yellow laser allows us to treat closer to the fovea, is more effective for vascular structures and offers a more uniform effect in patients with light or irregular fundus pigmentation. Newer retinal photocoagulation options along with their advantages is discussed in this review.

  7. Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems

    Science.gov (United States)

    Kenawy, E.; Abdel-Hay, F. I.; El-Newehy, M. H.; Wnek, G. E.

    The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative local chemotherapy. In this research, electrospun fibers were developed as a new system for the delivery of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer or polyurethane (PU) as a non-biodegradable polymer, or from the blends of the two. The release of the ketoprofen was followed by UV—VIS spectroscopy in phosphate buffer of pH 7.4 at 37°C and 20°C. The results showed that the release rates from the polycaprolactone, polyurethane and their blend were similar. However, the blend of the polycaprolactone with polyurethane improved its visual mechanical properties. Release profiles from the electrospun mats were compared to cast films of the various formulations.

  8. A Novel Drug Delivery System for Osteosarcoma Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A thermo-responsive chitosan hydrogel system (TRCHS) was prepared by chitosan ( CS ) andβ- glycerophosphate ( β- GP ) to deliver Adriamycin (ADM) locally for curing osteosarcoma . Release property was investigated by release experiments in vitro and results show that it can be applied to local drug release because it is able to release drug at high concentration for 17 days. The treatment effect was studied by injecting intratumorally to osteosarcoma tumors ( CRL- 1427) implanted subcutaneously on Specific Pathogen-free (SPF) mice. The statistical analytical results show that TRCHS delivering ADM is more efficacious than saline intratumoral injection,which loads the same quantity of ADM , but is less poisonous. Based on the analysis above, this novel biodegradable polymer implant is an effective and safe vehicle for sustained local delivery of ADM, and is supposed to be applied in neoadjuvant chemotherapy for osteosarcoma.

  9. Rapid cycling medical synchrotron and beam delivery system

    Science.gov (United States)

    Peggs, Stephen G.; Brennan, J. Michael; Tuozzolo, Joseph E.; Zaltsman, Alexander

    2008-10-07

    A medical synchrotron which cycles rapidly in order to accelerate particles for delivery in a beam therapy system. The synchrotron generally includes a radiofrequency (RF) cavity for accelerating the particles as a beam and a plurality of combined function magnets arranged in a ring. Each of the combined function magnets performs two functions. The first function of the combined function magnet is to bend the particle beam along an orbital path around the ring. The second function of the combined function magnet is to focus or defocus the particle beam as it travels around the path. The radiofrequency (RF) cavity is a ferrite loaded cavity adapted for high speed frequency swings for rapid cycling acceleration of the particles.

  10. In vitro digestion testing of lipid-based delivery systems

    DEFF Research Database (Denmark)

    Devraj, Ravi; Williams, Hywel D; Warren, Dallas B

    2012-01-01

    In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour...... of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water......-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces...

  11. Elastic vesicles as topical/transdermal drug delivery systems.

    Science.gov (United States)

    Choi, M J; Maibach, H I

    2005-08-01

    Skin acts a major target as well as a principle barrier for topical/transdermal drug delivery. Despite the many advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum corneum. Several methods have been assessed to increase the permeation rate of drugs temporarily. One simple and convenient approach is application of drugs in formulation with elastic vesicles or skin enhancers. Elastic vesicles are classified with phospholipid (Transfersomes((R)) and ethosomes) and detergent-based types. Elastic vesicles were more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. Their effectiveness strongly depends on their physicochemical properties: composition, duration and application volume, and entrapment efficiency and application methods. This review focuses on the effect of elastic liposomes for enhancing the drug penetration and defines the action mechanism of penetration into deeper skin.

  12. An overview of Ball Aerospace cryogen storage and delivery systems

    Science.gov (United States)

    Marquardt, J.; Keller, J.; Mills, G.; Schmidt, J.

    2015-12-01

    Starting on the Gemini program in the 1960s, Beech Aircraft (now Ball Aerospace) has been designing and manufacturing dewars for a variety of cryogens including liquid hydrogen and oxygen. These dewars flew on the Apollo, Skylab and Space Shuttle spacecraft providing fuel cell reactants resulting in over 150 manned spaceflights. Since Space Shuttle, Ball has also built the liquid hydrogen fuel tanks for the Boeing Phantom Eye unmanned aerial vehicle. Returning back to its fuel cell days, Ball has designed, built and tested a volume-constrained liquid hydrogen and oxygen tank system for reactant delivery to fuel cells on unmanned undersea vehicles (UUVs). Herein past history of Ball technology is described. Testing has been completed on the UUV specific design, which will be described.

  13. Conceptualizing the use of system products and system deliveries in the building industry

    DEFF Research Database (Denmark)

    Hvam, Lars; Mortensen, Niels Henrik; Thuesen, Christian;

    2013-01-01

    This article describes the concepts system products and system deliveries based on the use of product modularization and product configuration. The concepts are outlined and discussed based on examples from both the construction industry and related industry. The description focuses partly...

  14. Herpesvirus-mediated systemic delivery of nerve growth factor.

    Science.gov (United States)

    Wolfe, D; Goins, W F; Kaplan, T J; Capuano, S V; Fradette, J; Murphey-Corb, M; Robbins, P D; Cohen, J B; Glorioso, J C

    2001-01-01

    Sustained systemic dissemination of therapeutic proteins from peripheral sites is an attractive prospect for gene therapy applications. Replication-defective genomic herpes simplex virus type 1 (HSV-1) vectors were evaluated for their ability to express nerve growth factor (NGF) as a model gene product both locally and systemically. Intra-articular inoculation of NGF expression vectors in rabbits resulted in significant increases in joint lavage and blood plasma NGF that persisted for 1 year. A rhesus macaque injected intra-articularly displayed a comparable increase in plasma NGF for at least 6 months, at which time the serum NGF levels of this animal were sufficient to cause differentiation of PC12 cells in culture, but not to increase footpad epidermis innervation. Long-term reporter transgene expression was observed primarily in ligaments, a finding confirmed by direct inoculation of patellar ligament. Patellar ligament inoculation with a NGF vector resulted in elevated levels of circulating NGF similar to those observed following intra-articular vector delivery. These results represent the first demonstration of sustained systemic release of a transgene product using HSV vectors, raising the prospect of new applications for HSV-1 vectors in the treatment of systemic disease.

  15. The Coordinated Scheduling Support System of Production and Delivery

    Directory of Open Access Journals (Sweden)

    Ming-Feng Yang

    2009-01-01

    Full Text Available Problem statement: Traditional scheduling models which only address the sequence of jobs to be processed at the production stage under some criteria are no longer suitable and should be extended to cope with the distribution stage after production. In a rapidly changing environment, competition among enterprises has a tendency to turn towards competing between supply chain systems instead of competing between individual companies. Emphasizing on the coordination and the integration among various members of a supply chain has become one of the vital strategies for the modern manufacturers to gain competitive advantages. Approach: This research focuses mainly on a class of two-stage scheduling problem, in which jobs need to be delivered to customers by vehicles after the completion of their respective production. It is assumed that the transportation time of a vehicle is constant and jobs to be delivered occupy different physical spaces. Results: The result of this research is to show the scheduling problem with the objective of minimizing total completion time is intractable and to develop a heuristic by incorporating properties inherited in an the optimal schedule. In addition, we take a Decision Support System (DSS view to construct a Scheduling Support System (SSS for solving the scheduling problem with delivery coordination. Conclusion/Recommendations: The scheduling support system with an additional problem management subsystem can provide more useful information for users when the management makes a strategic decision than traditional scheduling methods can. It can give firms a competitive advantage on the global competitive market.

  16. New developments and opportunities in oral mucosal drug delivery for local and systemic disease.

    Science.gov (United States)

    Hearnden, Vanessa; Sankar, Vidya; Hull, Katrusha; Juras, Danica Vidović; Greenberg, Martin; Kerr, A Ross; Lockhart, Peter B; Patton, Lauren L; Porter, Stephen; Thornhill, Martin H

    2012-01-01

    The oral mucosa's accessibility, excellent blood supply, by-pass of hepatic first-pass metabolism, rapid repair and permeability profile make it an attractive site for local and systemic drug delivery. Technological advances in mucoadhesives, sustained drug release, permeability enhancers and drug delivery vectors are increasing the efficient delivery of drugs to treat oral and systemic diseases. When treating oral diseases, these advances result in enhanced therapeutic efficacy, reduced drug wastage and the prospect of using biological agents such as genes, peptides and antibodies. These technologies are also increasing the repertoire of drugs that can be delivered across the oral mucosa to treat systemic diseases. Trans-mucosal delivery is now a favoured route for non-parenteral administration of emergency drugs and agents where a rapid onset of action is required. Furthermore, advances in drug delivery technology are bringing forward the likelihood of transmucosal systemic delivery of biological agents.

  17. Implications of nanoscale based drug delivery systems in delivery and targeting tubulin binding agent, noscapine in cancer cells.

    Science.gov (United States)

    Chandra, Ramesh; Madan, Jitender; Singh, Prashant; Chandra, Ankush; Kumar, Pradeep; Tomar, Vartika; Dass, Sujata K

    2012-12-01

    Noscapine, a tubulin binding anticancer agent undergoing Phase I/II clinical trials, inhibits tumor growth in nude mice bearing human xenografts of breast, lung, ovarian, brain, and prostrate origin. The analogues of noscapine like 9-bromonoscapine (EM011) are 5 to 10-fold more active than parent compound, noscapine. Noscapinoids inhibit the proliferation of cancer cells that are resistant to paclitaxel and epothilone. Noscapine also potentiated the anticancer activity of doxorubicin in a synergistic manner against triple negative breast cancer (TNBC). However, physicochemical and pharmacokinetic (ED50˜300-600 mg/kg bodyweight) limitations of noscapine present hurdle in development of commercial anticancer formulations. Therefore, objectives of the present review are to summarize the chemotherapeutic potential of noscapine and implications of nanoscale based drug delivery systems in enhancing the therapeutic efficacy of noscapine in cancer cells. We have constructed noscapine-enveloped gelatin nanoparticles, NPs and poly (ethylene glycol) grafted gelatin NPs as well as inclusion complex of noscapine in β-cyclodextrin (β-CD) and evaluated their physicochemical characteristics. The Fe3O4 NPs were also used to incorporate noscapine in its polymeric nanomatrix system where molecular weight of the polymer governed the encapsulation efficiency of drug. The enhanced noscapine delivery using μPAR-targeted optical-MR imaging trackable NPs offer a great potential for image directed targeted delivery of noscapine. Human Serum Albumin NPs (150-300 nm) as efficient noscapine drug delivery systems have also been developed for potential use in breast cancer.

  18. Approaches and Challenges of Engineering Implantable Microelectromechanical Systems (MEMS Drug Delivery Systems for in Vitro and in Vivo Applications

    Directory of Open Access Journals (Sweden)

    Ken-Tye Yong

    2012-11-01

    Full Text Available Despite the advancements made in drug delivery systems over the years, many challenges remain in drug delivery systems for treating chronic diseases at the personalized medicine level. The current urgent need is to develop novel strategies for targeted therapy of chronic diseases. Due to their unique properties, microelectromechanical systems (MEMS technology has been recently engineered as implantable drug delivery systems for disease therapy. This review examines the challenges faced in implementing implantable MEMS drug delivery systems in vivo and the solutions available to overcome these challenges.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Systemic drug delivery systems for bone tissue regeneration- a mini review.

    Science.gov (United States)

    Xinluan, Wang; Yuxiao, Lai; Helena, Ng HueiLeng; Zhijun, Yang; Ling, Qin

    2015-01-01

    Musculoskeletal metabolic diseases such as osteoporosis have become the major public health problems worldwide in our aging society. Pharmaceutical therapy is one of the approaches to prevent and treat related medical conditions. Most of the clinically used anti-osteoporotic drugs are administered systemically and have demonstrated some side effects in non-skeletal tissues. One of the innovative approaches to prevent potential adverse effects is the development of bone-targeting drug delivery technologies that not only minimizes the systemic toxicity but also improves the pharmacokinetic profile and therapeutic efficacy of chemical drugs. This paper reviews the currently available bone targeting drug delivery systems with emphasis as bone-targeting moieties, including the bonesurface- site-specific (bone formation dominant or bone resorption dominant) and cell-specific moieties. In addition, the connections of drug-bone-targeting moieties-carrier are also summarized, and the newly developed liposomes and nanoparticles are discussed for their potential use and main challenges in delivering therapeutic agents to bone tissue. As a rapid-developing biotechnology, systemic bonetargeting delivery system is promising but still in its infancy where challenges are ahead of us, including the stability and the toxicity issues, especially to fulfill the regulatory requirement to realize bench-to-bedside translation. Newly developed biomaterials and technologies with potential for safer and more effective drug delivery require multidisciplinary collaborations with preclinical and clinical scientists that are essential to facilitate their clinical applications.

  1. Multiple sclerosis: Therapeutic applications of advancing drug delivery systems.

    Science.gov (United States)

    Dolati, Sanam; Babaloo, Zohreh; Jadidi-Niaragh, Farhad; Ayromlou, Hormoz; Sadreddini, Sanam; Yousefi, Mehdi

    2017-02-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, which is accompanying with demyelination, neurodegeneration and sensibility to oxidative stress. In MS, auto-reactive lymphocytes cross the blood-brain barrier (BBB) and reside in the perivenous demyelinating lesions which create various distinct inflammatory demyelinated plaques situated predominantly in the white matter. The current MS-related therapeutic approaches can be classified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs suppress circulating immune cells, inhibit passing the BBB and decrease the inflammatory responses. Recent advances have remarkably delayed disease development and improved the quality of life for numerous patients. In spite of major improvements in therapeutic options, there are some limitations regarding the routes of administration and the necessity for repeated and long-term dosing in which cause to systemic disadvantageous consequences and patient non-compliance. Nanotechnology presents promising approaches to improve autoimmune disease treatment with the capability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we emphasis on nanomedicine-based drug delivery approaches of biological immunomodulatory mediators for the treatment of multiple sclerosis. This comprehensive review details the most successful drugs in MS therapy and also focuses on conceptions and clinical potential of novel nanomedicine attitudes for inducing immunosuppression and immunological tolerance in MS to modulate abnormal and pathologic immune responses.

  2. CARBON NANOTUBES: AN APPROACH TO NOVEL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    M. H. Alai et al.

    2012-01-01

    Full Text Available Carbon nanotubes are cylindrical carbon molecules have novel properties, making them potentially useful in many applications in nanotechnology, electronics, optics, and other fields of material science as well as potential uses in architectural fields. They have unique electronic, mechanical, optical and chemical properties that make them good candidates for a wide variety of applications, including drug transporters, new therapeutics, delivery systems and diagnostics. Their unique surface area, stiffness, strength and resilience have led to much excitement in the field of pharmacy. Nanotubes are categorized as single-walled nanotubes, multiple walled nanotubes. Various techniques have been developed to produce nanotubes in sizeable quantities, including arc discharge, laser ablation, chemical vapor deposition. They can pass through membranes, carrying therapeutic drugs, vaccines and nucleic acids deep into the cell to targets previously unreachable. Purification of the tubes can be divided into a couple of main techniques: oxidation, acid treatment, annealing, sonication, filtering and functionalization techniques. The main problem of insolubility in aqueous media has been solved by developing a synthetic protocol that allows highly water-soluble carbon NTs to be obtained. The modifications are done to improve efficiency of carbon nanotubes by formulating luminescent carbon nanotubes, ultrathin carbon nanoneedles, magnetically guided nanotubes. The application of carbon nanotube in tissue engineering, drug carrier release system, wound healing, in cancer treatment and as biosensor. Researchers have recently developed a new approach to Boron Neutron Capture Therapy in the treatment of cancer using substituted Carborane-Appended Water-Soluble single-wall carbon nanotubes.

  3. An experimental platform for systemic drug delivery to the retina.

    LENUS (Irish Health Repository)

    Campbell, Matthew

    2009-10-20

    Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders--major causes of world blindness--are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-\\/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment.

  4. Marketed New Drug Delivery Systems for Opioid Agonists/Antagonists Administration: A Rapid Overview.

    Science.gov (United States)

    Soltani, Hoda; Pardakhty, Abbas

    2016-04-01

    Novel drug delivery systems for controlled-release of opioid agonists as a long time painkillers or opioid antagonists for opium, heroin, and alcohol addiction are under development or in clinical use today. In this article, the field of "new drug delivery systems" is momentarily reviewed from the viewpoint of the marketed opioid agonists/antagonists dosage forms today.

  5. 21 CFR 876.5600 - Sorbent regenerated dialysate delivery system for hemodialysis.

    Science.gov (United States)

    2010-04-01

    ... hemodialysis. 876.5600 Section 876.5600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND....5600 Sorbent regenerated dialysate delivery system for hemodialysis. (a) Identification. A sorbent regenerated dialysate delivery system for hemodialysis is a device that is part of an artificial kidney...

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

    Directory of Open Access Journals (Sweden)

    Jafar Ezzati Nazhad Dolatabadi

    2015-06-01

    Full Text Available 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.

  7. Autoantibodies against nuclear, nucleolar, and mitochondrial antigens in systemic sclerosis (scleroderma).

    Science.gov (United States)

    Reimer, G

    1990-02-01

    One of the most characteristic serologic features of systemic sclerosis (scleroderma) is the occurrence of autoantibodies against nuclear and most notably against nucleolar antigens. This humoral autoimmune response is one of best studied immunologic phenomena in scleroderma. Detailed molecular information on the structure and function, as well as on reactive epitopes of autoantigens targeted by specific serum antibodies, has been revealed by clinical, immunologic, and biochemic studies in several laboratories. Autoantigens such as DNA topoisomerase I (Scl-70), centromere proteins, RNA polymerase I, U3 RNP-associated fibrillarin, PM-Scl, and 7-2 RNP antigens were shown to be specific targets of scleroderma patients and were observed to have clinical correlates within the scleroderma disease spectrum. Therefore, autoantibodies in scleroderma are not only valuable diagnostic tools but also prognosticators of the disease. Although autoantibodies in scleroderma do not appear to play a pathogenetic role in the disease process, the knowledge of the structure and function of their reactive antigens may help in answering questions concerning the etiology of the disease.

  8. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients

    Directory of Open Access Journals (Sweden)

    Anette Holck Draborg

    2016-01-01

    Full Text Available We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV antigens in systemic lupus erythematosus (SLE patients and healthy controls (HCs to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired EBV-directed T-cell response. The concentrations of 14 cytokines (IL2, IL4, IL5, IL6, IL10, IL12, IL17, IL18, IL1β, IFNγ, TNFα, TNFβ, TGFβ, and GM-CSF were quantified upon stimulation of whole blood with latent state antigen EBNA1, lytic cycle antigen EBV-EA/D, and the superantigen SEB. To avoid results affected by lack of lymphocytes, we focused on SLE patients with normal levels. Decreased induction of IL12, IFNγ, IL17, and IL6 upon EBNA1 stimulation and that of IFNγ, IL6, TNFβ, IL1β, and GM-CSF upon EBV-EA/D stimulation were detected in SLE patients compared to HCs. IFNγ responses, especially, were shown to be reduced. Induction of several cytokines was furthermore impaired in SLE patients upon SEB stimulation, but no difference was observed in basic levels. Results substantiate the previously proposed impaired regulation of the immune response against latent and lytic cycle EBV infection in SLE patients without lymphopenia. Furthermore, results indicate general dysfunction of leukocytes and their cytokine regulations in SLE patients.

  9. Antigen presenting cells in the skin of a patient with hair loss and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2009-01-01

    Full Text Available Context: Hair loss is one of the most striking clinical features of active systemic lupus erythematosus (SLE, however, very few studies have investigated the immunological features of this process. Case report: We describe a 33 years old female who presented with scalp hair loss and arthralgias. Physical examination revealed erythematous plaques on the nose and scalp, with bitemporal hair loss. Scalp biopsies revealed epidermal hyperkeratosis, with a mild interface infiltrate of lymphocytes and histiocytes and a superficial and deep, perivascular and periadnexal infiltrate of mostly CD4 positive cells. Antibodies to HAM 56, CD68, CD1a, S-100, mast cell tryptase and c-kit/CD117 were strongly positive around the hair follicles, and in the adjacent sebaceous glands. Conclusion : We present the first report showing a significant presence of several antigen presenting cells around the hair follicular units in a patient with alopecia in active SLE. Today, antigen presenting cells and dendritic cells (DC are modeled as the master regulators of human immunity. One aspect that has become clearly appreciated is the great diversity of DC subtypes, each with considerable functional differences. Thus, we suggest that APC and DCs are equipped with Pattern Recognition Receptors (PRRs to some hair follicular unit antigens; that these innate sensors recognize conserved molecular patterns on self- tissue, and play a significant role in the pathophysiology of alopecia in SLE patients

  10. Requirements for Electronic Delivery Systems in eGovernment - An Austrian Experience

    Science.gov (United States)

    Tauber, Arne

    Electronic mailing systems are the dominant communication systems in private and business matters. Public administrations deliver documents to citizens and businesses - subpoenas, legal verdicts, notifications, administrative penalties etc. However, official activities are more strongly linked to legal regulations than in civil law. Delivery of crucial and strictly personal documents raises the demand for qualified identification and non-repudiation services as featured by registered mail in the paper world. Legal requirements for electronic delivery carried-out by public administrations (eDelivery) cannot be fulfilled by standard certified mailing systems. Although the requirements for eDelivery systems may differ due to national legal regulations, this paper discusses common requirements and challenges on an abstract level. Moreover, we show how these requirements have been addressed by introducing the Austrian eDelivery system for eGovernment applications.

  11. RECENT ADVANCEMENT OF LIPID DRUG CONJUGATE AS NANOPARTICULATE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Ratna Jyoti Das

    2013-01-01

    Full Text Available Nanotechnology by manipulation of characteristics of materials such as polymers and fabrication of nanostructures is able to provide superior drug delivery systems for better management and treatment of diseases. The nanostructures employed as drug delivery systems have multiple advantages which make them superior to conventional delivery systems. Nanotechnology is one approach to overcome challenges of conventional drug delivery systems based on the development and fabrication of nanostructures. Some challenges associated with the technology as it relates to drug effectiveness, toxicity, stability and pharmacokinetics and drug regulatory control. Nanotechnology is a welcome development that is set to transform drug delivery and drug supply chain management, if optimally developed. Lipid Drug Conjugates (LDCs are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Due to their unique size dependent properties, lipid nanoparticles offer possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could use for drug targeting. Hence lipid drug conjugates hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. Solid lipid nanoparticle technology represents a promising new approach to lipophile drug delivery.

  12. Nanobiotechnology and its applications in drug delivery system: a review.

    Science.gov (United States)

    Khan, Imran; Khan, Momin; Umar, Muhammad Naveed; Oh, Deog-Hwan

    2015-12-01

    Nanobiotechnology holds great potential in various regimes of life sciences. In this review, the potential applications of nanobiotechnology in various sectors of nanotechnologies, including nanomedicine and nanobiopharmaceuticals, are highlighted. To overcome the problems associated with drug delivery, nanotechnology has gained increasing interest in recent years. Nanosystems with different biological properties and compositions have been extensively investigated for drug delivery applications. Nanoparticles fabricated through various techniques have elevated therapeutic efficacy, provided stability to the drugs and proved capable of targeting the cells and controlled release inside the cell. Polymeric nanoparticles have shown increased development and usage in drug delivery as well as in diagnostics in recent decades.

  13. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  14. 黏膜疫苗传递系统的研究进展%Progress of Mucosal Vaccine Delivery Systems

    Institute of Scientific and Technical Information of China (English)

    陈志祥; 陆伟根

    2011-01-01

    Mucosal vaccine is considered as the most suitable type of vaccination agents to combat infectious diseases because of their ability to induce both systemic and local mucosal immune response. However, mucosal vaccines suffer from two main problems: inefficient antigen uptake from the mucosal surfaces and difficulty in eliciting effective immune responses. Therefore, developing new delivery systems for mucosal vaccines must overcome these obstacles.The progress of the mechanism of mucosal immunity, features of mucosal vaccines, and current situation in research of their delivery systems are summarized.%黏膜疫苗能同时诱导系统和局部黏膜免疫应答,是预防感染性疾病最理想的一类疫苗.但黏膜疫苗存在两大障碍:抗原无效摄取和难以引发有效免疫反应.因此,研发新型黏膜疫苗传递系统必须要克服这些障碍.本文综述了黏膜免疫的作用机制、黏膜疫苗的特点及其传递系统的研究现状.

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

    Energy Technology Data Exchange (ETDEWEB)

    Shu Shujun; Sun Lei; Zhang Xinge, E-mail: zhangxinge@nankai.edu.cn [Nankai University, Key Laboratory of Functional Polymer Materials Ministry of Education, Institute of Polymer Chemistry (China); Wu Zhongming [Tianjin Medical University, Metabolic Diseases Hospital (China); Wang Zhen; Li Chaoxing, E-mail: lcx@nankai.edu.cn [Nankai University, Key Laboratory of Functional Polymer Materials Ministry of Education, Institute of Polymer Chemistry (China)

    2011-09-15

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

  16. Heparin-based nanocapsules as potential drug delivery systems.

    Science.gov (United States)

    Baier, Grit; Winzen, Svenja; Messerschmidt, Claudia; Frank, Daniela; Fichter, Michael; Gehring, Stephan; Mailänder, Volker; Landfester, Katharina

    2015-06-01

    Herein, the synthesis and characterization of heparin-based nanocapsules (NCs) as potential drug delivery systems is described. For the synthesis of the heparin-based NCs, the versatile method of miniemulsion polymerization at the droplets interface was achieved resulting in narrowly distributed NCs with 180 nm in diameter. Scanning and transmission electron microscopy images showed clearly NC morphology. A highly negative charge density for the heparin-based NCs was determined by measuring the electro-kinetic potential. Measuring the activated clotting time demonstrated the biological intactness of the polymeric shell. The ability of heparin-based NCs to bind to antithrombin (AT III) was investigated using isothermal titration calorimetry and dynamic light scattering experiments. The chemical stability of the NCs was studied in physiological protein-containing solutions and also in medically interesting fluids such as sodium chloride 0.9%, Ringer's solution, and phosphate buffer saline using dynamic light scattering and measuring the fluorescence intensity. The impressive uptake of NCs in different cells was confirmed by fluorescence-activated cell sorting, confocal laser scanning microscopy, and transmission electron microscopy. The low toxicity of all types of NCs was demonstrated.

  17. Buccoadhesive drug delivery system of isosorbide dinitrate: Formulation and evaluation

    Directory of Open Access Journals (Sweden)

    Doijad R

    2006-01-01

    Full Text Available Buccoadhesive buccal delivery systems for isosorbide dinitrate in the form of unidirectional buccal films were developed and characterized for improving bioavailability. The films were formulated by solvent casting method using different bioadhesive polymers like Carbopol 934P and polyvinyl pyrrolidone by using two different plasticizers propylene glycol and diethyl phthalate. Unidirectional release was achieved by preparing composite films with backing membrane. The films were characterized on the basis of their physical characteristics, bioadhesive performance, and other parameters. In vitro studies revealed that release rate of isosorbide dinitrate was higher from carbopol films containing ratio of Eudragit RL100 and polyvinyl pyrrolidine in proportion of 1:2 and 2:1, respectively by using both plasticizers. Drug diffusion from buccal films showed apparently zero order kinetics and release mechanism was diffusion controlled after considerable swelling. All the films exhibited sufficient in vitro bioadhesion strength. Promising formulations were further studied for temperature dependent stability studies. Results of our preliminary experiments indicate that, therapeutic level of isosorbide dinitrate can be achieved using this buccaladhesive formulation.

  18. Investigation of different emulsion systems for dermal delivery of nicotinamide.

    Science.gov (United States)

    Tuncay, Sakine; Özer, Özgen

    2013-01-01

    Nicotinamide (NA) has been shown to have beneficial effects on several skin diseases such as tumor, acne vulgaris, photodamage, cellulite and atopic dermatitis. The purpose of this study was to develop a multiple emulsion and a microemulsion formulation as delivery systems for NA. A two-step process was used to prepare the W/O/W multiple emulsion. Optimum microemulsion formulation was selected by using construction of pseudo-ternary phase diagram. The physicochemical properties such as droplet size and viscosity measurements, stability studies were also evaluated. Ex-vivo permeation studies were performed with Franz-type diffusion cells and the samples were analysed by high performance liquid chromatography (HPLC). The permeation data showed that there was no significant difference between multiple emulsion and microemulsion (p > 0.05). Transepidermal water loss (TEWL) was also measured. As a result of TEWL studies, a slight increase of TEWL values was observed for microemulsion formulation on rat skin when compared with multiple emulsion and commercial formulation. The results suggested that microemulsion and multiple emulsion formulations could be new and alternative dosage forms for topical application of NA.

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

    Science.gov (United States)

    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.

  20. Liposome-Based Delivery Systems in Plant Polysaccharides

    Directory of Open Access Journals (Sweden)

    Meiwan Chen

    2012-01-01

    Full Text Available Plant polysaccharides consist of many monosaccharide by α- or β-glycosidic bond which can be extracted by the water, alcohol, lipophile liquid from a variety of plants including Cordyceps sinensis, astragalus, and mushrooms. Recently, many evidences illustrate that natural plant polysaccharides possess various biological activities including strengthening immunity, lowering blood sugar, regulating lipid metabolism, antioxidation, antiaging, and antitumour. Plant polysaccharides have been widely used in the medical field due to their special features and low toxicity. As an important drug delivery system, liposomes can not only encapsulate small-molecule compound but also big-molecule drug; therefore, they present great promise for the application of plant polysaccharides with unique physical and chemical properties and make remarkable successes. This paper summarized the current progress in plant polysaccharides liposomes, gave an overview on their experiment design method, preparation, and formulation, characterization and quality control, as well as in vivo and in vitro studies. Moreover, the potential application of plant polysaccharides liposomes was prospected as well.

  1. Design and optimization of floating drug delivery system of acyclovir

    Directory of Open Access Journals (Sweden)

    Kharia A

    2010-01-01

    Full Text Available The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1 and hydroxypropylmethylcellulose K4M (X2 were selected as independent variables. The times required for 50% (t 50% and 70% (t 70% drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2. The closeness of predicted and observed values for t 50% and t 70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi′s kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

  2. A novel colonic drug delivery system of ibuprofen

    Directory of Open Access Journals (Sweden)

    Gohel M

    2009-01-01

    Full Text Available The present endeavor was directed towards fabrication of the novel colonic drug delivery system of ibuprofen. To begin with, the hydroxypropyl methylcellulose capsules containing adsorbate of eutectic mixture of ibuprofen and menthol and pregelatinized starch were coated with ethyl cellulose. These ethyl cellulose coated capsules were filled in another capsule and the capsules were coated with a Eudragit; S100. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2 (two hour, 6.0 (1hr, 7.2 (two hour and 6.4 (three hour mimicking different regions of gastrointestinal tract. The optimized batch with two per cent and 6.5% weight gain of ethyl cellulose and Eudragit; S100 showed less than eight per cent drug release in stomach and intestinal pH. The remaining 92% drug release was obtained thereafter from the optimized batch within two hours in colonic pH. Scanning electron microscopy study of the optimized batch confirmed presence of ibuprofen crystals (rod shape in the formulation. The infrared spectroscopy study of the optimized batch indicated stability of ibuprofen during processing of the formulation.

  3. Leadership Perspectives on Operationalizing the Learning Health Care System in an Integrated Delivery System

    Science.gov (United States)

    Psek, Wayne; Davis, F. Daniel; Gerrity, Gloria; Stametz, Rebecca; Bailey-Davis, Lisa; Henninger, Debra; Sellers, Dorothy; Darer, Jonathan

    2016-01-01

    Introduction: Healthcare leaders need operational strategies that support organizational learning for continued improvement and value generation. The learning health system (LHS) model may provide leaders with such strategies; however, little is known about leaders’ perspectives on the value and application of system-wide operationalization of the LHS model. The objective of this project was to solicit and analyze senior health system leaders’ perspectives on the LHS and learning activities in an integrated delivery system. Methods: A series of interviews were conducted with 41 system leaders from a broad range of clinical and administrative areas across an integrated delivery system. Leaders’ responses were categorized into themes. Findings: Ten major themes emerged from our conversations with leaders. While leaders generally expressed support for the concept of the LHS and enhanced system-wide learning, their concerns and suggestions for operationalization where strongly aligned with their functional area and strategic goals. Discussion: Our findings suggests that leaders tend to adopt a very pragmatic approach to learning. Leaders expressed a dichotomy between the operational imperative to execute operational objectives efficiently and the need for rigorous evaluation. Alignment of learning activities with system-wide strategic and operational priorities is important to gain leadership support and resources. Practical approaches to addressing opportunities and challenges identified in the themes are discussed. Conclusion: Continuous learning is an ongoing, multi-disciplinary function of a health care delivery system. Findings from this and other research may be used to inform and prioritize system-wide learning objectives and strategies which support reliable, high value care delivery. PMID:27683668

  4. 7 CFR 246.12 - Food delivery systems.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS SPECIAL SUPPLEMENTAL NUTRITION PROGRAM FOR WOMEN, INFANTS AND CHILDREN... the delivery of health and nutrition education services to participants. (e) Retail food...

  5. The effect of carbon nanotubes on drug delivery in an electro-sensitive transdermal drug delivery system.

    Science.gov (United States)

    Im, Ji S; Bai, Byong Ch; Lee, Young-Seak

    2010-02-01

    An electro-sensitive transdermal drug delivery system was prepared by the electrospinning method to control drug release. A semi-interpenetrating polymer network was prepared as the matrix with polyethylene oxide and pentaerythritol triacrylate polymers. Multi-walled carbon nanotubes were used as an additive to increase the electrical sensitivity. The release experiment was carried out under different electric voltage conditions. Carbon nanotubes were observed in the middle of the electrospun fibers by SEM and TEM. The amount of released drug was effectively increased with higher applied electric voltages. These results were attributed to the excellent electrical conductivity of the carbon additive. The suggested mechanism of drug release involves polyethylene oxide of the semi-interpenetrating polymer network being dissolved under the effects of carbon nanotubes, thereby releasing the drug. The effects of the electro-sensitive transdermal drug delivery system were enhanced by the carbon nanotubes.

  6. Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors

    Science.gov (United States)

    Zhu, Yu

    Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo

  7. A Fully Integrated Microneedle-based Transdermal Drug Delivery System

    OpenAIRE

    Roxhed, Niclas

    2007-01-01

    Patch-based transdermal drug delivery offers a convenient way to administer drugs without the drawbacks of standard hypodermic injections relating to issues such as patient acceptability and injection safety. However, conventional transdermal drug delivery is limited to therapeutics where the drug can diffuse across the skin barrier. By using miniaturized needles, a pathway into the human body can be established which allow transport of macromolecular drugs such as insulins or vaccines. These...

  8. Miniature Sample Collection and Delivery System using Gas-Entrained Powder Transport Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose to develop a miniature system for acquisition and delivery of solid samples to landed planetary instruments. This system would entrain powder produced by...

  9. Amino-functionalized poly(L-lactide lamellar single crystals as a valuable substrate for delivery of HPV16-E7 tumor antigen in vaccine development

    Directory of Open Access Journals (Sweden)

    Di Bonito P

    2015-05-01

    Full Text Available Paola Di Bonito,1 Linda Petrone,1 Gabriele Casini,2 Iolanda Francolini,2 Maria Grazia Ammendolia,3 Luisa Accardi,1 Antonella Piozzi,2 Lucio D’Ilario,2 Andrea Martinelli2 1Department of Infectious, Parasitic and Immune-mediated Diseases, Italian National Institute of Health, 2Department of Chemistry, Sapienza University of Rome, Rome, Italy; 3Department of Technology and Health, Italian National Institute of Health, Rome, Italy Background: Poly(L-lactide (PLLA is a biodegradable polymer currently used in many biomedical applications, including the production of resorbable surgical devices, porous scaffolds for tissue engineering, nanoparticles and microparticles for the controlled release of drugs or antigens. The surfaces of lamellar PLLA single crystals (PLLAsc were provided with amino groups by reaction with a multifunctional amine and used to adsorb an Escherichia coli-produced human papillomavirus (HPV16-E7 protein to evaluate its possible use in antigen delivery for vaccine development.Methods: PLLA single crystals were made to react with tetraethylenepentamine to obtain amino-functionalized PLLA single crystals (APLLAsc. Pristine and amino-functionalized PLLAsc showed a two-dimensional microsized and one-dimensional nanosized lamellar morphology, with a lateral dimension of about 15–20 µm, a thickness of about 12 nm, and a surface specific area of about 130 m2/g. Both particles were characterized and loaded with HPV16-E7 before being administered to C57BL/6 mice for immunogenicity studies. The E7-specific humoral-mediated and cell-mediated immune response as well as tumor protective immunity were analyzed in mice challenged with TC-1 cancer cells.Results: Pristine and amino-functionalized PLLAsc adsorbed similar amounts of E7 protein, but in protein-release experiments E7-PLLAsc released a higher amount of protein than E7-APLLAsc. When the complexes were dried for observation by scanning electron microscopy, both samples showed a

  10. ROLE OF XANTHAN GUM (XANTHOMONAS COMPESTRIS IN GASTRORETENTIVE DRUG DELIVERY SYSTEM: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Uday Prakash

    2013-04-01

    Full Text Available Floating drug delivery system is the form of gastro-retentive drug delivery system. That controls kinetic release rate of drug to a specific site for its pharmacological action. These are achieved by use of various polymeric substances including natural polymer such as xanthan gum. This delivery system prolongs the retention time of the drug in the stomach as compared to conventional dosage form. The present article highlights the use of xanthan gum for the formulation of the gastro-retentive drug delivery system especially with natural polymer (xanthan gum. The main goal of any drug delivery system is to achieve desired concentration of the drug in blood or tissue, which is therapeutically effective and non toxic for a prolonged period. Oral delivery of drugs is by far the most preferable route of drug delivery due to the ease of administration, patient compliance and flexibility in formulation etc. From immediate release to cite specific delivery, oral dosage forms have really progressed.

  11. Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.

    Science.gov (United States)

    Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

    2015-05-01

    Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.

  12. Antigen 43-mediated autotransporter display, a versatile bacterial cell surface presentation system

    DEFF Research Database (Denmark)

    Kjærgaard, Kristian; Hasman, Henrik; Schembri, Mark;

    2002-01-01

    Antigen 43 (Ag43), a self-recognizing outer membrane protein of Escherichia coli, has been converted into an efficient and versatile tool for surface display of foreign protein segments. Ag43 is an autotransporter protein characterized by the feature that all information required for transport...... to the outer membrane and secretion through the cell envelope is contained within the protein itself. Ag43 consists of two subunits (alpha and beta), where the beta-subunit forms an integral outer membrane translocator to which the alpha-subunit is noncovalently attached. The simplicity of the Ag43 system...

  13. Live bacterial delivery systems for development of mucosal vaccines

    NARCIS (Netherlands)

    Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.

    2000-01-01

    By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

  14. Based on 3G and RFID logistic delivery management system application and practice analysis

    Science.gov (United States)

    Li, Xiaojun; Peng, Longjun; Zhong, Kaiwen; Huang, Jianming

    2008-10-01

    This article in view of the Logistic Delivery Management characteristic, analysis the logistic delivery management cannot satisfy requests rapid reaction and conformity transportation at present and so on. This article elaborated based on 3G (GIS, GPS, and GPRS) and RFID technology logistic delivery contents and so on management system, system design and architecture design, and its effective integration. The system design mentality uses the systems engineering method, follows the humanist idea, and embarks from user's demand, according to the user demand and the network request, divides according to the laminated structure into the decision-making strata, the service level, the management maintenance level and the technical support level 4 levels. The overall structural design including the system function structural design and the software system design, and take some province logistic delivery management system in management service as an example, introduced the design mentality and the application way.

  15. Systemic activation of antigen-presenting cells via RNA-loaded nanoparticles

    Science.gov (United States)

    Sayour, Elias J.; Pham, Christina; Grippin, Adam; Kemeny, Hanna; Chua, Joshua; Sampson, John H.; Sanchez-Perez, Luis; Flores, Catherine; Mitchell, Duane A.

    2017-01-01

    ABSTRACT While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction. We screened commercially available nanoliposomal preparations and identified the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as an efficient mRNA courier to antigen-presenting cells (APCs). When administered intravenously, RNA-NPs mediate systemic activation of APCs in reticuloendothelial organs such as the spleen, liver, and bone marrow. RNA-NPs increase percent expression of MHC class I/II, B7 co-stimulatory molecules, and maturation markers on APCs (all vital for T-cell activation). RNA-NPs also increase activation markers on tumor APCs and elicit potent expansion of antigen-specific T-cells superior to peptide vaccines formulated in complete Freund's adjuvant. We demonstrate that both model antigen-encoding and physiologically-relevant tumor-derived RNA-NPs expand potent antitumor T-cell immunity. RNA-NPs were shown to induce antitumor efficacy in a vaccine model and functioned as a suitable alternative to DCs in a stringent cellular immunotherapy model for a radiation/temozolomide resistant invasive murine high-grade glioma. Although cancer vaccines have suffered from weak immunogenicity, we have advanced a RNA-NP formulation that systemically activates host APCs precipitating activated T-cell frequencies necessary to engender antitumor efficacy. RNA-NPs can thus be harnessed as a more feasible and effective immunotherapy to re-program host-immunity. PMID:28197373

  16. 75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Science.gov (United States)

    2010-08-03

    ... and Related Drug Delivery Systems; Availability AGENCY: Food and Drug Administration, HHS. ACTION... guidance for industry entitled ``Residual Drug in Transdermal and Related Drug Delivery Systems.'' This draft guidance provides recommendations to developers and manufacturers of transdermal drug...

  17. Nano-microdelivery systems for oral delivery of an active ingredient

    DEFF Research Database (Denmark)

    2014-01-01

    A composition for oral delivery of one or more active ingredients in the form of a lipid nano-micro-delivery system comprising a lipid nano-micro-structure comprising at least one lipid and at least one active ingredient, said at least one active ingredient being immobilized in said lipid nano...

  18. Marketed New Drug Delivery Systems for Opioid Agonists/Antagonists Administration: A Rapid Overview

    OpenAIRE

    Soltani, Hoda; Pardakhty, Abbas

    2016-01-01

    Novel drug delivery systems for controlled-release of opioid agonists as a long time painkillers or opioid antagonists for opium, heroin, and alcohol addiction are under development or in clinical use today. In this article, the field of “new drug delivery systems” is momentarily reviewed from the viewpoint of the marketed opioid agonists/antagonists dosage forms today.

  19. Superficial fascial system repair: an abdominoplasty technique to reduce local complications after caesarean delivery.

    Science.gov (United States)

    Al-Benna, Sammy; Al-Ajam, Yazan; Tzakas, Elias

    2009-05-01

    Abdominal incision complications are a major source of morbidity after caesarean delivery. Repair of the superficial fascial system may avert local complications after caesarean delivery by minimising tension to the skin and increasing the initial biomechanical strength of wound which has the potential to decrease early wound dehiscence and as a by-product correct suprapubic bulging.

  20. Solid lipid nanoparticles as nucleic acid delivery system : Properties and molecular mechanisms

    NARCIS (Netherlands)

    Bispo de Jesus, Marcelo; Zuhorn, Inge S.

    2015-01-01

    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 im

  1. Buccal and sublingual vaccine delivery.

    Science.gov (United States)

    Kraan, Heleen; Vrieling, Hilde; Czerkinsky, Cecil; Jiskoot, Wim; Kersten, Gideon; Amorij, Jean-Pierre

    2014-09-28

    Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination. An important characteristic of mucosal vaccination is its ability to elicit local immune responses, which act against infection at the site of pathogen entry. However, mucosal surfaces are endowed with potent and sophisticated tolerance mechanisms to prevent the immune system from overreacting to the many environmental antigens. Hence, mucosal vaccination may suppress the immune system instead of induce a protective immune response. Therefore, mucosal adjuvants and/or special antigen delivery systems as well as appropriate dosage forms are required in order to develop potent mucosal vaccines. Whereas oral, nasal and pulmonary vaccine delivery strategies have been described extensively, the sublingual and buccal routes have received considerably less attention. In this review, the characteristics of and approaches for sublingual and buccal vaccine delivery are described and compared with other mucosal vaccine delivery sites. We discuss recent progress and highlight promising developments in the search for vaccine formulations, including adjuvants and suitable dosage forms, which are likely critical for designing a successful sublingual or buccal vaccine. Finally, we outline the challenges, hurdles to overcome and formulation issues relevant for sublingual or buccal vaccine delivery.

  2. A novel HBV antisense RNA gene delivery system targeting hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chun-Hong Ma; Xiao-Hong Liang; Wen-Sheng Sun; Pei-Kun Tian; Li-Fen Gao; Su-Xia Liu; Xiao-Yan Wang; Li-Ning Zhang; Ying-Lin Cao; Li-Hui Han

    2003-01-01

    AIM: To construct a novel HBV antisense RNA delivery system targeting hapatocellular carcinoma and study its inhibitory effect in vitro and in vivo.METHODS: GE7,a 16-peptide specific to EGFR, and HA20,a homologue of N-terminus of haemagglutinin of influenza viral envelope protein, were synthesized and conjugated with polylysin. The above conjugates were organized into the pEBAF-as-preS2, a hepatocarcinoma specific HBV antisense expression vector, to construct a novel HBV antisense RNA delivery system, named AFP-enhancing 4-element complex. Hepatocelluar carcinoma HepG2.2.15 cells was used to assay the in vitro inhibition of the complex on HBV. Expression of HBV antigen was assayed by ELISA. BALB/c nude mice bearing HepG2.2.15 cells were injected with AFP-enhancing 4-element complex. The expression of HBV antisense RNA was examined by RT-PCR and the size of tumor in nude mice were measured.RESULTS: The AFP-enhancing 4-element complex was constructed and DNA was completely trapped at the slot with no DNA migration when the ratio of polypeptide to plasmid was 1:1.The expression of HBsAg and HBeAg of HepG2.2.15 cells was greatly decreased after being transfected by AFP-enhancing 4-element complex. The inhibitory rates were 33.4 % and 58.5 % respectively. RTPCR showed HBV antisense RNA expressed specifically in liver tumor cells of tumor-bearing nude mice. After 4injections of AFP-enhancing 4-element complex containing 0.2 μg DNA, the diameter of the tumor was 0.995 cm±0.35,which was significantly smaller than that of the control groups (2.215 cm±0.25, P<0.05).CONCLUSION: AFP-enhancing 4-element complex could deliver HBV antisense RNA targeting on hepatocarcinoma and inhibit both HBV and liver tumor cells in vitro and in vivo.

  3. Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing

    DEFF Research Database (Denmark)

    Werdelin, O; Mouritsen, S; Petersen, B L;

    1988-01-01

    The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic ...

  4. Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV Based Delivery System.

    Directory of Open Access Journals (Sweden)

    Sukalyani Banik

    Full Text Available Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA, chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100 doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

  5. Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV) Based Delivery System.

    Science.gov (United States)

    Banik, Sukalyani; Mansour, Ahd Ahmed; Suresh, Ragavan Varadharajan; Wykoff-Clary, Sherri; Malik, Meenakshi; McCormick, Alison A; Bakshi, Chandra Shekhar

    2015-01-01

    Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA), chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100) doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

  6. Effect of a cyclosporine A delivery system in corneal transplantation

    Institute of Scientific and Technical Information of China (English)

    谢立信; 史伟云; 王治宇; 贝建中; 王身国

    2002-01-01

    Objective To test the immunosuppressive effect of cyclosporine (Cs) in a polymer placed in the anterior chamber of corneal allograft recipients. Methods Wistar inbred rats with vascularized corneas were recipients of corneal allografts from Sprague-Dawley donor rats. Rats underwent penetrating keratoplasty and were divided randomly into four groups: untreated control animals (UCA); Cs-polymer anterior chamber recipients (CPA); co-polymer subconjunctival recipients (CPS); and Cs-olive oil drop recipients (COO). Grafts were examined by slit lamp every 3 days and clinical conditions were scored. Cs concentration in the aqueous humor was assayed at 1, 2, and 4 weeks. At 1, 2 and 4 weeks after transplantation, the operated eyes were collected for histopathological evaluation of the grafts. Results The median survival time of the allografts was 8.2±1.48 days for the UCA group, 11.4±2.50 days for the CPS group, and 17.0±2.00 days for the CPA group. There was a statistically significant difference (P<0.05) between survival time of the allografts in the animals of the CPA group compared to the other groups of graft recipients. Significantly higher concentrations of Cs were found in the eyes given an anterior chamber implant of Cs-polymer, compared to other treatment groups or untreated rats. A transient inflammatory response in the anterior chamber was observed in the CPA group. Conclusions Cs-polymer placed in the anterior chamber significantly prolongs corneal allograft survival time in a high risk corneal graft rejection model. This intraocular delivery system may be a valuable adjunct for the suppression of immune graft rejection.

  7. Systemic oxygen delivery and consumption in dogs with heartworm disease.

    Science.gov (United States)

    Kitagawa, H; Kitoh, K; Yasuda, K; Sasaki, Y

    1995-02-01

    To investigate systemic oxygen (O2) transport, we calculated the oxygen delivery index (Do2I), oxygen consumption index (Vo2I) and oxygen extraction ratio (ER) in dogs with heartworm (HW) disease. The Do2I was 770 +/- 331 ml/min/kg in dogs mildly affected with pulmonary HW disease showing respiratory signs, mild anemia and mild cardiac insufficiency (n = 34); 238 +/- 155 ml/min/kg in dogs with ascitic pulmonary HW disease (n = 7); and 577 +/- 320 ml/min/kg in dogs with caval syndrome (CS) which survived (n = 15) or died (n = 7) after surgical HW removal. The Do2I was lower (P < 0.01) in all HW-infected groups, especially in ascites and CS-non-surviving dogs, than in HW-free dogs (n = 11, 1041 +/- 264 ml/min/kg). The Vo2I was higher in some mildly affected dogs (161 +/- 88 ml/min/kg), and lower (P < 0.01) in ascitic dogs (45 +/- 53 ml/min/kg) than in HW-free dogs (123 +/- 44 ml/min/kg). The ER was higher (P < 0.01) in all HW-infected groups than in HW-free dogs. The Do2I correlated significantly with Vo2I (r = 0.84, P < 0.01), and the Vo2I correlated significantly with ER (r = 0.48, P < 0.01). The Do2I correlated significantly with arterial O2 tension (r = 0.33), serum LDH (r = -0.46) and CK (r = -0.46) activities, serum urea nitrogen (UN, r = -0.32) and lactic acid (LA, r = -0.39) concentrations and cardiac index (r = 0.64).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Matrix embedded microspherules containing indomethacin as controlled drug delivery systems.

    Science.gov (United States)

    Swamy, K M Lokamatha; Satyanath, B; Shantakumar, S M; Manjula, D; Mohammedi, Hafsa; Farhana, Ayesha

    2008-10-01

    This work is focused on the development of controlled drug delivery systems using different wax/fat embedded indomethacin (IM). Discrete wax/fat embedded microspherules containing indomethacin were prepared by using cetostearyl alcohol, paraffin wax and stearic acid by employing emulsification-phase separation method. These matrices have been used as barrier coatings due to their hydrophobic nature. Chemically inert and tasteless nature of wax/fats promotes their use as taste masking agents for bitter drugs. Various waxes and fats are available having different physicochemical properties to suit the needs of formulation. Methyl cellulose (MC) 1% w/v, sodium alginate (SA) 0.5% w/v and Tween-80 (TW) 1% w/v were used as emulgents. The resulting microspherules were discrete, large, spherical and also free flowing. It is revealed from the literature that natures of wax/fat emulgents were found to influence the rate of drug release. In the present work the drug content in all the batches of microspherules were found to be uniform. The rate of drug release corresponded best to first order kinetics, followed by Higuchi and zero-order equations. The release of the model drug from these wax/fat microspherules was prolonged over an extended period of time and the drug release mechanism followed anomalous (non-Fickian) diffusion controlled as well as Super Case II transport. Among the three matrix materials used, paraffin wax retarded the drug release more than the other two. Surface characteristics of microspherules have been studied by Scanning Electron Microscope (SEM). A fair degree rank of correlation was found to exist between the size and release retardation in all the three-wax/fat emulgent combinations.

  9. Nanolipoprotein Particles (NLPs) as Versatile Vaccine Platforms for Co-delivery of Multiple Adjuvants with Subunit Antigens from Burkholderia spp. and F. tularensis - Annual Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-04-16

    The goal of this proposal is to demonstrate that co-localization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of recombinant subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. NLPs are are biocompatible, high-density lipoprotein mimetics that are amenable to the incorporation of multiple, chemically-disparate adjuvant and antigen molecules. We hypothesize that the ability to co-localize optimized adjuvant formulations with subunit antigens within a single particle will enhance the stimulation and activation of key immune effector cells, increasing the protective efficacy of subunit antigen-based vaccines. While Burkholderia spp. and F. tularensis subunit antigens are the focus of this proposal, we anticipate that this approach is applicable to a wide range of DOD-relevant biothreat agents. The F344 rat aerosol challenge model for F. tularensis has been successfully established at Battelle under this contract, and Year 3 efficacy studies performed at Battelle demonstrated that an NLP vaccine formulation was able to enhance survival of female F344 rats relative to naïve animals. In addition, Year 3 focused on the incorporation of multiple Burkholderia antigens (both polysaccharides and proteins) onto adjuvanted NLPs, with immunological analysis poised to begin in the next quarter.

  10. PNIPAM Poly (N-isopropylacrylamide: A Thermoresponsive “Smart” Polymer in Novel Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Hardik R Mody

    2012-07-01

    Full Text Available Over the past years, extensive research has been carried out in designing and optimizing various drug delivery systems in order to maximize therapeutic effect and minimize unwanted effects of drugs. Many drug carrier systems have been developed on the basis of nanotechnology including systems based on polymeric nanoparticles. Polymeric drug delivery research has been extended to targeting of the drug at the specific site by utilizing various stimuli responsive systems which depend upon physiological conditions of the body such as pH of biological fluids and temperature of the human body. Thermoresponsive polymers with Lower Critical Solution Temperature (LCST have been investigated for various biomedical and pharmaceutical formulations. One such polymer of considerable focus is PNIPAM Poly (N-isopropylacrylamide. PNIPAM is a thermosensitive polymer which has been utilized in many drug delivery systems including for cancer therapeutics. The present article deals with the properties of PNIPAM and their applications in different drug delivery systems.

  11. NMR characterisation and transdermal drug delivery potential of microemulsion systems

    DEFF Research Database (Denmark)

    Kreilgaard, Mads; Pedersen, E J; Jaroszewski, J W

    2000-01-01

    The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride......), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T(1) relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through...... and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating...

  12. 20 CFR 652.202 - May local Employment Service Offices exist outside of the One-Stop service delivery system?

    Science.gov (United States)

    2010-04-01

    ... outside of the One-Stop service delivery system? 652.202 Section 652.202 Employees' Benefits EMPLOYMENT... SERVICES Wagner-Peyser Act Services in a One-Stop Delivery System Environment § 652.202 May local Employment Service Offices exist outside of the One-Stop service delivery system? (a) No, local...

  13. 47 CFR 63.02 - Exemptions for extensions of lines and for systems for the delivery of video programming.

    Science.gov (United States)

    2010-10-01

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

  14. An in situ gelling liquid crystalline system based on monoglycerides and polyethylenimine for local delivery of siRNAs

    NARCIS (Netherlands)

    Borgheti-Cardoso, Lívia Neves; Depieri, Lívia Vieira; Kooijmans, Sander A A; Diniz, Henrique; Calzzani, Ricardo Alexandre Junqueira; De Carvalho Vicentini, Fabiana Testa Moura; Van Der Meel, Roy; De Abreu Fantini, Márcia Carvalho; Iyomasa, Mamie Mizusaki; Schiffelers, Raymond M.; Bentley, Maria Vitória Lopes Badra; Schiffelers, Raymond

    2015-01-01

    The development of delivery systems able to complex and release siRNA into the cytosol is essential for therapeutic use of siRNA. Among the delivery systems, local delivery has advantages over systemic administration. In this study, we developed and characterized non-viral carriers to deliver siRNA

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

    Science.gov (United States)

    Diana, Mark L

    2009-12-01

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

  16. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Feng Jiang

    2015-10-01

    Full Text Available Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX, are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

  17. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.

    Science.gov (United States)

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

    2015-01-01

    Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

  18. Microneedle-based drug delivery systems for transdermal route.

    Science.gov (United States)

    Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina

    2014-03-01

    Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.

  19. Proniosomes as a carrier system for transdermal delivery of tenoxicam.

    Science.gov (United States)

    Ammar, H O; Ghorab, M; El-Nahhas, S A; Higazy, I M

    2011-02-28

    Tenoxicam is a non steroidal anti-inflammatory drug (NSAID) widely used in the treatment of rheumatic diseases and characterized by its good efficacy and less side effects compared to other NSAIDs. Its oral administration is associated with severe side effects in the gastrointestinal tract. Transdermal drug delivery has been recognized as an alternative route to oral delivery. Proniosomes offer a versatile vesicle delivery concept with the potential for drug delivery via the transdermal route. In this study, different proniosomal gel bases were prepared, characterized by light microscopy, revealing vesicular structures, and assessed for their drug entrapment efficiency, stability, their effect on in vitro drug release and ex vivo drug permeation. The lecithin-free proniosomes prepared from Tween 20:cholesterol (9:1) proved to be stable with high entrapment and release efficiencies. The in vivo behaviour of this formula was studied on male rats and compared to that of the oral market product. The investigated tenoxicam loaded proniosomal formula proved to be non-irritant, with significantly higher anti-inflammatory and analgesic effects compared to that of the oral market tenoxicam tablets.

  20. In Vivo Delivery Systems for Therapeutic Genome Editing.

    Science.gov (United States)

    Wang, Luyao; Li, Fangfei; Dang, Lei; Liang, Chao; Wang, Chao; He, Bing; Liu, Jin; Li, Defang; Wu, Xiaohao; Xu, Xuegong; Lu, Aiping; Zhang, Ge

    2016-04-27

    Therapeutic genome editing technology has been widely used as a powerful tool for directly correcting genetic mutations in target pathological tissues and cells to cure of diseases. The modification of specific genomic sequences can be achieved by utilizing programmable nucleases, such as Meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly-interspaced short palindromic repeat-associated nuclease Cas9 (CRISPR/Cas9). However, given the properties, such as large size, negative charge, low membrane penetrating ability, as well as weak tolerance for serum, and low endosomal escape, of these nucleases genome editing cannot be successfully applied unless in vivo delivery of related programmable nucleases into target organisms or cells is achieved. Here, we look back at delivery strategies having been used in the in vivo delivery of three main genome editing nucleases, followed by methodologies currently undergoing testing in clinical trials, and potential delivery strategies provided by analyzing characteristics of nucleases and commonly used vectors.

  1. In Vivo Delivery Systems for Therapeutic Genome Editing

    Directory of Open Access Journals (Sweden)

    Luyao Wang

    2016-04-01

    Full Text Available Therapeutic genome editing technology has been widely used as a powerful tool for directly correcting genetic mutations in target pathological tissues and cells to cure of diseases. The modification of specific genomic sequences can be achieved by utilizing programmable nucleases, such as Meganucleases, zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs, and the clustered regularly-interspaced short palindromic repeat-associated nuclease Cas9 (CRISPR/Cas9. However, given the properties, such as large size, negative charge, low membrane penetrating ability, as well as weak tolerance for serum, and low endosomal escape, of these nucleases genome editing cannot be successfully applied unless in vivo delivery of related programmable nucleases into target organisms or cells is achieved. Here, we look back at delivery strategies having been used in the in vivo delivery of three main genome editing nucleases, followed by methodologies currently undergoing testing in clinical trials, and potential delivery strategies provided by analyzing characteristics of nucleases and commonly used vectors.

  2. In Vivo Delivery Systems for Therapeutic Genome Editing

    Science.gov (United States)

    Wang, Luyao; Li, Fangfei; Dang, Lei; Liang, Chao; Wang, Chao; He, Bing; Liu, Jin; Li, Defang; Wu, Xiaohao; Xu, Xuegong; Lu, Aiping; Zhang, Ge

    2016-01-01

    Therapeutic genome editing technology has been widely used as a powerful tool for directly correcting genetic mutations in target pathological tissues and cells to cure of diseases. The modification of specific genomic sequences can be achieved by utilizing programmable nucleases, such as Meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly-interspaced short palindromic repeat-associated nuclease Cas9 (CRISPR/Cas9). However, given the properties, such as large size, negative charge, low membrane penetrating ability, as well as weak tolerance for serum, and low endosomal escape, of these nucleases genome editing cannot be successfully applied unless in vivo delivery of related programmable nucleases into target organisms or cells is achieved. Here, we look back at delivery strategies having been used in the in vivo delivery of three main genome editing nucleases, followed by methodologies currently undergoing testing in clinical trials, and potential delivery strategies provided by analyzing characteristics of nucleases and commonly used vectors. PMID:27128905

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

    Science.gov (United States)

    Anselmo, Aaron C; Mitragotri, Samir

    2014-09-28

    Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems.

  4. Human leukocyte antigen-G in the male reproductive system and in seminal plasma

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Bzorek, Michael; Pass, Malene B

    2011-01-01

    -eclampsia. We have investigated whether HLA-G protein is present in human seminal plasma and in different tissue samples of the male reproductive system. Western blot technique and a soluble HLA-G (sHLA-G) assay were used to detect sHLA-G in human seminal plasma samples. Immunohistochemical staining......One of the non-classical human leukocyte antigen (HLA) class Ib proteins, HLA-G, is believed to exert important immunoregulatory functions, especially during pregnancy. The presence of HLA protein in paternal seminal fluid has been suggested to have an influence on the risk of developing pre...... was performed on paraffin-embedded tissue samples. We detected sHLA-G protein in seminal plasma, and HLA-G expression in normal testis and in epididymal tissue of the male reproductive system but not in the seminal vesicle. Furthermore, the results indicated a weak expression of HLA-G in hyperplastic prostatic...

  5. Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study.

    Science.gov (United States)

    Patel, Rashmin Bharatbhai; Patel, Mrunali Rashmin; Bhatt, Kashyap K; Patel, Bharat G; Gaikwad, Rajiv V

    2016-01-01

    This study reports the development and evaluation of Carbamazepine (CMP)-loaded microemulsions (CMPME) for intranasal delivery in the treatment of epilepsy. The CMPME was prepared by the spontaneous emulsification method and characterized for physicochemical parameters. All formulations were radiolabeled with (99m)Tc (technetium) and biodistribution of CMP in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rats was also performed to determine the uptake of the CMP into the brain. CMPME were found crystal clear and stable with average globule size of 34.11 ± 1.41 nm. (99m)Tc-labeled CMP solution (CMPS)/CMPME/CMP mucoadhesive microemulsion (CMPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMPMME compared to intravenous CMPME was found to be 2- to 3-fold higher signifying larger extent of distribution of the CMP in brain. Drug targeting efficiency and direct drug transport were found to be highest for CMPMME post-intranasal administration compared to intravenous CMP. Rat brain scintigraphy also demonstrated higher intranasal uptake of the CMP into the brain. This investigation demonstrates a prompt and larger extent of transport of CMP into the brain through intranasal CMPMME, which may prove beneficial for treatment of epilepsy.

  6. Crosstalk between ABO and Forssman (FORS) blood group systems: FORS1 antigen synthesis by ABO gene-encoded glycosyltransferases

    Science.gov (United States)

    Yamamoto, Miyako; Cid, Emili; Yamamoto, Fumiichiro

    2017-01-01

    A and B alleles at the ABO genetic locus specify A and B glycosyltransferases that catalyze the biosynthesis of A and B oligosaccharide antigens, respectively, of blood group ABO system which is important in transfusion and transplantation medicine. GBGT1 gene encodes Forssman glycolipid synthase (FS), another glycosyltransferase that produces Forssman antigen (FORS1). Humans are considered to be Forssman antigen-negative species without functional FS. However, rare individuals exhibiting Apae phenotype carry a dominant active GBGT1 gene and express Forssman antigen on RBCs. Accordingly, FORS system was recognized as the 31st blood group system. Mouse ABO gene encodes a cis-AB transferase capable of producing both A and B antigens. This murine enzyme contains the same GlyGlyAla tripeptide sequence as FSs at the position important for the determination of sugar specificity. We, therefore, transfected the expression construct into appropriate recipient cells and examined whether mouse cis-AB transferase may also exhibit FS activity. The result was positive, confirming the crosstalk between the ABO and FORS systems. Further experiments have revealed that the introduction of this tripeptide sequence to human A transferase conferred some, although weak, FS activity, suggesting that it is also involved in the recognition/binding of acceptor substrates, in addition to donor nucleotide-sugars. PMID:28134301

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

    NARCIS (Netherlands)

    Chen, Wei; Meng, F.; Cheng, R.; Deng, C.; Feijen, J.; Zhong, Z.

    2014-01-01

    Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention

  8. Biophysics and Thermodynamics: The Scientific Building Blocks of Bio-inspired Drug Delivery Nano Systems.

    Science.gov (United States)

    Demetzos, Costas

    2015-06-01

    Biophysics and thermodynamics are considered as the scientific milestones for investigating the properties of materials. The relationship between the changes of temperature with the biophysical variables of biomaterials is important in the process of the development of drug delivery systems. Biophysics is a challenge sector of physics and should be used complementary with the biochemistry in order to discover new and promising technological platforms (i.e., drug delivery systems) and to disclose the 'silence functionality' of bio-inspired biological and artificial membranes. Thermal analysis and biophysical approaches in pharmaceuticals present reliable and versatile tools for their characterization and for the successful development of pharmaceutical products. The metastable phases of self-assembled nanostructures such as liposomes should be taken into consideration because they represent the thermal events can affect the functionality of advanced drug delivery nano systems. In conclusion, biophysics and thermodynamics are characterized as the building blocks for design and development of bio-inspired drug delivery systems.

  9. Design and Implementation of Agricultural Information Data-Delivery System Based on Web

    Institute of Scientific and Technical Information of China (English)

    TANG Xinzhong; SUN Hongmin; HU Xinyi

    2009-01-01

    Data-delivery of agricultural information is a very tedious work, traditional data-delivery patterns and methods can not meet the requirements of the practical work. This paper provided the design idea and implement method for data-delivery system of agricultural information based on Web. Report and data will be separated in this system, and the person can change template and data at any time on demand. The problem that report template and data fixed together would be solved. The agricultural information resources sharing would be also implemented.

  10. Stabilization challenges and formulation strategies associated with oral biologic drug delivery systems.

    Science.gov (United States)

    Truong-Le, Vu; Lovalenti, Phillip M; Abdul-Fattah, Ahmad M

    2015-10-01

    Delivery of proteins to mucosal tissues of GI tract typically utilize formulations which protect against proteolysis and target the mucosal tissues. Using case studies from literature and the authors' own work, the in-process stability and solid state storage stability of biopharmaceuticals formulated in delivery systems designed for oral delivery to the GI tract will be reviewed. Among the range of delivery systems, biodegradable polymer systems for protection and controlled release of proteins have been the most studied; hence these systems will be covered in greater depth. These delivery systems include polymeric biodegradable microspheres or nanospheres that contain proteins or vaccines, which are designed to reduce the number of administrations/inoculations and the total protein dose required to achieve the desired biological effect. Specifically, this review will include a landscape survey of the systems that have been studied, the manufacturing processes involved, stability through the manufacturing process, key pharmaceutical formulation parameters that impact stability of the encased proteins, and storage stability of the encapsulated proteins in these delivery systems.

  11. Higher Throughput Maintenance Using Average Time Standard for Multipath Data Delivery Ad-hoc Network System

    Directory of Open Access Journals (Sweden)

    A.P.Shanmugasundaram

    2014-07-01

    Full Text Available Wireless network has come out as one of the key enablers for reliable data delivery for different types of applications.Ad-hoc network consists of self-actuated node that collaborates in order to transfer the information.Trajectory-based Statistical Forwarding (TSF method used optimal target point selection algorithm to forward packets in order to satisfy probability of packet delivery over multi-hopbut failed provide higher throughputon the multipath data delivery. TheVoid Aware Pressure Routing (VAPR method used hop count and intensity information to build a directional data delivery system but performance of specialized geographic routing based multipath data delivery was not attained. To maintain the higher throughput level on ad-hoc network data delivery, Median Multicast Throughput Data Delivery (MMTDD mechanism is proposed in thispaper.The basic idea of MMTDD mechanism is to divide a message into multiple shares and deliver them via multiple independent source paths to the destination. MMTDD mechanism with the average time standard takes the best threshold value for every data (i.e., packet partitioning by avoiding packet loss. By this means, MMTDD mechanism uses the Average Time Standard (ATS to guarantee the required packet allocationwith higher throughput level. With the application of ATS, the MMTDD mechanism derives the theoretical model by attaining approximately 4% higher throughput level on the multipath data delivery in ad-hoc network.MMTDD mechanism makes use of time scheduling schemestodiscover and maintain data delivery paths with minimal time consumption.Median Multicast in MMTDD mechanism used the balanced state flow model to deliver data on multiple paths and experiment is conducted on factors such as time consumption, data delivery rate,average delivery delay and throughput level.

  12. A review on phospholipids and their main applications in drug delivery systems

    OpenAIRE

    Jing Li; Xuling Wang; Ting Zhang; Chunling Wang; Zhenjun Huang; Xiang Luo; Yihui Deng

    2015-01-01

    Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of t...

  13. A Review of Multi-Responsive Membranous Systems for Rate-Modulated Drug Delivery

    OpenAIRE

    Shaikh, Rubina P.; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M.K.; Bawa, Priya; Cooppan, Shivaan

    2010-01-01

    Membrane technology is broadly applied in the medical field. The ability of membranous systems to effectively control the movement of chemical entities is pivotal to their significant potential for use in both drug delivery and surgical/medical applications. An alteration in the physical properties of a polymer in response to a change in environmental conditions is a behavior that can be utilized to prepare ‘smart’ drug delivery systems. Stimuli-responsive or ‘smart’ polymers are polymers tha...

  14. Smart materials: in situ gel-forming systems for nasal delivery.

    Science.gov (United States)

    Karavasili, Christina; Fatouros, Dimitrios G

    2016-01-01

    In the last decade in situ gelling systems have emerged as a novel approach in intranasal delivery of therapeutics, capturing the interest of scientific community. Considerable advances have been currently made in the development of novel formulations containing both natural and synthetic polymers. In this paper we present recent developments on in situ gelling systems for nasal delivery, highlighting the mechanisms that govern their formation.

  15. In vitro characterization of microcontainers as an oral drug delivery system

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Keller, Stephan Sylvest; Petersen, Ritika Singh;

    We here present in vitro studies showing the promise of microcontainers (fabricated in either SU-8 or Poly(lactic acid) (PLLA)) as an oral drug delivery system for the poorly watersoluble drug, furosemide.......We here present in vitro studies showing the promise of microcontainers (fabricated in either SU-8 or Poly(lactic acid) (PLLA)) as an oral drug delivery system for the poorly watersoluble drug, furosemide....

  16. MICRONEEDLE AS A NOVEL DRUG DELIVERY SYSTEM: A REVIEW

    Directory of Open Access Journals (Sweden)

    Memon Shakeel

    2011-02-01

    Full Text Available Patch-based transdermal drug delivery offers a convenient way to administer drugs without the drawbacks of standard hypodermic injections relating to issues such as patient acceptability and injection safety. However, conventional transdermal drug delivery is limited to therapeutics where the drug can diffuse across the skin barrier. By using miniaturized needles, a pathway into the human body can be established which allow transport of macromolecular drugs such as insulin or vaccines. These microneedles only penetrate the outermost skin layers, superficial enough not to reach the nerve receptors of the lower skin. Thus, microneedle insertions are perceived as painless. These microneedle arrays could be easily inserted into skin without breaking and were shown to increase permeability of human skin in vitro to a model drug, calcein, by up to 4 orders of magnitude. Limited tests on human subjects indicated those microneedles were reported as painless.

  17. NANOTECHNOLOGY: A PROMISING CARRIER FOR INTRACELLULAR DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Malakar Jadupati

    2012-02-01

    Full Text Available Nanotechnology is on its way to make a big impact in Biotech, Pharmaceutical and Medical diagnostics sciences. Nanotechnology holds a tremendous potential when it applied in the fields of drug delivery. In this review it has been discussed how nanotechnology can implemented to design formulations which can effectively carry drug molecule to the targeted cell organelles. Introduction of certain functional groups or addition of surface active agents may alter the characteristics of the carrier molecule, thus increasing the sensitivity to site selection of the carrier. It has been predicted that in the near future, nanoparticles with the ability of carrying multiple drug molecules, will be designed. They can maintain the delivery of drugs at specific time interval.

  18. Recombinant AAV delivery to the central nervous system.

    Science.gov (United States)

    Bockstael, Olivier; Foust, Kevin D; Kaspar, Brian; Tenenbaum, Liliane

    2011-01-01

    Recombinant AAV-mediated gene delivery to the CNS can be performed either by direct delivery at the target site or from the periphery, using intramuscular injections and retrograde transport along motor neuron projections or intravenous injections and blood-brain barrier crossing.In this chapter, we describe: 1. Methods for recombinant virus administration, including stereotactic surgery, intramuscular, and intravenous administration. 2. Methods to evaluate the number and biodistribution of brain and spinal cord cells expressing the transgene by immunohistochemisty as well as the amount of transgene product by ELISA in the target region. 3. Methods to characterize the cellular specificity of transgene expression by double immunofluorescence. 4. Methods to quantify the amounts of viral DNA as well as of transgene mRNA by quantitative PCR and RT-PCR, respectively.

  19. Experimentation in family planning delivery systems: an overview.

    Science.gov (United States)

    Cuca, R; Pierce, C S

    1977-12-01

    Experiments in the delivery of family planning services are an important means of testing new approaches on a relatively small scale. Over the past 20 years, extensive experimental efforts have explored such key aspects of service delivery as personnel, the use of mass media, integration of family planning with other services, intensive efforts and camps, incentive payments to acceptors, and inudation or community-based distribution. Approaches that proved successful have often been incorporated into regular programs. An examination of the methodology and findings of family planning experiments, based on a survey of 96 projects testing various approaches, highlights successes, failures, and continuing problems. The discussion of past experience halps point to criteria that might be followed in formulating future experimental projects.

  20. Role of Components in the Formation of Self-microemulsifying Drug Delivery Systems.

    Science.gov (United States)

    Gurram, A K; Deshpande, P B; Kar, S S; Nayak, Usha Y; Udupa, N; Reddy, M S

    2015-01-01

    Pharmaceutical research is focused in designing novel drug delivery systems to improve the bioavailability of poorly water soluble drugs. Self-microemulsifying drug delivery systems, one among the lipid-based dosage forms were proven to be promising in improving the oral bioavailability of such drugs by enhancing solubility, permeability and avoiding first-pass metabolism via enhanced lymphatic transport. Further, they have been successful in avoiding both inter and intra individual variations as well as the dose disproportionality. Aqueous insoluble drugs, in general, show greater solubility in lipid based excipients, and hence they are formulated as lipid based drug delivery systems. The extent of solubility of a hydrophobic drug in lipid excipients i.e. oil, surfactant and co-surfactant (components of self-microemulsifying drug delivery systems) greatly affects the drug loading and in producing stable self-microemulsifying drug delivery systems. The present review highlighted the influence of physicochemical factors and structural features of the hydrophobic drug on its solubility in lipid excipients and an attempt was made to explore the role of each component of self-microemulsifying drug delivery systems in the formation of stable microemulsion upon dilution.

  1. Texosome-based drug delivery system for cancer therapy:from past to present

    Institute of Scientific and Technical Information of China (English)

    Hamideh Mahmoodzadeh Hosseini; Raheleh Halabian; Mohsen Amin; Abbas Ali Imani Fooladi

    2015-01-01

    Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Malfunction of the immune system, particularly in the tumor microenvironment, causes tumor growth and enhances tumor progression. Thus, cancer immunotherapy can be an appropriate approach to provoke the systemic immune system to combat tumor expansion. Texosomes, which are endogenous nanovesicles released by all tumor cells, contribute to cell-cell communication and modify the phenotypic features of recipient cells due to the texosomes’ ability to transport biological components. For this reason, texosome-based delivery system can be a valuable strategy for therapeutic purposes. To improve the pharmaceutical behavior of this system and to facilitate its use in medical applications, biotechnology approaches and mimetic techniques have been utilized. In this review, we present the development history of texosome-based delivery systems and discuss the advantages and disadvantages of each system.

  2. Sublingual route for the systemic delivery of Ondansetron

    OpenAIRE

    Priyank Patel; Sandip Makwana; Urvish Jobanputra; Mihir Ravat; Ankit Ajmera,; Mandev Pate

    2011-01-01

    Drug delivery via sublingual mucous membrane is considered to be a promising alternative to the oral route. This route is useful when rapid onset of action is desired as in the case of antiemetics such as ondansetron. In terms of permeability, the sublingual area of the oral cavity is more permeable than cheek and palatal areas of mouth. The drug absorbed via sublingual blood vessels bypasses the hepatic first-pass metabolic processes giving acceptable bioavailability with low doses and hence...

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

    OpenAIRE

    Kooijmans SAA; Vader P; van Dommelen SM; van Solinge WW; Schiffelers RM

    2012-01-01

    Sander AA Kooijmans, Pieter Vader, Susan M van Dommelen, Wouter W van Solinge, Raymond M SchiffelersDepartment of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The NetherlandsAbstract: 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...

  4. BGMUT: NCBI dbRBC database of allelic variations of genes encoding antigens of blood group systems.

    Science.gov (United States)

    Patnaik, Santosh Kumar; Helmberg, Wolfgang; Blumenfeld, Olga O

    2012-01-01

    Analogous to human leukocyte antigens, blood group antigens are surface markers on the erythrocyte cell membrane whose structures differ among individuals and which can be serologically identified. The Blood Group Antigen Gene Mutation Database (BGMUT) is an online repository of allelic variations in genes that determine the antigens of various human blood group systems. The database is manually curated with allelic information collated from scientific literature and from direct submissions from research laboratories. Currently, the database documents sequence variations of a total of 1251 alleles of all 40 gene loci that together are known to affect antigens of 30 human blood group systems. When available, information on the geographic or ethnic prevalence of an allele is also provided. The BGMUT website also has general information on the human blood group systems and the genes responsible for them. BGMUT is a part of the dbRBC resource of the National Center for Biotechnology Information, USA, and is available online at http://www.ncbi.nlm.nih.gov/projects/gv/rbc/xslcgi.fcgi?cmd=bgmut. The database should be of use to members of the transfusion medicine community, those interested in studies of genetic variation and related topics such as human migrations, and students as well as members of the general public.

  5. Nanocapsules: The Weapons for Novel Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Radhika Parasuramrajam

    2012-04-01

    Full Text Available Introduction: Nanocapsules, existing in miniscule size, range from 10 nm to 1000 nm. They consist of a liquid/solid core in which the drug is placed into a cavity, which is surrounded by a distinctive polymer membrane made up of natural or synthetic polymers. They have attracted great interest, because of the protective coating, which are usually pyrophoric and easily oxidized and delay the release of active ingredients. Methods: Various technical approaches are utilized for obtaining the nanocapsules; however, the methods of interfacial polymerization for monomer and the nano-deposition for preformed polymer are chiefly preferred. Most important characteristics in their preparation is particle size and size distribution which can be evaluated by using various techniques like X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, superconducting quantum interference device, multi angle laser light scattering and other spectroscopic techniques. Results: Nanocapsules possessing extremely high reproducibility have a broad range of life science applications. They may be applied in agrochemicals, genetic engineering, cosmetics, cleansing products, wastewater treatments, adhesive component applications, strategic delivery of the drug in tumors, nanocapsule bandages to fight infection, in radiotherapy and as liposomal nanocapsules in food science and agriculture. In addition, they can act as self-healing materials. Conclusion: The enhanced delivery of bioactive molecules through the targeted delivery by means of a nanocapsule opens numerous challenges and opportunities for the research and future development of novel improved therapies.

  6. MAGNETIC MICROSPHERES: A LATEST APPROACH IN NOVEL DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Mukherjee S

    2012-10-01

    Full Text Available Magnetic microspheres are at the forefront of the rapidly developing field of pharmaceutical technology with several potential applications in drug delivery, clinical medicine and research as well as in other varied sciences. Due to their unique size-dependent properties, magnetic microspheres offer the possibility to develop new therapeutics. The ability to incorporate drugs into carriers offers a new prototype in drug delivery that could be used for secondary and tertiary levels of drug targeting. Hence, magnetic microspheres hold great promise for reaching the goal of controlled and site specific drug delivery and hence have attracted wide attention of researchers. This review presents a broad treatment of magnetic microspheres discussing their advantages, limitations and their possible remedies. Different production methods which are suitable for large scale production and applications of magnetic microspheres are described. Appropriate analytical techniques for characterization of magnetic microspheres like Photon correlation spectroscopy, scanning electron microscopy, differential scanning calorimetry are highlighted. Aspects of magnetic microspheres route of administration and their biodistribution are also incorporated. If appropriately investigated, magnetic microspheres may open new vistas in therapy of complex diseases.

  7. A review on phospholipids and their main applications in drug delivery systems

    Directory of Open Access Journals (Sweden)

    Jing Li

    2015-04-01

    Full Text Available Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of the species of phospholipids on the efficiency of drug delivery. We refer to some relevant literatures, starting from the structures, main sources and properties of phospholipids to introduce their applications in drug delivery systems. The present article focuses on introducing five types of carriers based on phospholipids, including liposomes, intravenous lipid emulsions, micelles, drug-phospholipids complexes and cochleates.

  8. Innovations in existing routes and novel drug delivery systems for local anaesthetics

    Directory of Open Access Journals (Sweden)

    Diwanshu Sharma

    2016-06-01

    Full Text Available New drug delivery systems (NDDS are developed for improvement in efficacy of the drugs, provide maximum benefit to the patient and to minimize the adverse drug reactions. For local anaesthetics (LAs, the development of new effective delivery systems modulate the release rate, extend their anaesthetic effect , and helps to enhance their localisation as desired. The various routes of local anaesthetic delivery (epidural, peripheral, wound catheters, intra-nasal, intra-vesical, intra-articular, intra-osseous are under innovation these days. Different methods such as include iontophoresis, electroporation, sonophoresis, and magnetophoresis are being used to enhance local anaesthetic permeation. Adjuvants are added to potentiate drug effects. The use of different delivery systems should help to keep the LA at the target site for longer periods prolonging the anesthetic or analgesic effect with an extended range of agents. [Int J Basic Clin Pharmacol 2016; 5(3.000: 566-572

  9. Extracellular matrix-inspired growth factor delivery systems for bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Martino, Mikaël M. [Osaka Univ. (Japan). Immunology Frontier Research Center; Briquez, Priscilla S. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Maruyama, Kenta [Osaka Univ. (Japan). Immunology Frontier Research Center; Hubbell, Jeffrey A. [Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering; Univ. of Chicago, IL (United States). Inst. for Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-04-17

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

  10. THE USE OF CHRONOTHERAPEUTICS IN DESIGN OF PULSATILE DELIVERY SYSTEMS- A REVIEW

    Directory of Open Access Journals (Sweden)

    D’Souza A

    2012-04-01

    Full Text Available Many therapeutic agents are most effective when made available at constant rates, near the absorption sites or at correct time of administration. Recently a greater effort has been taken in designing delivery systems which synchronize drug delivery with circadian rhythms in order to optimize efficacy and /or minimize side effects. Pulsatile systems deliver the drug at right site of action at the right time and in the right amount. Chronotherapeutics is the discipline concerned with the delivery of drugs according to inherent activities of a disease over a certain period of time. Chronotherapy can particularly benefit patients suffering from allergic rhinitis, rheumatoid arthritis and related disorders, asthma, cancer, cardiovascular diseases, and peptic ulcer disease. This review gives an outline as to how pulsatile drug delivery systems based on circadian rhythms are developed.

  11. A new lactobacilli in vivo expression system for the production and delivery of heterologous proteins at mucosal surfaces.

    Science.gov (United States)

    Allain, Thibault; Mansour, Nahla M; Bahr, May M A; Martin, Rebeca; Florent, Isabelle; Langella, Philippe; Bermúdez-Humarán, Luis G

    2016-07-01

    Food-grade lactic acid bacteria, such as lactobacilli, represent good candidates for the development of mucosal vectors. Indeed, they are generally recognized as safe microorganisms and some strains display beneficial effects (probiotics). In this study, we described a new lactobacilli in vivo expression (LIVE) system for the production and delivery of therapeutic molecules at mucosal surfaces. The versatility and functionality of this system was successfully validated in several lactobacilli species; furthermore, we assessed in vivo LIVE system in two different mouse models of human pathologies: (i) a model of therapy against intestinal inflammation (inflammatory bowel diseases) and (ii) a model of vaccination against dental caries. We demonstrated that Lactobacillus gasseri expressing the anti-inflammatory cytokine IL-10 under LIVE system efficiently delivered the recombinant protein at mucosal surfaces and display anti-inflammatory effects. In the vaccination model against caries, LIVE system allowed the heterologous expression of Streptococcus mutans antigen GbpB by L. gasseri, leading to a stimulation of the host immune response.

  12. Role of very late antigen-1 in T-cell-mediated immunity to systemic viral infection

    DEFF Research Database (Denmark)

    Ørding Kauffmann, Susanne; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard

    2006-01-01

    The T-cell response to lymphocytic choriomeningitis virus was studied in mice lacking very late antigen-1 (VLA-1). The generation of virus-specific effector T cells was unimpaired in VLA-1(-/-) mice. In the memory phase, VLA-1 deficiency did not influence the number of memory CD8(+) T cells or th......, the current findings indicate that the expression of VLA-1 is not pivotal for T-cell-mediated antiviral immunity to a systemic infection.......-cell-mediated inflammation, no significant influence of VLA-1 was found either in the primary response or in the memory phase. However, alpha-VLA-4 antibody reduced the DTH-like reaction in VLA-1(-/-) mice to a higher degree than in wt mice, suggesting a synergistic effect of blocking both integrins. Taken together...

  13. Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Harjeet Singh

    Full Text Available Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28 that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC in the presence of interleukin (IL-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT. We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼10(10 T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion.

  14. Half-Antibody Functionalized Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery to Carcinoembryonic Antigen (CEA) Presenting Pancreatic Cancer Cells

    Science.gov (United States)

    Hu, Che-Ming Jack; Kaushal, Sharmeela; Tran Cao, Hop S.; Aryal, Santosh; Sartor, Marta; Esener, Sadik; Bouvet, Michael; Zhang, Liangfang

    2010-01-01

    Current chemotherapy regimens against pancreatic cancer are met with little success as poor tumor vascularization significantly limits the delivery of oncological drugs. High-dose targeted drug delivery, through which a drug delivery vehicle releases a large payload upon tumor localization, is thus a promising alternative strategy against this lethal disease. Herein, we synthesize anti-CEA half-antibody conjugated lipid-polymer hybrid nanoparticles and characterize their ligand conjugation yields, physicochemical properties, and targeting ability against pancreatic cancer cells. Under the same drug loading, the half-antibody targeted nanoparticles show enhanced cancer killing effect compared to the corresponding non-targeted nanoparticles. PMID:20394436

  15. Nanolipoprotein Particles (NLPs) as Versatile Vaccine Platforms for Co-delivery of Multiple Adjuvants with Subunit Antigens from Burkholderia spp. and F. tularensis - Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-01-13

    The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the third quarter of the third year, F344 rats vaccinated with adjuvanted NLP formulations were challenged with F. tularensis SCHU S4 at Battelle. Preliminary data indicate that up to 65% of females vaccinated intranasally with an NLP-based formulation survived this challenge, compared to only 20% survival of naïve animals. In addition, NLPs were successfully formulated with Burkholderia protein antigens. IACUC approval for immunological assessments in BALB/c mice was received and we anticipate that these assessments will begin by March 2015, pending ACURO approval.

  16. A Model System for Concurrent Detection of Antigen and Antibody Based on Immunological Fluorescent Method

    Directory of Open Access Journals (Sweden)

    Yuan-Cheng Cao

    2015-01-01

    Full Text Available This paper describes a combined antigen/antibody immunoassay implemented in a 96-well plate using fluorescent spectroscopic method. First, goat anti-human IgG was used to capture human IgG (model antigen; goat anti-human IgG (Cy3 or FITC was used to detect the model antigen; a saturating level of model antigen was then added followed by unlabelled goat anti-human IgG (model antibody; finally, Cy3 labelled rabbit anti-goat IgG was used to detect the model antibody. Two approaches were applied to the concomitant assay to analyze the feasibility. The first approach applied FITC and Cy3 when both targets were present at the same time, resulting in 50 ng/mL of the antibody detection limit and 10 ng/mL of antigen detection limit in the quantitative measurements of target concentration, taking the consideration of FRET efficiency of 68% between donor and acceptor. The sequential approach tended to lower the signal/noise (S/N ratio and the detection of the model antigen (lower than 1 ng/mL had better sensitivity than the model antibody (lower than 50 ng/mL. This combined antigen/antibody method might be useful for combined detection of antigens and antibodies. It will be helpful to screen for both antigen and antibody particularly in the situations of the multiserotype and high-frequency mutant virus infections.

  17. Delivery of drugs to intracellular organelles using drug delivery systems: Analysis of research trends and targeting efficiencies.

    Science.gov (United States)

    Maity, Amit Ranjan; Stepensky, David

    2015-12-30

    Targeting of drug delivery systems (DDSs) to specific intracellular organelles (i.e., subcellular targeting) has been investigated in numerous publications, but targeting efficiency of these systems is seldom reported. We searched scientific publications in the subcellular DDS targeting field and analyzed targeting efficiency and major formulation parameters that affect it. We identified 77 scientific publications that matched the search criteria. In the majority of these studies nanoparticle-based DDSs were applied, while liposomes, quantum dots and conjugates were used less frequently. The nucleus was the most common intracellular target, followed by mitochondrion, endoplasmic reticulum and Golgi apparatus. In 65% of the publications, DDSs surface was decorated with specific targeting residues, but the efficiency of this surface decoration was not analyzed in predominant majority of the studies. Moreover, only 23% of the analyzed publications contained quantitative data on DDSs subcellular targeting efficiency, while the majority of publications reported qualitative results only. From the analysis of publications in the subcellular targeting field, it appears that insufficient efforts are devoted to quantitative analysis of the major formulation parameters and of the DDSs' intracellular fate. Based on these findings, we provide recommendations for future studies in the field of organelle-specific drug delivery and targeting.

  18. Nanolipoprotein Particles (NLPs) as Versatile Vaccine Platforms for Co-delivery of Multiple Adjuvants with Subunit Antigens from Burkholderia spp. and F. tularensis - Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-01-06

    The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the second quarter of the third year, LLNL finalized all immunological assessments of NLP vaccine formulations in the F344 model. Battelle has immunized rats with three unique NLP formulations by either intramuscular or intranasal administration. All inoculations have been completed, and protective efficacy against an aerosolized challenge will begin at the end of October, 2014.

  19. Feasibility Implementation of Voltage-Current Waveform Telemetry System in Power Delivery System

    Science.gov (United States)

    Furukawa, Tatsuya; Akagi, Keita; Fukumoto, Hisao; Itoh, Hideaki; Wakuya, Hiroshi; Hirata, Kenji; Ohchi, Masashi

    The electric power is indispensable for modern life. However, there is a problem of harmonic disturbance when the harmonic power runs into electronic devices. To overcome the problem and realize a stable supply of the electric power is an important issue. In this study, we have developed a voltage-current waveform telemetry system for the remote measurement of the harmonics in the power delivery lines. The system consists of sensors, preamplifiers, a single board computer, and power collectors. Improvements are made on all of these components except the sensors. The power collector is a coil that can be placed around the same power line that we measure. We have designed the power collector by a finite element method(FEM) so that it can provide enough electricity for the computer to work properly. Thus, no other power source such as a battery except the secondary rechargeable battery for the recovery is necessary at the measurement place. The preamplifier in the new system is a single-supply differential amplifier circuit, and the single board computer has an inexpensive SH-3 CPU. Through experiments, we have confirmed that the power collector can provide sufficient electricity and that the new system can successfully measure the waveforms and the harmonics in power delivery systems.

  20. Analysis of referal Delivery System of Jamkesmas and Jampersal Members coordinated by Surabaya Municipality Health Office

    Directory of Open Access Journals (Sweden)

    Rukmini Rukmini

    2015-01-01

    Full Text Available background:Policy issues states that referral delivery system of Jamkesmas and Jampersal have not been implemented properly. The study aims to determine of referal delivery systems for members of Jamkesmas and Jampersal social schemes coordinated by Surabaya municipality health office. Method: It was an observational study with a cross-sectional design. The study was carried outfrom March to December 2013 in Surabaya Municipality. Data were collected by indepth interviews to head of Surabaya municipality health office, chiefs of Jamkesmas/Jampersal and basic health services section in that office. Secondary data were collected to determine number of health facilities, personnels and finance related to service delivery for Jamkesmas and Jampersal members. It also conducted study of documents. Qualitative and quantitative data were analyzed descriptively. results: The implementation level of referral system for members of Jamkesmas and Jampersal social scheme in Surabaya have not been optimal due to the number of referal hospital was very limited and limited capacity of bed hospitals and community factors. The availability of health facilities and health workers for delivery services is sufficient, but those having MOU with Jamkesmas and Jampersal were very few, especially on midwife private services. The financing of Jamkesmas and Jampersal social scheme were sufficient and increase every year. The referral screening of pregnancy using a score of Puji Rohyati cards and the referral screening of delivery using child birth screening form of normal delivery care. Monitoring and evaluation of the referral delivery system were conducted in the form programs meeting, supervision, reports and complaints managemen. conclusion:In Surabaya, the coordination of referral delivery systems for members of Jamkesmas and Jampersal have been conducted, by structures & levels but not optimal. The availability of health facilities, health workers and financing were