Science.gov

Sample records for antigen delivery system

  1. Transcutaneous antigen delivery system

    PubMed Central

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

    2013-01-01

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

  2. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:26065009

  6. Induction of cytotoxic T lymphocyte response against Mycobacterial antigen using domain I of anthrax edema factor as antigen delivery system

    SciTech Connect

    Chandra, Subhash; Kaur, Manpreet; Midha, Shuchi; Gorantala, Jyotsna; Bhatnagar, Rakesh . E-mail: rakbhat01@yahoo.com

    2007-05-25

    We have investigated the efficiency of N-terminal 1-260 residues of Edema factor (EFn) as a delivery system for ESAT-6, an antigenic protein of Mycobacterium tuberculosis H{sub 37}R{sub v}, into the cytosol of mammalian cells. The EFn.ESAT-6 recombinant protein was obtained by genetic fusion of EFn and ESAT-6 DNA. Our data shows that in the presence of PA, EFn.ESAT-6 fusion protein is internalized into the cytosol of antigen presenting cells, and the splenocytes produced both Th1 and Th2 cytokines in vitro. Further, EFn.ESAT-6 elicited effective cytotoxicT lymphocyte (CTL) response in an in vitro CTL assay. This study for the first time demonstrates that EFn can be used as a vehicle to deliver heterologous proteins of therapeutic importance.

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

    PubMed

    Langella, P; Le Loir, Y

    1999-02-01

    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) epitopeprotein 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.

  8. Poly-ε-caprolactone/Chitosan and Chitosan Particles: Two Recombinant Antigen Delivery Systems for Intranasal Vaccination.

    PubMed

    Jesus, Sandra; Soares, Edna; Borges, Olga

    2016-01-01

    Several evidences converge on the idea that among the mucosal administration routes, the nasal mucosa is the most attractive site for the delivery of vaccines. Mucoadhesive particulate adjuvants should be able to increase the residence time of antigens in nasal cavity in order to increase their probability of being taken up by nasopharynx-associated lymphoid tissue (NALT) cells and subsequently to initiate the innate and adaptive immune response. Focusing on chitosan, a mucoadhesive biopolymer, we describe in this chapter a method to prepare antigen loaded chitosan nanoparticles and a second method to prepare antigen loaded poly-ε-caprolactone/chitosan nanoparticles. Additionally the methodology for the assessment of mucoadhesivity of the delivery system is also described. The two critical procedures in mice intranasal immunization experiments include challenges in the intranasal administration itself due to the small mouse nose, and the other is related with the collection of mucosal secretions to assess the sIgA. The techniques are difficult to perform without advanced training. Therefore, protocols followed in our laboratory, as well as some tips, are described in this chapter.

  9. Virus-mimetic nanovesicles as a versatile antigen-delivery system.

    PubMed

    Zhang, Pengfei; Chen, Yixin; Zeng, Yun; Shen, Chenguang; Li, Rui; Guo, Zhide; Li, Shaowei; Zheng, Qingbing; Chu, Chengchao; Wang, Zhantong; Zheng, Zizheng; Tian, Rui; Ge, Shengxiang; Zhang, Xianzhong; Xia, Ning-Shao; Liu, Gang; Chen, Xiaoyuan

    2015-11-10

    It is a critically important challenge to rapidly design effective vaccines to reduce the morbidity and mortality of unexpected pandemics. Inspired from the way that most enveloped viruses hijack a host cell membrane and subsequently release by a budding process that requires cell membrane scission, we genetically engineered viral antigen to harbor into cell membrane, then form uniform spherical virus-mimetic nanovesicles (VMVs) that resemble natural virus in size, shape, and specific immunogenicity with the help of surfactants. Incubation of major cell membrane vesicles with surfactants generates a large amount of nano-sized uniform VMVs displaying the native conformational epitopes. With the diverse display of epitopes and viral envelope glycoproteins that can be functionally anchored onto VMVs, we demonstrate VMVs to be straightforward, robust and tunable nanobiotechnology platforms for fabricating antigen delivery systems against a wide range of enveloped viruses. PMID:26504197

  10. Virus-mimetic nanovesicles as a versatile antigen-delivery system

    PubMed Central

    Zhang, Pengfei; Chen, Yixin; Zeng, Yun; Shen, Chenguang; Li, Rui; Guo, Zhide; Li, Shaowei; Zheng, Qingbing; Chu, Chengchao; Wang, Zhantong; Zheng, Zizheng; Tian, Rui; Ge, Shengxiang; Zhang, Xianzhong; Xia, Ning-Shao; Liu, Gang; Chen, Xiaoyuan

    2015-01-01

    It is a critically important challenge to rapidly design effective vaccines to reduce the morbidity and mortality of unexpected pandemics. Inspired from the way that most enveloped viruses hijack a host cell membrane and subsequently release by a budding process that requires cell membrane scission, we genetically engineered viral antigen to harbor into cell membrane, then form uniform spherical virus-mimetic nanovesicles (VMVs) that resemble natural virus in size, shape, and specific immunogenicity with the help of surfactants. Incubation of major cell membrane vesicles with surfactants generates a large amount of nano-sized uniform VMVs displaying the native conformational epitopes. With the diverse display of epitopes and viral envelope glycoproteins that can be functionally anchored onto VMVs, we demonstrate VMVs to be straightforward, robust and tunable nanobiotechnology platforms for fabricating antigen delivery systems against a wide range of enveloped viruses. PMID:26504197

  11. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.

    PubMed

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel ('nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination. PMID:20562880

  12. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

    NASA Astrophysics Data System (ADS)

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

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

    PubMed

    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.

  14. Attenuated Salmonella sp. as a DNA Delivery System for Trypanosoma cruzi Antigens.

    PubMed

    Bivona, Augusto E; Cerny, Natacha; Alberti, Andrés Sánchez; Cazorla, Silvia I; Malchiodi, Emilio L

    2016-01-01

    Chagas disease is an important neglected disease affecting thousands of people in the Americas. Novel strategies for prophylactic and therapeutic vaccines against the etiological agent, the intracellular protozoan Trypanosoma cruzi, are urgently needed. Vaccines based on attenuated virus and bacteria as a foreign DNA delivery system represent a strong advantage over naked DNA-based vaccines. Here we describe the use of attenuated Salmonella carrying a eukaryotic expression plasmid encoding a T. cruzi antigen. The main advantages of the methodology are the oral administration of the Salmonella-based vaccine and the induction of a strong humoral and cell-mediated immune response at both mucosal and systemic level, favored by the adjuvant effect elicited by the bacteria pathogen-associated molecular patterns. PMID:27076330

  15. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

    PubMed Central

    2014-01-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC. PMID:25232295

  16. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

    NASA Astrophysics Data System (ADS)

    Hu, Yun; Ehrich, Marion; Fuhrman, Kristel; Zhang, Chenming

    2014-08-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC.

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

    PubMed Central

    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

  18. Lipid Nanoparticles with Accessible Nickel as a Vaccine Delivery System for Single and Multiple His-tagged HIV Antigens.

    PubMed

    Yan, Weili; Jain, Anekant; O'Carra, Ronan; Woodward, Jerold G; Li, Wenxue; Li, Guanhan; Nath, Avindra; Mumper, Russell J

    2009-07-01

    Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the HIV his-tagged Tat protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by s.c. injection with his-Tat/Ni-NP formulation (1.5 μg Tat-his/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific IgG titer with his-Tat/Ni-NP was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity than Tat-coated anionic NPs made with sodium dodecyl sulfate (SDS/NPs), they were less toxic than SDS/NPs. The initial results indicated that co-immunization of mice using his-p24/his-Nef/Ni-NP induced greater antibody response compared to using Alum/his-p24/his-Nef. Co-delivery of two antigens using Ni-NPs also increased the immunogenicity of individual antigens compared to delivery of a single antigen by Ni-NPs. In conclusion, Ni-NPs are an efficient delivery system for HIV vaccines including both single antigen delivery and multiple antigen co-delivery. PMID:21966230

  19. Lipid nanoparticles with accessible nickel as a vaccine delivery system for single and multiple his-tagged HIV antigens

    PubMed Central

    Yan, Weili; Jain, Anekant; O’Carra, Ronan; Woodward, Jerold G; Li, Wenxue; Li, Guanhan; Nath, Avindra; Mumper, Russell J

    2009-01-01

    Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the human immunodeficiency virus (HIV) his-tagged Tat (his-Tat) protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by subcutaneous injection with his-Tat/Ni-NP formulation (1.5 μg his-Tat/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific immunoglobulin G titer with his-Tat/Ni-NPs was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP-immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity than Tat-coated anionic NPs made with sodium dodecyl sulfate (SDS/NPs), they were less toxic than SDS/NPs. The initial results indicated that co-immunization of mice using his-p24/his-Nef/Ni-NP induced greater antibody response compared to using Alum/his-p24/his-Nef. Co-delivery of two antigens using Ni-NPs also increased the immunogenicity of individual antigens compared to delivery of a single antigen by Ni-NPs. In conclusion, Ni-NPs are an efficient delivery system for HIV vaccines including both single antigen delivery and multiple antigen co-delivery. PMID:21966230

  20. Lentinan-Modified Carbon Nanotubes as an Antigen Delivery System Modulate Immune Response in Vitro and in Vivo.

    PubMed

    Xing, Jie; Liu, Zhenguang; Huang, Yifan; Qin, Tao; Bo, Ruonan; Zheng, Sisi; Luo, Li; Huang, Yee; Niu, Yale; Wang, Deyun

    2016-08-01

    Adjuvants enhance immunogenicity and sustain long-term immune responses. As vital components of vaccines, efficient adjuvants are highly desirable. Recent evidence regarding the potential of carbon nanotubes (CNTs) to act as a support material has suggested that certain properties, such as their unique hollow structure, high specific surface area, and chemical stability, make CNTs desirable for a variety of antigen-delivery applications. Lentinan, a β-1,3-glucohexaose with β-1,6-branches that is extracted from the mushroom Lentinus edodes, is an effective immunostimulatory drug that has been clinically used in Japan and China, and recent studies have proved that specific beta-glucans can bind to various immune receptors. In this research, we covalently attached lentinan to multiwalled carbon nanotubes (MWCNTs) and tested their ability to enhance immune responses as a vaccine delivery system. In vitro study results showed that the nanotube constructs could rapidly enter dendritic cells and carry large amounts of antigen. Moreover, maturation markers were significantly upregulated versus the control. Thus, lentinan-modified multiwalled carbon nanotubes (L-MWCNTs) were regarded as an effective intracellular antigen depot and a catalyzer that could induce phenotypic and functional maturation of dendritic cells. Furthermore, compared with L-MWCNTs (35 μg/mL), a corresponding concentration of carboxylic carbon nanotubes (C-MWCNTs, 31.8 μg/mL) and an equivalent concentration of lentinan (3.2 μg/mL) did not remarkably influence the immune reaction in vitro or in vivo. Hence, we can hypothesize that the capability of L-MWCNTs was a consequence of the increased intracellular quantity of lentinan grafted onto the nanotubes. Overall, our studies demonstrated that L-MWCNTs significantly increased antigen accumulation in the cells and potentiated cellular and humoral immunity. In conclusion, L-MWCNTs constitute a potential vaccine delivery system to enhance immunogenicity

  1. Lentinan-Modified Carbon Nanotubes as an Antigen Delivery System Modulate Immune Response in Vitro and in Vivo.

    PubMed

    Xing, Jie; Liu, Zhenguang; Huang, Yifan; Qin, Tao; Bo, Ruonan; Zheng, Sisi; Luo, Li; Huang, Yee; Niu, Yale; Wang, Deyun

    2016-08-01

    Adjuvants enhance immunogenicity and sustain long-term immune responses. As vital components of vaccines, efficient adjuvants are highly desirable. Recent evidence regarding the potential of carbon nanotubes (CNTs) to act as a support material has suggested that certain properties, such as their unique hollow structure, high specific surface area, and chemical stability, make CNTs desirable for a variety of antigen-delivery applications. Lentinan, a β-1,3-glucohexaose with β-1,6-branches that is extracted from the mushroom Lentinus edodes, is an effective immunostimulatory drug that has been clinically used in Japan and China, and recent studies have proved that specific beta-glucans can bind to various immune receptors. In this research, we covalently attached lentinan to multiwalled carbon nanotubes (MWCNTs) and tested their ability to enhance immune responses as a vaccine delivery system. In vitro study results showed that the nanotube constructs could rapidly enter dendritic cells and carry large amounts of antigen. Moreover, maturation markers were significantly upregulated versus the control. Thus, lentinan-modified multiwalled carbon nanotubes (L-MWCNTs) were regarded as an effective intracellular antigen depot and a catalyzer that could induce phenotypic and functional maturation of dendritic cells. Furthermore, compared with L-MWCNTs (35 μg/mL), a corresponding concentration of carboxylic carbon nanotubes (C-MWCNTs, 31.8 μg/mL) and an equivalent concentration of lentinan (3.2 μg/mL) did not remarkably influence the immune reaction in vitro or in vivo. Hence, we can hypothesize that the capability of L-MWCNTs was a consequence of the increased intracellular quantity of lentinan grafted onto the nanotubes. Overall, our studies demonstrated that L-MWCNTs significantly increased antigen accumulation in the cells and potentiated cellular and humoral immunity. In conclusion, L-MWCNTs constitute a potential vaccine delivery system to enhance immunogenicity

  2. Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG-PLA Conjugate for Tuning Immunity.

    PubMed

    Coumes, Fanny; Huang, Chiung-Yi; Huang, Chung-Hsiung; Coudane, Jean; Domurado, Dominique; Li, Suming; Darcos, Vincent; Huang, Ming-Hsi

    2015-11-01

    Cancer vaccines are considered to be a promising tool for cancer immunotherapy. However, a well-designed cancer vaccine should combine a tumor-associated antigen (TAA) with the most effective immunomodulatory agents and/or delivery system to provoke intense immune responses against the TAA. In the present study, we introduced a new approach by conjugating the immunomodulatory molecule LD-indolicidin to the hydrophilic chain end of the polymeric emulsifier poly(ethylene glycol)-polylactide (PEG-PLA), allowing the molecule to be located close to the surface of the resulting emulsion. A peptide/polymer conjugate, named LD-indolicidin-PEG-PLA, was synthesized by conjugation of the amine end-group of LD-indolicidin to the N-hydroxysuccinimide-activated carboxyl end-group of PEG. As an adjuvant for cancer immunotherapeutic use, TAA vaccine candidate formulated with the LD-indolicidin-PEG-PLA-stabilized squalene-in-water emulsion could effectively help to elicit a T helper (Th)1-dominant antigen-specific immune response as well as antitumor ability, using ovalbumin (OVA) protein/EG7 cells as a TAA/tumor cell model. Taken together, these results open up a new approach to the development of immunomodulatory antigen delivery systems for vaccine adjuvants and cancer immunotherapy technologies. PMID:26473322

  3. Live attenuated Salmonella vaccines against Mycobacterium tuberculosis with antigen delivery via the type III secretion system.

    PubMed

    Juárez-Rodríguez, María Dolores; Arteaga-Cortés, Lourdes T; Kader, Rebin; Curtiss, Roy; Clark-Curtiss, Josephine E

    2012-02-01

    Tuberculosis remains a global health threat, and there is dire need to develop a vaccine that is safe and efficacious and confers long-lasting protection. In this study, we constructed recombinant attenuated Salmonella vaccine (RASV) strains with plasmids expressing fusion proteins consisting of the 80 amino-terminal amino acids of the type 3 secretion system effector SopE of Salmonella and the Mycobacterium tuberculosis antigens early secreted antigenic target 6-kDa (ESAT-6) protein and culture filtrate protein 10 (CFP-10). We demonstrated that the SopE-mycobacterial antigen fusion proteins were translocated into the cytoplasm of INT-407 cells in cell culture assays. Oral immunization of mice with RASV strains synthesizing SopE-ESAT-6-CFP-10 fusion proteins resulted in significant protection of the mice against aerosol challenge with M. tuberculosis H37Rv that was similar to the protection afforded by immunization with Mycobacterium bovis bacillus Calmette-Guérin (BCG) administered subcutaneously. In addition, oral immunization with the RASV strains specifying these mycobacterial antigens elicited production of significant antibody titers to ESAT-6 and production of ESAT-6- or CFP-10-specific gamma interferon (IFN-γ)-secreting and tumor necrosis factor alpha (TNF-α)-secreting splenocytes. PMID:22144486

  4. B-cell follicle development remodels the conduit system and allows soluble antigen delivery to follicular dendritic cells

    PubMed Central

    Germain, Ronald N.

    2009-01-01

    Afferent lymph is transported throughout lymph nodes (LNs) by the conduit system. Whereas this conduit network is dense in the T-cell zone, it is sparse in B-cell follicles. In this study, we show that this differential organization emerges during lymph node development. Neonatal LNs lack B follicles, but have a developed T-cell zone and a dense conduit network. As new T and B cells enter the developing LN, the conduit network density is maintained in the T, but not the B zone, leading to a profound remodeling of the follicular network that nevertheless maintains its connectivity. In adults, the residual follicular conduits transport soluble antigen to deep regions, where follicular dendritic cells are abundant and appear to replace the fibroblastic reticular cells that enwrap conduits in the T zone. This strategic location correlates with the capacity of the follicular dendritic cells to capture antigen even in the absence of antigen-specific antibodies. Together, these results describe how the stromal organization of the T and B regions of LNs diverges during development, giving rise to distinct antigen transport and delivery modes in the 2 compartments. PMID:19713459

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

    PubMed

    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.

  6. Delivery Systems.

    ERIC Educational Resources Information Center

    Hutchison, Betty

    This paper on delivery systems for preparing and training early childhood educators focuses on three main topics: (1) adequacy of delivery systems and access; (2) market influences on delivery systems; and (3) linking preparation and professional development components. Questions addressed include the following: Would the current preparation and…

  7. Escherichia coli Nissle 1917 bacterial ghosts retain crucial surface properties and express chlamydial antigen: an imaging study of a delivery system for the ocular surface.

    PubMed

    Montanaro, Jacqueline; Inic-Kanada, Aleksandra; Ladurner, Angela; Stein, Elisabeth; Belij, Sandra; Bintner, Nora; Schlacher, Simone; Schuerer, Nadine; Mayr, Ulrike Beate; Lubitz, Werner; Leisch, Nikolaus; Barisani-Asenbauer, Talin

    2015-01-01

    To target chronic inflammatory ocular surface diseases, a drug delivery platform is needed that is safe, possesses immunomodulatory properties, and can be used either for drug delivery, or as a foreign antigen carrier. A new therapeutic approach that we have previously proposed uses nonliving bacterial ghosts (BGs) as a carrier-delivery system which can be engineered to carry foreign antigens and/or be loaded with therapeutic drugs. The parent strain chosen for development of our BG delivery system is the probiotic Escherichia coli strain Nissle 1917 (EcN), whose intrinsic properties trigger the innate immune system with the flagella and fimbriae used to attach and stimulate epithelial cells. In previous studies, we have shown that EcN BGs are safe for the ocular surface route, but evidence that EcN BGs retain flagella and fimbriae after transformation, has never been visually confirmed. In this study, we used different visualization techniques to determine whether flagella and fimbriae are retained on EcN BGs engineered either for drug delivery or as a foreign antigen carrier. We have also shown by immunoelectron microscopy that EcN retains two foreign antigens after processing to become EcN BGs. Furthermore, we demonstrated that BGs derived from EcN and expressing a foreign antigen attachment to conjunctival epithelial cells in vitro without causing reduced cell viability. These results are an important step in constructing a delivery system based on a nonliving probiotic that is suitable for use in ocular surface diseases pairing immunomodulation and targeted delivery. PMID:26229437

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

    PubMed

    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.

  9. Heat shock protein derivatives for delivery of antigens to antigen presenting cells.

    PubMed

    Nishikawa, Makiya; Takemoto, Seiji; Takakura, Yoshinobu

    2008-04-16

    Delivery of antigens to antigen presenting cells (APCs) is a key issue for developing effective cancer vaccines. Controlling the tissue distribution of antigens can increase antigen-specific immune responses, including the induction of cytotoxic T lymphocytes (CTL). Heat shock protein 70 (Hsp70) forms complexes with a variety of tumor-related antigens via its polypeptide-binding domain. Because Hsp70 is taken up by APCs through recognition by Hsp receptors, such as CD91 and LOX-1, its application to antigen delivery systems has been examined both in experimental and clinical settings. A tissue distribution study revealed that Hsp70 is mainly taken up by the liver, especially by hepatocytes, after intravenous injection in mice. A significant amount of Hsp70 was also delivered to regional lymph nodes when it was injected subcutaneously, supporting the hypothesis that Hsp70 is a natural targeting system for APCs. Model antigens were complexed with or conjugated to Hsp70, resulting in greater antigen-specific immune responses. Cytoplasmic delivery of Hsp70-antigen further increased the efficacy of the Hsp70-based vaccines. These findings indicate that effective cancer therapy can be achieved by developing Hsp70-based anticancer vaccines when their tissue and intracellular distribution is properly controlled. PMID:17980980

  10. Modular Three-component Delivery System Facilitates HLA Class I Antigen Presentation and CD8(+) T-cell Activation Against Tumors.

    PubMed

    Umlauf, Benjamin J; Chung, Chin-Ying; Brown, Kathlynn C

    2015-06-01

    Cell-mediated immunotherapies have potential as stand-alone and adjuvant therapies for cancer. However, most current protocols suffer from one or more of three major issues: cost, safety, or efficacy. Here we present a nanoparticle delivery system that facilitates presentation of an immunogenic measles antigen specifically in cancer cells. The delivery system does not contain viral particles, toxins, or biologically derived material. Treatment with this system facilitates activation of a secondary immune response against cancer cells, bypassing the need to identify tumor-associated antigens or educate the immune system through a primary immune response. The delivery system consists of a stealth liposome displaying a cancer-specific targeting peptide, named H1299.3, on its exterior surface and encapsulating H250, an immunogenic human leukocyte antigen class 1 restricted peptide. This targeted-nanoparticle facilitates presentation of the H250 peptide in major histocompatibility complex class I molecules. Activation is dependent on the targeting peptide, previous antigen exposure, and utilizes a novel autophagy-mediated mechanism to facilitate presentation. Treatment with this liposome results in a significant reduction of tumor growth using an aggressive LLC1 model in vaccinated C57BL/6 mice. These data provide proof-of-principle for a novel cell-mediated immunotherapy that is scalable, contains no biologically derived material, and is an efficacious cancer therapy.

  11. Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy.

    PubMed

    Hassan, Hatem A F M; Smyth, Lesley; Wang, Julie T-W; Costa, Pedro M; Ratnasothy, Kulachelvy; Diebold, Sandra S; Lombardi, Giovanna; Al-Jamal, Khuloud T

    2016-10-01

    Although anti-cancer immuno-based combinatorial therapeutic approaches have shown promising results, efficient tumour eradication demands further intensification of anti-tumour immune response. With the emerging field of nanovaccinology, multi-walled carbon nanotubes (MWNTs) have manifested prominent potentials as tumour antigen nanocarriers. Nevertheless, the utilization of MWNTs in co-delivering antigen along with different types of immunoadjuvants to antigen presenting cells (APCs) has not been investigated yet. We hypothesized that harnessing MWNT for concurrent delivery of cytosine-phosphate-guanine oligodeoxynucleotide (CpG) and anti-CD40 Ig (αCD40), as immunoadjuvants, along with the model antigen ovalbumin (OVA) could potentiate immune response induced against OVA-expressing tumour cells. We initially investigated the effective method to co-deliver OVA and CpG using MWNT to the APC. Covalent conjugation of OVA and CpG prior to loading onto MWNTs markedly augmented the CpG-mediated adjuvanticity, as demonstrated by the significantly increased OVA-specific T cell responses in vitro and in C57BL/6 mice. αCD40 was then included as a second immunoadjuvant to further intensify the immune response. Immune response elicited in vitro and in vivo by OVA, CpG and αCD40 was significantly potentiated by their co-incorporation onto the MWNTs. Furthermore, MWNT remarkably improved the ability of co-loaded OVA, CpG and αCD40 in inhibiting the growth of OVA-expressing B16F10 melanoma cells in subcutaneous or lung pseudo-metastatic tumour models. Therefore, this study suggests that the utilization of MWNTs for the co-delivery of tumour-derived antigen, CpG and αCD40 could be a competent approach for efficient tumours eradication.

  12. 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.

    PubMed

    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.

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2016-01-01

    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. PMID:27251373

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

    PubMed Central

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

    2016-01-01

    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. PMID:27251373

  17. Immune response induced by conjunctival immunization with polymeric antigen BLSOmp31 using a thermoresponsive and mucoadhesive in situ gel as vaccine delivery system for prevention of ovine brucellosis.

    PubMed

    Díaz, Alejandra Graciela; Quinteros, Daniela Alejandra; Gutiérrez, Silvina Elena; Rivero, Mariana Alejandra; Palma, Santiago Daniel; Allemandi, Daniel Alberto; Pardo, Romina Paola; Zylberman, Vanesa; Goldbaum, Fernando Alberto; Estein, Silvia Marcela

    2016-10-01

    Control of ovine brucellosis with subcellular vaccines can solve some drawbacks associated with the use of Brucella melitensis Rev.1. Previous studies have demonstrated that the polymeric antigen BLSOmp31 administered by parenteral route was immunogenic and conferred significant protection against B. ovis in rams. Immunization with BLSOmp31 by conjunctival route could be efficient for the induction of mucosal and systemic immune responses. In this work, we evaluated the conjunctival immunization using a thermoresponsive and mucoadhesive in situ gel composed of Poloxamer 407 (P407) and chitosan (Ch) as vaccine delivery system for BLSOmp31 in rams. Serum samples, saliva, lacrimal, preputial and nasal secretions were analyzed to measure specific IgG and IgA antibodies. Cellular immune response was evaluated in vivo and in vitro. Immunization with BLSOmp31-P407-Ch induced high IgG antibody levels in serum and preputial secretions which remained at similar levels until the end of the experiment. Levels of IgG in saliva, lacrimal and nasal secretions were also higher compared to unvaccinated control group but decreased more rapidly. IgA antibodies were only detected in nasal and preputial secretions. BLSOmp31-P407-Ch stimulated a significant cellular immune response in vivo and in vitro. The induction of systemic and local immune responses indicates a promising potential of P407-Ch for the delivery of BLSOmp31 by conjunctival route.

  18. Immune response induced by conjunctival immunization with polymeric antigen BLSOmp31 using a thermoresponsive and mucoadhesive in situ gel as vaccine delivery system for prevention of ovine brucellosis.

    PubMed

    Díaz, Alejandra Graciela; Quinteros, Daniela Alejandra; Gutiérrez, Silvina Elena; Rivero, Mariana Alejandra; Palma, Santiago Daniel; Allemandi, Daniel Alberto; Pardo, Romina Paola; Zylberman, Vanesa; Goldbaum, Fernando Alberto; Estein, Silvia Marcela

    2016-10-01

    Control of ovine brucellosis with subcellular vaccines can solve some drawbacks associated with the use of Brucella melitensis Rev.1. Previous studies have demonstrated that the polymeric antigen BLSOmp31 administered by parenteral route was immunogenic and conferred significant protection against B. ovis in rams. Immunization with BLSOmp31 by conjunctival route could be efficient for the induction of mucosal and systemic immune responses. In this work, we evaluated the conjunctival immunization using a thermoresponsive and mucoadhesive in situ gel composed of Poloxamer 407 (P407) and chitosan (Ch) as vaccine delivery system for BLSOmp31 in rams. Serum samples, saliva, lacrimal, preputial and nasal secretions were analyzed to measure specific IgG and IgA antibodies. Cellular immune response was evaluated in vivo and in vitro. Immunization with BLSOmp31-P407-Ch induced high IgG antibody levels in serum and preputial secretions which remained at similar levels until the end of the experiment. Levels of IgG in saliva, lacrimal and nasal secretions were also higher compared to unvaccinated control group but decreased more rapidly. IgA antibodies were only detected in nasal and preputial secretions. BLSOmp31-P407-Ch stimulated a significant cellular immune response in vivo and in vitro. The induction of systemic and local immune responses indicates a promising potential of P407-Ch for the delivery of BLSOmp31 by conjunctival route. PMID:27496742

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

    PubMed

    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.

  20. A liposome-based antigen delivery system using pH-sensitive fusogenic polymers for cancer immunotherapy.

    PubMed

    Yuba, Eiji; Harada, Atsushi; Sakanishi, Yuichi; Watarai, Shinobu; Kono, Kenji

    2013-04-01

    Highly pH-sensitive liposomes that deliver antigenic molecules into cytosol through fusion with or destabilization of endosome were prepared by surface modification of egg yolk phosphatidylcholine/dioleoylphosphatidylethanolamine (1/1, mol/mol) liposomes with 3-methylglutarylated poly(glycidol) of linear (MGlu-LPG) or hyperbranched structure (MGlu-HPG). These polymer-modified liposomes were stable at neutral pH, but they became strongly destabilized below pH 6, which corresponds to the pH of endosome. These polymer-modified liposomes were taken up by murine dendritic cells (DCs) more efficiently than the unmodified liposomes were through an endocytic pathway. They introduced entrapped ovalbumin (OVA) molecules into cytosol. Subcutaneous or nasal administration of the polymer-modified liposomes loaded with OVA induced generation of OVA-specific cytotoxic T cells (CTL) much more effectively than the unmodified liposomes loaded with OVA. Furthermore, administration of the polymer-modified OVA-loaded liposomes to mice bearing E.G7-OVA tumor significantly reduced the tumor burden, although the OVA-loaded unmodified liposomes only slightly affected tumor growth. Results suggest that the polymer-modified liposomes with highly pH-sensitive destabilizing property are promising as antigen carriers for efficient cancer immunotherapy.

  1. Delivery of foreign antigens by engineered outer membrane vesicle vaccines.

    PubMed

    Chen, David J; Osterrieder, Nikolaus; Metzger, Stephan M; Buckles, Elizabeth; Doody, Anne M; DeLisa, Matthew P; Putnam, David

    2010-02-16

    As new disease threats arise and existing pathogens grow resistant to conventional interventions, attention increasingly focuses on the development of vaccines to induce protective immune responses. Given their admirable safety records, protein subunit vaccines are attractive for widespread immunization, but their disadvantages include poor immunogenicity and expensive manufacture. We show here that engineered Escherichia coli outer membrane vesicles (OMVs) are an easily purified vaccine-delivery system capable of greatly enhancing the immunogenicity of a low-immunogenicity protein antigen without added adjuvants. Using green-fluorescent protein (GFP) as the model subunit antigen, genetic fusion of GFP with the bacterial hemolysin ClyA resulted in a chimeric protein that elicited strong anti-GFP antibody titers in immunized mice, whereas immunization with GFP alone did not elicit such titers. Harnessing the specific secretion of ClyA to OMVs, the ClyA-GFP fusion was found localized in OMVs, resulting in engineered recombinant OMVs. The anti-GFP humoral response in mice immunized with the engineered OMV formulations was indistinguishable from the response to the purified ClyA-GFP fusion protein alone and equal to purified proteins absorbed to aluminum hydroxide, a standard adjuvant. In a major improvement over current practice, engineered OMVs containing ClyA-GFP were easily isolated by ultracentrifugation, effectively eliminating the need for laborious antigen purification from cell-culture expression systems. With the diverse collection of heterologous proteins that can be functionally localized with OMVs when fused with ClyA, this work signals the possibility of OMVs as a robust and tunable technology platform for a new generation of prophylactic and therapeutic vaccines. PMID:20133740

  2. Gut adhesive Bacillus subtilis spores as a platform for mucosal delivery of antigens.

    PubMed

    Tavares Batista, Milene; Souza, Renata D; Paccez, Juliano D; Luiz, Wilson B; Ferreira, Ewerton L; Cavalcante, Rafael C M; Ferreira, Rita C C; Ferreira, Luís C S

    2014-04-01

    Bacillus subtilis spores have been used as safe and heat-resistant antigen delivery vectors. Nonetheless, the oral administration of spores typically induces weak immune responses to the passenger antigens, which may be attributed to the fast transit through the gastrointestinal tract. To overcome this limitation, we have developed B. subtilis spores capable of binding to the gut epithelium by means of expressing bacterial adhesins on the spore surface. The resulting spores bound to in vitro intestinal cells, showed a longer transit through the mouse intestinal tract, and interacted with Peyer's patch cells. The adhesive spores increased the systemic and secreted antibody responses to the Streptococcus mutans P1 protein, used as a model antigen, following oral, intranasal, and sublingual administration. Additionally, P1-specific antibodies efficiently inhibited the adhesion of the oral pathogen Streptococcus mutans to abiotic surfaces. These results support the use of gut-colonizing B. subtilis spores as a new platform for the mucosal delivery of vaccine antigens.

  3. Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells

    PubMed Central

    Kwon, Kwang-Chul; Verma, Dheeraj; Singh, Nameirakpam D.; Herzog, Roland; Daniell, Henry

    2012-01-01

    Among 12 billion injections administered annually, unsafe delivery leads to >20 million infections and >100 million reactions. In an emerging new concept, freeze-dried plant cells (lettuce) expressing vaccine antigens/biopharmaceuticals are protected in the stomach from acids/enzymes but are released to the immune or blood circulatory system when plant cell walls are digested by microbes that colonize the gut. Vaccine antigens bioencapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. Oral delivery of autoantigens was effective against complications of type 1diabetes and hemophilia, by developing tolerance. Oral delivery of proinsulin or exendin-4 expressed in plant cells regulated blood glucose levels similar to injections. Therefore, this new platform offers a low cost alternative to deliver different therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections. PMID:23099275

  4. Efficient delivery of antigen to DCs using yeast-derived microparticles.

    PubMed

    Pan, Ying; Li, Xiaopeng; Kang, Tianyi; Meng, Hui; Chen, Zhouli; Yang, Li; Wu, Yang; Wei, Yuquan; Gou, Maling

    2015-01-01

    Some pathogens can be naturally recognized and internalized by antigen presentation cells (APCs) in vivo, providing a platform for efficient vaccine delivery. However, the biosafety concerns discourage the clinical applications of live pathogens. Here, yeast-derived microparticles were prepared for cancer vaccine delivery. By chemical treatment of bread yeast, capsular yeast shell (YS) microparticles were obtained. Ovalbumin (OVA), as a model antigen, was conjugated to the surface of YS. Results indicated that these YS microparticles with a uniform size of ~3.4 μm can be recognized and internalized by dendritic cells (DCs). The YS-mediated antigen delivery can enhance the cellular uptake of antigen by DCs, promote the maturation of DCs, and trigger DCs to release immune co-stimulatory molecules. Immunization with YS-mediated antigen can induce an effective immune response against tumor cells in vivo, with contributions from both humoral and cellular immunity. This work suggests that yeast shell microparticles as efficient vaccine delivery system has promising applications in cancer immunotherapy. PMID:26022399

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

    PubMed

    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.

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

    PubMed

    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

    2011-12-01

    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.

  7. Antigen detection systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious agents or their constituent parts (antigens or nucleic acids) can be detected in fresh, frozen, or fixed tissues or other specimens, using a variety of direct or indirect assays. The assays can be modified to yield the greatest sensitivity and specificity but in most cases a particular m...

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

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

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

  9. Antigen discovery and delivery of subunit vaccines by nonliving bacterial ghost vectors.

    PubMed

    Walcher, Petra; Mayr, Ulrike B; Azimpour-Tabrizi, Chakameh; Eko, Francis O; Jechlinger, Wolfgang; Mayrhofer, Peter; Alefantis, Tim; Mujer, Cesar V; DelVecchio, Vito G; Lubitz, Werner

    2004-12-01

    The bacterial ghost (BG) platform system is a novel vaccine delivery system endowed with intrinsic adjuvant properties. BGs are nonliving Gram-negative bacterial cell envelopes which are devoid of their cytoplasmic contents, yet maintain their cellular morphology and antigenic structures, including bioadhesive properties. The main advantages of BGs as carriers of subunit vaccines include their ability to stimulate a high immune response and to target the carrier itself to primary antigen-presenting cells. The intrinsic adjuvant properties of BGs enhance the immune response to target antigens, including T-cell activation and mucosal immunity. Since native and foreign antigens can be carried in the envelope complex of BGs, combination vaccines with multiple antigens of diverse origin can be presented to the immune system simultaneously. Beside the capacity of BGs to function as carriers of protein antigens, they also have a high loading capacity for DNA. Thus, loading BGs with recombinant DNA takes advantage of the excellent bioavailability for DNA-based vaccines and the high expression rates of the DNA-encoded antigens in target cell types such as macrophages and dendritic cells. There are many spaces within BGs including the inner and outer membranes, the periplasmic space and the internal lumen which can carry antigens, DNA or mediators of the immune response. All can be used for subunit antigen to design new vaccine candidates with particle presentation technology. In addition, the fact that BGs can also carry piggyback large-size foreign antigen particles, increases the technologic usefulness of BGs as combination vaccines against viral and bacterial pathogens. Furthermore, the BG antigen carriers can be stored as freeze-dried preparations at room temperature for extended periods without loss of efficacy. The potency, safety and relatively low production cost of BGs offer a significant technical advantage over currently utilized vaccine technologies.

  10. pH-sensitive polymer-liposome-based antigen delivery systems potentiated with interferon-γ gene lipoplex for efficient cancer immunotherapy.

    PubMed

    Yuba, Eiji; Kanda, Yuhei; Yoshizaki, Yuta; Teranishi, Ryoma; Harada, Atsushi; Sugiura, Kikuya; Izawa, Takeshi; Yamate, Jyoji; Sakaguchi, Naoki; Koiwai, Kazunori; Kono, Kenji

    2015-10-01

    Potentiation of pH-sensitive liposome-based antigen carriers with IFN-γ gene lipoplexes was attempted to achieve efficient induction of tumor-specific immunity. 3-Methylglutarylated poly(glycidol) (MGluPG)-modified liposomes and cationic liposomes were used, respectively, for the delivery of antigenic protein ovalbumin (OVA) and IFN-γ-encoding plasmid DNA (pDNA). The MGluPG-modified liposomes and the cationic liposome-pDNA complexes (lipoplexes) formed hybrid complexes via electrostatic interactions after their mixing in aqueous solutions. The hybrid complexes co-delivered OVA and IFN-γ-encoding pDNA into DC2.4 cells, a murine dendritic cell line, as was the case of MGluPG-modified liposomes for OVA or the lipoplexes for pDNA. Both the lipoplexes and the hybrid complexes transfected DC2.4 cells and induced IFN-γ protein production, but transfection activities of the hybrid complexes were lower than those of the parent lipoplexes. Subcutaneous administration of hybrid complexes to mice bearing E.G7-OVA tumor reduced tumor volumes, which might result from the induction of OVA-specific cytotoxic T lymphocytes (CTLs). However, the hybrid complex-induced antitumor effect was the same level of the MGluPG-modified liposome-mediated antitumor immunity. In contrast, an extremely strong antitumor immune response was derived when these liposomes and lipoplexes without complexation were injected subcutaneously at the same site of tumor-bearing mice. Immunohistochemical analysis of tumor sections revealed that immunization through the liposome-lipoplex combination promoted the infiltration of CTLs to tumors at an early stage of treatment compared with liposomes, resulting in strong therapeutic effects.

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

    PubMed Central

    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. PMID:26158754

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

    PubMed

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

    2013-06-21

    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. PMID:23657437

  13. Chitosan based nanoparticles as protein carriers for efficient oral antigen delivery.

    PubMed

    Gao, Ping; Xia, Guixue; Bao, Zixian; Feng, Chao; Cheng, Xiaojie; Kong, Ming; Liu, Ya; Chen, Xiguang

    2016-10-01

    This study aimed to investigate the efficacy of nanoparticles based on chitosan as a vehicle for oral antigen delivery in fish vaccination. Carboxymethyl chitosan/chitosan nanoparticles (CMCS/CS-NPs) loaded extracellular products (ECPs) of Vibrio anguillarum were successfully developed by ionic gelation method. The prepared ECPs-loaded CMCS/CS-NPs were characterized for various parameters including morphology, particle size (312±7.18nm), zeta potential (+17.4±0.38mV), loading efficiency (57.8±2.54%) and stability under the simulated gastrointestinal (GI) tract conditions in turbot. The in vitro profile showed that the cumulative release of ECPs from nanoparticles was higher in pH 7.4 (58%) than in pH 2.0 (37%) and pH 4.5 (29%) after 48h. Fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) was used as model protein antigen and encapsulated in CMCS/CS-NPs for investigating the biodistribution of antigen after oral delivery to turbot in 24h. Oral immunization of ECPs-loaded CMCS/CS-NPs group in turbot showed elevated specific antibody and higher concentrations of lysozyme activity and complement activity in fish serum than ECPs solution. CMCS/CS-NPs loaded with ECPs could enhance both adaptive and innate immune responses than the group treated with ECPs solution and suggested to be a potential antigen delivery system. PMID:27287772

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

  15. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug

  16. Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens.

    PubMed

    Sheppard, Neil C; Brinckmann, Sarah A; Gartlan, Kate H; Puthia, Manoj; Svanborg, Catharina; Krashias, George; Eisenbarth, Stephanie C; Flavell, Richard A; Sattentau, Quentin J; Wegmann, Frank

    2014-10-01

    Polyethyleneimine (PEI) is an organic polycation used extensively as a gene and DNA vaccine delivery reagent. Although the DNA targeting activity of PEI is well documented, its immune activating activity is not. We recently reported that PEI has robust mucosal adjuvanticity when administered intranasally with glycoprotein antigens. Here, we show that PEI has strong immune activating activity after systemic delivery. PEI administered subcutaneously with viral glycoprotein (HIV-1 gp140) enhanced antigen-specific serum IgG production in the context of mixed Th1/Th2-type immunity. PEI elicited higher titers of both antigen binding and neutralizing antibodies than alum in mice and rabbits and induced an increased proportion of antibodies reactive with native antigen. In an intraperitoneal model, PEI recruited neutrophils followed by monocytes to the site of administration and enhanced antigen uptake by antigen-presenting cells. The Th bias was modulated by PEI activation of the Nlrp3 inflammasome; however its global adjuvanticity was unchanged in Nlrp3-deficient mice. When coformulated with CpG oligodeoxynucleotides, PEI adjuvant potency was synergistically increased and biased toward a Th1-type immune profile. Taken together, these data support the use of PEI as a versatile systemic adjuvant platform with particular utility for induction of secondary structure-reactive antibodies against glycoprotein antigens. PMID:24844701

  17. Educational Telecommunications Delivery Systems.

    ERIC Educational Resources Information Center

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

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

  18. PLGA-Listeriolysin O microspheres: Opening the gate for cytosolic delivery of cancer antigens.

    PubMed

    Gilert, Ariel; Baruch, Limor; Bronshtein, Tomer; Machluf, Marcelle

    2016-04-01

    Strategies for cancer protein vaccination largely aim to activate the cellular arm of the immune system against cancer cells. This approach, however, is limited since protein vaccines mostly activate the system's humoral arm instead. One way to overcome this problem is to enhance the cross-presentation of such proteins by antigen-presenting cells, which may consequently lead to intense cellular response. Here we examined the ability of listeriolysin O (LLO) incorporated into poly-lactic-co-glycolic acid (PLGA) microspheres to modify the cytosolic delivery of low molecular weight peptides and enhance their cross-presentation. PLGA microspheres were produced in a size suitable for uptake by phagocytic cells. The peptide encapsulation and release kinetics were improved by adding NaCl to the preparation. PLGA microspheres loaded with the antigenic peptide and incorporated with LLO were readily up-taken by phagocytic cells, which exhibited an increase in the expression of peptide-MHC-CI complexes on the cell surface. Furthermore, this system enhanced the activation of a specific T hybridoma cell line, thus simulating cytotoxic T cells. These results establish, for the first time, a proof of concept for the use of PLGA microspheres incorporated with a pore-forming agent and the antigen peptide of choice as a unique cancer protein vaccination delivery platform.

  19. Improvement of different vaccine delivery systems for cancer therapy

    PubMed Central

    2011-01-01

    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. PMID:21211062

  20. Biomaterials for Nanoparticle Vaccine Delivery Systems

    PubMed Central

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

    2014-01-01

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

  1. Biodegradable nanoparticle mediated antigen delivery to human cord blood derived dendritic cells for induction of primary T cell responses.

    PubMed

    Diwan, Manish; Elamanchili, Praveen; Lane, Helena; Gainer, Anita; Samuel, John

    2003-01-01

    Dendritic cells (DCs) in the peripheral tissues act as sentinels of the immune system. They detect and capture pathogens entering the body and present their antigens to T cells to trigger responses directed towards elimination of the pathogen. The induction of peripheral tolerance against self and certain foreign antigens is also believed to be mediated through DCs. The outcome of any immune response is largely controlled by the microenvironment of antigen capture, processing and presentation by DCs. The "context" of antigen delivery to DCs will directly influence the microenvironment of antigen presentation and hence the regulation of immune responses. We report here preliminary investigations describing the formulation of a pharmaceutically acceptable, biodegradable, and strategic nanoparticulate delivery system, and its application for efficient antigen loading of DCs to achieve antigen specific T cell activation. "Pathogen-mimicking" nanoparticles capable of interacting with DCs were fabricated by incorporating monophosphoryl lipid A (MPLA; toll-like receptor (TLR) 4 ligand) or CpG ODN (seq #2006; TLR9 ligand) in biodegradable copolymer, poly(D,L,-lactic-co-glycolic acid) (PLGA). The uptake of PLGA nanoparticles by human umbilical cord blood derived DCs (DCs propagated from CD34 progenitors) was conclusively demonstrated by scanning electron microscopy (SEM), fluorescence activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM). Cell phenotype at day 12 of cultures was determined as immature DC using specific cell surface markers, i.e. CD11c (approximately 90%), MHC-II (approximately 70%), CD86 (approximately 20%), CD83 (approximately 5%), CD80 (approximately 40%), CD40 (approximately 40%), and CCR7 (approximately 5%). Tetanus toxoid (TT), a model antigen, was encapsulated in nanoparticles along with an immunomodulator, i.e. either MPLA or CpG ODN. DCs pulsed with various antigen formulations were co-cultured with autologous naïve T cells at

  2. Advanced antigen delivery of murine survivin: chimeric virus-like particles in cancer vaccine research.

    PubMed

    Schumacher, Thomas; Ruehland, Claus; Schultheiss, Christine; Brinkman, Marc; Roedel, Franz; Reiser, Christian O A; Hess, Juergen; Reichel, Christoph

    2007-09-01

    Success in cancer immunotherapy depends on the identification and efficient targeting of specific tumor-associated antigens. Two pivotal strategies to prime patients' immune system against malignant cells are tumor-specific adoptive T-cell therapy and tumor-specific vaccination. Here, we will focus on immunotherapeutic vaccination and discuss the advantages and disadvantages of different strategies to deliver tumor-specific T-cell epitopes. A particular focus will be put on virus-like particles (VLPs) as vehicle to deliver tumor-specific epitopes in the context of full-length proteins, as multi-epitope constructs or as individual tumor-associated T-cell epitopes. VLPs represent non-infectious and non-replicating antigen delivery systems devoid of any nucleic acid. They constitute innovative immunotherapeutic agents against cancer due to their superior, adjuvant-like antigenicity. We will present various tumor-associated antigens currently in different stages of development including survivin, as promising candidates for targeted tumor therapies. PMID:23675044

  3. Advanced Antigen Delivery of Murine Survivin: Chimeric Virus-Like Particles in Cancer Vaccine Research

    PubMed Central

    Schumacher, Thomas; Ruehland, Claus; Schultheiss, Christine; Brinkman, Marc; Roedel, Franz; Reiser, Christian O. A.; Hess, Juergen; Reichel, Christoph

    2007-01-01

    Success in cancer immunotherapy depends on the identification and efficient targeting of specific tumor-associated antigens. Two pivotal strategies to prime patients’ immune system against malignant cells are tumor-specific adoptive T-cell therapy and tumor-specific vaccination. Here, we will focus on immunotherapeutic vaccination and discuss the advantages and disadvantages of different strategies to deliver tumor-specific T-cell epitopes. A particular focus will be put on virus-like particles (VLPs) as vehicle to deliver tumor-specific epitopes in the context of full-length proteins, as multi-epitope constructs or as individual tumor-associated T-cell epitopes. VLPs represent non-infectious and non-replicating antigen delivery systems devoid of any nucleic acid. They constitute innovative immunotherapeutic agents against cancer due to their superior, adjuvant-like antigenicity. We will present various tumor-associated antigens currently in different stages of development including survivin, as promising candidates for targeted tumor therapies. PMID:23675044

  4. Advanced antigen delivery of murine survivin: chimeric virus-like particles in cancer vaccine research.

    PubMed

    Schumacher, Thomas; Ruehland, Claus; Schultheiss, Christine; Brinkman, Marc; Roedel, Franz; Reiser, Christian O A; Hess, Juergen; Reichel, Christoph

    2007-09-01

    Success in cancer immunotherapy depends on the identification and efficient targeting of specific tumor-associated antigens. Two pivotal strategies to prime patients' immune system against malignant cells are tumor-specific adoptive T-cell therapy and tumor-specific vaccination. Here, we will focus on immunotherapeutic vaccination and discuss the advantages and disadvantages of different strategies to deliver tumor-specific T-cell epitopes. A particular focus will be put on virus-like particles (VLPs) as vehicle to deliver tumor-specific epitopes in the context of full-length proteins, as multi-epitope constructs or as individual tumor-associated T-cell epitopes. VLPs represent non-infectious and non-replicating antigen delivery systems devoid of any nucleic acid. They constitute innovative immunotherapeutic agents against cancer due to their superior, adjuvant-like antigenicity. We will present various tumor-associated antigens currently in different stages of development including survivin, as promising candidates for targeted tumor therapies.

  5. Mucoadhesive drug delivery systems

    PubMed Central

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

    2011-01-01

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

  6. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

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

  7. Nanovehicular Intracellular Delivery Systems

    PubMed Central

    PROKOP, ALES; DAVIDSON, JEFFREY M.

    2013-01-01

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

  8. Secondary fuel delivery system

    DOEpatents

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

    2010-02-23

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

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

    PubMed Central

    Allahyari, Mojgan; Mohit, Elham

    2016-01-01

    abstract Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

  10. Antigens and cytokine genes in antitumor vaccines: the importance of the temporal delivery sequence in antitumor signals.

    PubMed

    Herrero, María José; Botella, Rafael; Dasí, Francisco; Algás, Rosa; Sánchez, María; Aliño, Salvador F

    2006-12-01

    Studies against cancer, including clinical trials, have shown that a correct activation of the immune system can lead to tumor rejection whereas incorrect signaling results in no positive effects or even anergy. We have worked assuming that two signals, GM-CSF (granulocyte and macrophage colony-stimulating factor) and tumor antigens are necessary to mediate an antitumor effective response. To study which is the ideal temporal sequence for their administration, we have used a murine model of antimelanoma vaccine employing whole B16 tumor cells or their membrane protein antigens (TMPs) in combination with gm-csf transfer before or after the antigen delivery. Our results show that: (i) When gm-csf tisular transfection is performed before TMP delivery, a tumor growth inhibition is observed, but with a limit effect when administering high antigen doses; in contrast, when signals are inverted, the limited effect is lost and greater antitumor efficacy is obtained. (ii) A similar behavior, but with stronger positive results, is observed employing gm-csf transfection and whole tumor cells as antigens. While negative results are obtained with gm-csf before cells, the best results (total survival of treated mice) are obtained when GM-CSF is administered in transfected cells. We conclude that optimal antitumoral response can be obtained when the antigen signal is given before (or simultaneous with) GM-CSF production, while the inversion of the signals could result in the undesired inhibition or anergy of the immune response.

  11. Type VI secretion system sheaths as nanoparticles for antigen display

    PubMed Central

    Del Tordello, Elena; Danilchanka, Olga; McCluskey, Andrew J.; Mekalanos, John J.

    2016-01-01

    The bacterial type 6 secretion system (T6SS) is a dynamic apparatus that translocates proteins between cells by a mechanism analogous to phage tail contraction. T6SS sheaths are cytoplasmic tubular structures composed of stable VipA-VipB (named for ClpV-interacting protein A and B) heterodimers. Here, the structure of the VipA/B sheath was exploited to generate immunogenic multivalent particles for vaccine delivery. Sheaths composed of VipB and VipA fused to an antigen of interest were purified from Vibrio cholerae or Escherichia coli and used for immunization. Sheaths displaying heterologous antigens generated better immune responses against the antigen and different IgG subclasses compared with soluble antigen alone. Moreover, antigen-specific antibodies raised against sheaths presenting Neisseria meningitidis factor H binding protein (fHbp) antigen were functional in a serum bactericidal assay. Our results demonstrate that multivalent nanoparticles based on the T6SS sheath represent a versatile scaffold for vaccine applications. PMID:26929342

  12. Why new delivery systems?

    PubMed

    Calkins, J M

    1984-01-01

    Although anesthetists have accomplished a remarkable safety record with commercially available anesthetic machines, these results have been obtained in spite of machine design, which could best be described as a nonsystem. In cases involving severely compromised patients, surgical procedures that severely alter patient physiology, and untoward events during "routine" anesthesia, it is a tribute to the flexibility and resourcefulness of anesthetists that more incidents do not occur. Industry has long sought precision, reliability, automatic control, and human-factors engineering in nonmedical applications, such as aircraft cockpit design, word-processing stations, and manufacturing processes. The relentless accretion of more and more nonintegrated gadgets onto an antiquated technology has exceeded the boundaries of proper function. Neither the patient nor the anesthetist is being served well by failure to implement state-of-the-art technology in anesthesic delivery systems. Anesthesiologists and others who are vitally interested in the welfare of their patients must insist that development of radically new integrated modular systems proceed at full speed. Their checkbooks can speak as loudly as the facts; it is time the manufacturers are aware that deep concern will be translated into purchasing decisions.

  13. A long acting biodegradable controlled delivery of chitosan microspheres loaded with tetanus toxoide as model antigen.

    PubMed

    Varma, Sujith; Sadasivan, C

    2014-03-01

    The chitosan microspheres formulated by emulsion cross-linking method were found to be smooth and spherical without aggregation. The particle size range was between 1 and 90μm. The particle sizes were found to be influenced by the concentration of the chitosan gel. Tetanus toxoide (TT) vaccine was loaded by passive adsorption from an aqueous solution into the preformed chitosan microspheres cross-linked with glutaraldehyde. The loaded TT on to microspheres was estimated by ELISA method. The loading capacity was found to be 40% with microspheres prepared with 1% chitosan gel, 43% for 2% and 46% for the mixed batch of microspheres prepared from 1% and 2% chitosan gel. The loading efficiency was found to decrease with increase in the concentration of chitosan gel. The in vitro release of the antigenic TT into the phosphate buffer at 37°C from different batch of microspheres was studied and release had a remarkable dependence on the size of micropsheres. The percentage release of TT from chitosan microspheres prepared from 1% chitosan gel was 2.7% in 120days and that from 2% chitosan gel was only 2%. The mixed batch of microspheres could release 2.3% in 120days. The antigen integrity was investigated by SDS-PAGE with brilliant blue staining. The SDS-PAGE analysis confirmed that the antigen integrity was not affected by passive adsorption of protein antigen to preformed chitosan microspheres. The study revealed that the cross-linked chitosan microspheres would be an interesting system for long-term delivery of macromolecules drugs.

  14. Polymers for Drug Delivery Systems

    PubMed Central

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

    2012-01-01

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

  15. Delivery methods for LVSD systems

    NASA Astrophysics Data System (ADS)

    Kasner, James H.; Brower, Bernard V.

    2011-06-01

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

  16. In Vivo Delivery of Antigens by Adenovirus Dodecahedron Induces Cellular and Humoral Immune Responses to Elicit Antitumor Immunity

    PubMed Central

    Villegas-Mendez, Ana; Garin, Marina I; Pineda-Molina, Estela; Veratti, Eugenia; Bueren, Juan A; Fender, Pascal; Lenormand, Jean-Luc

    2010-01-01

    Cancer vaccines based on virus-like particles (VLPs) vectors may offer many advantages over other antigen-delivery systems and represent an alternative to the ex vivo cell therapy approach. In this study, we describe the use of penton-dodecahedron (Pt-Dd) VLPs from human adenovirus type 3 (Ad3) as cancer vaccine vehicle for specific antigens, based on its unique cellular internalization properties. WW domains from the ubiquitin ligase Nedd4 serve as an adapter to bind the antigen to Pt-Dd. By engineering fusion partners of WW with the model antigen ovalbumin (OVA), Pt-Dd can efficiently deliver WW-OVA in vitro and the Pt-Dd/WW complex can be readily internalized by dendritic cells (DCs). Immunization with WW-OVA/Pt-Dd results in 90% protection against B16-OVA melanoma implantation in syngeneic mice. This high level of protection correlates with the development of OVA-specific CD8+ T cells. Moreover, vaccination with WW-OVA Pt-Dd induces robust humoral responses in mice as shown by the high levels of anti-OVA antibodies (Abs) detected in serum. Importantly, treatment of mice bearing B16-OVA tumors with WW-OVA/Pt-Dd results in complete tumor regression in 100% of cases. Thus, our data supports a dual role of Pt-Dd as antigen-delivery vector and natural adjuvant, able to generate integrated cellular and humoral responses of broad immunogenic complexity to elicit specific antitumor immunity. Antigen delivery by Pt-Dd vector is a promising novel strategy for development of cancer vaccines with important clinical applications. PMID:20179681

  17. An overview of adjuvant formulations and delivery systems.

    PubMed

    García, Alexis; De Sanctis, Juan B

    2014-04-01

    Adjuvants may promote immune responses: by recruiting professional antigen-presenting cells (APCs) to the vaccination site, increasing the delivery of antigens to APCs, or by activating APCs to produce cytokines and by triggering T cell responses. Aluminium salts have been effective at promoting protective humoral immunity; however, they are not effective in generating cell-mediated immunity. A number of different approaches have been developed to potentiate immune response and they have been partially successful. Research has been conducted into vaccine delivery systems (VDS); enhancing cross-presentation by targeting antigens to (APCs). Antigen discovery has increased over the past decade, and consequently, it has accelerated vaccine development demanding a new generation of VDS that combines different types of adjuvants into specific formulations with greater activity. The new approaches offer a wide spectrum of opportunities in vaccine research with direct applications in the near future. PMID:23919674

  18. Radiation delivery system and method

    DOEpatents

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

    2002-01-01

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

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

    PubMed

    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. Fluid delivery control system

    DOEpatents

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

    2006-06-06

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

  1. Antigen presenting cell-selective drug delivery by glycan-decorated nanocarriers.

    PubMed

    Frenz, Theresa; Grabski, Elena; Durán, Verónica; Hozsa, Constantin; Stępczyńska, Anna; Furch, Marcus; Gieseler, Robert K; Kalinke, Ulrich

    2015-09-01

    Targeted drug delivery systems hold promise for selective provision of active compounds to distinct tissues or cell subsets. Thus, locally enhanced drug concentrations are obtained that would confer improved efficacy. As a consequence adverse effects should be diminished, as innocent bystander cells are less affected. Currently, several controlled drug delivery systems based on diverse materials are being developed. Some systems exhibit material-associated toxic effects and/or show low drug loading capacity. In contrast, liposomal nanocarriers are particularly favorable because they are well tolerated, poorly immunogenic, can be produced in defined sizes, and offer a reasonable payload capacity. Compared with other immune cells, professional antigen-presenting cells (APCs) demonstrate enhanced liposome uptake mediated by macropinocytosis, phagocytosis and presumably also by clathrin- and caveolae-mediated endocytosis. In order to further enhance the targeting efficacy toward APCs, receptor-mediated uptake appears advisable. Since APC subsets generally do not express single linage-specific receptors, members of the C-type lectin receptor (CLR) family are compelling targets. Examples of CLR expressed by APCs include DEC-205 (CD205) expressed by myeloid dendritic cells (DC) and monocytes, the mannose receptor C type 1 (MR, CD206) expressed by DC, monocytes and macrophages, DC-SIGN (CD209) expressed by DC, and several others. These receptors bind glycans, which are typically displayed by pathogens and thus support pathogen uptake and endocytosis. Further research will elucidate whether glycan-decorated liposomes will not only enhance APCs targeting but also enable preferential delivery of their payload to discrete subcellular compartments. PMID:25701806

  2. Particle-mediated Intravenous Delivery of Antigen mRNA Results in Strong Antigen-specific T-cell Responses Despite the Induction of Type I Interferon

    PubMed Central

    Broos, Katrijn; Van der Jeught, Kevin; Puttemans, Janik; Goyvaerts, Cleo; Heirman, Carlo; Dewitte, Heleen; Verbeke, Rein; Lentacker, Ine; Thielemans, Kris; Breckpot, Karine

    2016-01-01

    Cancer vaccines based on mRNA are extensively studied. The fragile nature of mRNA has instigated research into carriers that can protect it from ribonucleases and as such enable its systemic use. However, carrier-mediated delivery of mRNA has been linked to production of type I interferon (IFN) that was reported to compromise the effectiveness of mRNA vaccines. In this study, we evaluated a cationic lipid for encapsulation of mRNA. The nanometer-sized, negatively charged lipid mRNA particles (LMPs) efficiently transfected dendritic cells and macrophages in vitro. Furthermore, i.v. delivery of LMPs resulted in rapid expression of the mRNA-encoded protein in spleen and liver, predominantly in CD11c+ cells and to a minor extent in CD11b+ cells. Intravenous immunization of mice with LMPs containing ovalbumin, human papilloma virus E7, and tyrosinase-related protein-2 mRNA, either combined or separately, elicited strong antigen-specific T-cell responses. We further showed the production of type I IFNs upon i.v. LMP delivery. Although this decreased the expression of the mRNA-encoded protein, it supported the induction of antigen-specific T-cell responses. These data question the current notion that type I IFNs hamper particle-mediated mRNA vaccines. PMID:27327138

  3. Adenosine-Associated Delivery Systems

    PubMed Central

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

    2016-01-01

    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

  4. Nanoparticulate systems for polynucleotide delivery

    PubMed Central

    Basarkar, Ashwin; Singh, Jagdish

    2007-01-01

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

  5. Novel central nervous system drug delivery systems.

    PubMed

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

    2014-05-01

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

  6. Career Information Delivery Systems Inventory.

    ERIC Educational Resources Information Center

    Olson, Gerald T.; Whitman, Patricia D.

    This inventory highlights similarities and differences between 19 computerized career information delivery systems (CIDS) so practitioners may make more informed choices concerning the adoption of such systems, and policymakers may monitor the developing scope of system features and costs. It was developed through a survey of computer products…

  7. Delivery System, 2003-2004.

    ERIC Educational Resources Information Center

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

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

  8. Teleteach Expanded Delivery System: Evaluation.

    ERIC Educational Resources Information Center

    Christopher, G. Ronald; Milam, Alvin L.

    In order to meet the demand for Air Force Institute of Technology (AFIT) professional continuing education (PCE) courses within the School of Systems and Logistics and the School of Engineering, the Teleteach Expanded Delivery System (TEDS) for instruction of Air Force personnel at remote locations was developed and evaluated. TEDS uses a device…

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-04-01

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

  11. PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses

    PubMed Central

    Ma, Wenxue; Chen, Mingshui; Kaushal, Sharmeela; McElroy, Michele; Zhang, Yu; Ozkan, Cengiz; Bouvet, Michael; Kruse, Carol; Grotjahn, Douglas; Ichim, Thomas; Minev, Boris

    2012-01-01

    The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-γ ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96® Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund’s adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of −15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund’s adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor

  12. Lactic acid bacteria as oral delivery systems for biomolecules.

    PubMed

    Berlec, A; Ravnikar, M; Strukelj, B

    2012-11-01

    Lactic acid bacteria (LAB) have become increasingly studied over the last two decades as potential delivery systems for various biological molecules to the gastrointestinal tract. This article presents an overview of characteristics of LAB as delivery systems and of the applications which have already been developed. The majority of LAB strains are able to survive the intestinal passage and some are also able to persist and colonize the intestine. Several strains were in fact described as members of the human commensal flora. They can interact with their host and are able to deliver large molecular weight biomolecules across the epithelium via M-cells or dendritic cells. The most widely applied LAB species has been Lactococcus lactis; however species from genus Lactobacillus are gaining popularity and the first examples from genus Bifidobacterium are starting to emerge. Bacteria are mostly applied live and enable continuous delivery of the biomolecules. However, killed bacteria (e.g. gram-positive enhancer matrix), with bound biomolecules or as adjuvants, are also being developed. The techniques for genetic modification of LAB are well known. This review focuses on the delivery of recombinant proteins and DNA, which can cause either local or systemic effects. We divide recombinant proteins into antigens and therapeutic proteins. Delivery of antigens for the purpose of vaccination represents the most abundant application with numerous successful demonstrations of the efficacy on the animal model. Therapeutic proteins have mostly been developed for the treatment of the inflammatory bowel disease, by the delivery of anti-inflammatory cytokines, or downregulation of proinflammatory cytokines. Delivery of allergens for the modulation of allergic disorders represents the second most popular application of therapeutic proteins. The delivery of DNA by LAB was demonstrated and offers exciting opportunities, especially as a vaccine. New discoveries may eventually lead to the

  13. Insulin Delivery System

    NASA Technical Reports Server (NTRS)

    1988-01-01

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

  14. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

    Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology. PMID:26891564

  15. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

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

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

    PubMed Central

    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

  17. Delivery of antigen to sialoadhesin or CD163 improves the specific immune response in pigs.

    PubMed

    Poderoso, Teresa; Martínez, Paloma; Álvarez, Belén; Handler, Ana; Moreno, Sara; Alonso, Fernando; Ezquerra, Ángel; Domínguez, Javier; Revilla, Concepción

    2011-06-24

    Delivery of antigens to antigen presenting cell surface receptors represents a promising strategy to improve immune response to weak immunogenic antigens. We have analyzed the potential of porcine sialoadhesin (Sn) and CD163 as antigen targeting receptors using mouse Igs as surrogate antigens. Sn and CD163 are two endocytic receptors mainly expressed on macrophages located in antigen-sampling zones of secondary lymphoid organs. MAbs to CD163 induced in vitro PBMC proliferation at concentrations 50-80 fold lower than the control mAb when using, as responder cells, cells from pigs immunized with mouse serum IgGs. To evaluate in vivo targeting, pigs were immunized s.c. with anti-Sn, anti-CD163 or control mAbs, and the immune response induced to mouse Ig was analyzed. Two weeks after the first immunization, pigs receiving either anti-Sn or anti-CD163 mAbs started to show higher anti-mouse-IgG serum titres than controls. Boosting 6 weeks later, further increased the anti-IgG titres up to 15-60 fold those of controls. In addition, differences in the relative predominance of IgG1 or IgG2 subclasses in the response depending on Sn or CD163 targeting were observed. Peripheral blood mononuclear cells from pigs immunized with anti-Sn mAb showed a higher proliferative response to mouse IgG than cells from pigs immunized with control mAb. These results show that targeting antigen to Sn or CD163 can enhance the immune response in pigs.

  18. Enhanced Delivery of Exogenous Peptides into the Class I Antigen Processing and Presentation Pathway

    PubMed Central

    de Haan, Lolke; Hearn, Arron R.; Rivett, A. Jennifer; Hirst, Timothy R.

    2002-01-01

    Current immunization strategies, using peptide or protein antigens, generally fail to elicit cytotoxic-T-lymphocyte responses, since these antigens are unable to access intracellular compartments where loading of major histocompatibility complex class I (MHC-I) molecules occurs. In an attempt to circumvent this, we investigated whether the GM1 receptor-binding B subunit of Escherichia coli heat-labile toxin (EtxB) could be used to deliver class I epitopes. When a class I epitope was conjugated to EtxB, it was delivered into the MHC-I presentation pathway in a GM1-binding-dependent fashion and resulted in the appearance of MHC-I-epitope complexes at the cell surface. Importantly, we show that the efficiency of EtxB-mediated epitope delivery could be strikingly enhanced by incorporating, adjacent to the class I epitope, a 10-amino-acid segment from the C terminus of the DNA polymerase (Pol) of herpes simplex virus. The replacement of this 10-amino-acid segment by a heterologous sequence or the introduction of specific amino acid substitutions within this segment either abolished or markedly reduced the efficiency of class I epitope delivery. If the epitope was extended at its C terminus, EtxB-mediated delivery into the class I presentation pathway was found to be completely dependent on proteasome activity. Thus, by combining the GM1-targeting function of EtxB with the 10-amino-acid Pol segment, highly efficient delivery of exogenous epitopes into the endogenous pathway of class I antigen processing and presentation can be achieved. PMID:12011020

  19. Transcutaneous immunization with Intercell's vaccine delivery system.

    PubMed

    Seid, Robert C; Look, Jee Loon; Ruiz, Christian; Frolov, Vladimir; Flyer, David; Schafer, Jason; Ellingsworth, Larry

    2012-06-19

    Transcutaneous immunization (TCI) has become an attractive alternate route of immunization due to increase understanding of the skin immune system and to recent technical innovations in skin patch delivery systems. Basic principles of TCI have been demonstrated in animal and human studies, covering a variety of bacterial, viral, and cancer diseases. At Intercell, we have advanced two major platforms of TCI: 1) a needle-free vaccine delivery patch (VDP) and 2) a vaccine enhancement patch (VEP). Simplified, the VDP contains an antigen with or without an adjuvant that is administered on the skin; while the VEP contains only the adjuvant and is used in combination with an injected vaccine. In many of our TCI studies, the VDP or VEP is routinely applied on pretreated skin, in which the stratum corneum has been partially removed by mild abrasion. Recently, we have achieved technical breakthroughs in formulating and stabilizing vaccines in a dry patch format. For instance, a microplate-based screening process has been implemented to rapidly identify excipients, singularly or in combination, to stabilize biological macromolecules in patch blend formulations. A second technical innovation is our nonwoven (patch) disc matrix-supported drying technology, which allows efficient drying of our patch formulation blend to produce dry stable dosage forms of VDP or VEP. The low cost and the facileness in the manufacturing of VDP (or VEP) combined with the development of thermostable dry patches should improve the supply chain efficiency and reduce the dependence on cold chain.

  20. Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins.

    PubMed Central

    Giannasca, P J; Boden, J A; Monath, T P

    1997-01-01

    The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological functions. Aggregates of nasal lymphoid tissue (NALT) located at the base of the nasal cavity are believed to be sites of induction of mucosal immune responses to airborne antigens. The epithelium overlying NALT contains M cells which are specialized for the transcytosis of immunogens, as demonstrated in other mucosal tissues. We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which influence antigen uptake and immune responses to transcytosed antigens. To identify glycoconjugates that may distinguish NALT M cells from other cells of the respiratory epithelium (RE), we performed lectin histochemistry on sections of the hamster nasal cavity with a panel of lectins. Many classes of glycoconjugates were found on epithelial cells in this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing alpha-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively. By morphological criteria, the FAE contains >90% M cells. To determine if apical glycoconjugates on M cells were accessible from the nasal cavity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did not. Lectin bound to M cells in vivo was efficiently endocytosed, consistent with the role of M cells in antigen transport. Intranasal immunization with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone or admixed with lectin did not. The selective recognition of NALT M cells by a lectin in vivo provides a model for microbial adhesin-host cell receptor interactions on M cells and the targeted delivery of immunogens to NALT following intranasal

  1. Phospholipid nanodisc engineering for drug delivery systems.

    PubMed

    Murakami, Tatsuya

    2012-06-01

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

  2. A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms.

    PubMed

    Phanse, Yashdeep; Carrillo-Conde, Brenda R; Ramer-Tait, Amanda E; Broderick, Scott; Kong, Chang Sun; Rajan, Krishna; Flick, Ramon; Mandell, Robert B; Narasimhan, Balaji; Wannemuehler, Michael J

    2014-01-20

    Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4(+) T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.

  3. A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms

    NASA Astrophysics Data System (ADS)

    Phanse, Yashdeep; Carrillo-Conde, Brenda R.; Ramer-Tait, Amanda E.; Broderick, Scott; Kong, Chang Sun; Rajan, Krishna; Flick, Ramon; Mandell, Robert B.; Narasimhan, Balaji; Wannemuehler, Michael J.

    2014-01-01

    Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4+ T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.

  4. Combinatorial Approach of Antigen Delivery Using M Cell-Homing Peptide and Mucoadhesive Vehicle to Enhance the Efficacy of Oral Vaccine.

    PubMed

    Singh, Bijay; Maharjan, Sushila; Jiang, Tao; Kang, Sang-Kee; Choi, Yun-Jaie; Cho, Chong-Su

    2015-11-01

    Orally ingested pathogens or antigens are taken up by microfold cells (M cells) in Peyer's patches of intestine to initiate protective immunity against infections. However, the uptake of orally delivered protein antigens through M cells is very low due to lack of specificity of proteins toward M cells and degradation of proteins in the harsh environment of gastrointestinal (GI) tract. To overcome these limitations, here we developed a pH-sensitive and mucoadhesive vehicle of thiolated eudragit (TE) microparticles to transport an M cell-targeting peptide-fused model protein antigen. Particularly, TE prolonged the particles transit time through the GI tract and predominantly released the proteins in ileum where M cells are abundant. Thus, oral delivery of TE microparticulate antigens exhibited high transcytosis of antigens through M cells resulting in strong protective sIgA as well as systemic IgG antibody responses. Importantly, the delivery system not only induced CD4(+) T cell immune responses but also generated strong CD8(+) T cell responses with enhanced production of IFN-γ in spleen. Given that M cells are considered a promising target for oral vaccination, this study could provide a new combinatorial method for the development of M-cell-targeted mucosal vaccines. PMID:26394158

  5. Potential of Translationally Controlled Tumor Protein-Derived Protein Transduction Domains as Antigen Carriers for Nasal Vaccine Delivery.

    PubMed

    Bae, Hae-Duck; Lee, Joohyun; Jin, Xing-Hai; Lee, Kyunglim

    2016-09-01

    Nasal vaccination offers a promising alternative to intramuscular (i.m.) vaccination because it can induce both mucosal and systemic immunity. However, its major drawback is poor absorption of large antigens in the nasal epithelium. Protein transduction domains (PTDs), also called cell-penetrating peptides, have been proposed as vehicles for nasal delivery of therapeutic peptides and proteins. Here, we evaluated the potential of a mutant PTD derived from translationally controlled tumor protein (designated TCTP-PTD 13) as an antigen carrier for nasal vaccines. We first compared the l- and d-forms of TCTP-PTD 13 isomers (l- or d-TCTP-PTD 13) as antigen carriers. Studies in mice demonstrated that nasally administered mixtures of the model antigen ovalbumin (OVA) and d-TCTP-PTD 13 induced higher plasma IgG titers and secretory IgA levels in nasal washes than nasally administered OVA alone, OVA/l-TCTP-PTD 13, or i.m.-injected OVA. Plasma IgG subclass responses (IgG1 and IgG2a) of mice nasally administered OVA/d-TCTP-PTD 13 showed that the predominant IgG subclass was IgG1, indicating a Th2-biased immune response. We also used synthetic CpG oligonucleotides (CpG) as a Th1 immune response-inducing adjuvant. Nasally administered CpG plus OVA/d-TCTP-PTD 13 was superior in eliciting systemic and mucosal immune responses compared to those induced by nasally administered OVA/d-TCTP-PTD 13. Furthermore, the OVA/CpG/d-TCTP-PTD 13 combination skewed IgG1 and IgG2a profiles of humoral immune responses toward a Th1 profile. These findings suggest that TCTP-derived PTD is a suitable vehicle to efficiently carry antigens and to induce more powerful antigen-specific immune responses and a more balanced Th1/Th2 response when combined with a DNA adjuvant. PMID:27454469

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

    PubMed

    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.

  7. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-04-01

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

  8. Collagen macromolecular drug delivery systems

    SciTech Connect

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t{sup {1/2}} and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and {sup 14}C-inulin release rates were evaluated subcutaneously in rats.

  9. Rapid Data Delivery System (RDDS)

    USGS Publications Warehouse

    Cress, Jill J.; Goplen, Susan E.

    2007-01-01

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

  10. Microfabricated injectable drug delivery system

    DOEpatents

    Krulevitch, Peter A.; Wang, Amy W.

    2002-01-01

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

  11. NANOPARTICLE DELIVERY SYSTEMS IN CANCER VACCINES

    PubMed Central

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

    2013-01-01

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

  12. Economical oxygen-delivery system.

    PubMed

    Olson, R M

    1976-04-01

    The conservation of aircraft oxygen supplies is becoming of considerable interest to the Air Force. Onboard oxygen-generating systems are being developed which could support an aircrew if oxygen produced by these systems were used conservatively. These experiments studied the conservation potential of a rebreather bag placed in a vented container near the regulator in an oxygen-delivery system. The bag's volume was close to that of the subject's physiologic dead space. When the subject exhaled, oxygen in the mouth, trachea, and mask dead space went to the rebreather bag, to be rebreathed with the next breath. The CO2-contaminated oxygen from the alveoli was vented to the cabin. The dead-space oxygen could be separated from contaminated oxygen because dead-space air is exhaled first with each breath. When the rebreather-bag volume matched the subject's physiologic dead space so that no CO2 accumulated, a 30% oxygen savings was realized. When the bag was large enough to realize a 50% savings, CO2 accumulation was only 2%.

  13. Fiber coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan

    2008-08-12

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

  14. Physically facilitating drug-delivery systems

    PubMed Central

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

    2012-01-01

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

  15. Adenovirus-mediated delivery of an anti-V antigen monoclonal antibody protects mice against a lethal Yersinia pestis challenge.

    PubMed

    Sofer-Podesta, Carolina; Ang, John; Hackett, Neil R; Senina, Svetlana; Perlin, David; Crystal, Ronald G; Boyer, Julie L

    2009-04-01

    Pneumonic plague, caused by inhalation of Yersinia pestis, represents a major bioterrorism threat for which no vaccine is available. Based on the knowledge that genetic delivery of monoclonal antibodies (MAbs) with adenovirus (Ad) gene transfer vectors results in rapid, high-level antibody expression, we evaluated the hypothesis that Ad-mediated delivery of a neutralizing antibody directed against the Y. pestis V antigen would protect mice against a Y. pestis challenge. MAbs specific for the Y. pestis V antigen were generated, and the most effective in protecting mice against a lethal intranasal Y. pestis challenge was chosen for further study. The coding sequences for the heavy and light chains were isolated from the corresponding hybridoma and inserted into a replication-defective serotype 5 human Ad gene transfer vector (AdalphaV). Western analysis of AdalphaV-infected cell supernatants demonstrated completely assembled antibodies reactive with V antigen. Following AdalphaV administration to mice, high levels of anti-V antigen antibody titers were detectable as early as 1 day postadministration, peaked by day 3, and remained detectable through a 12-week time course. When animals that received AdalphaV were challenged with Y. pestis at day 4 post-AdalphaV administration, 80% of the animals were protected, while 0% of control animals survived (P < 0.01). Ad-mediated delivery of a V antigen-neutralizing antibody is an effective therapy against plague in experimental animals and could be developed as a rapidly acting antiplague therapeutic.

  16. Microdosed Lipid-Coated (67)Ga-Magnetite Enhances Antigen-Specific Immunity by Image Tracked Delivery of Antigen and CpG to Lymph Nodes.

    PubMed

    Ruiz-de-Angulo, Ane; Zabaleta, Aintzane; Gómez-Vallejo, Vanessa; Llop, Jordi; Mareque-Rivas, Juan C

    2016-01-26

    Development of vaccines to prevent and treat emerging new pathogens and re-emerging infections and cancer remains a major challenge. An attractive approach is to build the vaccine upon a biocompatible NP that simultaneously acts as accurate delivery vehicle and radiotracer for PET/SPECT imaging for ultrasensitive and quantitative in vivo imaging of NP delivery to target tissues/organs. Success in developing these nanovaccines will depend in part on having a "correct" NP size and accommodating and suitably displaying antigen and/or adjuvants (e.g., TLR agonists). Here we develop and evaluate a NP vaccine based on iron oxide-selective radio-gallium labeling suitable for SPECT((67)Ga)/PET((68)Ga) imaging and efficient delivery of antigen (OVA) and TLR 9 agonists (CpGs) using lipid-coated magnetite micelles. OVA, CpGs and rhodamine are easily accommodated in the hybrid micelles, and the average size of the construct can be controlled to be ca. 40 nm in diameter to target direct lymphatic delivery of the vaccine cargo to antigen presenting cells (APCs) in the lymph nodes (LNs). While the OVA/CpG-loaded construct showed effective delivery to endosomal TLR 9 in APCs, SPECT imaging demonstrated migration from the injection site to regional and nonregional LNs. In correlation with the imaging results, a range of in vitro and in vivo studies demonstrate that by using this microdosed nanosystem the cellular and humoral immune responses are greatly enhanced and provide protection against tumor challenge. These results suggest that these nanosystems have considerable potential for image-guided development of targeted vaccines that are more effective and limit toxicity. PMID:26678549

  17. Gene gun delivery systems for cancer vaccine approaches.

    PubMed

    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.

  18. Delivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigen

    PubMed Central

    Liao, Xiaoli; Rabideau, Amy E; Pentelute, Bradley L

    2014-01-01

    Antibody mimics have significant scientific and therapeutic utility for the disruption of protein–protein interactions inside cells; however, their delivery to the cell cytosol remains a major challenge. Here we show that protective antigen (PA), a component of anthrax toxin, efficiently transports commonly used antibody mimics to the cytosol of mammalian cells when conjugated to the N-terminal domain of LF (LFN). In contrast, a cell-penetrating peptide (CPP) was not able to deliver any of these antibody mimics into the cell cytosol. The refolding and binding of a transported tandem monobody to Bcr-Abl (its protein target) in chronic myeloid leukemia cells were confirmed by co-immunoprecipitation. We also observed inhibition of Bcr-Abl kinase activity and induction of apoptosis caused by the monobody. In a separate case, we show disruption of key interactions in the MAPK signaling pathway after PA-mediated delivery of an affibody binder that targets hRaf-1. We show for the first time that PA can deliver bioactive antibody mimics to disrupt intracellular protein–protein interactions. This technology adds a useful tool to expand the applications of these modern agents to the intracellular milieu. PMID:25250705

  19. Tax exemption and integrated delivery systems.

    PubMed

    Aseltyne, W J; Peters, G R

    1994-01-01

    This chapter discusses tax exemption of integrated delivery systems, including the requirements for exemption, the charitable purposes test, the private inurement and private benefit tests, and an application to integrated delivery systems. It also discusses the structure of the Friendly Hills and Facey Nonprofit Medical Foundations, including the analysis of the Internal Revenue Service. Finally, it discusses the process for obtaining tax exemption.

  20. Development of the Choctaw Health Delivery System.

    ERIC Educational Resources Information Center

    Nguyen, Binh N.

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

  1. Viral and nonviral delivery systems for gene delivery.

    PubMed

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

    2012-01-01

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

  2. Drug delivery systems: An updated review

    PubMed Central

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

    2012-01-01

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

  3. 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.

    PubMed

    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. Starch Applications for Delivery Systems

    NASA Astrophysics Data System (ADS)

    Li, Jason

    2013-03-01

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

  5. Direct Delivery of Antigens to Dendritic Cells via Antibodies Specific for Endocytic Receptors as a Promising Strategy for Future Therapies

    PubMed Central

    Lehmann, Christian H. K.; Heger, Lukas; Heidkamp, Gordon F.; Baranska, Anna; Lühr, Jennifer J.; Hoffmann, Alana; Dudziak, Diana

    2016-01-01

    Dendritic cells (DCs) are the most potent professional antigen presenting cells and are therefore indispensable for the control of immunity. The technique of antibody mediated antigen targeting to DC subsets has been the basis of intense research for more than a decade. Many murine studies have utilized this approach of antigen delivery to various kinds of endocytic receptors of DCs both in vitro and in vivo. Today, it is widely accepted that different DC subsets are important for the induction of select immune responses. Nevertheless, many questions still remain to be answered, such as the actual influence of the targeted receptor on the initiation of the immune response to the delivered antigen. Further efforts to better understand the induction of antigen-specific immune responses will support the transfer of this knowledge into novel treatment strategies for human diseases. In this review, we will discuss the state-of-the-art aspects of the basic principles of antibody mediated antigen targeting approaches. A table will also provide a broad overview of the latest studies using antigen targeting including addressed DC subset, targeted receptors, outcome, and applied coupling techniques. PMID:27043640

  6. Multi-channel gas-delivery system

    DOEpatents

    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.

  7. Fiber laser coupled optical spark delivery system

    DOEpatents

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

    2008-03-04

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

  8. Organized Athletics as a Leisure Delivery System.

    ERIC Educational Resources Information Center

    Kidd, Thomas R.; Mendell, Ron

    1980-01-01

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

  9. Delivery system for laser medical instrument

    NASA Astrophysics Data System (ADS)

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

    2003-10-01

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

  10. Delivery systems for intradermal vaccination.

    PubMed

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

    2012-01-01

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

  11. New delivery systems and propellants.

    PubMed

    Dolovich, M

    1999-01-01

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

  12. Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides

    NASA Astrophysics Data System (ADS)

    Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong

    2015-07-01

    We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments. Electronic supplementary information (ESI

  13. Heart-targeted nanoscale drug delivery systems.

    PubMed

    Liu, Meifang; Li, Minghui; Wang, Guangtian; Liu, Xiaoying; Liu, Daming; Peng, Haisheng; Wang, Qun

    2014-09-01

    The efficacious delivery of drugs to the heart is an important treatment strategy for various heart diseases. Nanocarriers have shown increasing promise in targeted drug delivery systems. The success of nanocarriers for delivering drugs to therapeutic sites in the heart mainly depends on specific target sites, appropriate drug delivery carriers and effective targeting ligands. Successful targeted drug delivery suggests the specific deposition of a drug in the heart with minimal effects on other organs after administration. This review discusses the pathological manifestations, pathogenesis, therapeutic limitations and new therapeutic advances in various heart diseases. In particular, we summarize the recent advances in heart-targeted nanoscale drug delivery systems, including dendrimers, liposomes, polymer-drug conjugates, microparticles, nanostents, nanoparticles, micelles and microbubbles. Current clinical trials, the commercial market and future perspective are further discussed in the conclusions.

  14. Alternative delivery systems in rural areas.

    PubMed Central

    Christianson, J B

    1989-01-01

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

  15. Hydrogen storage and delivery system development

    SciTech Connect

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

    1995-09-01

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

  16. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation. PMID:24936306

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

    PubMed

    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.

  18. Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides.

    PubMed

    Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong

    2015-08-01

    We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments. PMID:26129929

  19. Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides.

    PubMed

    Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong

    2015-08-01

    We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.

  20. Evaluation of two rapid group B streptococcal antigen tests in labor and delivery patients.

    PubMed

    Skoll, M A; Mercer, B M; Baselski, V; Gray, J P; Ryan, G; Sibai, B M

    1991-02-01

    Two rapid group B streptococcal antigen tests were compared with nonselective blood agar culture in 1062 unselected patients admitted to labor and delivery. Vaginal specimens taken from each patient on admission were used to perform each of two rapid tests and corresponding cultures. The rapid tests were the Streptex latex agglutination assay and the Equate Strep B test, which uses a solid-phase immunoassay. Overall, 105 patients (9.9%) had at least one positive culture. The sensitivities for the rapid tests were 15.1% for Streptex and 21.5% for Equate. Specificities were 99.3 and 98.7%, respectively. Sensitivity was minimally increased in the setting of ruptured membranes for both tests. Likewise, use of separate swabs for streaking the culture plate and performing the rapid test increased the sensitivity, but this was not significant for either test. In control experiments, the limit of sensitivity of both rapid tests was 5 x 10(6) colony-forming units. We conclude that at present, these tests are not sensitive enough for routine use in this type of clinical setting.

  1. WEDDS: The WITS Encrypted Data Delivery System

    NASA Technical Reports Server (NTRS)

    Norris, J.; Backes, P.

    1999-01-01

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

  2. Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system.

    PubMed

    Widera, Georg; Johnson, Juanita; Kim, Lomi; Libiran, Luz; Nyam, Kofi; Daddona, Peter E; Cormier, Michel

    2006-03-01

    Immunization to the model antigen ovalbumin was investigated using a novel intracutaneous delivery system consisting of antigen-coated microneedle arrays. The influence of the following parameters on the resulting immune responses was investigated: depth of vaccine delivery, dose of vaccine delivered, density of microneedles on the array, and area of application. The immune response was found to be dose dependent, and mostly independent of depth of delivery, density of microneedles, or area of application. Our studies show that the shortest, most tolerable microneedle arrays can be used for achieving consistent and high antibody titers. Overall, the microneedle array proves to be a very versatile delivery technology, allowing easy and reproducible antigen delivery to skin for efficient vaccination without the use of a needle and syringe. PMID:16246466

  3. Cyclodextrins in delivery systems: Applications

    PubMed Central

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

    2010-01-01

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

  4. Alginate Nanoparticles as a Promising Adjuvant and Vaccine Delivery System

    PubMed Central

    Sarei, F.; Dounighi, N. Mohammadpour; Zolfagharian, H.; Khaki, P.; Bidhendi, S. Moradi

    2013-01-01

    During last decades, diphtheria has remained as a serious disease that still outbreaks and can occur worldwide. Recently, new vaccine delivery systems have been developed by using the biodegradable and biocompatible polymers such as alginate. Alginate nanoparticles as a carrier with adjuvant and prolong release properties that enhance the immunogenicity of vaccines. In this study diphtheria toxoid loaded nanoparticles were prepared by ionic gelation technique and characterized with respect to size, zeta potential, morphology, encapsulation efficiency, release profile, and immunogenicity. Appropriate parameters (calcium chloride and sodium alginate concentration, homogenization rate and homogenization time) redounded to the formation of suitable nanoparticles with a mean diameter of 70±0.5 nm. The loading studies of the nanoparticles resulted in high loading capacities (>90%) and subsequent release studies showed prolong profile. The stability and antigenicity of toxoid were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and ouchterlony test and proved that the encapsulation process did not affect the antigenic integrity and activity. Guinea pigs immunized with the diphtheria toxoid-loaded alginate nanoparticles showed highest humoral immune response than conventional vaccine. It is concluded that, with regard to the desirable properties of nanoparticles and high immunogenicity, alginate nanoparticles could be considered as a new promising vaccine delivery and adjuvant system. PMID:24302799

  5. Planetary Regolith Delivery Systems for ISRU

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  6. Goals for Postsecondary Instructional Delivery Systems.

    ERIC Educational Resources Information Center

    Knapp, Stuart E.; Valentine, Carol A.

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

  7. Kontrollierte therapeutische Systeme (Controlled drug delivery systems)

    NASA Astrophysics Data System (ADS)

    Ha, Suk-Woo; Wintermantel, Erich

    Es gibt eine grosse Anzahl von Arzneistoffen, die nicht mit der höchsten Effizienz eingesetzt werden können, weil das geeignete therapeutische System (drug delivery system) für die optimale Applikation fehlt. Viele Arzneistoffe setzen eine häufige Anwendung voraus und sind oft mit mehr oder weniger starken Nebenwirkungen oder aber mit Beeinträchtigungen von Arbeits- und Lebensrhythmus der Patienten verbunden. Der therapeutische Erfolg einer medikamentösen Behandlung setzt eine korrekte Diagnose, die Wahl der richtigen Wirksubstanz sowie ihr Vorliegen in geeigneter Darreichungsform voraus. Zudem muss ein genauer Verabreichungsplan erstellt werden, dessen Einhaltung seitens der Patienten eine wesentliche Voraussetzung für die optimale Wirkung des Arzneistoffes ist. Das Mass, mit dem eine Wirksubstanz therapeutisch voll genutzt werden kann, korreliert direkt mit der Darreichungsform, in der sie angewandt wird. Da viele hochwirksame Arzneimittel bereits existieren, hat sich, neben Neuentwicklungen, das Interesse im vergangenen Jahrzehnt der Optimierung von Arzneimittelwirkungen durch neue Darreichungsformen zugewandt.

  8. Nanomedicine-nanoscale drugs and delivery systems.

    PubMed

    Singh, Surya

    2010-12-01

    Significant progress has been made in nanoscale drugs and delivery systems employing diverse chemical formulations to facilitate the rate of drug delivery and release from the human body. The biocompatible nanomaterials have been used in biological markers, contrast agents for biological imaging, healthcare products, pharmaceuticals, drug-delivery systems as well as in detection, diagnosis and treatment of various types of diseases. Nanomedicines offer delivery of potential drugs to human organs which were previously beyond reach of microscale drugs due to specific biological barriers. The nanoscale systems work as nanocarriers for the delivery of drugs. The nanocarriers are made of biocompatible and biodegradable materials such as synthetic proteins, peptides, lipids, polysaccharides, biodegradable polymers and fibers. This review article reports the recent developments in the field of nanomedicine covering biodegradable polymers, nanoparticles, cyclodextrin, dendrimeres, liposomes and lipid-based nanocarriers, nanofibers, nanowires and carbon nanotubes and their chemical functionalization for distribution to different organs, their solubility, surface, chemical and biological properties, stability and release systems. The toxicity and safety of nanomaterials on human health is also briefly discussed.

  9. Educational Power Tools: New Instructional Delivery Systems.

    ERIC Educational Resources Information Center

    Van Horn, Royal

    1991-01-01

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

  10. New aspects of nanopharmaceutical delivery systems.

    PubMed

    Marcato, Priscyla D; Durán, Nelson

    2008-05-01

    Nanobiotechnology, involving biological systems manufactured at the molecular level, is a multidisciplinary field that has fostered the development of nanoscaled pharmaceutical delivery devices. Micelles, liposomes, solid lipid nanoparticles, polymeric nanoparticles, functionalized nanoparticles, nanocrystals, cyclodextrins, dendrimers, nanotubes and metallic nanoparticles have been used as strategies to deliver conventional pharmaceuticals or substances such as peptides, recombinant proteins, vaccines and nucleotides. Nanoparticles and other colloidal pharmaceutical delivery systems modify many physicochemical properties, thus resulting in changes in the body distribution and other pharmacological processes. These changes can lead to pharmaceutical delivery at specific sites and reduce side effects. Therefore, nanoparticles can improve the therapeutic efficiency, being excellent carriers for biological molecules, including enzymes, recombinant proteins and nucleic acid. This review discusses different pharmaceutical carrier systems, and their potential and limitations in the field of pharmaceutical technology. Products with these technologies which have been approved by the FDA in different clinical phases and which are on the market will be also discussed.

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

    PubMed

    Fan, Yuchen; Moon, James J

    2015-08-27

    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.

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

    PubMed

    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. PMID:26350600

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

    PubMed Central

    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. PMID:26350600

  14. Nanotechnology-based drug delivery systems

    PubMed Central

    Suri, Sarabjeet Singh; Fenniri, Hicham; Singh, Baljit

    2007-01-01

    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. PMID:18053152

  15. Targeting the neonatal fc receptor for antigen delivery using engineered fc fragments.

    PubMed

    Mi, Wentao; Wanjie, Sylvia; Lo, Su-Tang; Gan, Zhuo; Pickl-Herk, Beatrix; Ober, Raimund J; Ward, E Sally

    2008-12-01

    The development of approaches for Ag delivery to the appropriate subcellular compartments of APCs and the optimization of Ag persistence are both of central relevance for the induction of protective immunity or tolerance. The expression of the neonatal Fc receptor, FcRn, in APCs and its localization to the endosomal system suggest that it might serve as a target for Ag delivery using engineered Fc fragment-epitope fusions. The impact of FcRn binding characteristics of an Fc fragment on in vivo persistence allows this property to also be modulated. We have therefore generated recombinant Fc (mouse IgG1-derived) fusions containing the N-terminal epitope of myelin basic protein that is associated with experimental autoimmune encephalomyelitis in H-2(u) mice. The Fc fragments have distinct binding properties for FcRn that result in differences in intracellular trafficking and in vivo half-lives, allowing the impact of these characteristics on CD4(+) T cell responses to be evaluated. To dissect the relative roles of FcRn and the "classical" FcgammaRs in Ag delivery, analogous aglycosylated Fc-MBP fusions have been generated. We show that engineered Fc fragments with increased affinities for FcRn at pH 6.0-7.4 are more effective in delivering Ag to FcRn-expressing APCs in vitro relative to their lower affinity counterparts. However, higher affinity of the FcRn-Fc interaction at near neutral pH results in decreased in vivo persistence. The trade-off between improved FcRn targeting efficiency and lower half-life becomes apparent during analyses of T cell proliferative responses in mice, particularly when Fc-MBP fusions with both FcRn and FcgammaR binding activity are used.

  16. Renewable energy delivery systems and methods

    DOEpatents

    Walker, Howard Andrew

    2013-12-10

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

  17. SERF: a new antigen in the Cromer blood group system.

    PubMed

    Banks, J; Poole, J; Ahrens, N; Seltsam, A; Salama, A; Hue-Roye, K; Storry, J R; Palacajornsuk, P; Ma, B-W; Lublin, D M; Reid, M E

    2004-08-01

    The Cromer blood group system consists of eight high incidence and three low incidence antigens carried on decay-accelerating factor (DAF). This report describes the identification and characterization of a new Cromer high incidence antigen, named SERF. Sequence analyses of DNA from a Thai female whose serum contained the alloantibody to a high incidence antigen in the Cromer blood group system (anti-SERF) and from her two children were performed. Reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence analysis on cDNA from the proband and PCR-restriction fragment length polymorphism analysis on DNA from Thais were also performed. To map the epitope, DAF deletion mutants were tested by immunoblotting with anti-SERF. Sequence analysis revealed a substitution of 647C>T in exon 5 DAF in the proband. The proband's two children and two of 100 Thais were heterozygotes 647C/T. Analysis using DAF deletion mutants revealed the antigenic determinant to be within short consensus repeat 3 (SCR3), which is encoded by exon 5. This study describes a novel high incidence antigen (SERF) in the Cromer blood group system characterized by the amino acid proline at position 182 in SCR3 of DAF. The SERF-negative proband has a substitution mutation that predicts for leucine at this position. SERF has been provisionally assigned the International Society of Blood Transfusion number 021.012 (CROM 12).

  18. Deep Space Systems Technology Program Future Deliveries

    NASA Technical Reports Server (NTRS)

    Salvo, Christopher G.; Keuneke, Matthew S.

    2000-01-01

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

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

    PubMed

    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.

  20. Tomotherapy and other innovative IMRT delivery systems.

    PubMed

    Fenwick, John D; Tomé, Wolfgang A; Soisson, Emilie T; Mehta, Minesh P; Rock Mackie, T

    2006-10-01

    Fixed-field treatments, delivered using conventional clinical linear accelerators fitted with multileaf collimators, have rapidly become the standard form of intensity-modulated radiotherapy (IMRT). Several innovative nonstandard alternatives also exist, for which delivery and treatment planning systems are now commercially available. Three of these nonstandard IMRT approaches are reviewed here: tomotherapy, robotic linear accelerators (CyberKnife, Accuray Inc., Sunnyvale, CA), and standard linear accelerators modulated by jaws alone or by their jaws acting together with a tertiary beam-masking device. Rationales for the nonstandard IMRT approaches are discussed, and elements of their delivery system designs are briefly described. Differences between fixed-field IMRT dose distributions and the distributions that can be delivered by using the nonstandard technologies are outlined. Because conventional linear accelerators are finely honed machines, innovative design enhancement of one aspect of system performance often limits another facet of machine capability. Consequently the various delivery systems may prove optimal for different types of treatment, with specific machine designs excelling for disease sites with specific target volume and normal structure topologies. However it is likely that the delivery systems will be distinguished not just by the optimality of the dose distributions they deliver, but also by factors such as the efficiency of their treatment process, the integration of their onboard imaging systems into that process, and their ability to measure and minimize or compensate for target movement, including the effects of respiratory motion.

  1. Brain drug delivery systems for neurodegenerative disorders.

    PubMed

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

    2012-09-01

    Neurodegenerative disorders (NDs) are rapidly increasing as population ages. However, successful treatments for NDs have so far been limited and drug delivery to the brain remains one of the major challenges to overcome. There has recently been growing interest in the development of drug delivery systems (DDS) for local or systemic brain administration. DDS are able to improve the pharmacological and therapeutic properties of conventional drugs and reduce their side effects. The present review provides a concise overview of the recent advances made in the field of brain drug delivery for treating neurodegenerative disorders. Examples include polymeric micro and nanoparticles, lipidic nanoparticles, pegylated liposomes, microemulsions and nanogels that have been tested in experimental models of Parkinson's, Alzheimer's and Huntington's disease. Overall, the results reviewed here show that DDS have great potential for NDs treatment. PMID:23016644

  2. Recent trends in vaccine delivery systems: A review

    PubMed Central

    Saroja, CH; Lakshmi, PK; Bhaskaran, Shyamala

    2011-01-01

    Vaccines are the preparations given to patients to evoke immune responses leading to the production of antibodies (humoral) or cell-mediated responses that will combat infectious agents or noninfectious conditions such as malignancies. Alarming safety profile of live vaccines, weak immunogenicity of sub-unit vaccines and immunization, failure due to poor patient compliance to booster doses which should potentiate prime doses are few strong reasons, which necessitated the development of new generation of prophylactic and therapeutic vaccines to promote effective immunization. Attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and targeting. Hence, lower doses of weak immunogens can be effectively directed to stimulate immune responses and eliminate the need for the administration of prime and booster doses as a part of conventional vaccination regimen. This paper reviews carrier systems such as liposomes, microspheres, nanoparticles, dendrimers, micellar systems, ISCOMs, plant-derived viruses which are now being investigated and developed as vaccine delivery systems. This paper also describes various aspects of “needle-free technologies” used to administer the vaccine delivery systems through different routes into the human body. PMID:23071924

  3. Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

    PubMed Central

    Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

    2016-01-01

    Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

  4. Waste Feed Delivery Transfer System Analysis

    SciTech Connect

    JULYK, L.J.

    2000-05-05

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

  5. Distance Learning Delivery Systems: Instructional Options.

    ERIC Educational Resources Information Center

    Steele, Ray L.

    1993-01-01

    Discusses the availability of satellite and cable programing to provide distance education opportunities in school districts. Various delivery systems are described, including telephones with speakers, personal computers, and satellite dishes; and a sidebar provides a directory of distance learning opportunities, including telecommunications…

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

    PubMed

    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.

  7. Systemic delivery of artemether by dissolving microneedles.

    PubMed

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

    2016-07-11

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

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

    PubMed

    2005-03-01

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

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

    PubMed

    2005-03-01

    Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver. PMID:15889632

  10. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

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

  11. A wireless actuating drug delivery system

    NASA Astrophysics Data System (ADS)

    Jo, Won-Jun; Baek, Seung-Ki; Park, Jung-Hwan

    2015-04-01

    A wireless actuating drug delivery system was devised. The system is based on induction heating for drug delivery. In this study, thermally generated nitrogen gas produced by induction heating of azobisisobutyronitrile (AIBN) was utilized for pressure-driven release of the drug. The delivery device consists of an actuator chamber, a drug reservoir, and a microchannel. A semicircular copper disc (5 and 6 mm in diameter and 100 µm thick), and thermal conductive tape were integrated as the heating element in the actuator chamber. The final device was 2.7 mm thick. 28 µl of drug solution were placed in the reservoir and the device released the drug quickly at the rate of 6 µl s-1 by induction heating at 160 µT of magnetic intensity. The entire drug solution was released and dispersed after subcutaneous implantation under identical experimental condition. This study demonstrates that the device was simply prepared and drug delivery could be achieved by wireless actuation of a thin, pressure-driven actuator.

  12. Hydrogen storage and delivery system development: Fabrication

    SciTech Connect

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

    1996-10-01

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

  13. Hydrogen storage and delivery system development: Analysis

    SciTech Connect

    Handrock, J.L.

    1996-10-01

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

  14. Recent technologies in pulsatile drug delivery systems

    PubMed Central

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

    2011-01-01

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

  15. Rural medical care: an experimental delivery system.

    PubMed

    Reid, R A; Eberle, B J; Gonzales, L; Quenk, N L; Oseasohn, R

    1975-05-01

    The experimental medical care delivery system has been operational since February, 1969. An average of over 200 patient visits per month were managed at the clinic during the past year. The average visit cost is $23.00, which is competitive with cost rates at neighborhood health centers. The average time per patient visit has been approximately 1 hr and 20 min. Of persons using the clinic, the largest number are women of childbearing age. Elderly patients have visited the clinic most frequently. Illness problems have accounted for the majority of patient visits. The program represents a cooperative effort between a rural community and a university to solve a problem of national interest. The implementation of this program has provided the opportunity to operationalize the family nurse practitioner concept in a system of medical care delivery. The feasibility of providing high quality medical care in a rural community by extending medical resources concentrated in an urban area has been demonstrated. This type of delivery system does provide a viable alternative for extending medical care to rural communities. A clinic manned by paramedical personnel offers the urban medical center along with concerned physicians the opportunity to extend their resources to rural areas which have been unable to attract and retain physicians.

  16. Drug delivery system and breast cancer cells

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed

    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).

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

    PubMed

    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). PMID:18359615

  19. Assessment of Alternative Student Aid Delivery Systems. A Context Paper.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    Background questions to support a federally-sponsored assessment of major student aid delivery system options are addressed. Attention is directed to: (1) information needed by the U.S. Secretary of Education to decide about changes to the delivery system; (2) reasons that delivery system redesign is a critical issue; (3) what can be learned from…

  20. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    PubMed Central

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

    2014-01-01

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

  1. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

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

    2016-01-01

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

  2. Tumor antigen ROR1 targeted drug delivery mediated selective leukemic but not normal B cell cytotoxicity in chronic lymphocytic leukemia

    PubMed Central

    Mani, Rajeswaran; Mao, Yicheng; Frissora, Frank W.; Chiang, Chi-Ling; Wang, Jiang; Zhao, Yuan; Wu, Yun; Yu, Bo; Yan, Ribai; Mo, Xiaokui; Yu, Lianbo; Flynn, Joseph; Jones, Jeffrey; Andritsos, Leslie; Baskar, Sivasubramanian; Rader, Christoph; Phelps, Mitch A; Chen, Ching-Shih; Lee, Robert J.; Byrd, John C.; Lee, L. James; Muthusamy, Natarajan

    2014-01-01

    Selective cytotoxicity to cancer cells without compromising their normal counterparts pose a huge challenge for traditional drug design. Here we developed a tumor antigen targeted delivery of immunonanoparticle carrying a novel non-immunosuppressive FTY720 derivative OSU-2S with potent cytotoxicity against leukemic B cells. OSU-2S induces activation of protein phosphatase 2A, phosphorylation and nuclear translocation of SHP1S591 and deregulation of multiple cellular processes in chronic lymphocytic leukemia (CLL) resulting in potent cytotoxicity. To preclude OSU-2S mediated effects on these ubiquitous phosphatases in unintended cells and avoid potential adverse effects we developed a OSU-2S targeted delivery immunonanoparticles (2A2-OSU-2S-ILP), that mediated selective cytotoxicity of CLL but not normal B cells through targeting receptor tyrosine kinase ROR1 expressed in leukemic but not normal B cells. Developing a novel spontaneous CLL mouse model expressing human ROR1 (hROR1) in all leukemic B cells, we demonstrate the therapeutic benefit of enhanced survival with 2A2-OSU-2S-ILP in-vivo. The newly developed non-immunosuppressive OSU-2S, its delivery using human CLL directed immunonanoparticles and the novel transgenic mouse model of CLL that expresses hROR1 exclusively in leukemic B cell surface are highly innovative and can be applied to CLL and other ROR1+ malignancies including mantle cell lymphoma and acute lymphoblastic leukemia. PMID:24947019

  3. Generation of an attenuated Salmonella-delivery strains expressing adhesin and toxin antigens for progressive atrophic rhinitis, and evaluation of its immune responses in a murine model.

    PubMed

    Byeon, Hoyeon; Hur, Jin; Kim, Bo Ram; Lee, John Hwa

    2014-09-01

    An expression/secretion plasmid containing genes encoding the FimA, CP39, PtfA, ToxA and F1P2 antigens associated with porcine pneumonic pasteurellosis and progressive atrophic rhinitis (PAR) was constructed and harbored in an attenuated Salmonella Typhimurium, which was used as the vaccine candidate. The immune responses induced by this delivery strain were investigated in a murine model. Each antigen secreted from the delivery strain was confirmed by Western blot analysis. Thirty BALB/c mice were divided equally into two groups; group A were intranasally inoculated with the mixture of the five delivery strains, and group B were inoculated with sterile PBS. In group A, all antigen-specific serum IgG were significantly increased compared to those of group B from the 2nd week post-inoculation (WPI) till the 8th WPI. All antigen-specific mucosal IgA in group A were also significantly greater than those of group B. In addition, the significant splenic lymphocyte proliferative responses, the elevations of CD3(+)CD4(+), CD3(+)CD8(+) and B-cell populations, and the induction of IFN-γ expression in group A were observed. In conclusion, the mixture of five delivery strains expressing specific antigen for these diseases was found to be capable of inducing significant humoral and cellular immune responses. PMID:25045826

  4. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

    A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative. PMID:22124008

  5. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

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

  6. Sizing the optimal dimensions of a vaccine delivery system: a particulate matter.

    PubMed

    Slütter, Bram; Jiskoot, Wim

    2016-01-01

    Encapsulation of subunit antigens into particulate vaccine delivery systems is a promising strategy to enhance their immunogenicity. The most basic physical parameter of these particles, their size, has a profound effect on the immunogenicity of the vaccine. Interestingly, the optimal particle size varies depending on the desired type of immunological memory and the route of administration. In this editorial, we draw attention to the effect of particle size on the resulting immune response and accentuate the importance of adequate particle sizing methods, within and beyond the intended size range of the delivery vehicle, to assess vaccine quality.

  7. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tumor-associated antigen immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor Associated Antigen immunological Test Systems § 866.6010 Tumor-associated antigen immunological test system. (a) Identification....

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

    PubMed

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

    2016-01-01

    Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects. PMID:27483234

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

    PubMed

    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

    2016-06-16

    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. PMID:27281205

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  12. Microemulsions based transdermal drug delivery systems.

    PubMed

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

    2014-01-01

    Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored. PMID:25466399

  13. Making the health care delivery system accountable.

    PubMed

    Wilen, S B; Stone, B M

    1998-01-01

    Accountability has become the fact of life for the health care provider and the delivery system. Until recently, accountability has been viewed primarily through the judicial process as issues of fraud and liability, or by managed care entities through evaluation of the financial bottom line. It is this second consideration and its ramifications that will be explored in this article. Appropriate measurement tools are needed to evaluate services, delivery, performance, customer satisfaction, and outcomes assessment. Measurement tools will be considered in light of the industry's unique considerations and realities. All participants, including insurers, employers, management, and health care providers and recipients, bear responsibilities which necessitate assessment and analysis. However, until the basic question, "Who is the customer?" is resolved, accountability issues remain complex and obscured. Accountability costs and impacts must be evaluated over time. They go way beyond bottom line cost containment and reduction. Accountability will be accomplished when the health care industry implements quality and measurement concepts that yield the highest levels of validity and appropriateness for health care delivery.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27173765

  16. Modeling the Delivery Physiology of Distributed Learning Systems.

    ERIC Educational Resources Information Center

    Paquette, Gilbert; Rosca, Ioan

    2003-01-01

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

  17. Mucosal adjuvants and delivery systems for protein-, DNA- and RNA-based vaccines.

    PubMed

    Vajdy, Michael; Srivastava, Indresh; Polo, John; Donnelly, John; O'Hagan, Derek; Singh, Manmohan

    2004-12-01

    Almost all vaccinations today are delivered through parenteral routes. Mucosal vaccination offers several benefits over parenteral routes of vaccination, including ease of administration, the possibility of self-administration, elimination of the chance of injection with infected needles, and induction of mucosal as well as systemic immunity. However, mucosal vaccines have to overcome several formidable barriers in the form of significant dilution and dispersion; competition with a myriad of various live replicating bacteria, viruses, inert food and dust particles; enzymatic degradation; and low pH before reaching the target immune cells. It has long been known that vaccination through mucosal membranes requires potent adjuvants to enhance immunogenicity, as well as delivery systems to decrease the rate of dilution and degradation and to target the vaccine to the site of immune function. This review is a summary of current approaches to mucosal vaccination, and it primarily focuses on adjuvants as immunopotentiators and vaccine delivery systems for mucosal vaccines based on protein, DNA or RNA. In this context, we define adjuvants as protein or oligonucleotides with immunopotentiating properties co-administered with pathogen-derived antigens, and vaccine delivery systems as chemical formulations that are more inert and have less immunomodulatory effects than adjuvants, and that protect and deliver the vaccine through the site of administration. Although vaccines can be quite diverse in their composition, including inactivated virus, virus-like particles and inactivated bacteria (which are inert), protein-like vaccines, and non-replicating viral vectors such as poxvirus and adenovirus (which can serve as DNA delivery systems), this review will focus primarily on recombinant protein antigens, plasmid DNA, and alphavirus-based replicon RNA vaccines and delivery systems. This review is not an exhaustive list of all available protein, DNA and RNA vaccines, with related

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

    PubMed

    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.

  19. Fuel delivery system including heat exchanger means

    NASA Technical Reports Server (NTRS)

    Coffinberry, G. A. (Inventor)

    1978-01-01

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

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

    PubMed

    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.

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

    PubMed Central

    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

  2. Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response.

    PubMed

    Sartorius, Rossella; D'Apice, Luciana; Trovato, Maria; Cuccaro, Fausta; Costa, Valerio; De Leo, Maria Giovanna; Marzullo, Vincenzo Manuel; Biondo, Carmelo; D'Auria, Sabato; De Matteis, Maria Antonietta; Ciccodicola, Alfredo; De Berardinis, Piergiuseppe

    2015-07-01

    Filamentous bacteriophage fd particles delivering antigenic determinants via DEC-205 (fdsc-αDEC) represent a powerful delivery system that induces CD8(+) T-cell responses even when administered in the absence of adjuvants or maturation stimuli for dendritic cells. In order to investigate the mechanisms of this activity, RNA-Sequencing of fd-pulsed dendritic cells was performed. A significant differential expression of genes involved in innate immunity, co-stimulation and cytokine production was observed. In agreement with these findings, we demonstrate that induction of proinflammatory cytokines and type I interferon by fdsc-αDEC was MYD88 mediated and TLR9 dependent. We also found that fdsc-αDEC is delivered into LAMP-1-positive compartments and co-localizes with TLR9. Thus, phage particles containing a single-strand DNA genome rich in CpG motifs delivered via DEC-205 are able to intercept and trigger the active TLR9 innate immune receptor into late endosome/lysosomes and to enhance the immunogenicity of the displayed antigenic determinants. These findings make fd bacteriophage a valuable tool for immunization without administering exogenous adjuvants.

  3. Antigen delivery by filamentous bacteriophage fd displaying an anti-DEC-205 single-chain variable fragment confers adjuvanticity by triggering a TLR9-mediated immune response

    PubMed Central

    Sartorius, Rossella; D'Apice, Luciana; Trovato, Maria; Cuccaro, Fausta; Costa, Valerio; De Leo, Maria Giovanna; Marzullo, Vincenzo Manuel; Biondo, Carmelo; D'Auria, Sabato; De Matteis, Maria Antonietta; Ciccodicola, Alfredo; De Berardinis, Piergiuseppe

    2015-01-01

    Filamentous bacteriophage fd particles delivering antigenic determinants via DEC-205 (fdsc-αDEC) represent a powerful delivery system that induces CD8+ T-cell responses even when administered in the absence of adjuvants or maturation stimuli for dendritic cells. In order to investigate the mechanisms of this activity, RNA-Sequencing of fd-pulsed dendritic cells was performed. A significant differential expression of genes involved in innate immunity, co-stimulation and cytokine production was observed. In agreement with these findings, we demonstrate that induction of proinflammatory cytokines and type I interferon by fdsc-αDEC was MYD88 mediated and TLR9 dependent. We also found that fdsc-αDEC is delivered into LAMP-1-positive compartments and co-localizes with TLR9. Thus, phage particles containing a single-strand DNA genome rich in CpG motifs delivered via DEC-205 are able to intercept and trigger the active TLR9 innate immune receptor into late endosome/lysosomes and to enhance the immunogenicity of the displayed antigenic determinants. These findings make fd bacteriophage a valuable tool for immunization without administering exogenous adjuvants. PMID:25888235

  4. Engineered PRINT(®) nanoparticles for controlled delivery of antigens and immunostimulants.

    PubMed

    Beletskii, Anton; Galloway, Ashley; Rele, Shyam; Stone, Michele; Malinoski, Frank

    2014-01-01

    Particle replication in non-wetting templates (PRINT) is a novel nanoparticle platform that provides compositional flexibility with the ability to specify size and shape in formulating vaccines. The PRINT platform also offers manufacturing and cost advantages over traditional particle technologies. Across multiple antigen and adjuvant formulations, robust antibody and cellular responses have been achieved using PRINT particles in mouse models. Preclinical studies applying PRINT technology in the disease areas of influenza, malaria, and pneumonia are described in this commentary. The proof of principle studies pave the way toward significant cost-effective solutions to global vaccine supply needs.

  5. Provesicles as novel drug delivery systems.

    PubMed

    Bayindir, Zerrin S; Yuksel, Nilufer

    2015-01-01

    Vesicular systems exhibit many attractive properties such as controlled drug release, ability to carry both hydrophilic and hydrophobic drugs, targetability and good biocompatibility. With these unique properties they can provide improved drug bioavailability and reduced side effects. Until now, many vesicular formulations have been studied in clinical and preclinical stages. Nevertheless, the major concern about these systems is their low physicochemical stability and high manufacturing expenses. The stability problems (fusion, aggregation, sedimentation, swelling, and drug leakage during storage) associated with the aqueous nature of vesicular systems hinders their effective usage. The advances on improving the stability of vesicular systems led to the emergence of provesicular systems, which are commonly described as dry, free flowing preformulations of vesicular drug delivery systems. Provesicles form vesicular systems upon hydratation with water and exhibit the advantages of vesicular systems with improved stability. The present article briefly reviews vesicular systems (particularly liposomes and niosomes) and enlightens about the innovations in the field. Overall investigations are reviewed and the provesicle approach is explained by giving detailed information on the composition, preparation, administration and characterization methods of provesicular systems (proliposomes and proniosomes). The scope of this article is expected to give insight to the researchers and industrialists to perform further research in this area. PMID:25658383

  6. The application of pH-sensitive polymer-lipids to antigen delivery for cancer immunotherapy.

    PubMed

    Yuba, Eiji; Kono, Yoshikazu; Harada, Atsushi; Yokoyama, Shoichi; Arai, Masaya; Kubo, Kazuhiro; Kono, Kenji

    2013-07-01

    For production of pH-sensitive liposomes, we developed pH-sensitive polymer-lipids that consists of pH-sensitive fusogenic polymer moieties such as 3-methyl glutarylated poly(glycidol) and 2-carboxycyclohexane-1-carboxylated poly(glycidol), connected to a phosphatidylethanolamine head group. Incorporation of these pH-sensitive polymer-lipids into egg yolk phosphatidylcholine liposomes produced highly pH-sensitive liposomes that were stable at neutral pH but which destabilized markedly in response to very small pH change in weakly acidic pH region. These liposomes delivered their contents (pyranine) into cytosol of dendritic cell-derived DC2.4 cells. When these polymer-lipid-incorporated liposomes loaded with antigenic protein ovalbumin (OVA) were administered subcutaneously to mice, the antigen-specific cellular immunity was induced efficiently in the mice. Furthermore, immunization of mice with these OVA-loaded pH-sensitive polymer-lipid-incorporated liposomes induced strong OVA-specific immunity, which achieved complete rejection of OVA-expressing E.G7-OVA cells and marked regression of E.G7-OVA tumors.

  7. Silk Electrogel Based Gastroretentive Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Wang, Qianrui

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

  8. Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery

    PubMed Central

    Davoodi-Semiromi, Abdoreza; Schreiber, Melissa; Nallapali, Samson; Verma, Dheeraj; Singh, Nameirakpam D.; Banks, Robert K.; Chakrabarti, Debopam; Daniell, Henry

    2009-01-01

    Summary Cholera and malaria are major diseases causing high mortality. The only licensed cholera vaccine is expensive; immunity is lost in children within 3 years and adults are not fully protected. No vaccine is yet available for malaria. Therefore, in this study, the cholera toxin-B subunit (CTB) of Vibrio cholerae fused to malarial vaccine antigens apical membrane antigen-1 (AMA1) and merozoite surface protein-1 (MSP1) was expressed in lettuce and tobacco chloroplasts. Southern blot analysis confirmed homoplasmy and stable integration of transgenes. CTB-AMA1 and CTB-MSP1 fusion proteins accumulated up to 13.17% and 10.11% (total soluble protein, TSP) in tobacco and up to 7.3% and 6.1% (TSP) in lettuce respectively. Nine groups of mice (n = 10/group) were immunized subcutaneously (SQV) or orally (ORV) with purified antigens or transplastomic tobacco leaves. Significant levels of antigen-specific antibody titres of immunized mice completely inhibited proliferation of the malarial parasite and cross-reacted with the native parasite proteins in immunoblots and immunofluorescence studies. Protection against cholera toxin challenge in both ORV (100%) and SQV (89%) mice correlated with CTB-specific titres of intestinal, serum IgA and IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. Increasing numbers of interleukin-10+ T cell but not Foxp3+ regulatory T cells, suppression of interferon-γ and absence of interleukin-17 were observed in protected mice, suggesting that immunity is conferred via the Tr1/Th2 immune response. Dual immunity against two major infectious diseases provided by chloroplast-derived vaccine antigens for long-term (>300 days, 50% of mouse life span) offers a realistic platform for low cost vaccines and insight into mucosal and systemic immunity. PMID:20051036

  9. Bacterial protoplast-derived nanovesicles as vaccine delivery system against bacterial infection.

    PubMed

    Kim, Oh Youn; Choi, Seng Jin; Jang, Su Chul; Park, Kyong-Su; Kim, Sae Rom; Choi, Jun Pyo; Lim, Ji Hwan; Lee, Seung-Woo; Park, Jaesung; Di Vizio, Dolores; Lötvall, Jan; Kim, Yoon-Keun; Gho, Yong Song

    2015-01-14

    The notion that widespread infectious diseases could be best managed by developing potent, adjuvant-free vaccines has resulted in the use of various biological immune-stimulating components as new vaccine candidates. Recently, extracellular vesicles, also known as exosomes and microvesicles in mammalian cells and outer membrane vesicles in Gram-negative bacteria, have gained attention for the next generation vaccine. However, the more invasive and effective the vaccine is in delivery, the more risk it holds for severe immune toxicity. Here, in optimizing the current vaccine delivery system, we designed bacterial protoplast-derived nanovesicles (PDNVs), depleted of toxic outer membrane components to generate a universal adjuvant-free vaccine delivery system. These PDNVs exhibited significantly higher productivity and safety than the currently used vaccine delivery vehicles and induced strong antigen-specific humoral and cellular immune responses. Moreover, immunization with PDNVs loaded with bacterial antigens conferred effective protection against bacterial sepsis in mice. These nonliving nanovesicles derived from bacterial protoplast open up a new avenue for the creation of next generation, adjuvant-free, less toxic vaccines to be used to prevent infectious diseases. PMID:25506626

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

    NASA Astrophysics Data System (ADS)

    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

  11. A telemedicine health care delivery system

    NASA Technical Reports Server (NTRS)

    Sanders, Jay H.

    1991-01-01

    The Interactive Telemedicine Systems (ITS) system was specifically developed to address the ever widening gap between our medical care expertise and our medical care delivery system. The frustrating reality is that as our knowledge of how to diagnose and treat medical conditions has continued to advance, the system to deliver that care has remained in an embryonic stage. This has resulted in millions of people being denied their most basic health care needs. Telemedicine utilizes an interactive video system integrated with biomedical telemetry that allows a physician at a base station specialty medical complex or teaching hospital to examine and treat a patient at multiple satellite locations, such as rural hospitals, ambulatory health centers, correctional institutions, facilities caring for the elderly, community hospital emergency departments, or international health facilities. Based on the interactive nature of the system design, the consulting physician at the base station can do a complete history and physical examination, as if the patient at the satellite site was sitting in the physician's office. This system is described.

  12. Fluid Delivery System For Capillary Electrophoretic Applications.

    DOEpatents

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

    2002-04-23

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  15. Leadership Dynamics Promoting Systemic Reform for Inclusive Service Delivery

    ERIC Educational Resources Information Center

    Scanlan, Martin

    2009-01-01

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

  16. Stable cationic microparticles for enhanced model antigen delivery to dendritic cells.

    PubMed

    Wischke, Christian; Borchert, Hans-Hubert; Zimmermann, Julian; Siebenbrodt, Ingo; Lorenzen, Dirk R

    2006-09-12

    The objectives of this work were (i) to prepare physically stable cationic microparticles and (ii) to study the impact of the surface properties on microparticle phagocytosis and the phenotype of dendritic cells (DC). Protein loaded biodegradable microparticles from poly(lactic-co-glycolic acid) [PLGA] were produced in a micromixer-based w/o/w solvent evaporation procedure. Anionic particles were obtained by using polyvinyl alcohol (PVA) as stabilizing agent; for cationic surfaces cetyltrimethylammonium bromide (CTAB) and chitosan/PVA or DEAE-dextran/PVA blends were evaluated. In phagocytosis studies human monocytes and monocyte-derived DC were incubated with microparticles and analysed by flow cytometry. While CTAB modified microparticles lost their positive charge and aggregated due to CTAB desorption from the particle surface, the modification with chitosan and DEAE-dextran resulted in stable microparticles without cell toxicity. Due to a very low endotoxin content, phagocytosis of anionic and cationic microparticles did not induce an upregulation of maturation-associated surface markers on DC. DEAE-dextran modified microparticles showed an enhanced model protein delivery into phagocytic cells. Overall, PLGA microparticles are suitable vehicles for protein delivery to DC, which might be used for DC-based cell therapies.

  17. Biomedical Imaging in Implantable Drug Delivery Systems

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta

    2016-01-01

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

  19. Ocular drug delivery systems: An overview

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

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

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

  1. The SL autoantibody-antigen system: clinical and biochemical studies.

    PubMed Central

    Bernstein, R M; Morgan, S H; Bunn, C C; Gainey, R C; Hughes, G R; Mathews, M B

    1986-01-01

    A recently described autoantibody, SL, was found in serum from 27 patients with autoimmune disease, including 20 with systemic lupus erythematosus (SLE) where the frequently was 7%. Analysis of clinical, serological, and HLA data from 119 SLE patients showed no positive associations with anti-SL antibody apart from a higher frequency of non-infective fever. Most SL positive sera contained other precipitins, notably antibodies to Ro(SS-A) and the proliferating cell nuclear antigen, PCNA. Anti-SL IgG recognised a protein of 32 000 daltons without associated RNA. This polypeptide was distinguished from a similarly sized component of the Sm and RNP ribonucleoprotein particles by demonstrating different products of partial proteolysis. Although anti-SL antibody is of limited clinical importance, it occurs with twice the frequency of anti-SM antibody in white patients with SLE. Preliminary studies indicate that SL and the Japanese Ki system are identical. Images PMID:3487291

  2. Potentiation of pH-sensitive polymer-modified liposomes with cationic lipid inclusion as antigen delivery carriers for cancer immunotherapy.

    PubMed

    Yoshizaki, Yuta; Yuba, Eiji; Sakaguchi, Naoki; Koiwai, Kazunori; Harada, Atsushi; Kono, Kenji

    2014-09-01

    Cationic lipid-incorporated liposomes modified with pH-sensitive polymers were prepared by introducing 3, 5-didodecyloxybenzamidine as a cationic lipid to egg yolk phosphatidylcholine liposomes modified with 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG) as a pH-sensitive polymer. These liposomes were stable at neutral pH, but were destabilized below pH 6.0 because MGlu-HPG changed its characteristics from hydrophilic to hydrophobic in response to the pH decrease. Cationic lipid inclusion improved their pH sensitivity at weakly acidic pH and association of liposomes with murine dendritic cell (DC) lines. Cationic lipid-incorporated liposomes delivered entrapped ovalbumin (OVA) molecules not only to cytosol but also to endosome/lysosome. Treatment with cationic lipid-incorporated liposomes induced up-regulation of antigen presentation-involved molecules on DCs, the promotion of cytokine production, and antigen presentation via both major histocompatibility complex (MHC) class I and II molecules. Especially, antigen presentation via MHC class II was promoted by cationic lipid inclusion, which might correspond to efficient endosome/lysosome delivery of OVA. Subcutaneous administration of OVA-loaded cationic lipid-incorporated liposomes induced antigen-specific antibody production in serum and Th1-dominant immune responses in the spleen. Furthermore, administration of the cationic lipid-incorporated liposomes to mice bearing E.G7-OVA tumor more significantly reduced the tumor volume than liposomes without cationic lipids. Therefore, cationic lipid inclusion into pH-sensitive polymer-modified liposomes, which can achieve both efficient antigen intracellular delivery and activation of antigen presenting cell, is an effective approach to develop antigen carriers for efficient cancer immunotherapy.

  3. Micro injector sample delivery system for charged molecules

    DOEpatents

    Davidson, James C.; Balch, Joseph W.

    1999-11-09

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

  4. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

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

    2012-01-01

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

  5. Targeting of Synthetic Gene Delivery Systems

    PubMed Central

    2003-01-01

    Safe, efficient, and specific delivery of therapeutic genes remains an important bottleneck for the development of gene therapy. Synthetic, nonviral systems have a unique pharmaceutical profile with potential advantages for certain applications. Targeting of the synthetic vector improves the specificity of gene medicines through a modulation of the carriers' biodistribution, thus creating a dose differential between healthy tissue and the target site. The biodistribution of current carrier systems is being influenced to a large extent by intrinsic physicochemical characteristics, such as charge and size. Consequently, such nonspecific interactions can interfere with specific targeting, for example, by ligands. Therefore, a carrier complex should ideally be inert, that is, free from intrinsic properties that would bias its distribution away from the target site. Strategies such as coating of DNA carrier complexes with hydrophilic polymers have been used to mask some of these intrinsic targeting effects and avoid nonspecific interactions. Preexisting endogenous ligand-receptor interactions have frequently been used for targeting to certain cell types or tumours. Recently exogenous ligands have been derived from microorganisms or, like antibodies or phage-derived peptides, developed de novo. In animal models, such synthetic vectors have targeted remote sites such as a tumour. Furthermore, the therapeutic proof of the concept has been demonstrated for fitting combinations of synthetic vectors and therapeutic gene. PMID:12721518

  6. Guidelines for Psychological Practice in Health Care Delivery Systems

    ERIC Educational Resources Information Center

    American Psychologist, 2013

    2013-01-01

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

  7. New Delivery Systems for the 21st Century.

    ERIC Educational Resources Information Center

    Van Patten, James J.

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

  8. Nanosized particulate systems for dermal and transdermal delivery.

    PubMed

    Hassan, Amany O Kamel; Elshafeey, Ahmed H

    2010-12-01

    Nanosized particles have received much attention in industry, biology, and medicine. Today nanotechnology is finding growing applications in pharmaceutical formulation for skin delivery. This review surveys some of the approaches in the field of nanosized particulate systems for both dermal and transdermal delivery, highlighting the nanosized microemulsion, vesicular systems, solid lipid nanoaprticles (SLN), nanostructured lipid carriers (NLC) and polymeric nanoparticles. PMID:21361126

  9. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 4 2011-01-01 2011-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  10. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  11. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 4 2013-01-01 2013-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  12. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  13. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

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

    PubMed

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

    2015-01-01

    The transdermal route of drug delivery has gained immense interest for pharmaceutical researchers. The major hurdle for diffusion of drugs and bioactives through transdermal route is the stratum corneum, the outermost layer of the skin. Currently, various approaches such as physical approach, chemical approach, and delivery carriers have been used to augment the transdermal delivery of bioactives. This review provides a brief overview of mechanism of drug transport across skin, different lipid vesicular systems, with special emphasis on lipid vesicular systems including transfersomes, liposomes, niosomes, ethosomes, virosomes, and pharmacosomes and their application for the delivery of different bioactives. PMID:24564350

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

    PubMed Central

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

    2013-01-01

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

  16. Presence of hepatitis-associated antigen in systemic lupus erythematosus

    PubMed Central

    Alarcón-Segovia, D.; Fishbein, Eugenia; Díaz-Jouanen, E.

    1972-01-01

    Presence of hepatitis-associated antigen (HAA) was investigated in 504 sera from 116 patients with SLE and was found in 41% of them. HAA was present in at least one serum in 75% of the patients but there were variations in presence and titres in the same patient at different times. Except for a tendency of HAA to appear or rise in titre with lupusi nactivation following corticosteroid or immunosuppresive therapy, there was no correlation between its presence and disease activity, specific organ involvement, antinuclear antibodies or immunoglobulin levels. All but one of twelve lupus patients with recurrent bacterial infections had HAA at high titres. HAA appeared in the serum of a patient upon development of IgA deficiency. HAA antigenaemia in systemic lupus erythematosus seems a consequence rather than a cause of the immunological derangement in this disease. PMID:4538860

  17. Delivery system reform tracking: a framework for understanding change.

    PubMed

    Tollen, Laura; Enthoven, Alain; Crosson, Francis J; Taylor, Nancy; Audet, Anne-Marie; Schoen, Cathy; Ross, Murray

    2011-06-01

    The health care delivery system is changing rapidly, with providers forming patient-centered medical homes and exploring the creation of accountable care organizations. Enactment of the Affordable Care Act will likely accelerate these changes. Significant delivery system reforms will simultaneously affect the structures, capabilities, incentives, and outcomes of the delivery system. With so many changes taking place at once, there is a need for a new tool to track progress at the community level. Many of the necessary data elements for a delivery system reform tracking tool are already being collected in various places and by different stakeholders. The authors propose that all elements be brought together in a unified whole to create a detailed picture of delivery system change. This brief provides a rationale for creating such a tool and presents a framework for doing so. PMID:21638935

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

    PubMed

    Park, Kinam

    2014-09-28

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

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

    PubMed Central

    Mok, Hyejung; Zhang, Miqin

    2014-01-01

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

  20. Liposomes as vaccine delivery systems: a review of the recent advances

    PubMed Central

    2014-01-01

    Liposomes and liposome-derived nanovesicles such as archaeosomes and virosomes have become important carrier systems in vaccine development and the interest for liposome-based vaccines has markedly increased. A key advantage of liposomes, archaeosomes and virosomes in general, and liposome-based vaccine delivery systems in particular, is their versatility and plasticity. Liposome composition and preparation can be chosen to achieve desired features such as selection of lipid, charge, size, size distribution, entrapment and location of antigens or adjuvants. Depending on the chemical properties, water-soluble antigens (proteins, peptides, nucleic acids, carbohydrates, haptens) are entrapped within the aqueous inner space of liposomes, whereas lipophilic compounds (lipopeptides, antigens, adjuvants, linker molecules) are intercalated into the lipid bilayer and antigens or adjuvants can be attached to the liposome surface either by adsorption or stable chemical linking. Coformulations containing different types of antigens or adjuvants can be combined with the parameters mentioned to tailor liposomal vaccines for individual applications. Special emphasis is given in this review to cationic adjuvant liposome vaccine formulations. Examples of vaccines made with CAF01, an adjuvant composed of the synthetic immune-stimulating mycobacterial cordfactor glycolipid trehalose dibehenate as immunomodulator and the cationic membrane forming molecule dimethyl dioctadecylammonium are presented. Other vaccines such as cationic liposome–DNA complexes (CLDCs) and other adjuvants like muramyl dipeptide, monophosphoryl lipid A and listeriolysin O are mentioned as well. The field of liposomes and liposome-based vaccines is vast. Therefore, this review concentrates on recent and relevant studies emphasizing current reports dealing with the most studied antigens and adjuvants, and pertinent examples of vaccines. Studies on liposome-based veterinary vaccines and experimental therapeutic

  1. Systemic administration of antigen-pulsed dendritic cells induces experimental allergic asthma in mice upon aerosol antigen rechallenge.

    PubMed

    Graffi, Sebastian J; Dekan, Gerhard; Stingl, Georg; Epstein, Michelle M

    2002-05-01

    Antigen-pulsed dendritic cells (DCs) have been used extensively as cellular vaccines to induce a myriad of protective immune responses. Adoptive transfer of antigen-pulsed DCs is especially effective at generating Th1 and CD8 immune responses. However, recently this strategy has been shown to induce Th2 cells when DCs are administered locally into the respiratory tract. We sought to address whether systemic rather than local antigen-pulsed DC administration could induce Th2 experimental allergic asthma. We found that OVA-pulsed splenic DCs injected intraperitoneally induced polarized Th2 allergic lung disease upon secondary OVA aerosol challenge. Disease was characterized by eosinophilic lung inflammation, excess mucus production, airway hyperresponsiveness, and OVA-specific IgG1 and IgE. In addition, unusual pathology characterized by macrophage alveolitis and multinucleated giant cells was observed. These data show that systemic administration of antigen-pulsed DCs and subsequent aeroantigen challenge induces Th2 immunity. These findings have important implications for the development of DC-based vaccines.

  2. Development of a gene delivery system in Streptococcus gordonii using thymidylate synthase as a selection marker.

    PubMed

    Lee, Song F; Hulbah, Maram; Halperin, Scott A

    2016-06-01

    Streptococcus gordonii, a commensal bacterium of the human oral cavity, is a potential live vaccine vector. In this study, we have developed a system that delivers a vaccine antigen gene onto the chromosome of S. gordonii. The system consisted of a recipient strain, that is a thymidine auxotroph constructed by deletion of a portion of thyA gene, and a linear gene delivery construct, composed of the functional thyA gene, the vaccine antigen gene, and a DNA fragment immediately downstream of thyA. The construct is assembled by a ligation and polymerase chain reaction strategy. Upon introduction into the thyA mutant, the vaccine antigen gene integrated into the chromosome via a double crossing-over event. Using the above strategy, a test vaccine antigen gene coding for a fusion protein composed of the Bordetella pertussis filamentous hemagglutinin type I domain and the single chain antibody against complement receptor 1 was successfully delivered to S. gordonii. The resulting S. gordonii expressed the fusion protein and the delivered gene was stable in the bacterium in vitro and in a mouse colonization experiment. Mice colonized by the fusion protein-expressing S. gordonii developed antibodies that recognized the native filamentous hemagglutinin protein suggesting that an immune response was elicited. PMID:27062990

  3. Co-delivery of PLGA encapsulated invariant NKT cell agonist with antigenic protein induce strong T cell-mediated antitumor immune responses

    PubMed Central

    Dölen, Yusuf; Kreutz, Martin; Gileadi, Uzi; Tel, Jurjen; Vasaturo, Angela; van Dinther, Eric A. W.; van Hout-Kuijer, Maaike A.; Cerundolo, Vincenzo; Figdor, Carl G.

    2016-01-01

    ABSTRACT Antitumor immunity can be enhanced by the coordinated release and delivery of antigens and immune-stimulating agents to antigen-presenting cells via biodegradable vaccine carriers. So far, encapsulation of TLR ligands and tumor-associated antigens augmented cytotoxic T cell (CTLs) responses. Here, we compared the efficacy of the invariant NKT (iNKT) cell agonist α-galactosylceramide (α-GalCer) and TLR ligands (R848 and poly I:C) as an adjuvant for the full length ovalbumin (OVA) in PLGA nanoparticles. We observed that OVA+α-GalCer nanoparticles (NP) are superior over OVA+TLR-L NP in generating and stimulating antigen-specific cytotoxic T lymphocytes without the need for CD4+ T cell help. Not only a 4-fold higher induction of antigen-specific T cells was observed, but also a more profound IFN-γ secretion was obtained by the addition α-GalCer. Surprisingly, we observed that mixtures of OVA containing NP with α-GalCer were ineffective, demonstrating that co-encapsulation of both α-GalCer and antigen within the same nanoparticle is essential for the observed T cell responses. Moreover, a single immunization with OVA+α-GalCer NP provided substantial protection from tumor formation and even delayed the growth of already established tumors, which coincided with a prominent and enhanced antigen-specific CD8+ T cell infiltration. The provided evidence on the advantage of antigen and α-GalCer coencapsulation should be considered in the design of future nanoparticle vaccines for therapeutic purposes. PMID:26942088

  4. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tumor-associated antigen immunological test system. 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... immunological Test Systems § 866.6010 Tumor-associated antigen immunological test system. (a) Identification....

  5. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tumor-associated antigen immunological test system. 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... immunological Test Systems § 866.6010 Tumor-associated antigen immunological test system. (a) Identification....

  6. The use of halloysite clay and carboxyl-functionalised multi-walled carbon nanotubes for recombinant LipL32 antigen delivery enhanced the IgG response

    PubMed Central

    Hartwig, Daiane D; Bacelo, Kátia L; Oliveira, Thaís L; Schuch, Rodrigo; Seixas, Fabiana K; Collares, Tiago; Rodrigues, Oscar; Hartleben, Cláudia P; Dellagostin, Odir A

    2015-01-01

    We studied the feasibility of using halloysite clay nanotubes (HNTs) and carboxyl-functionalised multi-walled carbon nanotubes (COOH-MWCNTs) as antigen carriers to improve immune responses against a recombinant LipL32 protein (rLipL32). Immunisation using the HNTs or COOH-MWCNTs significantly increased the rLipL32-specific IgG antibody titres (p < 0.05) of Golden Syrian hamsters. None of the vaccines tested conferred protection against a challenge using a virulent Leptospira interrogans strain. These results demonstrated that nanotubes can be used as antigen carriers for delivery in hosts and the induction of a humoral immune response against purified leptospiral antigens used in subunit vaccine preparations. PMID:25742273

  7. The use of halloysite clay and carboxyl-functionalised multi-walled carbon nanotubes for recombinant LipL32 antigen delivery enhanced the IgG response.

    PubMed

    Hartwig, Daiane D; Bacelo, Kátia L; Oliveira, Thaís L; Schuch, Rodrigo; Seixas, Fabiana K; Collares, Tiago; Rodrigues, Oscar; Hartleben, Cláudia P; Dellagostin, Odir A

    2015-02-01

    We studied the feasibility of using halloysite clay nanotubes (HNTs) and carboxyl-functionalised multi-walled carbon nanotubes (COOH-MWCNTs) as antigen carriers to improve immune responses against a recombinant LipL32 protein (rLipL32). Immunisation using the HNTs or COOH-MWCNTs significantly increased the rLipL32-specific IgG antibody titres (p < 0.05) of Golden Syrian hamsters. None of the vaccines tested conferred protection against a challenge using a virulent Leptospira interrogans strain. These results demonstrated that nanotubes can be used as antigen carriers for delivery in hosts and the induction of a humoral immune response against purified leptospiral antigens used in subunit vaccine preparations.

  8. Marine Origin Polysaccharides in Drug Delivery Systems

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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.

  11. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    PubMed

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

    2015-09-15

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

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

    PubMed

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

    2016-01-01

    Biodegradable polymer based drug delivery has emerged as a promising and successful clinical tool for specific targeting and controlled drug release delivery system. Various other unique advantages associated with this delivery system include prolonged circulation, biocompatibility, degradation in nontoxic by-products etc. Till date, various biopharmaceutical agents have been successfully encapsulated within biodegradable polymers and used in clinics. However, before the clinical implementation of such nanocarriers different parameters have to be considered which influence the success of these nanocarriers such as drug release profile, size of nanocarrier, degradation mechanism, toxicity profile, type of polymer used, appropriate synthesis method, selection of mode of delivery etc. The following review focuses on such considerations to explore the area of designing and development of biodegradable polymeric nanosystems which when encapsulated with biopharmaceutical agents can be efficient for clinical application. PMID:26951099

  13. Chitosan hydrogels containing liposomes and cubosomes as particulate sustained release vaccine delivery systems.

    PubMed

    Gordon, Sarah; Young, Katherine; Wilson, Rachel; Rizwan, Shakila; Kemp, Roslyn; Rades, Thomas; Hook, Sarah

    2012-09-01

    Sustained release depot systems have been widely investigated for their potential to improve the efficacy of subunit vaccines and reduce the requirement for boosting. The present study aimed to further enhance the immunogenicity of a sustained release vaccine by combining a depot formulation with a particulate antigen delivery system. Sustained release of the model subunit antigen, ovalbumin (OVA), was observed in vivo from chitosan thermogel-based formulations containing cationic, nanosized liposomes loaded with OVA and the immunopotentiator, Quil A (QA). Such formulations demonstrated the ability to induce cluster of differentiation (CD)8(+) and CD4(+) T-cell proliferation and interferon (IFN)-γ production, as well as the production of OVA-specific antibody. However, gel-incorporated liposomes showed evidence of instability and similar in vivo immune responses to liposomes in gel formulations were induced by gel-based systems loaded with soluble OVA and QA. The immunogenicity of chitosan thermogels containing cubosomes, a more stable lipidic particulate system, was therefore examined. Similarly, all gel-based formulations produced comparable effector immune responses in experimental mice, irrespective of whether the antigen and immunopotentiator were present in gels within cubosomes or in a soluble form. This work demonstrates the potential for sustained release thermogelling systems and highlights the importance of matching the physicochemical and immunological properties of the particulate system to that of the depot.

  14. The LITA Drill and Sample Delivery System

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  15. Optical diagnostics integrated with laser spark delivery system

    DOEpatents

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

    2008-09-02

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    2009-01-01

    We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system. PMID:19209604

  18. Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response

    SciTech Connect

    Chandra, Subhash; Kaur, Manpreet; Midha, Shuchi; Bhatnagar, Rakesh . E-mail: rakbhat01@yahoo.com; Banerjee-Bhatnagar, Nirupama . E-mail: nirupama@icgeb.res.in

    2006-12-22

    We report the ability of N-terminal fragment of lethal factor of Bacillus anthracis to deliver genetically fused ESAT-6 (early secretory antigen target), a potent T cell antigen of Mycobacterium tuberculosis, into cytosol to elicit Cytotoxic T lymphocyte (CTL) response. In vitro Th1 cytokines data and CTL assay proved that efficient delivery of LFn.ESAT-6 occurs in cytosol, in the presence of protective antigen (PA), and leads to generation of effective CTL response. Since CTL response is essential for protection against intracellular pathogens and, it is well known that only single T cell epitope or single antigenic protein is not sufficient to elicit protective CTL response due to variation or polymorphism in MHC-I alleles among the individuals, we suggest that as a fusion protein LFn can be used to deliver multiepitopes of T cells or multiproteins which can generate effective CTLs against intracellular pathogens like M. tuberculosis. It can be used to enhance the protective efficacy of BCG vaccine.

  19. Delivery system for molten salt oxidation of solid waste

    DOEpatents

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

    2002-01-01

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

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

    PubMed

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

    2015-03-01

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

  1. Laser prostatectomy using a right angle delivery system

    NASA Astrophysics Data System (ADS)

    Rocha, Flavio T.; Mitre, Anuar I.; Chavantes, Maria C.; Arap, Sami

    1995-05-01

    Benign prostate hyperplasia (BPH) represents a major health problem in old men. In the present transurethral resection of the prostate (TURP) is the gold standard treatment for BPH. Although TURP is related to low mortality rates its mobidity is quite high. To evaluate the efficacy and safety of a new surgical treatment for BPH we undertook 30 patients with symptomatic BPH. All of them were submitted to a laser prostatectomy using a lateral delivery system (non contact) connected to a Nd-YAG laser font. The preoperative evaluation showed a prostate weight ranging from 30,5 to 86 grams (mean equals 42,5). The preoperative prostatic specific antigen (PSA) ranged from 0,9 to 10,2 ng/dl (mean equals 4.3). The International prostate symptom score (I-PSS) ranged from 16 to 35 points (means equals 23,58). The flow rate ranged from 0 to m 12.8 ml/sec (mean equals 4,65) and the postvoid residual urine from 20 to 400 ml (mean equals 100). We obtained follow-up in 20 patients. After three months after the procedure the parameters were: I-PSS from 4 to 20 points (mean equals 7,0) p < 0.05. Flow rate from 6,5 to m 19.4 ml/sec (mean equals 12,95) p < 0.05 and the postvoid residual urine from 17 to 70 ml (mean equals 30 ml) p < 0.05. No blood transfusion was required. The complications were persistent disuria in two patients, bladder neck contracture in one patient and urethral stenosis in one patient. We concluded that laser prostatectomy is a safe and effective treatment for BPH.

  2. Novel delivery systems for improving the clinical use of peptides.

    PubMed

    Kovalainen, Miia; Mönkäre, Juha; Riikonen, Joakim; Pesonen, Ullamari; Vlasova, Maria; Salonen, Jarno; Lehto, Vesa-Pekka; Järvinen, Kristiina; Herzig, Karl-Heinz

    2015-07-01

    Peptides have long been recognized as a promising group of therapeutic substances to treat various diseases. Delivery systems for peptides have been under development since the discovery of insulin for the treatment of diabetes. The challenge of using peptides as drugs arises from their poor bioavailability resulting from the low permeability of biological membranes and their instability. Currently, subcutaneous injection is clinically the most common administration route for peptides. This route is cost-effective and suitable for self-administration, and the development of appropriate dosing equipment has made performing the repeated injections relatively easy; however, only few clinical subcutaneous peptide delivery systems provide sustained peptide release. As a result, frequent injections are needed, which may cause discomfort and additional risks resulting from a poor administration technique. Controlled peptide delivery systems, able to provide required therapeutic plasma concentrations over an extended period, are needed to increase peptide safety and patient compliancy. In this review, we summarize the current peptidergic drugs, future developments, and parenteral peptide delivery systems. Special emphasis is given to porous silicon, a novel material in peptide delivery. Biodegradable and biocompatible porous silicon possesses some unique properties, such as the ability to carry exceptional high peptide payloads and to modify peptide release extensively. We have successfully developed porous silicon as a carrier material for improved parenteral peptide delivery. Nanotechnology, with its different delivery systems, will enable better use of peptides in several therapeutic applications in the near future. PMID:26023145

  3. Information Delivery Systems: The Future Is Here.

    ERIC Educational Resources Information Center

    O'Malley, Penelope Grenoble

    1993-01-01

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

  4. Trends in Health Care Systems Delivery.

    ERIC Educational Resources Information Center

    Hughes, Edward F. X.

    1989-01-01

    The trend now driving American health care is that the payors are refusing to pay the true economic costs. Health care technology and the public's demand for it, the growth of managed care (Health Maintenance Organizations), and the need to increase the effectiveness of health care are affecting health care delivery. (MLW)

  5. Microneedles As a Delivery System for Gene Therapy

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  7. Subunit Protein Vaccine Delivery System for Tuberculosis Based on Hepatitis B Virus Core VLP (HBc-VLP) Particles.

    PubMed

    Dhanasooraj, Dhananjayan; Kumar, R Ajay; Mundayoor, Sathish

    2016-01-01

    Despite the development of modern medicine, tuberculosis (TB), caused by the pathogenic bacterium, Mycobacterium tuberculosis (Mtb), remains one of the deadliest diseases. This bacterium can lay dormant in individuals and get activated when immunity goes down and has also shown considerable prowess in mutating into drug resistant forms. The global emergence of such drug resistant Mtb and the lack of efficacy of Bacille Calmette Guérin (BCG), the only vaccine available so far, have resulted in a situation which cries out for a safe and effective tuberculosis vaccine.Number of different strategies has been used for developing new anti-TB vaccines and several protective antigens have been identified so far. One strategy, the use of protein subunits, has the potential to develop into a powerful tuberculosis vaccine, not only because of its efficacy and safety, but also because they are economical. The proper delivery of protein subunit vaccines with adjuvants or novel delivery systems is necessary for inducing protective immune responses. The available adjuvants or delivery systems are inadequate for generating such a response. In the present method, we have constructed a vaccine delivery system for tuberculosis based on Virus-Like Particles (VLPs). Hepatitis B Virus core antigen gene was recombinantly modified using Overlap Extension PCR (OEPCR). The final construct was designed to express HBc-VLP carrying external antigen (fusion VLP). Mycobacterium tuberculosis antigen CFP-10 was used for the construction of fusion VLP. The recombinant gene for the construct was cloned into a pET expression system and transformed into E. coli BL21(DE3) and induced with IPTG to express the protein. The fusion protein was purified using the Histidine tag and allowed to form VLPs. The preformed VLPs were purified by sucrose density gradient centrifugation. The VLPs were characterized using Transmission Electron Microscopy (TEM). PMID:27076312

  8. Variable Delivery Systems for Peer Associated Token Reinforcement

    ERIC Educational Resources Information Center

    Edwards, Clifford H.

    1975-01-01

    This study focused on normal junior high school students in the natural school environment. Its purpose was to determine if different token delivery systems would differentially affect the disruptive behavior patterns of students in the normal classroom. (Author/RK)

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

    PubMed Central

    Meng, Ellis; Hoang, Tuan

    2013-01-01

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

  10. Silk-based delivery systems of bioactive molecules

    PubMed Central

    Numata, Keiji; Kaplan, David L

    2010-01-01

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

  11. Preparation of Multifunctional Liposomes as a Stable Vaccine Delivery-Adjuvant System by Procedure of Emulsification-Lyophilization.

    PubMed

    Wang, Ning; Wang, Ting

    2016-01-01

    Liposomes have been proven to be useful carriers for vaccine antigens and can be modified as a versatile vaccine adjuvant-delivery system (VADS). To fulfill efficiently both functions of adjuvant and delivery, the liposomes are often modified with different functional molecules, such as lipoidal immunopotentiators, APC (antigen-presenting cell) targeting ligands, steric stabilization polymers, and charged lipids. Also, to overcome the weakness of instability, vaccines are often lyophilized as a dry product. In this chapter the procedure of emulsification-lyophilization (PEL) is introduced as an efficient method for preparing a stable anhydrous precursor to the multifunctional liposomes which bear dual modifications with APC targeting molecule of the mannosylated cholesterol and the adjuvant material of monophosphoryl lipid A. The techniques and procedures for synthesis of APC targeting molecule, i.e., the mannosylated cholesterol, and for characterization of the multifunctional liposomes are also described. PMID:27076327

  12. 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

    PubMed Central

    Pan, Li; Zhang, Zhongwang; Lv, Jianliang; Zhou, Peng; Hu, Wenfa; Fang, Yuzhen; Chen, Haotai; Liu, Xinsheng; Shao, Junjun; Zhao, Furong; Ding, Yaozhong; Lin, Tong; Chang, Huiyun; Zhang, Jie; Zhang, Yongguang; Wang, Yonglu

    2014-01-01

    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. PMID:25506214

  13. Development of Small RNA Delivery Systems for Lung Cancer Therapy

    PubMed Central

    Fujita, Yu; Kuwano, Kazuyoshi; Ochiya, Takahiro

    2015-01-01

    RNA interference (RNAi) has emerged as a powerful tool for studying target identification and holds promise for the development of therapeutic gene silencing. Recent advances in RNAi delivery and target selection provide remarkable opportunities for translational medical research. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications. Lung cancer is still the leading cause of cancer death worldwide, for which novel therapeutic strategies are critically needed. Recently, we have reported a novel platform (PnkRNA™ and nkRNA®) to promote naked RNAi approaches through inhalation without delivery vehicles in lung cancer xenograft models. We suggest that a new class of RNAi therapeutic agent and local drug delivery system could also offer a promising RNAi-based strategy for clinical applications in cancer therapy. In this article, we show recent strategies for an RNAi delivery system and suggest the possible clinical usefulness of RNAi-based therapeutics for lung cancer treatment. PMID:25756380

  14. Vaccine delivery using nanoparticles

    PubMed Central

    Gregory, Anthony E.; Titball, Richard; Williamson, Diane

    2013-01-01

    Vaccination has had a major impact on the control of infectious diseases. However, there are still many infectious diseases for which the development of an effective vaccine has been elusive. In many cases the failure to devise vaccines is a consequence of the inability of vaccine candidates to evoke appropriate immune responses. This is especially true where cellular immunity is required for protective immunity and this problem is compounded by the move toward devising sub-unit vaccines. Over the past decade nanoscale size (<1000 nm) materials such as virus-like particles, liposomes, ISCOMs, polymeric, and non-degradable nanospheres have received attention as potential delivery vehicles for vaccine antigens which can both stabilize vaccine antigens and act as adjuvants. Importantly, some of these nanoparticles (NPs) are able to enter antigen-presenting cells by different pathways, thereby modulating the immune response to the antigen. This may be critical for the induction of protective Th1-type immune responses to intracellular pathogens. Their properties also make them suitable for the delivery of antigens at mucosal surfaces and for intradermal administration. In this review we compare the utilities of different NP systems for the delivery of sub-unit vaccines and evaluate the potential of these delivery systems for the development of new vaccines against a range of pathogens. PMID:23532930

  15. Production of recombinant botulism antigens: a review of expression systems.

    PubMed

    Moreira, G M S G; Cunha, C E P; Salvarani, F M; Gonçalves, L A; Pires, P S; Conceição, F R; Lobato, F C F

    2014-08-01

    Botulism is a paralytic disease caused by intoxication with neurotoxins produced by Clostridium botulinum. Despite their similar mechanism of action, the botulinum neurotoxins (BoNT) are classified in eight serotypes (A to H). As to veterinary medicine, the impact of this disease is essentially economic, since different species of production animals can be affected, especially by BoNT/C and D. In human health, botulism is feared in a possible biological warfare, what would involve mainly the BoNT/A, B, E and F. In both cases, the most effective way to deal with botulism is through prevention, which involves vaccination. However, the current vaccines against this disease have several drawbacks on their process of production and, besides this, can be dangerous to producers since it requires certain level of biosafety. This way, recombinant vaccines have been shown to be a great alternative for the development of vaccines against both animal and human botulism. All BoNTs have a 50-kDa light chain (LC) and a 100-kDa heavy chain (HC). The latter one presents two domains of 50 kDa, called the N-terminal (HN) and C-terminal (HC) halves. Among these regions, the HC alone seem to confer the proper immune response against intoxication. Since innumerous studies describe the expression of these distinct regions using different systems, strategies, and protocols, it is difficult to define the best option for a viable vaccine production. Thereby, the present review describes the problematic of botulism and discusses the main advances for the viable production of vaccines for both human and veterinary medicine using recombinant antigens.

  16. Production of recombinant botulism antigens: a review of expression systems.

    PubMed

    Moreira, G M S G; Cunha, C E P; Salvarani, F M; Gonçalves, L A; Pires, P S; Conceição, F R; Lobato, F C F

    2014-08-01

    Botulism is a paralytic disease caused by intoxication with neurotoxins produced by Clostridium botulinum. Despite their similar mechanism of action, the botulinum neurotoxins (BoNT) are classified in eight serotypes (A to H). As to veterinary medicine, the impact of this disease is essentially economic, since different species of production animals can be affected, especially by BoNT/C and D. In human health, botulism is feared in a possible biological warfare, what would involve mainly the BoNT/A, B, E and F. In both cases, the most effective way to deal with botulism is through prevention, which involves vaccination. However, the current vaccines against this disease have several drawbacks on their process of production and, besides this, can be dangerous to producers since it requires certain level of biosafety. This way, recombinant vaccines have been shown to be a great alternative for the development of vaccines against both animal and human botulism. All BoNTs have a 50-kDa light chain (LC) and a 100-kDa heavy chain (HC). The latter one presents two domains of 50 kDa, called the N-terminal (HN) and C-terminal (HC) halves. Among these regions, the HC alone seem to confer the proper immune response against intoxication. Since innumerous studies describe the expression of these distinct regions using different systems, strategies, and protocols, it is difficult to define the best option for a viable vaccine production. Thereby, the present review describes the problematic of botulism and discusses the main advances for the viable production of vaccines for both human and veterinary medicine using recombinant antigens. PMID:24930432

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Madry, Henning

    2016-01-01

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

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

    PubMed

    Rey-Rico, Ana; Madry, Henning; Cucchiarini, Magali

    2016-01-01

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

  1. Functionalized nanofibers as drug-delivery systems for osteochondral regeneration.

    PubMed

    Amler, Evžen; Filová, Eva; Buzgo, Matej; Prosecká, Eva; Rampichová, Michala; Nečas, Alois; Nooeaid, Patcharakamon; Boccaccini, Aldo R

    2014-05-01

    A wide range of drug-delivery systems are currently attracting the attention of researchers. Nanofibers are very interesting carriers for drug delivery. This is because nanofibers are versatile, flexible, nanobiomimetic and similar to extracellular matrix components, possible to be functionalized both on their surface as well as in their core, and also because they can be produced easily and cost effectively. There have been increasing attempts to use nanofibers in the construction of a range of tissues, including cartilage and bone. Nanofibers have also been favorably engaged as a drug-delivery system in cell-free scaffolds. This short overview is devoted to current applications and to further perspectives of nanofibers as drug-delivery devices in the field of cartilage and bone regeneration, and also in osteochondral reconstruction. PMID:24978465

  2. Medical applications of 3 μm delivery waveguide system

    NASA Astrophysics Data System (ADS)

    Němec, Michal; Jelínkova, Helena; Koranda, Petr; Miyagi, Mitsunobu; Iwai, Katsumasa; Shi, Yi-Wei; Matsuura, Yuji

    2006-02-01

    Hollow glass waveguide is one from a few instruments favored in industrial and medical fields for the delivery of mid-infrared laser light. The article summarizes delivery of the Er:YAG laser radiation (λ = 2.94 μm) by the cyclic olefin polymer coated silver hollow glass waveguides with various inner diameters - 320 μm, 700 μm, and 1 mm, and with length of 0.1 - 1 m. For medical applications, the so called "contact mode" in which the end of the waveguide is in contact with the soft or hard tissues is discussed. For this treatment the special sealed caps were used for preventing the waveguide system damage. Delivery of long (free-running) and short (Q-switched) mid-infrared pulses was investigated. The delivery systems were investigated for the ophthalmic, urologic, and dental tissue treatments. The comparison of interaction effects caused by the laser pulses with various lengths was made.

  3. Self-assembled and nanostructured siRNA delivery systems.

    PubMed

    Jeong, Ji Hoon; Park, Tae Gwan; Kim, Sun Hwa

    2011-09-01

    A wide range of organic and inorganic materials have been used in the development of nano-scale self-assembling gene delivery systems to improve the therapeutic efficacy of nucleic acid drugs. Small interfering RNA (siRNA) has recently been recognized as a promising and potent nucleic acid medicine for the treatment of incurable genetic disorders including cancer; however, siRNA-based therapeutics suffer from the same delivery problems as conventional nucleic acid drugs such as plasmid DNA and antisense oligonucleotides. Many of the delivery strategies developed for nucleic acid drugs have been applied to siRNA therapeutics, but they have not produced satisfactory in vivo gene silencing efficiencies to warrant clinical trials. This review discusses recent progress in the development of self-assembled and nanostructured delivery systems for efficient siRNA-induced gene silencing and their potential application in clinical settings. PMID:21424157

  4. Targeted Delivery Systems for Molecular Therapy in Skeletal Disorders

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Madry, Henning

    2016-01-01

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

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

    PubMed

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

    2013-01-01

    The emergence of RNAi offers a potentially exciting new therapeutic paradigm for respiratory diseases. However, effective delivery remains a key requirement for their translation into the clinic and has been a major factor in the limited clinical success seen to date. Inhalation offers tissue-specific targeting of the RNAi to treat respiratory diseases and a diminished risk of off-target effects. In order to deliver RNAi directly to the respiratory tract via inhalation, 'smart' non-viral carriers are required to protect the RNAi during delivery/aerosolization and enhance cell-specific uptake to target cells. Here, we review the state-of-the-art in therapeutic aerosol bioengineering, and specifically non-viral siRNA delivery platforms, for delivery via inhalation. This includes developments in inhaler device engineering and particle engineering, including manufacturing methods and excipients used in therapeutic aerosol bioengineering that underpin the development of smart, cell type-specific delivery systems to target siRNA to respiratory epithelial cells and/or alveolar macrophages. PMID:23323781

  7. Immunostimulatory complexes containing Eimeria tenella antigens and low toxicity plant saponins induce antibody response and provide protection from challenge in broiler chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunostimulating complexes (ISCOMs) are unique multimolecular structures formed by encapsulating antigens, lipids and triterpene saponins and are one of the most successful antigen delivery systems for microbial antigens. In the current study, both the route of administration and the antigen conce...

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  10. The defined antigen substrate sphere system with direct immunohistoperoxidase for detection of soluble dengue antigen in sera of patients with dengue hemorrhagic fever.

    PubMed

    Boonpucknavig, S; Bunnag, C; Vuttiviroj, O; Nimmannitya, S

    1978-09-01

    The defined antigen substrate sphere system is a simple method for detecting antigen or antibody in the circulation. The technic is based on the coupling of antigen or antibody with Sepharose 4B beads that have been activated by cyanogen bromide. In this study the activated beads were exposed to dengue antigen in the serum from a patient with dengue hemorrhagic fever and then stained with antidengue antibody conjugated with horseradish peroxidase. The positive reaction showed brown beads by light microscopy, whereas the negative reaction gave colorless beads. The authors examined 134 specimens from 91 cases. The results were positive in 53.85%. The dengue antigen appeared in the sera on the day before shock or subsidence of fever. The percentages of sera containing soluble dengue antigen were greatest on the day of shock or subsidence of fever (33.33%) and on the fifth day of fever (28.07%). The highest titers of soluble dengue antigen (1:40 to 1:80) appeared in the sera of patients who had Grade III disease on the day of shock. The dengue antigen appeared most often in sera that had high titers of dengue antibody. It is postulated that this detected dengue antigen may be a part of soluble immune complexes formed during the hyperimmune stage of the immune response, and plays a significant role in the pathogenesis of dengue hemorrhagic fever and shock syndrome.

  11. Pulmonary drug delivery systems: recent developments and prospects.

    PubMed

    Courrier, H M; Butz, N; Vandamme, Th F

    2002-01-01

    Targeting drug delivery into the lungs has become one of the most important aspects of systemic or local drug delivery systems. Consequently, in the last few years, techniques and new drug delivery devices intended to deliver drugs into the lungs have been widely developed. Currently, the main drug targeting regimens include direct application of a drug into the lungs, mostly by inhalation therapy using either pressurized metered dose inhalers (pMDI) or dry powder inhalers (DPI). Intratracheal administration is commonly used as a first approach in lung drug delivery in vivo. To convey a sufficient dose of drug to the lungs, suitable drug carriers are required. These can be either solid, liquid, or gaseous excipients. Liposomes, nano- and microparticles, cyclodextrins, microemulsions, micelles, suspensions, or solutions are all examples of this type of pharmaceutical carrier that have been successfully used to target drugs into the lungs. The use of microreservoir-type systems offers clear advantages, such as high loading capacity and the possibility of controlling size and permeability, and thus of controlling the release kinetics of the drugs from the carrier systems. These systems make it possible to use relatively small numbers of vector molecules to deliver substantial amounts of a drug to the target. This review discusses the drug carriers administered or intended to be administered into the lungs. The transition to CFC-free inhalers and drug delivery systems formulated with new propellants are also discussed. Finally, in addition to the various advances made in the field of pulmonary-route administration, we describe new systems based on perfluorooctyl bromide, which guarantee oxygen delivery in the event of respiratory distress and drug delivery into the lungs.

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

    PubMed

    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. PMID:26027571

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

    PubMed

    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.

  14. Hydrocolloid-based nutraceutical delivery systems

    SciTech Connect

    Janaswamy, Srinivas; Youngren, Susanne R.

    2012-07-11

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

  15. Cyclodextrin-based gene delivery systems.

    PubMed

    Ortiz Mellet, Carmen; García Fernández, José M; Benito, Juan M

    2011-03-01

    Cyclodextrin (CD) history has been largely dominated by their unique ability to form inclusion complexes with guests fitting in their hydrophobic cavity. Chemical funcionalization was soon recognized as a powerful mean for improving CD applications in a wide range of fields, including drug delivery, sensing or enzyme mimicking. However, 100 years after their discovery, CDs are still perceived as novel nanoobjects of undeveloped potential. This critical review provides an overview of different strategies to promote interactions between CD conjugates and genetic material by fully exploiting the inside-outside/upper-lower face anisotropy of the CD nanometric platform. Covalent modification, self-assembling and supramolecular ligation can be put forward with the ultimate goal to build artificial viruses for programmed and efficient gene therapy (222 references).

  16. Improving vaccine delivery using novel adjuvant systems.

    PubMed

    Pichichero, Michael E

    2008-01-01

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

  17. MAST Propellant and Delivery System Design Methods

    NASA Technical Reports Server (NTRS)

    Nadeem, Uzair; Mc Cleskey, Carey M.

    2015-01-01

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

  18. COMPARISON OF SYSTEMIC AND MUCOSAL ROUTES OF SENSITIZATION TO OVALBUMIN ANTIGEN IN THREE MOUSE STRAINS

    EPA Science Inventory

    Several studies have shown strain differences in allergic lung responses following ovalbumin (OVA) antigen sensitization and challenge. The purpose of this study was to determine whether these differences were maintained between systemic and mucosal sensitization routes, and to ...

  19. Sodium ethylmercurithiosalicylate (Merthiolate) inhibition of antigen-antibody interactions in radioimmunoassay systems

    SciTech Connect

    Mori, M.; Wilber, J.F.

    1984-02-01

    Sodium ethylmercurithiosalicylate (Merthiolate), used for preservation of buffer solutions, was found to inhibit the antigen-antibody binding reactions in radioimmunoassay systems in a noncompetitive manner. This effect is attributable to mercury ion per se. 10 references. 2 figures.

  20. [Adaptation of the avidin-biotin system for identifying and quantifying Sendai virus antigens].

    PubMed

    Popa, L M; Marcheş, F; Repanovici, R; Iliescu, R; Muţiu, A; Cajal, N

    1989-01-01

    The avidin-biotin system was adapted in view of the identification and dosage of the Sendai parainfluenza virus and of its antigens, using the method of double antibodies (biotinylated and nonbiotinylated) in ELISA type tests. PMID:2549703

  1. Coacervate delivery systems for proteins and small molecule drugs

    PubMed Central

    Johnson, Noah R; Wang, Yadong

    2015-01-01

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

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

    PubMed

    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.

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2013-01-01

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

  5. Dendrimeric Systems and Their Applications in Ocular Drug Delivery

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. A new low-incidence antigen in the Kell blood group system: VLAN (KEL25).

    PubMed

    Jongerius, J M; Daniels, G L; Overbeeke, M A; Petty, A C; Reid, M; Oyen, R; Rijksen, H; van Leeuwen, E F

    1996-01-01

    A multilaboratory investigation has identified a new low-incidence antigen "VLAN' on the red cells of a blood donor. The VLAN antigen is destroyed by 2-aminoethylisothiouronium bromide treatment of the donor's red cells suggesting an association with the Kell system. Monoclonal antibody-specific immobilization of erythrocyte antigen analysis with anti-VLAN and with several mouse monoclonal antibodies directed at epitopes on the Kell glycoprotein gave positive results, indicating that the VLAN antigen is located on the Kell glycoprotein. The VLAN red blood cells have the common Kell phenotype: KEL:-1,2,-3,4,5,-6,7,-10,11,12,13,14,-17,18,19,-21,22,-23,-24. Additional serologic data indicate that the VLAN antigen is not part of any other ISBT blood group system, collection or series. A family study showed that the VLAN antigen is inherited since the red cells of two sisters and one niece of the propositus are also VLAN+. The ISBT Working Party on Terminology for Red Cell Surface Antigens has assigned VLAN to the Kell blood group system as KEL25 (number for computer listings 006025).

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Tesfamariam, Belay

    2016-09-28

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

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

    PubMed Central

    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 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. PMID:21861904

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

    ERIC Educational Resources Information Center

    Stedman, Donald J.; Wiegerink, Ronald

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

  12. RNAi delivery-whole plant systems reducing psyllids and leafhoppers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We developed a system for delivery of dsRNA constructs in whole-plant systems (herbaceous plants, woody grapevine and citrus seedlings and trees) which is currently being evaluated. Successful feeding of dsRNA in sucrose solutions to psyllids was followed by using flush shoots excised from trees. ...

  13. Engaging Faculty in Telecommunications-Based Instructional Delivery Systems.

    ERIC Educational Resources Information Center

    Swalec, John J.

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

  14. Carrier-Based Drug Delivery System for Treatment of Acne

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

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

  15. Charting the information technology direction for an integrated delivery system.

    PubMed

    Scott, H H

    1998-01-01

    Automating the healthcare integrated delivery system requires a special set of skills, talent, and communication that goes beyond the capability of the i.t. manager alone. Bringing together all elements of the integrated delivery system and forming a well-integrated information environment will require a level of teamwork rarely seen in any industry. Today's IT manager is like an orchestra conductor. He or she should look ahead in the musical composition, manage the tempo, and bring all the sounds of the eclectic set of instruments together in harmony and achievement of the melody. Following the key success factor outlined here may not guarantee success in automating the integrated delivery system, but following them should keep the process harmonious.

  16. Bioengineered Silk Gene Delivery System for Nuclear Targeting

    PubMed Central

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

    2015-01-01

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

  17. A clinical perspective on mucoadhesive buccal drug delivery systems

    PubMed Central

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

    2014-01-01

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

  18. Biologically erodable microspheres as potential oral drug delivery systems

    NASA Astrophysics Data System (ADS)

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

    1997-03-01

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

  19. Novel Therapeutic Approaches for Various Cancer Types Using a Modified Sleeping Beauty-Based Gene Delivery System

    PubMed Central

    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. PMID:24466025

  20. Physical and chemical stimuli-responsive drug delivery systems: targeted delivery and main routes of administration.

    PubMed

    Lopes, Joana R; Santos, Gory; Barata, Pedro; Oliveira, Rita; Lopes, Carla M

    2013-01-01

    In the area of drug delivery, novel tools and technological approaches have captured the attention of researchers in order to improve the performance of conventional therapeutics and patient compliance to pharmacological therapy. Stimuli-responsive drug delivery systems (DDS) appear as a promising approach to control and target drug delivery. When these DDS are administered, the drug release is activated and then modulated through some action or external input and facilitated by the energy supplied externally. The stimuli responsible to activate the drug release can be classified into three types according to their nature or the type of energy applied: physical (e.g. magnetic field, electric field, ultrasound, temperature and osmotic pressure); chemical (e.g. pH, ionic strength and glucose); and biological (enzymes and endogenous receptors). The present review gives an overview of the most significant physical and chemical stimuliresponsive DDS and elucidates about their current and relevant applications in controlled and targeted drug delivery attending different routes of administration.

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2012-01-01

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

  3. An artificial antigen-presenting cell with paracrine delivery of IL-2 impacts the magnitude and direction of the T cell response.

    PubMed

    Steenblock, Erin R; Fadel, Tarek; Labowsky, Michael; Pober, Jordan S; Fahmy, Tarek M

    2011-10-01

    Artificial antigen-presenting cells (aAPCs) are an emerging technology to induce therapeutic cellular immunity without the need for autologous antigen-presenting cells (APCs). To fully replace natural APCs, an optimized aAPC must present antigen (signal 1), provide costimulation (signal 2), and release cytokine (signal 3). Here we demonstrate that the spatial and temporal characteristics of paracrine release of IL-2 from biodegradable polymer aAPCs (now termed paAPCs) can significantly alter the balance in the activation and proliferation of CD8+ and CD4+ T cells. Paracrine delivery of IL-2 upon T cell contact with paAPCs induces significant IL-2 accumulation in the synaptic contact region. This accumulation increases CD25 (the inducible IL-2 Rα chain) on responding T cells and increases proliferation of CD8+ T cells in vitro to levels 10 times that observed with equivalent amounts of bulk IL-2. These CD8+ T cell responses critically depend upon close contact of T cells and the paAPCs and require sustained release of low levels of IL-2. The same conditions promote activation-induced cell death in CD4+ T cells. These findings provide insight into the response of T cell subsets to paracrine IL-2. PMID:21849500

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

    PubMed

    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.

  5. Bioengineered Silk Protein-Based Gene Delivery Systems

    PubMed Central

    Numata, Keiji; Subramanian, Balajikarthick; Currie, Heather A.; Kaplan, David L.

    2009-01-01

    Silk proteins self-assemble into mechanically robust material structures that are also biodegradable and non-cytotoxic, suggesting utility for gene delivery. Since silk proteins can also be tailored in terms of chemistry, molecular weight and other design features via genetic engineering, further control of this system for gene delivery can be considered. In the present study, silk-based block copolymers were bioengineered with poly(l-lysine) domains for gene delivery. Ionic complexes of these silk-polylysine based block copolymers with plasmid DNA (pDNA) were prepared for gene delivery to human embryonic kidney (HEK) cells. The material systems were characterized by agarose gel electrophoresis, atomic force microscopy, and dynamic light scattering. The polymers self-assembled in solution and complexed plasmid DNA through ionic interactions. The pDNA complexes with 30-lysine residues prepared at a polymer/nucleotide ratio of 10 and with a solution diameter of 380 nm, showed the highest efficiency for transfection. The pDNA complexes were also immobilized on silk films and demonstrated direct cell transfection from these surfaces. The results demonstrate the potential of bioengineered silk proteins as a new family of highly tailored gene delivery systems. PMID:19577803

  6. Programmable nanomedicine: synergistic and sequential drug delivery systems

    NASA Astrophysics Data System (ADS)

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

    2015-02-01

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

  7. Cyclosporine Amicellar delivery system for dry eyes

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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.

  9. Bicellar systems as a new colloidal delivery strategy for skin.

    PubMed

    Rubio, L; Rodríguez, G; Barbosa-Barros, L; Alonso, C; Cócera, M; de la Maza, A; Parra, J L; López, O

    2012-04-01

    The presented work evaluates the use of bicellar systems as new delivery vectors for controlled release of compounds through the skin. Two different active principles were introduced into the bicellar systems: diclofenac diethylamine (DDEA) and flufenamic acid (Ffa). Bicellar systems are discoidal aggregates formed by long and short alkyl chain phospholipids. Characterization of the bicellar systems by dynamic light scattering (DLS) and cryogenic transmission electron microscopy (Cryo-TEM) showed that particle size decreased when DDEA was encapsulated and increased when Ffa was included in the bicellar systems. Percutaneous absorption studies demonstrated a lower penetration of DDEA and Ffa through the skin when the drugs were included in the bicellar systems than when the drugs were applied in an aqueous solution (DDEA) and in an ethanolic solution (Ffa); the reduction in penetration was more pronounced with Ffa. These bicellar systems may have retardant effects on percutaneous absorption, which result in a promising strategy for future drug or cosmetic delivery applications.

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

    PubMed

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

    2005-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2016-07-01

    A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells. PMID:27297745

  14. Medicated chewing gum, a novel drug delivery system.

    PubMed

    Aslani, Abolfazl; Rostami, Farnaz

    2015-04-01

    New formulations and technologies have been developed through oral drug delivery systems' researches. Such researches display significance of oral route amongst patients. We've reviewed all the features associated with medicated chewing gum as a modern drug delivery by introducing the history, advantages and disadvantages, methods of manufacturing, composition differences, evaluation tests and examples of varieties of medicated chewing gums. Acceptance of medicated chewing gum has been augmented through years. The advantages and therapeutic benefits of chewing gum support its development as we can see new formulations with new drugs contained have been produced from past and are going to find a place in market by formulation of new medicated chewing gums. Potential applications of medicated chewing gums are highly widespread as they will be recognized in future. Nowadays standards for qualifying chewing gums are the same as tablets. Patient-centered studies include medicated chewing gums as a delivery system too which creates compliance for patients. PMID:26109999

  15. Prenatal typing of Rh and Kell blood group system antigens: the edge of a watershed.

    PubMed

    van der Schoot, C Ellen; Tax, G H Martine; Rijnders, Robbert J P; de Haas, Masja; Christiaens, Godelieve C M L

    2003-01-01

    Knowledge of the molecular basis of the blood group systems has enabled the development of assays for blood group genotyping. At this time, polymerase chain reaction (PCR)-based assays validated on fetal material obtained by invasive means (chorionic villus sampling or amniocentesis) are available for all clinically relevant fetal blood groups, However, only Rh typing (D, C, c, E, and e) and K1 genotyping assays are discussed in this review. Importantly, one must remember that results of genotyping assays will not always be concordant with serological typing. Thus, the RhD genotyping assays have to be modified in response to increased understanding of the molecular biology of this blood group system. RhD typing assays should produce negative results when tested on the black RhD-negative RHD alleles, RHDpsi and r's. PCR-based assays can be used to determine paternal zygosity. For RhD zygosity testing, the real-time quantitative PCR approach and the direct detection of the hybrid Rhesus box, which is the result of the deletion of the RHD gene are available. Recently, methods for noninvasive prenatal genotyping have been investigated. The use of fetal cells circulating in the maternal circulation has been explored; however, the scarcity of circulating fetal cells has limited the use of this approach. More promising are the results obtained with RhD typing assays with cell-free fetal DNA, which is present in the maternal circulation in a concentration of 25 genomic equivalents per milliliter of maternal blood in early pregnancy increasing to 100 copies per milliliter in the third trimester, which is cleared from the circulation within a few hours of delivery. The positive predictive value of this approach is virtually 100%, but false-negative results are (infrequently) encountered. Therefore, this assay can at present only be used for screening of RhD-negative women to make the use of antenatal prophylaxis more targeted and hence more cost-effective. For the clinical

  16. 4-1BB ligand as an effective multifunctional immunomodulator and antigen delivery vehicle for the development of therapeutic cancer vaccines

    PubMed Central

    Sharma, Rajesh K.; Schabowsky, Rich-Henry; Srivastava, Abhishek K.; Elpek, Kutlu G.; Madireddi, Shravan; Zhao, Hong; Zhong, Zhenping; Miller, Robert W.; MacLeod, Kathryn J.; Yolcu, Esma S.; Shirwan, Haval

    2010-01-01

    Therapeutic subunit vaccines based on tumor-associated antigens (TAAs) represent an attractive approach for the treatment of cancer. However, poor immunogenicity of TAAs requires potent adjuvants for therapeutic efficacy. We recently proposed the TNF family costimulatory ligands as potential adjuvants for therapeutic vaccines, and hence generated a soluble form of 4-1BBL chimeric with streptavidin (SA-4-1BBL) that has pleiotropic effects on cells of innate, adaptive, and regulatory immunity. We herein tested whether these effects can translate into effective cancer immunotherapy when SA-4-1BBL was also used as a vehicle to deliver TAAs in vivo to DCs constitutively expressing the 4-1BB receptor. SA-4-1BBL was internalized by DCs upon receptor binding, and immunization with biotinylated antigens conjugated to SA-4-1BBL resulted in increased antigen uptake and cross-presentation by DCs, leading to the generation of effective T cell immune responses. Conjugate vaccines containing human papilloma virus 16 (HPV-16) E7 oncoprotein or survivin as a self TAA had potent therapeutic efficacy against TC-1 cervical and 3LL lung carcinoma tumors, respectively. Therapeutic efficacy of the vaccines was associated with increased CD4+ T and CD8+ T cell effector and memory responses and higher intratumoral CD8+ T effector/CD4+CD25+Foxp3+ T regulatory cell ratio. Thus, potent pleiotropic immune functions of SA-4-1BBL combined with its ability to serve as a vehicle to increase delivery of antigens to DCs in vivo endow this molecule with the potential to serve as an effective immunomodulatory component of therapeutic vaccines against cancer and chronic infections. PMID:20406989

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier. PMID:22931500

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  2. Mercury sorbent delivery system for flue gas

    DOEpatents

    Klunder; ,Edgar B.

    2009-02-24

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

  3. Antigenic drift, antigenic shift and interferon antagonists: how bunyaviruses counteract the immune system.

    PubMed

    Weber, Friedemann; Elliott, Richard M

    2002-09-01

    Members of the Bunyaviridae family are amongst the most widespread viruses in the world. They can be found on every inhabited continent at virtually every latitude, and are able to infect a wide range of arthropods, plants and mammals including humans. More than 300 named viruses are contained within the family Bunyaviridae (Virus Taxonomy: Seventh Report of the International Committee on Taxonomy of Viruses (2000) 599), and several members cause significant disease in humans or domestic animals. Despite being recognised as an emerging threat, relatively little is known about their virulence mechanisms. Here, we try to summarise the current state of knowledge about how the viruses of the Bunyaviridae succeed in establishing infection in the face of a powerful immune system. PMID:12297332

  4. Coordination polymer particles as potential drug delivery systems.

    PubMed

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

    2010-07-14

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

  5. Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

    PubMed Central

    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. PMID:22496608

  6. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy.

    PubMed

    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.

  7. [Synthesis of nanoparticles for dental drug delivery systems].

    PubMed

    Bakó, József; Szepesi, Márta; Márton, Ildikó; Borbély, János; Hegedûs, Csaba

    2007-06-01

    Modern drug delivery systems are designed for targeted controlled slow drug release. Up to now polymer based hydrogels have been applied in dentistry, which systems can affect the rate of the release due to their structure. Recently, intensive research for other methods is performed all over the world in order to improve the effectiveness of delivery systems. Nanotechnology is one of the most dynamically developing disciplines and is a powerful tool to increase the bioavailability of drugs. The aim of this work is to synthesise biocompatible nanoparticles by free radical initiated copolymerization of the monomers, 2-hydroxyethyl methacrylate (HEMA) and polyethyleneglycol dimethacrylate (PEGDMA) in aqueous solution, which can support the formation of nanoparticles that can be used as a drug delivery system for dental applications. The polymer-based nanoparticles were prepared via micellar polymerisation, which resulted a well dispersible white powder material. The size of particles was determined by Dynamic Laser Light Scattering (DLS) and Scanning Electron Microscopy (SEM). The size of particles is in range of 50-180 nm, measured by SEM. These values are commensurable with the results obtained by DLS experiments, where two size ranges were observed, as 40 +/- 15 nm and 180 +/- 30 nm. The nanoparticles are suitable for incorporation into a hydrogel matrix and to design new drug delivery devices for dental applications.

  8. NimbleTools: A Universally Designed Test Delivery System

    ERIC Educational Resources Information Center

    Russell, Michael; Hoffmann, Thomas; Higgins, Jennifer

    2009-01-01

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

  9. Coordination polymer particles as potential drug delivery systems.

    PubMed

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

    2010-07-14

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

  10. Assessment of Alternative Student Aid Delivery Systems: Analytic Agenda for the Current System.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    A guide for analyzing the effects of the current student aid delivery system and for estimating the effects of system alternatives is presented. Attention is directed to measures, data sources, and analysis methods needed to evaluate the effects of each delivery system activity on the various participants (e.g., lenders, financial aid applicants,…

  11. Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

    PubMed Central

    Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

    2015-01-01

    Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2014-11-01

    Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines. PMID:25219511

  14. Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release.

    PubMed

    Ilyinskii, Petr O; Roy, Christopher J; O'Neil, Conlin P; Browning, Erica A; Pittet, Lynnelle A; Altreuter, David H; Alexis, Frank; Tonti, Elena; Shi, Jinjun; Basto, Pamela A; Iannacone, Matteo; Radovic-Moreno, Aleksandar F; Langer, Robert S; Farokhzad, Omid C; von Andrian, Ulrich H; Johnston, Lloyd P M; Kishimoto, Takashi Kei

    2014-05-19

    Augmentation of immunogenicity can be achieved by particulate delivery of an antigen and by its co-administration with an adjuvant. However, many adjuvants initiate strong systemic inflammatory reactions in vivo, leading to potential adverse events and safety concerns. We have developed a synthetic vaccine particle (SVP) technology that enables co-encapsulation of antigen with potent adjuvants. We demonstrate that co-delivery of an antigen with a TLR7/8 or TLR9 agonist in synthetic polymer nanoparticles results in a strong augmentation of humoral and cellular immune responses with minimal systemic production of inflammatory cytokines. In contrast, antigen encapsulated into nanoparticles and admixed with free TLR7/8 agonist leads to lower immunogenicity and rapid induction of high levels of inflammatory cytokines in the serum (e.g., TNF-a and IL-6 levels are 50- to 200-fold higher upon injection of free resiquimod (R848) than of nanoparticle-encapsulated R848). Conversely, local immune stimulation as evidenced by cellular infiltration of draining lymph nodes and by intranodal cytokine production was more pronounced and persisted longer when SVP-encapsulated TLR agonists were used. The strong local immune activation achieved using a modular self-assembling nanoparticle platform markedly enhanced immunogenicity and was equally effective whether antigen and adjuvant were co-encapsulated in a single nanoparticle formulation or co-delivered in two separate nanoparticles. Moreover, particle encapsulation enabled the utilization of CpG oligonucleotides with the natural phosphodiester backbone, which are otherwise rapidly hydrolyzed by nucleases in vivo. The use of SVP may enable clinical use of potent TLR agonists as vaccine adjuvants for indications where cellular immunity or robust humoral responses are required.

  15. Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release.

    PubMed

    Ilyinskii, Petr O; Roy, Christopher J; O'Neil, Conlin P; Browning, Erica A; Pittet, Lynnelle A; Altreuter, David H; Alexis, Frank; Tonti, Elena; Shi, Jinjun; Basto, Pamela A; Iannacone, Matteo; Radovic-Moreno, Aleksandar F; Langer, Robert S; Farokhzad, Omid C; von Andrian, Ulrich H; Johnston, Lloyd P M; Kishimoto, Takashi Kei

    2014-05-19

    Augmentation of immunogenicity can be achieved by particulate delivery of an antigen and by its co-administration with an adjuvant. However, many adjuvants initiate strong systemic inflammatory reactions in vivo, leading to potential adverse events and safety concerns. We have developed a synthetic vaccine particle (SVP) technology that enables co-encapsulation of antigen with potent adjuvants. We demonstrate that co-delivery of an antigen with a TLR7/8 or TLR9 agonist in synthetic polymer nanoparticles results in a strong augmentation of humoral and cellular immune responses with minimal systemic production of inflammatory cytokines. In contrast, antigen encapsulated into nanoparticles and admixed with free TLR7/8 agonist leads to lower immunogenicity and rapid induction of high levels of inflammatory cytokines in the serum (e.g., TNF-a and IL-6 levels are 50- to 200-fold higher upon injection of free resiquimod (R848) than of nanoparticle-encapsulated R848). Conversely, local immune stimulation as evidenced by cellular infiltration of draining lymph nodes and by intranodal cytokine production was more pronounced and persisted longer when SVP-encapsulated TLR agonists were used. The strong local immune activation achieved using a modular self-assembling nanoparticle platform markedly enhanced immunogenicity and was equally effective whether antigen and adjuvant were co-encapsulated in a single nanoparticle formulation or co-delivered in two separate nanoparticles. Moreover, particle encapsulation enabled the utilization of CpG oligonucleotides with the natural phosphodiester backbone, which are otherwise rapidly hydrolyzed by nucleases in vivo. The use of SVP may enable clinical use of potent TLR agonists as vaccine adjuvants for indications where cellular immunity or robust humoral responses are required. PMID:24593999

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

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

  17. Drug delivery systems, CNS protection, and the blood brain barrier.

    PubMed

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

  18. Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery.

    PubMed

    Jones, Charles H; Gollakota, Akhila; Chen, Mingfu; Chung, Tai-Chun; Ravikrishnan, Anitha; Zhang, Guojian; Pfeifer, Blaine A

    2015-07-01

    Given the rise of antibiotic resistant microbes, genetic vaccination is a promising prophylactic strategy that enables rapid design and manufacture. Facilitating this process is the choice of vector, which is often situationally-specific and limited in engineering capacity. Furthermore, these shortcomings are usually tied to an incomplete understanding of the structure-function relationships driving vector-mediated gene delivery. Building upon our initial report of a hybrid bacterial-biomaterial gene delivery vector, a comprehensive structure-function assessment was completed using a class of mannosylated poly(beta-amino esters). Through a top-down screening methodology, an ideal polymer was selected on the basis of gene delivery efficacy and then used for the synthesis of a stratified molecular weight polymer library. By eliminating contributions of polymer chemical background, we were able to complete an in-depth assessment of gene delivery as a function of (1) polymer molecular weight, (2) relative mannose content, (3) polymer-membrane biophysical properties, (4) APC uptake specificity, and (5) serum inhibition. In summary, the flexibility and potential of the hybrid design featured in this work highlights the ability to systematically probe vector-associated properties for the development of translational gene delivery candidates.

  19. Medicated chewing gum, a novel drug delivery system

    PubMed Central

    Aslani, Abolfazl; Rostami, Farnaz

    2015-01-01

    New formulations and technologies have been developed through oral drug delivery systems’ researches. Such researches display significance of oral route amongst patients. We’ve reviewed all the features associated with medicated chewing gum as a modern drug delivery by introducing the history, advantages and disadvantages, methods of manufacturing, composition differences, evaluation tests and examples of varieties of medicated chewing gums. Acceptance of medicated chewing gum has been augmented through years. The advantages and therapeutic benefits of chewing gum support its development as we can see new formulations with new drugs contained have been produced from past and are going to find a place in market by formulation of new medicated chewing gums. Potential applications of medicated chewing gums are highly widespread as they will be recognized in future. Nowadays standards for qualifying chewing gums are the same as tablets. Patient-centered studies include medicated chewing gums as a delivery system too which creates compliance for patients. PMID:26109999

  20. Unsteady jet in designing innovative drug delivery system

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  1. Electrohydrodynamics: A facile technique to fabricate drug delivery systems

    PubMed Central

    Chakraborty, Syandan; Liao, I-Chien; Adler, Andrew; Leong, Kam W.

    2009-01-01

    Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nano-structured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial-electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material’s functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nano-fiber/particles as drug delivery devices. PMID:19651167

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

    PubMed

    Gao, Yuan; Wang, Jingkang; Wang, Yongli; Yin, Qiuxiang; Glennon, Brian; Zhong, Jian; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun

    2015-01-01

    Low water solubility of drug products causes delivery problems such as low bioavailability. The reduced particle size and increased surface area of nanocrystals lead to the increasing of the dissolution rate. The formulation of drug nanocrystals is a robust approach and has been widely applied to drug delivery system (DDS) due to the significant development of nanoscience and nanotechnology. It can be used to improve drug efficacy, provide targeted delivery and minimize side-effects. Crystallization is the main and efficient unit operation to produce nanocrystals. Both traditional crystallization methods such as reactive crystallization, anti-solvent crystallization and new crystallization methods such as supercritical fluid crystallization, high-gravity controlled precipitation can be used to produce nanocrystals. The current mini-review outlines the main crystallization methods addressed in literature. The advantages and disadvantages of each method were summarized and compared.

  3. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    PubMed Central

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  4. [Systems for the delivery of health care].

    PubMed

    Kérouac, S; Duquette, A; Sandhu, B K

    1990-06-01

    Re-examining the role of the nurse, the authors remind us of the importance of understanding how our system of health care has evolved, as well as what it holds for the future. Presenting an historical overview of the past 50 years, they discuss concepts related to moving the profession forward and suggest the decade ahead offers key opportunities.

  5. Creating physician-driven integrated delivery systems.

    PubMed

    Wagner, L

    1995-03-01

    Put doctors in control of key strategic and clinical decisions? Make them part owners or give them financial performance incentives? Yes, say many experts, that's the road to success for integrated systems. Read how they're doing it and evaluate your physician integration initiatives on HSL's 10-question self-assessment.

  6. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    PubMed Central

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

    2014-01-01

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

  7. Interpenetrating polymer networks as innovative drug delivery systems.

    PubMed

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

    2014-01-01

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

  8. Chitosan nanoparticle based delivery systems for sustainable agriculture.

    PubMed

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

    2015-01-01

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

  9. [Prenatal typing of Rh- and Kell- blood group system antigens].

    PubMed

    Faas, B H; Maaskant-van Wijk, P A; Beuling, E A; Overbeeke, M A; van der Schoot, C E; Christiaens, G C

    1999-09-01

    Rhesus (Rh) and Kell blood group immunisations are the most frequent causes of haemolytic disease of the newborn. Recently, the molecular bases of the Rh and Kell antigens have been elucidated. Subsequently, specific polymerase chain reactions (PCRs) could be developed to determine the RhD, RhC/Rhc and RhE/Rhe genotypes as well as the KI genotype (from the Kell blood group) with genomic DNA. The tests were applied to genomically determine the foetal Rh and Kell blood groups with DNA obtained from amniotic fluid cells. The genotypes obtained were compared with the Rh phenotypes established by cord blood red cell serology. The PCRs to determine the RhD, Rhc, RhE and Rhe and KI genotypes were found to be reliable. The test for RhC however, resulted in false-positive C genotypes. Indeed, more than half of the subsequently tested C-negative Negroid donors were false-positive with the DNA test. Thus, except for RhC, it is possible to reliably determine the Rh and KI genotypes of a foetus with DNA isolated from amniotic fluid cells. Amniocentesis, however, carries a risk for the pregnancy and therefore the tests will only be justified in pregnant women in whom an antibody has been detected and the father of the foetus is heterozygous for the specific antigen. Recently foetal RhD genotypes were determined in foetal DNA circulating in the plasma of RhD-negative pregnant women. This could eventually lead to the introduction of assays with which the foetal blood group can be determined without any risk to the foetus.

  10. Direct current power delivery system and method

    DOEpatents

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

    2016-09-06

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

  11. System modeling speeds clamshell unloader delivery

    SciTech Connect

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

    1995-04-01

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

  12. Synthetic Microbes As Drug Delivery Systems

    PubMed Central

    2015-01-01

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

  13. An alternate delivery system improves vaccine performance against foot-and-mouth disease virus (FMDV).

    PubMed

    Pandya, Mital; Pacheco, Juan M; Bishop, Elizabeth; Kenney, Mary; Milward, Francis; Doel, Timothy; Golde, William T

    2012-04-26

    Foot-and-mouth disease virus (FMDV) causes vesicular disease of cloven-hoofed animals with severe agricultural and economic implications. One of the most highly infectious and contagious livestock pathogens known, the disease spreads rapidly in naïve populations making it critical to have rapidly acting vaccines. Needle inoculation of killed virus vaccine is an efficient method of swiftly vaccinating large numbers of animals, either in eradication efforts or in outbreak situations in disease free countries, although, to be efficient, this requires utilizing the same needle with multiple animals. Here we present studies using a needle free system for vaccination with killed virus vaccine, FMDV strain O1 Manisa, as a rapid and consistent delivery platform. Cattle were vaccinated using a commercially available vaccine formulation at the manufacturer's recommended dose as well as four and sixteen fold less antigen load per dose. Animals were challenged intradermalingually (IDL) with live, virulent virus, homologous strain O1 Manisa, at various times following vaccination. All non-vaccinated control cattle exhibited clinical disease, including fever, viremia and lesions, specifically vesicle formation. Cattle vaccinated with the 1/16× and 1/4× doses using the needle free device were protected when challenged at both 7 and 28 days after vaccination. These data suggest that effective protection against disease can be achieved with 1/16 of the recommended vaccine dose when delivered using the needle free, intradermal delivery system, indicating the current vaccine stockpile that can be extended by many fold using this system.

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

    PubMed Central

    Hanagata, Nobutaka

    2012-01-01

    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 system, the application of CpG ODNs for the treatment of cancers, infectious diseases, and allergies holds great promise. PMID:22619554

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

    PubMed

    Mahmoud, Sheha; Mohammad, Alhawi

    2010-11-01

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

  16. Using DNA nanotechnology to produce a drug delivery system

    NASA Astrophysics Data System (ADS)

    Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang

    2013-03-01

    Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October-2 November, 2012, Ha Long, Vietnam.

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

    PubMed Central

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

    2012-01-01

    The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics. PMID:22619510

  18. Health care delivery system reform: accountable care organizations.

    PubMed

    Dove, James T; Weaver, W Douglas; Lewin, Jack

    2009-09-01

    Health care reform is moving forward at a frantic pace. There have been 3 documents released from the Senate Finance Committee and proposed legislation from the Senate HELP Committee and the House of Representatives Tri-Committee on Health Reform. The push for legislative action has not been sidetracked by the economic conditions. Integrated health care delivery is the current favored approach to aligning resource use and cost. Accountable care organizations (ACOs), a concept included in health care reform legislation before both the House and Senate, propose to translate the efficiencies and lessons learned from large integrated systems and apply them to nonintegrated practices. The ACO design could be real or virtual integration of local delivery providers. This new structure is complicated, and clinicians, patients, and payers should have input regarding the design and function of it. Because most of health care is delivered in the ambulatory setting, it remains to be determined whether the ACOs are best developed in parallel among physician practices and hospitals or as partnerships between hospitals and physicians. Many are concerned that hospital-led ACOs will force physician employment by hospitals with possible unintended negative consequences for physicians, hospitals, and patients. Patients, physicians, other providers, and payers are in a better position to guide the redesign of the health care delivery system than government agencies, policy organizations, or elected officials, no matter how well intended. We strongly believe-and ACC has proclaimed-that change in health care delivery must be accomplished with patients and physicians at the table.

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

    PubMed

    Ulker, Zeynep; Erkey, Can

    2014-03-10

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

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

    PubMed

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

    2014-11-01

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

  1. Reprogramming the Local Lymph Node Microenvironment Promotes Tolerance that Is Systemic and Antigen Specific.

    PubMed

    Tostanoski, Lisa H; Chiu, Yu-Chieh; Gammon, Joshua M; Simon, Thomas; Andorko, James I; Bromberg, Jonathan S; Jewell, Christopher M

    2016-09-13

    Many experimental therapies for autoimmune diseases, such as multiple sclerosis (MS), aim to bias T cells toward tolerogenic phenotypes without broad suppression. However, the link between local signal integration in lymph nodes (LNs) and the specificity of systemic tolerance is not well understood. We used intra-LN injection of polymer particles to study tolerance as a function of signals in the LN microenvironment. In a mouse MS model, intra-LN introduction of encapsulated myelin self-antigen and a regulatory signal (rapamycin) permanently reversed paralysis after one treatment during peak disease. Therapeutic effects were myelin specific, required antigen encapsulation, and were less potent without rapamycin. This efficacy was accompanied by local LN reorganization, reduced inflammation, systemic expansion of regulatory T cells, and reduced T cell infiltration to the CNS. Our findings suggest that local control over signaling in distinct LNs can promote cell types and functions that drive tolerance that is systemic but antigen specific. PMID:27626664

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-10-15

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

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

    PubMed

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

    2013-10-15

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

  5. Development and validation of an HPLC/UV assay for separation and quantification of peptide antigens from a liposomal vaccine delivery platform.

    PubMed

    Penwell, Andrea; Sharp, Kendall; Mansour, Marc; Sammatur, Leeladhar

    2012-07-01

    The development and validation of an HPLC method for the quantification of eight peptide antigens from the therapeutic cancer vaccine DPX-0907 is described. The antigens were formulated in DepoVax™, a patented liposomal vaccine delivery platform used in a phase 1 study for breast, ovarian, and prostate cancers. A gradient reversed-phase method with UV detection was optimized for separating and quantifying the peptide mixture. Several extraction methods investigated to extract the peptides from the lipids led to poor recovery of one or more of the peptides. A simple, reproducible, and high-recovery extraction procedure for the simultaneous quantification of hydrophilic and hydrophobic peptides was discovered using a liquid-liquid extraction with water-saturated n-butanol and sodium bicarbonate (0.1 M). The method was found to be specific, linear, accurate, precise, and reliable within the range of 50-150% of the nominal concentration for DPX-0907. The validated method was successfully applied to the assay of peptide content in pre-clinical and clinical batches of DPX-0907. PMID:22516680

  6. Delivery of Large Heterologous Polypeptides across the Cytoplasmic Membrane of Antigen-Presenting Cells by the Bordetella RTX Hemolysin Moiety Lacking the Adenylyl Cyclase Domain

    PubMed Central

    Holubova, Jana; Jelinek, Jiri; Tomala, Jakub; Masin, Jiri; Kosova, Martina; Stanek, Ondrej; Bumba, Ladislav; Michalek, Jaroslav; Kovar, Marek; Sebo, Peter

    2012-01-01

    The Bordetella adenylate cyclase toxin-hemolysin (CyaA; also called ACT or AC-Hly) targets CD11b-expressing phagocytes and translocates into their cytosol an adenylyl cyclase (AC) that hijacks cellular signaling by conversion of ATP to cyclic AMP (cAMP). Intriguingly, insertion of large passenger peptides removes the enzymatic activity but not the cell-invasive capacity of the AC domain. This has repeatedly been exploited for delivery of heterologous antigens into the cytosolic pathway of CD11b-expressing dendritic cells by CyaA/AC− toxoids, thus enabling their processing and presentation on major histocompatibility complex (MHC) class I molecules to cytotoxic CD8+ T lymphocytes (CTLs). We produced a set of toxoids with overlapping deletions within the first 371 residues of CyaA and showed that the structure of the AC enzyme does not contain any sequences indispensable for its translocation across target cell membrane. Moreover, replacement of the AC domain (residues 1 to 371) with heterologous polypeptides of 40, 146, or 203 residues yielded CyaAΔAC constructs that delivered passenger CTL epitopes into antigen-presenting cells (APCs) and induced strong antigen-specific CD8+ CTL responses in vivo in mice and ex vivo in human peripheral blood mononuclear cell cultures. This shows that the RTX (repeats in toxin) hemolysin moiety, consisting of residues 374 to 1706 of CyaA, harbors all structural information involved in translocation of the N-terminal AC domain across target cell membranes. These results decipher the extraordinary capacity of the AC domain of CyaA to transport large heterologous cargo polypeptides into the cytosol of CD11b+ target cells and pave the way for the construction of CyaAΔAC-based polyvalent immunotherapeutic T cell vaccines. PMID:22215742

  7. Chronopharmaceutical Drug Delivery Systems: Hurdles, Hype or Hope?⊗

    PubMed Central

    Youan, Bi-Botti C.

    2010-01-01

    The current advances in chronobiology and the knowledge gained from chronotherapy of selected diseases strongly suggest that “the one size fits all at all times” approach to drug delivery is no longer substantiated, at least for selected bioactive agents and disease therapy or prevention. Thus, there is a critical and urgent need for chronopharmaceutical research (e.g., design and evaluation of robust, spatially and temporally controlled drug delivery systems that would be clinically intended for chronotherapy by different routes of administration). This review provides a brief overview of current delivery system intended for chronotherapy. In theory, such an ideal “magic pill” preferably with affordable cost, would improve the safety, efficacy and patient compliance of old and new drugs. However, currently, there are three major hurdles for the successful transition of such system from laboratory to patient bedside. These include the challenges to identify adequate (i) rhythmic biomaterials and systems, (ii) rhythm engineering modeling, perhaps using system biology and (iii) regulatory guidance. PMID:20438781

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

    PubMed

    Haggstrom, David A; Doebbeling, Bradley N

    2011-12-01

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

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

    PubMed

    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.

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

    PubMed Central

    Alyautdin, Renad; Khalin, Igor; Nafeeza, Mohd Ismail; Haron, Muhammad Huzaimi; Kuznetsov, Dmitry

    2014-01-01

    The protective properties of the blood–brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain’s vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual’s age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS. PMID:24550672

  11. Preparation of the Multifunctional Liposome-Containing Microneedle Arrays as an Oral Cavity Mucosal Vaccine Adjuvant-Delivery System.

    PubMed

    Wang, Ting; Wang, Ning

    2016-01-01

    Recently, the multifunctional liposome-constituted microneedle arrays (LiposoMAs) have been proven to be an interesting vaccine adjuvant-delivery system (VADS) that are stable and can be vaccinated via oral cavity mucosal route. When given to mice at oral mucosa, the LiposoMAs can effectively eliminate the ingredient loss caused by chewing, swallowing, and saliva flowing and can, thus, elicit robust systemic as well as mucosal immunoresponses against the loaded antigens. In addition, the LiposoMAs can induce a mixed Th1/Th2 immunoresponse and strong cellular/humoral immunity due to special adjuvanticity and targeting delivery functions of the nanoparticulate VADS. In this chapter, the preparation, characterization as well as mucosal vaccination of the LiposoMAs are introduced. In addition, the methods for sampling mouse organs, tissues, and cells and for evaluation of the immunization efficacy are mainly included. PMID:27076328

  12. Delivery.

    PubMed

    Miller, Thomas A

    2013-11-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms.

  13. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry PMID:23852646

  14. 20 CFR 662.100 - What is the One-Stop delivery system?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false What is the One-Stop delivery system? 662.100...) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT General Description of the One-Stop Delivery System § 662.100 What is the One-Stop delivery system? (a) In general, the...

  15. 20 CFR 662.100 - What is the One-Stop delivery system?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false What is the One-Stop delivery system? 662.100...) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT General Description of the One-Stop Delivery System § 662.100 What is the One-Stop delivery system? (a) In general, the...

  16. 20 CFR 662.100 - What is the One-Stop delivery system?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What is the One-Stop delivery system? 662.100... DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT General Description of the One-Stop Delivery System § 662.100 What is the One-Stop delivery system? (a) In general, the...

  17. 20 CFR 662.100 - What is the One-Stop delivery system?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false What is the One-Stop delivery system? 662.100...) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT General Description of the One-Stop Delivery System § 662.100 What is the One-Stop delivery system? (a) In general, the...

  18. Porous tube plant nutrient delivery system development: A device for nutrient delivery in microgravity

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    The Porous Tube Plant Nutrient Delivery Systems or PTPNDS (U.S. Patent #4,926,585) has been under development for the past six years with the goal of providing a means for culturing plants in microgravity, specifically providing water and nutrients to the roots. Direct applications of the PTPNDS include plant space biology investigations on the Space Shuttle and plant research for life support in the Space Station Freedom. In the past, we investigated various configurations, the suitability of different porous materials, and the effects of pressure and pore size on plant growth. Current work is focused on characterizing the physical operation of the system, examining the effects of solution aeration, and developing prototype configurations for the Plant Growth Unit (PGU), the flight system for the Shuttle mid-deck. Future developments will involve testing on KC-135 parabolic flights, the design of flight hardware and testing aboard the Space Shuttle.

  19. Intracellular Delivery System for Antibody–Peptide Drug Conjugates

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  1. Nanoengineered drug delivery systems for enhancing antibiotic therapy.

    PubMed

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

    2015-03-01

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

  2. The Delivery System of Environmental Education at the Tertiary Level in the Asia-Pacific Region.

    ERIC Educational Resources Information Center

    Sato, Masahisa; Bhandari, Bishnu; Abe, Osamu

    2001-01-01

    Analyzes the delivery system of environmental education at the tertiary level in relation to higher education attendance rate. Describes the characteristics of the delivery system in countries such as China, India, Australia, Japan, South Korea, and Indonesia. (Author/MM)

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

    PubMed

    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.

  4. Magnetic nanoparticle drug delivery systems for targeting tumor

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  5. Low-cost health delivery systems: lessons from Nicaragua.

    PubMed Central

    Heiby, J R

    1981-01-01

    In 1976 the Ministry of Health of Nicaragua began a low cost program to deliver simple health services in rural areas through trained traditional birth attendants or "parteras." After two years the program had prepared 768 parteras in a five-day training course. Parteras were equipped with a kit that included oral rehydration salts, an antihelminthic, multi-vitamins with iron, aspirin, contraceptives, and obstetrical equipment. The difficulties encountered in implementing this limited set of simple health services illustrate a number of potential obstacles to the achievement of universal, comprehensive primary health care in less developed countries. The most prominent difficulties involved elements of the health service delivery system itself: supervision, the collection and use of management information, training, partera selection, and logistics. The experience also provided examples of issues in the design of delivery systems that require specific applied research. PMID:7212140

  6. Systemic delivery of recombinant proteins by genetically modified myoblasts

    SciTech Connect

    Barr, E.; Leiden, J.M. )

    1991-12-06

    The ability to stably deliver recombinant proteins to the systemic circulation would facilitate the treatment of a variety of acquired and inherited diseases. To explore the feasibility of the use of genetically engineered myoblasts as a recombinant protein delivery system, stable transfectants of the murine C2C12 myoblast cell line were produced that synthesize and secrete high levels of human growth hormone (hGH) in vitro. Mice injected with hGH-transfected myoblasts had significant levels of hGH in both muscle and serum that were stable for at least 3 weeks after injection. Histological examination of muscles injected with {beta}-galactosidase-expressing C2C12 myoblasts demonstrated that many of the injected cells had fused to form multinucleated myotubes. Thus, genetically engineered myoblasts can be used for the stable delivery of recombinant proteins into the circulation.

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

    PubMed

    Zhou, Qi Tony; Leung, Sharon Shui Yee; Tang, Patricia; Parumasivam, Thaigarajan; Loh, Zhi Hui; Chan, Hak-Kim

    2015-05-01

    Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'.

  8. Influence of the host system on the pathogenicity, immunogenicity, and antigenicity of infectious bursal disease virus.

    PubMed

    Hassan, M K; Saif, Y M

    1996-01-01

    The effect of the host system on the pathogenicity, immunogenicity, and antigenicity of infectious bursal disease virus (IBDV) was investigated. One classic (SAL) and one variant strain (IN) of IBDV were passaged separately six times in three host systems, namely BGM-70 continuous cell line, primary chicken embryo fibroblast (CEF) cells, or embryonating chicken eggs (embryos) or one time in the bursa of Fabricius (BF) of specific-pathogen-free (SPF) chickens. Passage in BGM-70 cells or CEF cells resulted in loss of pathogenicity, but viruses passaged in embryos or BF maintained their pathogenicity. For the immunogenicity study, the viruses described above were used to prepare live and inactivated vaccines, containing 10(3) mean embryo infectious doses (EID50s) and 10(5) EID50s respectively. These vaccines induced different levels of protection. It was concluded that the antigen titration methodology employing embryonating chicken eggs was not suitable for titration of viruses propagated in other host systems because of varying degrees of adaptation and/or pathogenicity of the viruses resulting in variability in antigen mass of the tested vaccines. To test this assumption, an antigen-capture enzyme-linked immunosorbent assay was used as a titration system to compare the antigenicity of viruses propagated in BGM-70 cells or BF. Preparations containing similar antigen masses were inactivated then inoculated into two age groups of SPF chickens and antibody titers were monitored. During the experimental period, the geometric mean virus-neutralizing (VN) antibody titers of the vaccinated groups did not differ significantly (P > 0.05).

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

    SciTech Connect

    Springer, D.; Dakin, B.; Backman, C.

    2012-07-01

    The primary objectives of this study are to estimate potential energy savings relative to conventional ducted air distribution, and to identify equipment requirements, costs, and barriers with a focus on ductless hydronic delivery systems that utilize water-to-air terminal units in each zone. Results indicate that annual heating and cooling energy use can be reduced by up to 27% assuming replacement of the conventional 13 SEER heat pump and coil with a similarly rated air-to-water heat pump.

  10. Governance of integrated delivery systems/networks: a stakeholder approach.

    PubMed

    Savage, G T; Taylor, R L; Rotarius, T M; Buesseler, J A

    1997-01-01

    The health care environment is complex and turbulent, and traditional governance forms face many challenges. As integrated delivery systems/networks are formed, governance structures must be responsive to both internal and external stakeholders. Both internal efficiencies and socially responsible actions are required of these relatively new organizational forms. To meet these needs, a two-tier governance structure is presented that consists of overarching and facilitating boards. PMID:9058084

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

    PubMed

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

    2011-01-01

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

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

    PubMed

    Ma, Ping; Mumper, Russell J

    2013-02-18

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles.

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

    PubMed Central

    Zacchè, Martino Maria; Srikrishna, Sushma; Cardozo, Linda

    2015-01-01

    The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy. PMID:26649286

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

    PubMed

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

    2015-12-01

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

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

    PubMed

    Doroud, Delaram; Rafati, Sima

    2012-01-01

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

  16. Data delivery system for MAPPER using image compression

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    Lopes, Carla M; Bettencourt, Catarina; Rossi, Alessandra; Buttini, Francesca; Barata, Pedro

    2016-08-20

    In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems.

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

    PubMed

    Jauhari, Saurabh; Dash, Alekha K

    2006-01-01

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

  19. Polymeric nanoparticles for co-delivery of synthetic long peptide antigen and poly IC as therapeutic cancer vaccine formulation.

    PubMed

    Rahimian, Sima; Fransen, Marieke F; Kleinovink, Jan Willem; Christensen, Jonatan Riis; Amidi, Maryam; Hennink, Wim E; Ossendorp, Ferry

    2015-04-10

    The aim of the current study was to develop a cancer vaccine formulation for treatment of human papillomavirus (HPV)-induced malignancies. Synthetic long peptides (SLPs) derived from HPV16 E6 and E7 oncoproteins have been used for therapeutic vaccination in clinical trials with promising results. In preclinical and clinical studies adjuvants based on mineral oils (such as incomplete Freund's adjuvant (IFA) and Montanide) are used to create a sustained release depot at the injection site. While the depot effect of mineral oils is important for induction of robust immune responses, their administration is accompanied with severe adverse and long lasting side effects. In order to develop an alternative for IFA family of adjuvants, polymeric nanoparticles (NPs) based on hydrophilic polyester (poly(d,l lactic-co-hydroxymethyl glycolic acid) (pLHMGA)) were prepared. These NPs were loaded with a synthetic long peptide (SLP) derived from HPV16 E7 oncoprotein and a toll like receptor 3 (TLR3) ligand (poly IC) by double emulsion solvent evaporation technique. The therapeutic efficacy of the nanoparticulate formulations was compared to that of HPV SLP+poly IC formulated in IFA. Encapsulation of HPV SLP antigen in NPs substantially enhanced the population of HPV-specific CD8+ T cells when combined with poly IC either co-encapsulated with the antigen or in its soluble form. The therapeutic efficacy of NPs containing poly IC in tumor eradication was equivalent to that of the IFA formulation. Importantly, administration of pLHMGA nanoparticles was not associated with adverse effects and therefore these biodegradable nanoparticles are excellent substitutes for IFA in cancer vaccines. PMID:25660830

  20. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: I. Formulation development.

    PubMed

    Rao, Sripriya Venkata Ramana; Shao, Jun

    2008-10-01

    The global aim of this research project was to develop a self-nanoemulsifying drug delivery system (SNEDDS) for non-invasive delivery of protein drugs. The specific aim of this study was to develop SNEDDS formulations. An experimental design was adopted to develop SNEDDS. Fluorescent labeled beta-lactamase (FITC-BLM), a model protein, was loaded into SNEDDS through solid dispersion technique. The experimental design provided 720 compositions of different oil, surfactant, and co-surfactant at various ratios, of which 33 SNEDDS prototypes were obtained. Solid dispersion of FITC-BLM in SoyPC prepared was able to dissolve in 16 SNEDDS prototypes (approximately 2200 mU BLM in 1g SNEDDS). SNEDDS NE-12-7 (composition: Lauroglycol FCC, Cremophor EL and Transcutol; ratio: 5:4:3) formed O/W nanoemulsion with mean droplet size in the range of 22-50 nm when diluted with various pH media and different dilution factor with PBS (pH 7.4). The phase diagram of NE-12-7 indicated a broad region of nanoemulsion. BLM-loaded SNEDDS (NE-12-7) stored at 4 degrees C for 12 weeks indicated 10% loss of BLM activity. A SNEDDS was developed to load FITC-BLM into the oil phase which can spontaneously form O/W nanoemulsion upon the addition of water.

  1. A 400G optical wireless integration delivery system.

    PubMed

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

    2013-08-12

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

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

    PubMed

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

    2013-04-15

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

  3. [Development of topical drug delivery systems utilizing polymeric materials].

    PubMed

    Machida, Y

    1993-05-01

    Topical drug delivery is important from the view points of improvement of therapeutic effect and reduction of systemic side effects. Utilization of polymeric materials seemed to be as a key for the development of new topical dosage forms including targeting drug delivery systems. Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose (HPC) according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content. Double-layered mucoadhesive sticks for the treatment of uterine cervix cancer were prepared by direct compression of powder mixture of bleomycin, HPC and carboxyvinyl polymer (CP). Drug release property of the sticks could be controlled by the weight of outer layer, drug combining ratio to each layer and coating of core layer. The results suggested a possibility of a "once-a-week" treatment that is preferable for the patients. Magnetic granules for the treatment of esophageal cancer were prepared using ferrite, HPC and CP. Magnetic guidance and retainment of the granules on esophageal mucosa were confirmed using rabbits in vivo. Buoyant sustained release preparations were prepared using chitosan, soybean protein, HPC and other polymers. Usefulness of the buoyant preparations was suggested from the results in vitro and in vivo. Insulin microspheres (IMS) for targeting delivery to the small intestine were prepared by the newly developed method. Employment of enteric coating material (Eudragit) and combination of protease inhibitor protected insulin from enzymatic attack and gave decreased levels of blood glucose by oral administration.

  4. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tumor-associated antigen immunological test system. 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for...

  5. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tumor-associated antigen immunological test system. 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for...

  6. Bacterial vectors and delivery systems in cancer therapy.

    PubMed

    Gardlik, Roman; Fruehauf, Johannes H

    2010-10-01

    Live bacterial vectors may be useful tools for the development of novel cancer therapies that can be added to the repertoire of existing drugs. Several bacterial strains effectively colonize solid tumors and act as antitumor therapeutics. The naturally occurring tumor-colonizing characteristics of bacterial species such as Salmonella sp, Clostridium sp and Escherichia coli can be further modified by genetic manipulations, making these bacterial systems excellent vehicles for the production and targeted delivery of therapeutic molecules into cancer cells. This feature review summarizes recent research on cancer therapy using genetically modified bacteria. Different approaches - bactofection, DNA vaccination, and bacterially mediated protein and RNAi delivery - in which modified bacteria are used as anticancer therapeutics, are discussed.

  7. Development of a Production Ready Automated Wire Delivery System

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The current development effort is a Phase 3 research study entitled "A Production Ready Automated Wire Delivery System", contract number NAS8-39933, awarded to Nichols Research Corporation (NRC). The goals of this research study were to production harden the existing Automated Wire Delivery (AWDS) motion and sensor hardware and test the modified AWDS in a range of welding applications. In addition, the prototype AWDS controller would be moved to the VME bus platform by designing, fabricating and testing a single board VME bus AWDS controller. This effort was to provide an AWDS that could transition from the laboratory environment to production operations. The project was performed in two development steps. Step 1 modified and tested an improved MWG. Step 2 developed and tested the AWDS single board VME bus controller. Step 3 installed the Wire Pilot in a Weld Controller with the imbedded VME bus controller.

  8. Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery

    PubMed Central

    Torchilin, Vladimir P.

    2015-01-01

    The use of nanoparticulate pharmaceutical drug delivery systems (NDDSs) to enhance the in vivo effectiveness of drugs is now well established. The development of multifunctional and stimulus-sensitive NDDSs is an active area of current research. Such NDDSs can have long circulation times, target the site of the disease and enhance the intracellular delivery of a drug. This type of NDDS can also respond to local stimuli that are characteristic of the pathological site by, for example, releasing an entrapped drug or shedding a protective coating, thus facilitating the interaction between drug-loaded nanocarriers and target cells or tissues. In addition, imaging contrast moieties can be attached to these carriers to track their real-time biodistribution and accumulation in target cells or tissues. Here, I highlight recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases. PMID:25287120

  9. Advances in nanotechnology-based delivery systems for curcumin.

    PubMed

    Sun, Min; Su, Xun; Ding, Buyun; He, Xiuli; Liu, Xiuju; Yu, Aihua; Lou, Hongxiang; Zhai, Guangxi

    2012-07-01

    Curcumin (CUR), a bioactive component of turmeric, which is a commonly used spice and nutritional supplement, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). In recent years, the potential pharmacological actions of CUR in inflammatory disorders, cardiovascular disease, cancer, Alzheimer's disease and neurological disorders have been shown. However, the clinical application of CUR is severely limited by its main drawbacks such as instability, low solubility, poor bioavailability and rapid metabolism. Multifarious nanotechnology-based delivery approaches have been used to enhance the oral bioavailability, biological activity or tissue-targeting ability of CUR. This article reviews potential novel drug delivery systems for CUR including liposomes, polymeric nanoparticles, solid lipid nanoparticles, micelles, nanogels, nanosuspensions, nanoemulsions, complexes and dendrimer/dimer, which provide promising results for CUR to improve its biological activities. PMID:22846093

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

    PubMed

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

    2016-08-30

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

  11. Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery.

    PubMed

    Torchilin, Vladimir P

    2014-11-01

    The use of nanoparticulate pharmaceutical drug delivery systems (NDDSs) to enhance the in vivo effectiveness of drugs is now well established. The development of multifunctional and stimulus-sensitive NDDSs is an active area of current research. Such NDDSs can have long circulation times, target the site of the disease and enhance the intracellular delivery of a drug. This type of NDDS can also respond to local stimuli that are characteristic of the pathological site by, for example, releasing an entrapped drug or shedding a protective coating, thus facilitating the interaction between drug-loaded nanocarriers and target cells or tissues. In addition, imaging contrast moieties can be attached to these carriers to track their real-time biodistribution and accumulation in target cells or tissues. Here, I highlight recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases. PMID:25287120

  12. [Liposomal boron delivery system for neutron capture therapy].

    PubMed

    Nakamura, Hiroyuki

    2008-02-01

    Boron neutron capture therapy (BNCT) is a binary cancer treatment based on the nuclear reaction of two essentially nontoxic species, (10)B and thermal neutrons. High accumulation and selective delivery of boron into tumor tissue are the most important requirements to achieve efficient neutron capture therapy of cancers. This review focuses on the liposomal boron delivery system (BDS) as a recent promising approach that meets these requirements for BNCT. BDS involves two strategies: (1) encapsulation of boron in the aqueous core of liposomes and (2) accumulation of boron in the liposomal bilayer. Various boronated liposomes have been developed and significant boron accumulation into tumor tissue with high tumor/blood boron ratios has been achieved by BDS.

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

    PubMed

    Ajazuddin; Saraf, S

    2010-10-01

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

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

    PubMed

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

    2016-08-30

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

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

    PubMed

    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.

  16. Targeting Antigens to Dendritic Cell Receptors for Vaccine Development

    PubMed Central

    Apostolopoulos, Vasso; Thalhammer, Theresia; Tzakos, Andreas G.

    2013-01-01

    Dendritic cells (DCs) are highly specialized antigen presenting cells of the immune system which play a key role in regulating immune responses. Depending on the method of antigen delivery, DCs stimulate immune responses or induce tolerance. As a consequence of the dual function of DCs, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. In vaccine development, a major aim is to induce strong, specific T-cell responses. This is achieved by targeting antigen to cell surface molecules on DCs that efficiently channel the antigen into endocytic compartments for loading onto MHC molecules and stimulation of T-cell responses. The most attractive cell surface receptors, expressed on DCs used as targets for antigen delivery for cancer and other diseases, are discussed. PMID:24228179

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

    PubMed

    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. PMID:22306699

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

    PubMed

    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 (P<0.05). The expression peaked on day 5, remained detectable on day 40 and disappeared on day 60. No EGFP expression was detected in the other tissues and organs. The UTMD

  19. New Delivery Systems for Local Anaesthetics—Part 2

    PubMed Central

    Shipton, Edward A.

    2012-01-01

    Part 2 of this paper deals with the techniques for drug delivery of topical and injectable local anaesthetics. The various routes of local anaesthetic delivery (epidural, peripheral, wound catheters, intra-nasal, intra-vesical, intra-articular, intra-osseous) are explored. To enhance transdermal local anaesthetic permeation, additional methods to the use of an eutectic mixture of local anaesthetics and the use of controlled heat can be used. These methods include iontophoresis, electroporation, sonophoresis, and magnetophoresis. The potential clinical uses of topical local anaesthetics are elucidated. Iontophoresis, the active transportation of a drug into the skin using a constant low-voltage direct current is discussed. It is desirable to prolong local anaesthetic blockade by extending its sensory component only. The optimal release and safety of the encapsulated local anaesthetic agents still need to be determined. The use of different delivery systems should provide the clinician with both an extended range and choice in the degree of prolongation of action of each agent. PMID:22190921

  20. Applications of Magnetic Nanoparticles in Targeted Drug Delivery System.

    PubMed

    Mou, Xianbo; Ali, Zeeshan; Li, Song; He, Nongyue

    2015-01-01

    Magnetic nanoparticles (MNPs) are a special kind of nanomaterials and widely used in biomedical technology applications. Currently they are popularly customized for disease detection and treatment, particularly as drug carriers in drug targeted delivery systems, as a therapeutic in hyperthermia (treating tumors with heat), and as contrast agents in magnetic resonance imaging (MRI). Due to their biocompatibility and superparamagnetic properties, MNPs as next generation drug carriers have great attraction. Although the potential benefits of MNPs are considerable, any potential toxicity associated with these MNPs should be identified distinctly. The drug loading capability and the biomedical properties of MNPs generated by different surface coatings are the most sensitive parameters in toxicity. A lot of organic and inorganic materials are utilized as coating materials for surface functionalization and reducing toxicity of MNPs. pH or temperature sensitivity materials are widely used to manage drug loading and targeted release. In addition, MNPs can be controlled and directed to the desired pathological region by using external magnetic files (EMF). The realization of targeted drug delivery has decreased the dosage and improved the efficiency of drugs, which results in reduced side effects to normal tissues. This review discussed the possible organ toxicities of MNPs and their current advances as a drug delivery vehicle. PMID:26328305

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Panapisal, Vipaporn; Charoensri, Sawitree; Tantituvanont, Angkana

    2012-06-01

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

  3. A multi-drug delivery system with sequential release using titania nanotube arrays.

    PubMed

    Aw, Moom Sinn; Addai-Mensah, Jonas; Losic, Dusan

    2012-04-01

    A multi-drug delivery system with sequential release based on titania nanotube arrays and polymer micelles as drug carriers is presented. Delivery of multiple water insoluble and soluble drugs required for combined local therapy is demonstrated.

  4. Supersaturating drug delivery systems: fast is not necessarily good enough.

    PubMed

    Augustijns, Patrick; Brewster, Marcus E

    2012-01-01

    An emerging technology subtype that has been adopted by formulators to address low-solubility issues is the supersaturating drug delivery system; this system is based on the "spring" and "parachute" design elements, which have been applied to lipid-based formulations, S(M)EDDS, solid dispersions, nano-based systems, and many others. This broad formulation approach attempts to delicately balance the need of creating intraluminal drug concentrations in excess of its thermodynamic solubility while at the same time providing for sufficient solution stability to allow for useful drug absorption. The conundrum created is that the higher the extent of supersaturation, the lower the physical stability of the metastable solution based on an increased tendency for a solubilized drug to precipitate. Traditional dissolution testing is a touchstone of formulation development based on the need for useful dissolution rates and drug availability. Dissolution testing is likewise important in the development and characterization of enabling and supersaturating drug delivery systems; however, their execution and interpretation are distinct from that associated with conventional dosage forms. The nature of the dissolution assay (sink versus nonsink, apparatus type, and rate and extent of supersaturation) can impact the ability to efficiently use the dissolution data in the configuration of these enabling formulations.

  5. Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

    PubMed Central

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

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

    PubMed

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

    2012-01-01

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

  8. G2 Autonomous Control for Cryogenic Delivery Systems

    NASA Technical Reports Server (NTRS)

    Dito, Scott J.

    2014-01-01

    The Independent System Health Management-Autonomous Control (ISHM-AC) application development for cryogenic delivery systems is intended to create an expert system that will require minimal operator involvement and ultimately allow for complete autonomy when fueling a space vehicle in the time prior to launch. The G2-Autonomous Control project is the development of a model, simulation, and ultimately a working application that will control and monitor the cryogenic fluid delivery to a rocket for testing purposes. To develop this application, the project is using the programming language/environment Gensym G2. The environment is an all-inclusive application that allows development, testing, modeling, and finally operation of the unique application through graphical and programmatic methods. We have learned G2 through training classes and subsequent application development, and are now in the process of building the application that will soon be used to test on cryogenic loading equipment here at the Kennedy Space Center Cryogenics Test Laboratory (CTL). The G2 ISHM-AC application will bring with it a safer and more efficient propellant loading system for the future launches at Kennedy Space Center and eventually mobile launches from all over the world.

  9. Paclitaxel Nano-Delivery Systems: A Comprehensive Review

    PubMed Central

    Ma, Ping; Mumper, Russell J.

    2013-01-01

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

  10. Reliability review of the remote tool delivery system locomotor

    SciTech Connect

    Chesser, J.B.

    1999-04-01

    The locomotor being built by RedZone Robotics is designed to serve as a remote tool delivery (RID) system for waste retrieval, tank cleaning, viewing, and inspection inside the high-level waste tanks 8D-1 and 8D-2 at West Valley Nuclear Services (WVNS). The RTD systm is to be deployed through a tank riser. The locomotor portion of the RTD system is designed to be inserted into the tank and is to be capable of moving around the tank by supporting itself and moving on the tank internal structural columns. The locomotor will serve as a mounting platform for a dexterous manipulator arm. The complete RTD system consists of the locomotor, dexterous manipulator arm, cameras, lights, cables, hoses, cable/hose management system, power supply, and operator control station.

  11. THE SUPERCONDUCTION MAGNETS OF THE ILC BEAM DELIVERY SYSTEM.

    SciTech Connect

    PARKER,B.; ANEREELA, M.; ESCALLIE, J.; HE, P.; JAIN, A.; MARONE, A.; NOSOCHKOV, Y.; SERYI, A.

    2007-06-25

    The ILC Reference Design Report was completed early in February 2007. The Magnet Systems Group was formed to translate magnetic field requirements into magnet designs and cost estimates for the Reference Design. As presently configured, the ILC will have more than 13,000 magnetic elements of which more than 2300 will be based on superconducting technology. This paper will describe the major superconducting magnet needs for the ILC as presently determined by the Area Systems Groups, responsible for beam line design, working with the Magnet Systems Group. The superconducting magnet components include Main Linac quadrupoles, Positron Source undulators, Damping Ring wigglers, a complex array of Final Focus superconducting elements in the Beam Delivery System, and large superconducting solenoids in the e{sup +} and e{sup -} Sources, and the Ring to Main Linac lines.

  12. Nanotechnology: a focus on nanoparticles as a drug delivery system.

    PubMed

    Kingsley, Jeffrey D; Dou, Huanyu; Morehead, Justin; Rabinow, Barrett; Gendelman, Howard E; Destache, Christopher J

    2006-09-01

    This review will provide an in-depth discussion on the previous development of nanoparticle-based drug delivery systems (DDS) and discuss original research data that includes the therapeutic enhancement of antiretroviral therapy. The use of nanoparticle DDS will allow practitioners to use drugs to target specific areas of the body. In the treatment of malignancies, the use of nanoparticles as a DDS is making measurable treatment impact. Medical imaging will also utilize DDS to illuminate tumors, the brain, or other cellular functions in the body. The utility of nanoparticle DDS to improve human health is potentially enormous.

  13. Activity-based costing for integrated delivery systems.

    PubMed

    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. PMID:8820298

  14. Power Delivery from an Actual Thermoelectric Generation System

    NASA Astrophysics Data System (ADS)

    Kaibe, Hiromasa; Kajihara, Takeshi; Nagano, Kouji; Makino, Kazuya; Hachiuma, Hirokuni; Natsuume, Daisuke

    2014-06-01

    Similar to photovoltaic (PV) and fuel cells, thermoelectric generators (TEGs) supply direct-current (DC) power, essentially requiring DC/alternating current (AC) conversion for delivery as electricity into the grid network. Use of PVs is already well established through power conditioning systems (PCSs) that enable DC/AC conversion with maximum-power-point tracking, which enables commercial use by customers. From the economic, legal, and regulatory perspectives, a commercial PCS for PVs should also be available for TEGs, preferably as is or with just simple adjustment. Herein, we report use of a PV PCS with an actual TEG. The results are analyzed, and proper application for TEGs is proposed.

  15. [Studies on transdermal delivery system of dihydroetorphine hydrochloride].

    PubMed

    Chen, X P; Guo, Q D; Shi, T S

    1996-01-01

    A transdermal delivery system of dihydroetorphine hydrochloride (DHE-TDS) was developed. The DHE-TDS mainly composed of polyvinyl alcohol, polyvinyl pyrrolidone and lactose. Tests on rabbits showed only slight skin irritation according to federal hazardous substances act. By giving DHE-TDS to rabbits, DHE release was shown to be governed by first-order mechanism. When DHE-TDS was given to Wistar rats, a relatively stable blood drug concentration was observed from 4-32 h after drug administration. Writhing tests showed that one dose of DHE-TDS would maintain the narcotic action on rats for at least 48 h.

  16. Demonstrations of alternative delivery systems under Medicare and Medicaid.

    PubMed

    Galblum, T W; Trieger, S

    1982-03-01

    The current Administration supports competition as one method of helping to contain escalating costs. Proponents of competition claim many advantages to its implementation, but their claims have yet to be widely tested. Over the past several years, however, the Health Care Financing Administration has supported a number of Medicare and Medicaid demonstrations to yield information on plan participation, marketing, and reimbursement under alternative delivery systems. Much of these data are applicable to the competitive plans being considered by the Administration and Congress. This paper discusses recent findings from these projects.

  17. Activity-based costing for integrated delivery systems.

    PubMed

    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. The Superconducting Magnets of the ILC Beam Delivery System

    SciTech Connect

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

    2007-09-28

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

  19. Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

    PubMed

    Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Herrmann, Paulo S P; Araújo-Moreira, Fernando M; García-Hernández, Mar; Ruiz-Hitzky, Eduardo

    2014-12-30

    New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays.

  20. Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

    PubMed

    Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Herrmann, Paulo S P; Araújo-Moreira, Fernando M; García-Hernández, Mar; Ruiz-Hitzky, Eduardo

    2014-12-30

    New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays. PMID:25455784

  1. Delivery of Probiotics in the Space Food System

    NASA Technical Reports Server (NTRS)

    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 [1]. 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 [2-5]. 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. Delivery of Probiotics in the Space Food System

    NASA Technical Reports Server (NTRS)

    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.

  3. A Universal Delivery System for Percutaneous Heart Valve Implantation.

    PubMed

    Bartosch, Marco; Peters, Heiner; Spriestersbach, Hendrik; O H-Ici, Darach; Berger, Felix; Schmitt, Boris

    2016-09-01

    Transcatheter heart valve implantation is an emerging technology and an alternative to surgical valve replacement. Most existing systems consist of valves sewn into balloon-expandable stents with a delivery catheter functioning with the specific valve only. The aim of this study was to develop a universally applicable delivery system (DS) for plane stents, valves sewn into both balloon-expandable and self-expandable stents and feasible for use with different access routes. A DS was designed and manufactured in five different diameters. The requirements were derived from the implants, the implantation technique and the cardiovascular geometry of the experimental sheep. The combination of a self-expandable Nitinol stent and a jugular access point represented the major challenge as both flexibility and rigidity of the DS were required. To fulfill these contradicting mechanical properties the sheaths were comprised of a soft outer polymer tube with a stainless steel coiled spring inside. Tissue-engineered and pericardial pulmonary valves were implanted. Also polymeric and balloon-expandable stents were delivered to various positions in the vascular system. The initial success rate was 70.5%. After refinement of the DS, a success rate of 83.3% was achieved with the remaining failed implantations resulting from inadequate sizes of the prostheses. PMID:26864537

  4. Developing system for delivery of optical radiation in medicobiological researches

    NASA Astrophysics Data System (ADS)

    Loschenov, Victor B.; Taraz, Majid

    2004-06-01

    Methods of optical diagnostics and methods of photodynamic therapy are actively used in medico-biological researches. The system for delivery of optical radiation is one of the key methods in these researches. Usually these systems use flexible optical fibers with diameters from 200 to 1000 micron. Two types of systems for delivery are subdivided, first for diagnostic researches, second for therapeutic procedures. Existing diagnostic catheters, which have most widely applied in medicine, have bifurcated with diameter of the tip equal 1.8 mm. These devices, which are called fiber-optical catheters, satisfy the majority endoscopes researches. However, till now the problem of optical-diagnostics inside tissue is not soled. Especially it is important at diagnostics of a mammary gland, livers, thyroid glands tumor, tumor of a brain and some other studies connected with punctures. In these cases, it is necessary that diameter of fiber-optical catheters be less than one millimeter. This work is devoted to the development of these catheters. Also in clinical procedures such as photodynamic therapy (PDT) and interstitial laser photocoagulation (ILP), cylindrical light diffusing tips are rapidly becoming a popular device for the administration of the desired light dose for the illumination of hollow organs, such as bronchus, trachea and oesophagus. This work is devoted to the development of these catheters.

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

    PubMed

    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. PMID:22585045

  6. Demonstrated delivery/employment systems for unattended ground sensors

    NASA Astrophysics Data System (ADS)

    Taylor, Robert R.; Bendowski, Michael A.; McFeaters, Ryan C.

    1997-07-01

    This paper describes the payload delivery system developed and proven to deploy an electronic warfare device to specific, predetermined locations on the battlefield. Initially called the Artillery Delivered Expendable Jammer (AD/EXJAM), it is now designated the Air Delivered-Ground (Deployed) Expendable Jammer (AD-G/EXJAM). The initial units were demonstrated from 155 MM artillery; the later units, from UAV's, helicopters and slow moving, fixed wing aircraft. While these two delivery systems were originally designed specifically for the EXJAM system, the concept is directly applicable to unattended ground sensors that require unmanned remote emplacement. Keys to the success of the jammer included design, development and field testing of power supplies, antennas, deployment systems and packaging to allow payloads to withstand high-g impact and other severe environments typically encountered. The artillery deployed systems were designed to be `wooden' rounds needing no special handling and storing. These systems treat the payload as independent elements which are self-ejected from a fired M483A1 or M864 round and are completely automatic upon hitting the ground. The more recent payloads can be delivered from UAV's and include remote control capabilities, increased operating life and increased power output. The present payload is packaged into a cylindrical shape, approximately six inches in diameter and 6.5 inches long and are contained within a carrier, attached to an Unmanned Air Vehicle (UAV) or any other air vehicle. Upon reaching the dispensing point, the release command can be issue by either the UAV or a separate ground control unit in RF contact with the carrier. The carrier then begins a timed dispensing sequence that has been selected for optimum payload emplacement in the target area. New developments include a design and subsystem demonstration of a tactical munitions dispenser variant of the deployment system. Operational characteristics of any specific

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

    PubMed

    Ling, Hui

    2016-01-01

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

  8. Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs

    PubMed Central

    2015-01-01

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

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

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

    2015-01-01

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

  12. A novel liquid effervescent floating delivery system for sustained drug delivery.

    PubMed

    Ibrahim, H K

    2009-08-01

    An effervescent floating liquid formulation with in situ gelling properties has been assessed for its potential for sustaining drug delivery and targeting. The formulation consisted of sodium alginate and glyceryl monooleate (GMO). The developed formulation met all pre-requisites to become an in situ gelling floating system and it gelled and floated instantaneously in the pH conditions of the stomach. Moreover, the gels formed in situ remained intact for more than 48 h to facilitate sustained release of drugs. Increasing the mannuronic acid ratio of sodium alginate and the GMO concentration significantly retarded the release rate and extent. The in vitro release of both hydrophilic and hydrophobic drugs from the prepared formulations followed root-time kinetics during the sustained release period. Replacing the free drug with drug encapsulated microspheres enabled tailoring of the release profile and achieved zero-order release kinetics. The system retained its appearance and rheological properties for 12 months at ambient conditions. The values of the similarity factor Sd proved the absence of any significant difference in the release profile upon storage.

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

    PubMed

    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.

  14. Diagnosing delivery problems in the White House Information Distribution System

    SciTech Connect

    Nahabedian, M.; Shrobe, H.

    1996-12-31

    As part of a collaboration with the White House Office of Media Affairs, members of the MIT Artificial Intelligence Laboratory designed a system, called COMLINK, which distributes a daily stream of documents released by the Office of Media Affairs. Approximately 4000 direct subscribers receive information from this service but more than 100,000 people receive the information through redistribution channels. The information is distributed via Email and the World Wide Web. In such a large scale distribution scheme, there is a constant problem of subscriptions becoming invalid because the user`s Email account has terminated. This causes a backwash of hundreds of {open_quotes}bounced mail{close_quotes} messages per day which must be processed by the operators of the COMLINK system. To manage this annoying but necessary task, an expert system named BMES was developed to diagnose the failures of information delivery.

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

    PubMed

    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. PMID:22097584

  16. Noble gas storage and delivery system for ion propulsion

    NASA Technical Reports Server (NTRS)

    Back, Dwight Douglas (Inventor); Ramos, Charlie (Inventor)

    2001-01-01

    A method and system for storing and delivering a noble gas for an ion propulsion system where an adsorbent bearing a noble gas is heated within a storage vessel to desorb the noble gas which is then flowed through a pressure reduction device to a thruster assembly. The pressure and flow is controlled using a flow restrictor and low wattage heater which heats an adsorbent bed containing the noble gas propellant at low pressures. Flow rates of 5-60 sccm can be controlled to within about 0.5% or less and the required input power is generally less than 50 W. This noble gas storage and delivery system and method can be used for earth orbit satellites, and lunar or planetary space missions.

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

    PubMed

    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.

  18. Intranasal immunization of mice with CpG DNA induces strong systemic and mucosal responses that are influenced by other mucosal adjuvants and antigen distribution.

    PubMed Central

    McCluskie, M. J.; Weeratna, R. D.; Davis, H. L.

    2000-01-01

    BACKGROUND: Synthetic oligodeoxynucleotides (ODN) containing immunostimulatory cytosine-guanine phosphate-linked dinucleotide (CpG) motifs are potent systemic and mucosal adjuvants in mice that have synergistic action with numerous other adjuvants, including alum and cholera toxin (CT). Herein, we evaluate CpG ODN with intranasal (IN) delivery of purified hepatitis B surface antigen (HBsAg), relative to and in combination with CT, Escherichia coli heat labile enterotoxin (LT), the B subunit of CT (CTB), and a nontoxic derivative of LT (LTK63). MATERIALS AND METHODS: BALB/c mice were immunized by IN administration of HBsAg, alone or combined with CT, LT, CTB, or LTK63, and/or CpG ODN, or non-CpG control ODN. In addition, the effect of low-or high-volume administration was assessed, in order to target upper respiratory or entire respiratory tract, respectively. HBsAg-specific systemic (immunoglobulins: IgG, IgG1, IgG2a in plasma) and mucosal (IgA in fecal, lung, vaginal, saliva, and gut samples) humoral responses, as well as cell-mediated immune responses including T-cell proliferation and cytokines (interleukins: IL-4, IL-5; interferon: IFN-gamma) were evaluated. RESULTS: CpG ODN, CT, and LT augmented anti-HBs titers equally, and more so than did CTB or LTK63. CpG ODN acted synergistically with CT and LT, but not CTB or LTK63 to enhance anti-HBs titers. Nevertheless, CpG ODN induced a more Th1-like response for all combinations, compared with the same formulation without CpG. Strength of induced systemic and mucosal immune responses was better with IN delivery of a large volume. A small volume required multiple administrations and higher doses of antigen and adjuvant for equal results. This suggests that delivery of antigen to the lung and/or diges-tive system is superior to delivery to the nasal cavity. CONCLUSIONS: Our results suggest that the synergy between CpG ODN and native toxins (CT, LT) may depend on their enzymatic activity and that the lack of synergy

  19. Niosomes as Nano-Delivery Systems in the Pharmaceutical Field.

    PubMed

    Cerqueira-Coutinho, Cristal; Dos Santos, Elisabete P; Mansur, Claudia Regina E

    2016-01-01

    Nanosystems used in the pharmaceutical field aim to guarantee a controlled release and efficacy boost with dose reduction of the drug. The same active ingredient could be vehiculated in different concentrations in distinct nanosystems. Among these nanostructures, the vesicular ones present a versatile delivery system that could be applied to encapsulate lipophilic, amphiphilic, and hydrophilic compounds. Liposomes are the most well-known vesicular nanosystems; however, there are others, such as niosomes, that are composed of nonionic surfactants that are polymeric or conventional. Niosomes could be prepared using the thin film hydration method, in which the active ingredient is solubilized in organic solvent with the surfactant or in aqueous solution depending on its polarity. In addition, co-surfactants could be used to improve stabilization and vesicle integrity because they occupy regions in the interface where the mainly surfactant could not reach. Vesicular nanosystems could be characterized by different techniques, such as microscopy, dynamic light scattering, nuclear magnetic resonance, and others. These nanostructures could be applied to drugs (administered by different routes) or to gene and cosmetic delivery systems. PMID:27651102

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

    PubMed

    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. PMID:27375781

  1. Nanostructured lipid carriers: Promising drug delivery systems for future clinics.

    PubMed

    Beloqui, Ana; Solinís, María Ángeles; Rodríguez-Gascón, Alicia; Almeida, António J; Préat, Véronique

    2016-01-01

    During the past decade, the number of studies describing nanostructured lipid carriers (NLCs)-based formulations has been dramatically increased. The raise in NLC exploitation is essentially due to defeated barriers within the technological process of lipid-based nanoparticles' formulation and increased knowledge of the underlying mechanisms of transport of NLCs via different routes of administration. This review article aims to give an overview on the current state of the art of NLC as controlled drug delivery systems for future clinics through novel NLC applications providing examples of successfull outcomes. The reported data clearly illustrate the promise of these nanoparticles for novel treatments in the near future. From the Clinical Editor: The understanding of the nanostructured lipid carriers (NLC)-based formulations has improved with continuing research recently. The result has seen an increase in the use of these in the clinical setting. In this comprehensive review, the authors discussed the current state and major challenges in the use of nanostructured lipid carriers as controlled drug delivery systems. PMID:26410277

  2. Cubic and hexagonal liquid crystals as drug delivery systems.

    PubMed

    Chen, Yulin; Ma, Ping; Gui, Shuangying

    2014-01-01

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

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

    PubMed

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

    2011-08-01

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

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

    PubMed Central

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

    2011-01-01

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

  5. Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems

    PubMed Central

    Chen, Yulin; Ma, Ping; Gui, Shuangying

    2014-01-01

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

  6. Regulatory considerations on new adjuvants and delivery systems.

    PubMed

    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.

  7. The Smart Drug Delivery System and Its Clinical Potential

    PubMed Central

    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. PMID:27375781

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

    PubMed

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

    2015-12-28

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

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

    PubMed

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

    2014-01-01

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

  10. Design of a Multiple Drug Delivery System Directed at Periodontitis

    PubMed Central

    Sundararaj, Sharath C.; Thomas, Mark V.; Peyyala, Rebecca; Dziubla, Thomas D.; Puleo, David A.

    2013-01-01

    Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions. PMID:23948165

  11. Microparticulate based topical delivery system of clobetasol propionate.

    PubMed

    Badıllı, Ulya; Sen, Tangül; Tarımcı, Nilüfer

    2011-09-01

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

  12. Transdermal evaporation delivery system of praziquantel for schistosomiasis japonicum chemotherapy.

    PubMed

    Wang, Lei; Zheng, Xinsheng; Fang, Yan; Wang, Yi; Duan, Cunzheng; Yao, Baoan

    2011-07-01

    A transdermal evaporation delivery system (TEDS) of praziquantel (PZQ) was developed by selecting ethylene glycol monophenyl ether as a nonvolatile component solvent and ethanol as a volatile component solvent to control efficiently the transmission and morbidity of the global schistosomiasis, providing a convenient administration system of PZQ for both humans and domestic animals. The solubility of PZQ in TEDS was more than 400 mg/mL when the ethanol concentration was 50% (w/w) in the solvent mixture at 32 °C, enabling to adapt requirements for the treatment of schistosomiasis. The highest serum drug concentration reached 35.93 µg/mL after transdermal administration of TEDS of PZQ in rabbits, being 6.3-fold higher than that after oral administration at the same dose. The TEDS of PZQ achieved treatment efficacy with the worm reduction of 100% when it was applied in the experimental treatment of Schistosoma japonicum in rabbits. The TEDS of PZQ that provides passive and nonocclusive delivery, having the inexpensive cost, low skin irritation rates, and precise dose of administration, should find application in the transmission control and chemotherapy of global schistosomiasis.

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

    PubMed

    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.

  14. Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study

    SciTech Connect

    Lee, Don Haeng; Kang, Sung-Gwon Jeong, Seok; Yoon, Chang Jin; Choi, Jung-Ah; Byun, Ju Nam; Park, Jae Hyung; Lee, Kyu Back

    2006-10-15

    The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model.

  15. Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety

    PubMed Central

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

    2010-01-01

    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 < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered 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. PMID:20297904

  16. Preparing a health care delivery system for Space Station

    NASA Technical Reports Server (NTRS)

    Logan, J. S.; Stewart, G. R.

    1985-01-01

    NASA's Space Station is viewed as the beginning of man's permanent presence in space. This paper presents the guidelines being developed by NASA's medical community in preparing a quality, permanent health care delivery system for Space Station. The guidelines will be driven by unique Space Station requirements such as mission duration, crew size, orbit altitude and inclination, EVA frequency and rescue capability. The approach will emphasize developing a health care system that is modular and flexible. It will also incorporate NASA's requirements for growth capability, commonality, maintainability, and advanced technology development. Goals include preventing unnecessary rescue attempts, as well as maintaining the health and safety of the crew. Proper planning will determine the levels of prevention, diagnosis, and treatment necessary to achieve these goals.

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

    PubMed

    Masood, Farha

    2016-03-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    Masood, Farha

    2016-03-01

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

  20. Micelle-Based Adjuvants for Subunit Vaccine Delivery

    PubMed Central

    Trimaille, Thomas; Verrier, Bernard

    2015-01-01

    In the development of subunit vaccines with purified or recombinant antigens for cancer and infectious diseases, the design of improved and safe adjuvants able to efficiently target the antigen presenting cells, such as dendritic cells, represents a crucial challenge. Nanoparticle-based antigen delivery systems have been identified as an innovative strategy to improve the efficacy of subunit vaccines. Among them, self-assembled micellar nanoparticles from amphiphilic (macro)molecules have recently emerged as promising candidates. In this short review, we report on the recent research findings highlighting the versatility and potential of such systems in vaccine delivery. PMID:26426060