Kingsman, A J; Burns, N R; Layton, G T; Adams, S E
The development of technologies to produce recombinant proteins for use in the pharmaceutical industry has made substantial advances, in particular in the area of generating antigens containing multiple copies of important immunological regions. One such antigen-carrier system is based on the ability of a protein encoded by the yeast retrotransposon, Ty, to self-assemble into virus-like particles. Ty-fusion proteins retain this ability to form particles, and a range of hybrid VLPs carrying a variety of heterologous antigens have been produced and shown to induce potent immune responses. In particular, hybrid VLPs carrying the core protein p24 of HIV (p24-VLPs) have been shown to induce antibody and T-cell proliferative responses in both experimental animals and human volunteers, and immunization of rabbits with VLPs carrying the principal neutralizing determinant of HIV (V3-VLPs) resulted in the induction of neutralizing antibody responses and T-cell proliferation. Further studies with V3-VLPs have shown that this particulate antigen stimulates enhanced V3-specific lymphoproliferative responses as compared to whole recombinant gp120 or to V3 peptide conjugated to albumin. The V3-VLPs also induce potent CTL responses following immunization of mice in the absence of adjuvant. These responses are MHC class I restricted and are mediated by CD8-positive cells. These observations therefore demonstrate that hybrid Ty-VLPs induce both humoral and cellular immune responses against HIV and suggest that these immunogens may be important in combatting AIDS and other infections. PMID:7625653
Wu, Fang; Wuensch, Sherry A.; Azadniv, Mitra; Ebrahimkhani, Mohammad R.; Crispe, I. Nicholas
We aim to define the role of Kupffer cells in intrahepatic antigen presentation, using the selective delivery of antigen to Kupffer cells rather than other populations of liver antigen-presenting cells. To achieve this we developed a novel antigen delivery system that can target antigens to macrophages, based on a galactosylated low-density lipoprotein nano-scale platform. Antigen was delivered via the galactose particle receptor (GPr), internalized, degraded and presented to T cells. The con...
Wu, Fang; Wuensch, Sherry A; Azadniv, Mitra; Ebrahimkhani, Mohammad R; Crispe, I Nicholas
We aim to define the role of Kupffer cells in intrahepatic antigen presentation, using the selective delivery of antigen to Kupffer cells rather than other populations of liver antigen-presenting cells. To achieve this we developed a novel antigen delivery system that can target antigens to macrophages, based on a galactosylated low-density lipoprotein nanoscale platform. Antigen was delivered via the galactose particle receptor (GPr), internalized, degraded and presented to T cells. The conjugation of fluoresceinated ovalbumin (FLUO-OVA) and lactobionic acid with LDL resulted in a substantially increased uptake of FLUO-OVA by murine macrophage-like ANA1 cells in preference to NIH3T3 cells, and by primary peritoneal macrophages in preference to primary hepatic stellate cells. Such preferential uptake led to enhanced proliferation of OVA specific T cells, showing that the galactosylated LDL nanoscale platform is a successful antigen carrier, targeting antigen to macrophages but not to all categories of antigen presenting cells. This system will allow targeted delivery of antigen to macrophages in the liver and elsewhere, addressing the question of the role of Kupffer cells in liver immunology. It may also be an effective way of delivering drugs or vaccines directly at macrophages. PMID:19637876
Amidi, M.; Mastrobattista, E.; Jiskoot, W.; Hennink, W.E.
Therapeutic peptides/proteins and protein-based antigens are chemically and structurally labile compounds, which are almost exclusively administered by parenteral injections. Recently, non-invasive mucosal routes have attracted interest for administration of these biotherapeutics. Chitosan-based del
Full Text Available Lactic acid bacteria (LAB are Gram-positive bacteria and are generally regarded as safe (GRAS organisms. Therefore, LAB could be used for heterologous protein secretion and they are good potential candidates as antigen delivery vehicles. To develop such live vaccines, a better control of protein secretion is required. We developed an efficient secretion system in the model LAB, Lactococcus lactis. Staphylococcal nuclease (Nuc was used as the reporter protein. We first observed that the quantity of secreted Nuc correlated with the copy number of the cloning vector. The nuc gene was cloned on a high-copy number cloning vector and no perturbation of the metabolism of the secreting strain was observed. Replacement of nuc native promoter by a strong lactococcal one led to a significant increase of nuc expression. Secretion efficiency (SE of Nuc in L. lactis was low, i.e., only 60% of the synthesized Nuc was secreted. Insertion of a synthetic propeptide between the signal peptide and the mature moiety of Nuc increased the SE of Nuc. On the basis of these results, we developed a secretion system and we applied it to the construction of an L. lactis strain which secretes a bovine coronavirus (BCV epitope-protein fusion (BCV-Nuc. BCV-Nuc was recognized by both anti-BCV and anti-Nuc antibodies. Secretion of this antigenic fusion is the first step towards the development of a novel antigen delivery system based on LAB-secreting strains.
Mohammadpour Dounighi, N.
Full Text Available In recent years, chitosan nanoparticles have been studied widely for protein delivery. In this study, Hemiscorpius lepturus (HL venom was encapsulated in chitosan nanoparticles. The aim of the present work was to carry out a systematic study for preparing biocompatible and biodegradable nanoparticles for loading HL scorpion venom and to evaluate their potential as an antigen delivery system. In this study, HL venom loaded chitosan nanoparticles fabricated by ionic gelation of chitosan and tripolyphosphate and the factors which may be influenced in the preparation of nanoparticles were analyzed. Also, their physicochemical properties and in vitro release behavior were studied. The optimum encapsulation efficiency and capacity were observed when the chitosan concentration and HL venom were 2mg/ml and 500µg/ml, respectively. The HL venom loaded nanoparticles were in the size range of 130-160nm (polydispersity index values of 0.423 and exhibited the positive zeta potential. Transmission electron microscope imaging showed spherical and smooth surface of nanoparticles. The profiles of the release exhibited a burst releases about 50% in the first 4 hr and then slowed down at a constant rate. The obtained results suggested that the chitosan nanoparticles prepared in this work had the potential for antigen delivery.
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
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
Hu, Yun; Ehrich, Marion; Fuhrman, Kristel; Zhang, Chenming
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.
Berezin, V E; Bogoyavlenskiy, A P; Tolmacheva, V P; Makhmudova, N R; Khudyakova, S S; Levandovskaya, S V; Omirtaeva, E S; Zaitceva, I A; Tustikbaeva, G B; Ermakova, O S; Aleksyuk, P G; Barfield, R C; Danforth, H D; Fetterer, R H
Immunostimulating complexes (ISCOMs) are unique, multimolecular structures formed by encapsulating antigens, lipids, and triterpene saponins of plant origin, and are an effective delivery system for various kinds of antigens. The uses of ISCOMs formulated with saponins from plants collected in Kazakhstan, with antigens from the poultry coccidian parasite Eimeria tenella, were evaluated for their potential use in developing a vaccine for control of avian coccidiosis. Saponins isolated from the plants Aesculus hippocastanum and Glycyrrhiza glabra were partially purified by HPLC. The saponin fractions obtained from HPLC were evaluated for toxicity in chickens and chicken embryos. The HPLC saponin fractions with the least toxicity, compared to a commercial saponin Quil A, were used to assemble ISCOMs. When chicks were immunized with ISCOMs prepared with saponins from Kazakhstan plants and E. tenella antigens, and then challenged with E. tenella oocysts, significant protection was conveyed compared to immunization with antigen alone. The results of this study indicate that ISCOMs formulated with saponins isolated from plants indigenous to Kazakhstan are an effective antigen delivery system which may be successfully used, with low toxicity, for preparation of highly immunogenic coccidia vaccine. PMID:18564738
Full Text Available Yeasts are largely used as bioreactors for vaccine production. Usually, antigens are produced in yeast then purified and mixed with adjuvants before immunization. However, the purification costs and the safety concerns recently raised by the use of new adjuvants argue for alternative strategies. To this end, the use of whole yeast as both production and delivery system appears attractive. Here, we evaluated Pichia pastoris yeast as an alternative vaccine production and delivery system for the circumsporozoite protein (CS of Plasmodium, the etiologic agent of malaria. The CS protein from Plasmodium berghei (Pb was selected given the availability of the stringent C57Bl/6 mouse model of infection by Pb sporozoites, allowing the evaluation of vaccine efficacy in vivo. PbCS was multimerized by fusion to the measles virus (MV nucleoprotein (N known to auto-assemble in yeast in large-size ribonucleoprotein rods (RNPs. Expressed in P. pastoris, the N-PbCS protein generated highly multimeric and heterogenic RNPs bearing PbCS on their surface. Electron microscopy and immunofluorescence analyses revealed the shape of these RNPs and their localization in peripheral cytoplasmic inclusions. Subcutaneous immunization of C57Bl/6 mice with heat-inactivated whole P. pastoris expressing N-PbCS RNPs provided significant reduction of parasitemia after intradermal challenge with a high dose of parasites. Thus, in the absence of accessory adjuvants, a very low amount of PbCS expressed in whole yeast significantly decreased clinical damages associated with Pb infection in a highly stringent challenge model, providing a proof of concept of the intrinsic adjuvancy of this vaccine strategy. In addition to PbCS multimerization, the N protein contributed by itself to parasitemia delay and long-term mice survival. In the future, mixtures of whole recombinant yeasts expressing relevant Plasmodium antigens would provide a multivalent formulation applicable for antigen
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
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
Full Text Available Jacqueline Montanaro,1 Aleksandra Inic-Kanada,1 Angela Ladurner,1 Elisabeth Stein,1 Sandra Belij,1 Nora Bintner,1 Simone Schlacher,1 Nadine Schuerer,1 Ulrike Beate Mayr,2 Werner Lubitz,2 Nikolaus Leisch,3 Talin Barisani-Asenbauer11Laura Bassi Centres of Expertise, OCUVAC – Centre of Ocular Inflammation and Infection, Centre for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria; 2BIRD-C GmbH & Co KG, Kritzendorf, Austria; 3Department of Ecogenomics and Systems Biology, University of Vienna, Vienna, AustriaAbstract: 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
Full Text Available BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice. METHODOLOGY/PRINCIPAL FINDINGS: Promoters (nirB or pagC were used to express the antigen (Sj23LHDGST and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104-Sj23LHD-GST efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69. CONCLUSION/SIGNIFICANCE: Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.
textabstractMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (eNS) that affects eNS myelin which isolates nerve axons and allows saltatory pulse conduction. It is the most important chronic disabling neurological disease in young adults, with a mean age of onset around 30 years. It has a prevalence of approximately I per 1000 in Western European countries and it affects women versus men at a ratio of 1.5 to I (Sadovnick and Ebers, 1993). Although the cau...
Hotz, Christian; Fensterle, Joachim; Goebel, Werner; Meyer, Susanne R; Kirchgraber, Gabriel; Heisig, Martin; Fürer, Andreas; Dietrich, Guido; Rapp, Ulf R; Gentschev, Ivaylo
The attenuated Salmonella enterica serovar Typhi strain Ty21a (Ty21a) is the only attenuated live oral vaccine against typhoid fever. Ty21a is also an attractive carrier for the delivery of heterologous antigens. We have used Ty21a for antigen delivery via the hemolysin (HlyA) secretion system of Escherichia coli, the prototype of the type I secretion system (T1SS). In this study, we identified by genetic complementation that the specific mutation of rpoS correlated with the hemolysin production of strain Ty21a. We furthermore showed that complementation with a plasmid encoding rfaH, which is described to be a downstream target of rpoS, led to increased expression and secretion of hemolysin. Finally, we demonstrated a significant enhancement of antibody responses against the heterologous HlyA antigen of Ty21a after immunization of mice with rfaH complemented S. typhi strain secreting HlyA compared with the same strain without rfaH plasmid. PMID:18706861
Kim, Sae-Hae; Lee, Ha-Yan; Jang, Yong-Suk
Application of vaccine materials through oral mucosal route confers great economical advantage in animal farming industry due to much less vaccination cost compared with that of injection-based vaccination. In particular, oral administration of recombinant protein antigen against foot-and-mouth disease virus (FMDV) is an ideal strategy because it is safe from FMDV transmission during vaccine production and can induce antigen-specific immune response in mucosal compartments, where FMDV infecti...
Huang, Qingrui; Yu, Weili; Hu, Tao
Protein-based vaccine is promising to improve or replace Mycobacterium bovis BCG vaccine for its specificity, safety, and easy production. However, protein-based vaccine calls for potent adjuvants and improved delivery systems to protect against Mycobacterium tuberculosis. Poly(I:C) is one of the most potent pathogen-associated molecular patterns that signals primarily via TLR3. Arabinogalactan (AG) is a biocompatible polysaccharide that can increase splenocyte proliferation and stimulate macrophages. The AG-poly(I:C) conjugate (AG-P) showed an adjuvant potency through a synergistic interaction of AG and poly(I:C). Ag85B and HspX are two important virulent protein antigens of Mycobacterium tuberculosis and Ag85B-HspX fusion protein (AH) was prepared. An antigen-adjuvant delivery system (AH-AG-P) was developed by conjugation of AH with AG-P to ensure that both AH and AG-P reach the APCs simultaneously. AH-AG-P elicited high AH-specific IgG titers and stimulated lymphocyte proliferation. AH-AG-P provoked the secretion of Th1-type cytokines (TNF-α, IFN-γ, and IL-2) and Th2-type cytokines (IL-4 and IL-10). Pharmacokinetics revealed that conjugation with AG-P could prolong the serum exposure of AH to the immune system. Pharmacodynamics suggested that conjugation with AG-P led to a rapid and intense production of AH-specific IgG. Accordingly, conjugation with AG-P could promote a robust cellular and humoral immune response to AH. Thus, conjugation of AH with a potent adjuvant AG-P is an effective strategy to develop an efficacious protein-based vaccine against Mycobacterium tuberculosis. PMID:27002920
Gentschev, Ivaylo; Dietrich, Guido; Spreng, Simone; Neuhaus, Beatrice; Maier, Elke; Benz, Roland; Goebel, Werner; Fensterle, Joachim; Rapp, Ulf R
This study examined the suitability of the hemolysin secretion system of Escherichia coli for expression and delivery of alpha-hemolysin (HlyA) by the S. typhi Ty21a strain, the only live oral Salmonella vaccine strain licensed for human use, under in vitro and in vivo conditions. For this purpose, two plasmid vectors encoding either the whole alpha-hemolysin of E. coli (pANN202-812/pMOhly2) or the hemolysin secretion signal (pMOhly1) were transferred into S. typhi Ty21a. S. typhi Ty21a carrying pANN202-812/pMOhly2 revealed efficient secretion of hemolysin in vitro. After formulation according to a process suitable for commercial production of Salmonella-based live bacterial vaccines, plasmids were shown to be stable in Ty21a and hemolysin secretion was demonstrated even after storage of the strains under real-time and stress conditions. After intranasal immunization of mice with S. typhi Ty21a/pANN202-812 plasmids are stable in vivo, and immunization induced a profound immune response against the heterologous HlyA antigen. Therefore, the combination of the hemolysin secretion system and S. typhi Ty21a could form the basis for a new generation of live bacterial vaccines. PMID:15595386
Full Text Available The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases.
Sarkar Biresh K; Jain Devananda; Banerjee Angshu
Incorporating an existing medicine into a new drug delivery system can significantly improve its performance in terms of efficacy, safety, and improved patient compliance. The need for delivering drugs to patients efficiently and with fewer side effects has prompted pharmaceutical companies to engage in the development of new drug delivery systems. Today, drug delivery companies are engaged in the development of multiple platform technologies for controlled release, delivery of large molecule...
Sarkar Biresh K
Full Text Available Incorporating an existing medicine into a new drug delivery system can significantly improve its performance in terms of efficacy, safety, and improved patient compliance. The need for delivering drugs to patients efficiently and with fewer side effects has prompted pharmaceutical companies to engage in the development of new drug delivery systems. Today, drug delivery companies are engaged in the development of multiple platform technologies for controlled release, delivery of large molecules, liposome, taste-masking, oral fast- dispersing dosage forms, technology for in- soluble drugs, and delivery of drugs through intranasal, pulmonary, transdermal, vaginal, colon, and transmucosal routes.
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...
As business environments become increasingly competitive, companies seek more comprehensive solutions to the delivery of their projects. "Project Delivery System: Fourth Edition" describes the process-driven project delivery systems which incorporates the best practices from Total Quality and is aligned with the Project Management Institute and ISO Quality Standards is the means by which projects are consistently and efficiently planned, executed and completed to the satisfaction of clients and customers.
Stevens, F; Zee, J. van der
A health care delivery system is the organized response of a society to the health problems of its inhabitants. Societies choose from alternative health care delivery models and, in doing so, they organize and set goals and priorities in such a way that the actions of different actors are effective, meaningful, and socially accepted. From a sociological point of view, the analysis of health care delivery systems implies recognition of their distinct history over time, their specific values an...
Stevens, F.; Zee, J. van der
A health care delivery system is the organized response of a society to the health problems of its inhabitants. Societies choose from alternative health care delivery models and, in doing so, they organize and set goals and priorities in such a way that the actions of different actors are effective,
Gentschev, Ivaylo; Spreng, Simone; Sieber, Heike; Ures, Jose; Mollet, Fabian; Collioud, Andre; Pearman, Jon; Griot-Wenk, Monika E; Fensterle, Joachim; Rapp, Ulf R; Goebel, Werner; Rothen, Simon A; Dietrich, Guido
The attenuated Salmonella typhi strain Ty21a is the main constituent of Vivotif, the only attenuated live oral vaccine against typhoid fever. In comparison with antibiotics, the 'magic bullets' which Paul Ehrlich was striving for to treat infectious diseases, this vaccine should be viewed as a 'magic shield', because rather than treating typhoid fever after the infection has started, immunisation with this vaccine strain prevents infection and disease by the induction of specific immune responses. Ty21a is also an attractive carrier for the delivery of heterologous antigens. Recently, we successfully used Ty21a for antigen delivery via the haemolysin secretion system of Escherichia coli, which allows efficient protein secretion from the carrier bacteria. PMID:17347563
Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma
Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...
An antigen is any substance that causes your immune system to produce antibodies against it. This means your immune ... and is trying to fight it off. An antigen may be a substance from the environment, such ...
Flanary, Suzanne; Hoffman, Allan S.; Stayton, Patrick S.
While many infectious diseases are controlled by vaccine strategies, important limitations continue to motivate the development of better antigen delivery systems. This study focuses on the use of a pH-sensitive polymeric carrier based on poly(propylacrylic acid) (PPAA) to address the need for more potent CD8 cytotoxic T-cell (CTL) responses. An MHC-1/CD8 CTL cell model system with ovalbumin as the protein antigen was used to test whether PPAA could enhance the delivery of ovalbumin into the ...
Patel, P. K.
The future of pharmaceutical industry is now shifting from new drug research to novel drug delivery systems. Biopharmaceuticals present challenges because of their unique nature and difficulty in delivery through conventional routes. These challenges inspire for the invention of new medical grade polymers for novel drug delivery systems. Polymeric drug delivery systems bring a true benefit over glass. Polymer provide improved robustness against breakability and better ergonomy, while deliveri...
Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.
Kim, Sung Wan
Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16243067
Full Text Available Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal.
J.J. García-Vallejo; M. Ambrosini; A. Overbeek; W.E. van Riel; K. Bloem; W.W.J. Unger; F. Chiodo; J.G. Bolscher; K. Nazmi; H. Kalay; Y. van Kooyk
Dendritic cells are the most powerful type of antigen presenting cells. Current immunotherapies targeting dendritic cells have shown a relative degree of success but still require further improvement. One of the most important issues to solve is the efficiency of antigen delivery to dendritic cells
Prokop, Ales; Davidson, Jeffrey M
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
Allahyari, Mojgan; Mohit, Elham
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
Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.
Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is par
Frenz, Theresa; Grabski, Elena; Durán, Verónica; Hozsa, Constantin; Stępczyńska, Anna; Furch, Marcus; Gieseler, Robert K; Kalinke, Ulrich
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
Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali
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
Borges, Olga; Cordeiro-Da-Silva, Anabela; Tavares, Joana; Santarém, Nuno; Sousa, Adriano de; Borchard, Gerrit; Junginger, Hans E.
Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the antigen, adsorbed on the surface of those chitosan nanoparticles, from enzymatic degradation at mucosal surfaces. In this work, this new delivery system was loaded with the recombinant hepatitis B surface antigen (HBsAg) and applied to mice by the intranasal route. Adjuvant effect of the delivery system was studied by measuring anti-HBsAg IgG in serum, anti-HBsAg sIgA in faeces extracts or nasal an...
Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.
Pouniotis, Dodie; Tang, Choon-Kit; Apostolopoulos, Vasso; Pietersz, Geoffrey
Cell-penetrating peptides (CPP) or membrane-translocating peptides such as penetratin from Antennapedia homeodomain or TAT from human immunodeficiency virus are useful vectors for the delivery of protein antigens or their cytotoxic (Tc) or helper (Th) T cell epitopes to antigen-presenting cells. Mice immunized with CPP containing immunogens elicit antigen-specific Tc and/or Th responses and could be protected from tumor challenges. In the present paper, we investigate the mechanism of class I and class II antigen presentation of ovalbumin covalently linked to penetratin (AntpOVA) by bone marrow-derived dendritic cells with the use of biochemical inhibitors of various pathways of antigen processing and presentation. Results from our study suggested that uptake of AntpOVA is via a combination of energy-independent (membrane fusion) and energy-dependent pathways (endocytosis). Once internalized by either mechanism, multiple tap-dependent or independent antigen presentation pathways are accessed while not completely dependent on proteasomal processing but involving proteolytic trimming in the ER and Golgi compartments. Our study provides an understanding on the mechanism of antigen presentation mediated by CPP and leads to greater insights into future development of vaccine formulations. PMID:27138940
Full Text Available The human skin is a readily accessible surface for drug delivery. Skin of an average adult body covers a surface of approximately 2 m2 and receives about one-third of the blood circulating through the body. Over the past decades, developing controlled drug delivery has become increasingly important in the pharmaceutical industry. The human skin surface is known to contain, on an average, 10- 70 hair follicles and 200-250 sweat ducts on every square centimeters of the skin area. It is one of the most readily accessible organs of the human body. There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, the skin, in particular the stratum corneum, poses a formidable barrier to drug penetration thereby limiting topical and transdermal bioavailability. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drugs for which topical and transdermal delivery is a viable option. During the past decade, the number of drugs formulated in the patches has hardly increased, and there has been little change in the composition of the patch systems. Modifications have been mostly limited to refinements of the materials used. The present review article explores the overall study on transdermal drug delivery system (TDDS which leads to novel drug delivery system (NDDS.
Weihsu C Chen
Full Text Available Sialoadhesin (Sn, Siglec-1, CD169 is a member of the sialic acid binding Ig-like lectin (siglec family expressed on macrophages. Its macrophage specific expression makes it an attractive target for delivering antigens to tissue macrophages via Sn-mediated endocytosis. Here we describe a novel approach for delivering antigens to macrophages using liposomal nanoparticles displaying high affinity glycan ligands of Sn. The Sn-targeted liposomes selectively bind to and are internalized by Sn-expressing cells, and accumulate intracellularly over time. Our results show that ligand decorated liposomes are specific for Sn, since they are taken up by bone marrow derived macrophages that are derived from wild type but not Sn(-/- mice. Importantly, the Sn-targeted liposomes dramatically enhance the delivery of antigens to macrophages for presentation to and proliferation of antigen-specific T cells. Together, these data provide insights into the potential of cell-specific targeting and delivery of antigens to intracellular organelles of macrophages using Sn-ligand decorated liposomal nanoparticles.
Shen, Shan-Shan; Yang, Ya-Wun
This study investigates the intracellular transport of protein antigens facilitated by L121-adjuvants and examines the associated cytotoxic T lymphocyte (CTL) effect. EL4 mouse thymoma cells were treated with L121-adjuvant and stained with AnnexinV-propidium iodide (PI) followed by flow cytometric analysis. The intracellular trafficking dynamics of bovine serum albumin (BSA)-FITC in the J774.A.1 macrophages, influenced by the L121-adjuvant, was visualized by confocal microscopy. The antigen-specific cytotoxic T lymphocyte (CTL) effect induced by the L121-adjuvant was determined by the cleavage-specific fluorogenic caspase substrate. The trafficking of BSA-FITC in the J774A.1 cells by confocal microscopy illustrated that the L121-adjuvant facilitated the intracellular transport of proteins to the subcellular compartments, including the lysosome, endoplasmic reticulum (ER), and the cis-Golgi apparatus. The L121-adjuvant also facilitated antigen delivery to the dendritic cells in the lymph nodes. Immunization of mice with the L121-adjuvant resulted in cell-mediated cytotoxic responses in the target cells, as detected by PhiPhiLux, a fluorogenic caspase substrate. Taken together, the L121-adjuvant improved the dynamics of protein delivery to antigen presenting cells, and also induced caspase activation, thereby illustrating the mechanism of antigen-specific CTL effects. PMID:25917678
Medina, Marcela; Vintiñi, Elisa; Villena, Julio; Raya, Raul; Alvarez, Susana
Most studies of Lactococcus lactis as delivery vehicles of pneumococcal antigens are focused on the effectiveness of mucosal recombinant vaccines against Streptococcus pneumoniae in animal models. At present, there are three types of pneumococcal vaccines: capsular polysaccharide pneumococcal vaccines (PPV), protein-polysaccharide conjugate pneumococcal vaccines (PCV) and protein-based pneumococcal vaccines (PBPV). Only PPV and PCV have been licensed. These vaccines, however, do not represent...
Full Text Available This review highlights the several advantages of buccal drug delivery system (BDDS over the conventional and systemic formulation majorly. It helps to enhance bioavailability through bypassing the first pass metabolism. On this drug delivery system the formulation keeps in contact with the mucosal surface resulting in better absorption and prolonged resident time. Though all drugs are not suitable for this drug delivery system yet is useful for most of the drugs. Bioadhesive polymers roles a major part in this drug delivery system because the extent of Mucoadhesion is a very important phenomena for the buccal drug delivery system. This review covers merits and demerits of buccal drug delivery system, anatomy of oral mucosa, mechanism of drug permeation, polymers and permeation enhancer used in buccal drug delivery system. This review also covers available marketed product as buccal drug delivery system and future aspects of buccal drug delivery system.
Robey, Robert W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
This presentation deals with the hierarchy of software build and delivery systems. One of the goals is to maximize the success rate of new users and developers when first trying your software. First impressions are important. Early successes are important. This also reduces critical documentation costs. This is a presentation focused on computer science and goes into detail about code documentation.
Szecsi, Pal B; Andersen, Malene R; Bjørngaard, Brian;
, Denmark. POPULATION: Eight hundred and one women with expected normal pregnancies were investigated. Of these, 640 delivered vaginally, 82 by emergency cesarean section, and 79 by elective cesarean section; 720 women had uncomplicated pregnancies. METHODS: Samples were collected at gestational weeks 13...... gestational period and around delivery. RESULTS: CA-125 was fairly stable below 35 U/mL during pregnancy but increased markedly during vaginal delivery, to a minor degree during emergency cesarean section, and only slightly during elective cesarean section. In the early postpartum period, CA-125 decreased......OBJECTIVE: To establish reference intervals for cancer antigen 125 (CA-125) in women with expected normal pregnancy, delivery, and early postpartum period. DESIGN: Prospective observational study. SETTING: Department of Clinical Biochemistry and Obstetrics, Copenhagen University Hospital, Gentofte...
Transdermal drug delivery system (TDDS) are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. By this constant concentration of drug remain in blood for long time. Polymer matrix, drug, permeation enhancers are the main components of TDDS; polymers includes Zein, Shellac (as a natural) to syntheti...
KALPESH CHHOTALAL ASHARA; Jalpa S. Paun; M. M. Soniwala; J.R.CHAVDA; S. V. NATHAWANI; NITIN M. MORI; Mendapara, Vishal P.
A novel drug delivery system is that delivers drug at predetermined rate decided as per the requirement, pharmacological aspects, drug profile, physiological conditions of body etc. In current conditions not a single novel drug delivery system behaves ideally those high goals with fewer side effects. A Vesicular drug delivery system (VDDS) is the system in which encapsulation of active moieties in vesicular structure, which bridges gap between ideal and available of novel drug delivery system...
van Roosmalen, ML; Kanninga, R; El Khattabi, M; Neef, J; Audouy, S; Bosma, T; Kuipers, A; Post, E; Steen, A; Kok, J; Buist, G; Kuipers, OP; Robillard, G; Leenhouts, K
Mucosal immunization with subunit vaccines requires new types of antigen delivery vehicles and adjuvants for optimal immune responses. We have developed a non-living and non-genetically modified gram-positive bacterial delivery particle (GEM) that has built-in adjuvant activity and a high loading ca
Jorgensen, L; Moeller, E H; van de Weert, M;
From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping...... and long-term storage of the formulation. Therefore, the development and evaluation of successful and promising drug delivery systems is essential. In the present review, some of the particulate drug delivery systems for parenteral delivery of protein are presented and discussed. The challenge...... for incorporation of protein in particulate delivery systems is exemplified by water-in-oil emulsions....
Vaginal delivery is an important route of drug administration for both local and systemic diseases. The vaginal route has some advantages due to its large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to many drugs and self-insertion. The traditional commercial preparations, such as creams, foams, gels, irrigations and tablets, are known to reside in the vaginal cavity for a relatively short period of time owing to the self-cleaning action of the vaginal tract, and often require multiple daily doses to ensure the desired therapeutic effect. The vaginal route appears to be highly appropriate for bioadhesive drug delivery systems in order to retain drugs for treating largely local conditions, or for use in contraception. In particular, protection against sexually-transmitted diseases is critical. To prolong the residence time in the vaginal cavity, bioadhesive therapeutic systems have been developed in the form of semi-solid and solid dosage forms. The most commonly used mucoadhesive polymers that are capable of forming hydrogels are synthetic polyacrylates, polycarbophil, chitosan, cellulose derivatives (hydroxyethycellulose, hydroxy-propylcellulose and hydroxypropylmethylcellulose), hyaluronic acid derivatives, pectin, tragacanth, carrageenan and sodium alginate. The present article is a comprehensive review of the patents related to mucoadhesive vaginal drug delivery systems. PMID:19925443
U.S. Department of Health & Human Services — Explore the Electronic Nicotine Delivery Systems Key Facts Infographic which outlines key facts related to electronic nicotine delivery systems (ENDS), including...
Full Text Available Wenxue Ma1, Mingshui Chen1, Sharmeela Kaushal1,2, Michele McElroy1,2, Yu Zhang3, Cengiz Ozkan3, Michael Bouvet1,2, Carol Kruse4, Douglas Grotjahn5, Thomas Ichim6, Boris Minev1,7,81Moores Cancer Center, University of California San Diego, 2Department of Surgery, University of California San Diego, 3Laboratory of Biomaterials and Nanotechnology, University of California Riverside, 4UCLA Division of Neurosurgery, Los Angeles, 5Chemistry Department, San Diego State University, San Diego, 6MediStem Inc. San Diego, 7UCSD Division of Neurosurgery, San Diego, 8Genelux Corporation, San Diego, CA, USA Abstract: 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
Maharjan, Sushila; Singh, Bijay; Jiang, Tao; Yoon, So-Yeon; Li, Hui-Shan; Kim, Girak; Gu, Min Jeong; Kim, Soo Ji; Park, Ok-Jin; Han, Seung Hyun; Kang, Sang-Kee; Yun, Cheol-Heui; Choi, Yun-Jaie; Cho, Chong-Su
A successful delivery of antigen through oral route requires to overcome several barriers, such as enzymatic barrier of gastrointestinal tract and epithelial barrier that constitutes of microfold cells (M cells) for antigen uptake. Although each barrier represents a critical step in determining the final efficiency of antigen delivery, the transcytosis of antigen by M cells in the follicle-associated epithelium (FAE) to Peyer's patches appears to be a major bottleneck. Considering the systemic administration of receptor activator of nuclear factor (NF)-ĸB ligand (RANKL) induces differentiation of receptor activator of nuclear factor (NF)-ĸB (RANK)-expressing enterocytes into M cells, here, we illustrated a promising approach of antigen delivery using full length transmembrane RANKL (mRANKL). The results showed that the intraperitoneal injection of mRANKL increased the population of dendritic cells and macrophages in mesenteric lymph nodes and spleen. Subsequently, systemic administration of mRANKL resulted in significantly higher number of functional GP2(+) M cells leading higher transcytosis of fluorescent beads through them. To corroborate the effect of mRANKL in antigen delivery through M cells, we orally delivered microparticulate antigen to mice treated with mRANKL. Oral immunization induced strong protective IgA and systemic IgG antibody responses against orally delivered antigen in mRANKL-treated mice. The higher antibody responses are attributed to the higher transcytosis of antigens through M cells. Ultimately, the higher memory B cells and effector memory CD4 T cells after oral immunization in RANKL-treated mice confirmed potency of RANKL-mediated antigen delivery. To the best of our knowledge, this is the first study to demonstrate significant induction of mucosal and humoral immune responses to M cell targeted oral vaccines after the systemic administration of RANKL. PMID:26851393
Full Text Available Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable controlled drug delivery systems and could be employed as oral drug delivery systems. Various patents available for osmotic drug delivery system like Rose-Nelson pump, Higuchi leeper pump, Higuchi Theeuwes pump, Elementary Osmotic pump etc. ODDS are useful for poorly soluble drug, for pulsatile drug release, zero order release. Various techniques available for preparation of ODDS include push pull osmotic Pump, osmotic Brusting osmotic pump, liquid oral osmotic system, sandwiched osmotic tablets , delayed delivery osmotic device, monolithic osmotic System and controlled porosity osmotic Pump. Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active agents. These systems can be utilized for systemic as well as targeted delivery of drugs. The release of drugs from osmotic systems is governed by various formulation factors such as solubility and osmotic pressure of the core components, size of the delivery orifice, and nature of the rate-controlling membrane. In this Paper mainly focused on the Osmotic System with example, the basic component of osmotic system and evaluation parameter of the osmotic drug delivery system.
KALPESH CHHOTALAL ASHARA
Full Text Available A novel drug delivery system is that delivers drug at predetermined rate decided as per the requirement, pharmacological aspects, drug profile, physiological conditions of body etc. In current conditions not a single novel drug delivery system behaves ideally those high goals with fewer side effects. A Vesicular drug delivery system (VDDS is the system in which encapsulation of active moieties in vesicular structure, which bridges gap between ideal and available of novel drug delivery system.Varrious types of vesicular drug delivery system like liposome, niosome, archeosome, transferosome etc. were developed. Advances have since been made in vesicular drug delivery system. Focus of this review is to bring about a brief of vesicular drug delivery system as novel approach.
Noh, Young-Woock; Hong, Ji Hyun; Shim, Sang-Mu; Park, Hye Sun; Bae, Hee Ho; Ryu, Eun Kyoung; Hwang, Jung Hwan; Lee, Chul-Ho; Cho, Seong Hun; Sung, Moon-Hee; Poo, Haryoung; Lim, Yong Taik
Micelles for mucosal immunity: A mucosal vaccine system based on γ-PGA nanomicelles and viral antigens was synthesized. The intranasal administration of the vaccine system induces a high immune response both in the humoral and cellular immunity (see picture). PMID:23765547
Bae, Hae-Duck; Lee, Joohyun; Jin, Xing-Hai; Lee, Kyunglim
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
Raphael M. Ottenbrite; ZHAO Ruifeng; Sam Milstein
An oral drug delivery system using proteinoid microspheres is discussed with respect to its unique dependence on pH. It has been found that certain drugs such as insulin and heparin can be encapsulated in proteinoid spheres at stomach pH's (1-3). These spheres also dissemble at intestinal pH's (6-7) releasing the drug for absorption. Using this technique low molecular weight heparin and human growth hormone have been orally delivered successfully to several animal species. Future work has been proposed to study the interaction and binding of the specific drugs with synthesized oligopeptides.
Gallovic, Matthew D; Montjoy, Douglas G; Collier, Michael A; Do, Clement; Wyslouzil, Barbara E; Bachelder, Eric M; Ainslie, Kristy M
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. PMID:26753184
Full Text Available Transdermal drug delivery system (TDDS are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. By this constant concentration of drug remain in blood for long time. Polymer matrix, drug, permeation enhancers are the main components of TDDS; polymers includes Zein, Shellac (as a natural to synthetic ones (Polybutadiene, Polysiloxane, Polyvinyl chloride, Polyvinyl alcohol etc.. TDDS are of many types varying from single layer drug in adhesive to multi layer drug in adhesive and others are reservoir and the matrix systems. The market value of TDDS products are increasing with rapid rate, more than 35 products have now been approved for sale in US, and approximately 16 active ingredients are approved globally for use as a TDDS. Transdermal drug delivery is a recent technology which promises a great future it has a potential to limit the use of needles for administering wide variety of drugs but cost factor is a important thing to consider since developing nations like INDIA have second highest population, but due to higher cost TDDS are the hidden part of therapy used in general population.
Pathan Maksud; Zikriya Abrar; Quazi Aamer
Today though the oral drug delivery system is dominant still it is found to be need of ideal transdermal drug delivery system. “A micro emulsion is a system of water, oil and an amphiphile which is a single optically isotropic and thermodynamically stable liquid solution”. Microemulsions offer several advantages as drug delivery systems as these are thermodynamically stable and stability allows for self emulsification of the system with microemulsion acting as supersolvent of the drugs which...
S. R. Tajane et al.
The purpose for this review on pulsatile drug delivery systems (PDDS) is to compile the recent literatures with special focus on the different types and approaches involved in the development of the formulation. Pulsatile drug delivery system is the most interesting time and site-specific system. This system is designed for chronopharmacotherapy. Thus, to mimic the function of living systems and in view of emerging chronotherapeutic approaches, pulsatile delivery, which is meant to release a ...
Patel Mitul; Karigar Asif; Savaliya Pratik; Ramana MV; Dubal Ashwini
This review highlights the several advantages of buccal drug delivery system (BDDS) over the conventional and systemic formulation majorly. It helps to enhance bioavailability through bypassing the first pass metabolism. On this drug delivery system the formulation keeps in contact with the mucosal surface resulting in better absorption and prolonged resident time. Though all drugs are not suitable for this drug delivery system yet is useful for most of the drugs. Bioadhesive polymers roles a...
Steidler, Lothar; Robinson, K.; Chamberlain, L.; SCHOFIELD, KM; Remaut, Erik; LE PAGE, RWF; Wells, JM
Lactococcus lactis is a nonpathogenic and noncolonizing bacterium which is being developed as a vaccine delivery vehicle for immunization by mucosal routes. To determine whether lactococci can also deliver cytokines to the immune system, we have constructed novel constitutive expression strains of L. lactis which accumulate a test antigen, tetanus toxin fragment C (TTFC), within the cytoplasmic compartment and also secrete either murine interleukin-2 (IL-2) or IL-6. When mice were immunized i...
Sharma Nishu; Gnanarajan G
Controlled release local drug delivery systems offer advantages compared to systemic dosage forms for many dental diseases like gingivitis, periodontitis. The objective of this literature survey was to gain knowledge about various dental drug delivery systems for targeted delivery of the drug. The polymer ethyl cellulose was used in the formulation of dental films. The dental film was then evaluated for various parameters like thickness, folding endurance and weight variation and content unif...
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 t1/2 and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and 14C-inulin release rates were evaluated subcutaneously in rats
Malone, T A
The proliferation of Integrated Delivery Systems (IDSs) in regional health care markets has resulted in the movement of these markets from a monopolistic competitive model of behavior to an oligopoly. An oligopoly is synonymous with competition among the few, as a small number of firms supply a dominant share of an industry's total output. The basic characteristics of a market with competition among the few are: (1) A mutual interdependence among the actions and behaviors of competing firms; (2) competition tends to rely on the differentiation of products; (3) significant barriers to entering the market exist; (4) the demand curve for services may be kinked; and (5) firms can benefit from economies of scale. An understanding of these characteristics is essential to the survival of IDSs as regional managed care markets mature. PMID:10180497
Boks, Martine A; Bruijns, Sven C M; Ambrosini, Martino; Kalay, Hakan; van Bloois, Louis; Storm, Gert; de Gruijl, Tanja; van Kooyk, Yvette
Dendritic cells (DCs) have an important role in tumor control via the induction of tumor-specific T-cell responses and are therefore an ideal target for immunotherapy. The human skin is an attractive site for tumor vaccination as it contains various DC subsets. The simultaneous delivery of tumor antigen with an adjuvant is beneficial for cross-presentation and the induction of tumor-specific T-cell responses. We therefore developed liposomes that contain the melanoma-associated antigen glycoprotein 100280-288 peptide and Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) as adjuvant. These liposomes are efficiently taken up by monocyte-derived DCs, and antigen presentation to CD8(+) T cells was significantly higher with MPLA-modified liposomes as compared with non-modified liposomes or the co-administration of soluble MPLA. We used a human skin explant model to evaluate the efficiency of intradermal delivery of liposomes. Liposomes were efficiently taken up by CD1a(+) and especially CD14(+) dermal DCs. Induction of CD8(+) T-cell responses by emigrated dermal DCs was significantly higher when MPLA was incorporated into the liposomes as compared with non-modified liposomes or co-administration of soluble MPLA. Thus, the modification of antigen-carrying liposomes with TLR ligand MPLA significantly enhances tumor-specific T-cell responses by dermal DCs and is an attractive vaccination strategy in human skin. PMID:26083554
Babariya Nimeshkumar Arvindbhai
Full Text Available Purpose of writing this review on floating drug delivery system was to focus on the principle mechanism of floatation to achieve gastric retention. Technological attempts have been made in the research and development of rate controlled oral drug delivery system to overcome physiological adversities, such as short gastric residence time (GRT and unpredictable gastric emptying times. It is new drug delivery system maximize effectiveness and compliance. This review summarizes advantages of floating drug delivery system approaches to design single unit and multiple unit floating system, in-vitro and in-vivo technology to evaluate the performance of floating system. At attempt has been made in this review article to introduce the readers to current development in floating drug delivery system.
Šimšová, Marcela; Šebo, Peter; Leclerc, C.
Roč. 293, - (2004), s. 571-576. ISSN 1438-4221 R&D Projects: GA ČR GA310/01/0934; GA AV ČR IAA5020907 Grant ostatní: GA QLK2-CT-1999(XX) 00556 Keywords : cyaa * cellular immune response * antigen delivery Subject RIV: EE - Microbiology, Virology Impact factor: 2.919, year: 2004
Yalin, Azer; Willson, Bryan; Defoort, Morgan
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.
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…
Talukder, R; Fassihi, R
The objective of this study was to develop a floatable multiparticulate system with potential for intragastric sustained drug delivery. Cross-linked beads were made by using calcium and low methoxylated pectin (LMP), which is an anionic polysaccharide, and calcium, LMP, and sodium alginate. Beads were dried separately in an air convection type oven at 40 degrees C for 6 hours and in a freeze dryer to evaluate the changes in bead characteristics due to process variability. Riboflavin (B-2), tetracycline (TCN), and Methotrexate (MTX) were used as model drugs for encapsulation. Ionic and nonionic excipients were added to study their effects on the release profiles of the beads. The presence of noncross linking agents in low amounts (less than 2%) did not significantly interfere with release kinetics. For an amphoteric drug like TCN, which has pH dependent solubility, three different pHs (1.5, 5.0, and 8.0) of cross-linking media were used to evaluate the effects of pH on the drug entrapment capacity of the beads. As anticipated, highest entrapment was possible when cross-linking media pH coincided with least drug solubility. Evaluation of the drying process demonstrated that the freeze-dried beads remained buoyant over 12 hours in United States Pharmacopeia (USP) hydrochloride buffer at pH 1.5, whereas the air-dried beads remained submerged throughout the release study. Confocal laser microscopy revealed the presence of air-filled hollow spaces inside the freeze dried beads, which was responsible for the flotation property of the beads. However, the release kinetics from freeze dried beads was independent of hydrodynamic conditions. Calcium-pectinate-alginate beads released their contents at much faster rates than did calcium-pectinate beads (100% in 10 hours vs. 50% in 10 hours). It appears that the nature of cross-linking, drying method, drug solubility, and production approach are all important and provide the opportunity and potential for development of a
Full Text Available 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.
R.R. Bhagwat* and I.S. Vaidhya
Full Text Available ABSTRACT: Evolution of an existing drug molecule from a conventional form to a novel delivery system can significantly improve its performance in terms of patient compliance, safety and efficacy. In the form of a Novel Drug Delivery System an existing drug molecule can get a new life. An appropriately designed Novel Drug Delivery System can be a major advance for solving the problems related towards the release of the drug at specific site with specific rate. The need for delivering drugs to patients efficiently and with fewer side effects has prompted pharmaceutical companies to engage in the development of new drug delivery system. This article covers the basic information regarding Novel Drug Delivery Systems and also different types of the same.
Vidyavati S, Koppisetti
Full Text Available Magnetic drug delivery is a novel approach to delivery drug using engineered ’smart’ micro carriers which appears to overcome a number of limitations facing current methods of delivering medicines. The drug and a suitable ferrofluid are formulated into a pharmaceutically stable formulation which is usually injected through the artery that supplies the target organ or tumor in the presence of an external magnetic field. Depending on the fabrication method, particle size and nature they are named as magnetic microspheres, magnetic nanoparticles, magnetic liposomes etc. This review gives the information regarding the all possible formulations that can be designed using magnetism as the drug delivery mode.
Ru Wen; Umeano, Afoma C.; Lily Francis; Nivita Sharma; Smanla Tundup; Shanta Dhar
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 ...
McErlean, Emma M.; McCrudden, Cian M; McCarthy, Helen O.
This chapter examines key concepts with respect to cancer gene therapy and the current issues with respect to non-viral delivery. The biological and molecular barriers that need to be overcome before effective non-viral delivery systems can be appropriately designed for oncology applications are highlighted and ways to overcome these are discussed. Strategies developed to evade the immune response are also described and targeted gene delivery is examined with the most effective strategies hig...
Vidyavati S, Koppisetti; Sahiti. B
Magnetic drug delivery is a novel approach to delivery drug using engineered ’smart’ micro carriers which appears to overcome a number of limitations facing current methods of delivering medicines. The drug and a suitable ferrofluid are formulated into a pharmaceutically stable formulation which is usually injected through the artery that supplies the target organ or tumor in the presence of an external magnetic field. Depending on the fabrication method, particle size and nature they are nam...
De Pintu Kumar; De, Arnab
Pharmacosome is a potential approach in the vesicular drug delivery system which exhibit several advantages over conventional vesicular drug delivery systems. Pharmacosomes are amphiphilic lipid vesicular system possessing phospholipid complexes of drugs. Drugs bearing active hydrogen atom can be esterified to the lipid. This type of vesicular system improves permeation of drugs across the biomembranes and thus results in an improvement in the bioavailability and can also improve the pharmaco...
Chuan, Yap Pang; Zeng, Bi Yun; O'Sullivan, Brendan; Thomas, Ranjeny; Middelberg, Anton P J
Nanotechnology promises new drug carriers that can be tailored to specific applications. Here we report a new approach to drug delivery based on tailorable nanocarrier emulsions (TNEs), motivated by a need to co-deliver a protein antigen and a lipophilic drug for specific inhibition of nuclear factor kappa B (NF-κB) in antigen presenting cells (APCs). Co-delivery for NF-κB inhibition holds promise as a strategy for the treatment of rheumatoid arthritis. We used a highly surface-active peptide (SAP) to prepare a nanosized emulsion having defined surface properties predictable from the SAP sequence. Incorporating the lipophilic drug into the oil phase at the time of emulsion formation enabled its facile packaging. The SAP is depleted from bulk during emulsification, allowing simple subsequent addition of the drug-loaded oil-in-water emulsion to a solution of protein antigen. Decoration of emulsion surface with antigen was achieved via electrostatic deposition. In vitro data showed that the TNE prepared this way was internalized and well-tolerated by model APCs, and that good suppression of NF-κB expression was achieved. This work reports a new type of nanotechnology-based carrier, a TNE, which can potentially be tailored for co-delivery of multiple therapeutic components, and can be made using simple methods using only biocompatible materials. PMID:22153851
Yalin, Azer; Willson, Bryan; Defoort, Morgan; Joshi, Sachin; Reynolds, Adam
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.
Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong
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
Full Text Available The removal of chlorofluorocarbon (CFC propellants from industrial and household products has been agreed to by over 165 countires of which more than 135 are developing countries. The timetable for this process is outlined in the Montreal Protocol on Substances that Deplete the Ozone Layer document and in several subsequent amendments. Pressured metered dose inhalers (pMDIs for medical use have been granted temporary exemptions until replacement formulations, providing the same medication via the same route, and with the same efficacy and safety profiles, are approved for human use. Hydrofluoroalkanes (HFAs are the alternative propellants for CFCs-12 and -114. Their potential for damage to the ozone layer is nonexistent, and while they are greenhouse gases, their global warming potential is a fraction (one-tenth of that of CFCs. Replacement formulations for almost all inhalant respiratory medications have been or are being produced and tested; in Canada, it is anticipated that the transition to these HFA or CFC-free pMDIs will be complete by the year 2005. Initially, an HFA pMDI was to be equivalent to the CFC pMDI being replaced, in terms of aerosol properties and effective clinical dose. However, this will not necessarily be the situation, particularly for some corticosteroid products. Currently, only one CFC-free formulation is available in Canada – Airomir, a HFA salbutamol pMDI. This paper discusses the in vitro aerosol characteristics, in vivo deposition and clinical data for several HFA pMDIs for which there are data available in the literature. Alternative delivery systems to the pMDI, namely, dry powder inhalers and nebulizers, are briefly reviewed.
Full Text Available IN recent years several advancement has been made in research and development of Oral Drug Delivery System. Concept of Novel Drug Delivery System arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations. Purpose of this review is to compile the recent literature with special focus on various gastro retentive approaches that have recently become leading methodologies in the field of site-specific orally administered controlled release drug delivery. Technological attempts have been made in the research and development of ratecontrolled oral drug delivery systems to overcome physiological adversities, such as short gastric residence times (GRT and unpredictable gastric emptying times (GET. Therefore, gastro retentive drug delivery systems (GRDDS have been developed, which prolong the gastric emptying time. Several techniques such as floating drug delivery system, low density systems, raft systems, mucoadhesive systems, high density systems, super porous hydro gels and magnetic systems, have been employed. This review on GRDDS attempts to compile the available information with all the possible mechanism used to achieve gastric retention.
Jamil Faraz; Singh Arjun; Kumar Sunil; Sharma Ritika
The purpose for this review on pulsatile drug delivery systems (PDDS) is to compile the recent literatures with special focus on the different types and approaches involved in the development of the formulation. Pulsatile drug delivery system is the most interesting time and site-specific system. Diseases wherein PDDS are promising include asthma, peptic ulcer, cardiovascular diseases, arthritis,attention deficit syndrome in children, and hypercholesterolemia. PDDS can be classified into time...
Handrock, J.L.; Wally, K.; Raber, T.N. [Sandia National Labs., Livermore, CA (United States)
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.
Full Text Available The recent scientific and patented literature concluded that an increased interest in novel dosage forms which retained in the stomach for prolong and predictable period of time has been shown. Various technological attempts have been made in the research and development of rate-controlled oral drug delivery systems to overcome physiological diversities, as short gastric residence times and unpredictable gastric emptying times using gastro retentive drug delivery system. It is a well known fact that differences in gastric physiology, such as, gastric pH and motility exhibit both intra as well as inter-subject variability demonstrating significant impact on gastric retention time and drug delivery behavior. Various attempts have been made to develop Gastro retentive delivery systems. Several approaches are currently utilized in the prolongation of the GRT, including floating drug delivery systems, swelling and expanding systems, polymeric bio adhesive systems, high-density systems, modified-shape systems and other delayed gastric emptying devices. Floating dosage forms are emerging as a promising dosage forms. Floating dosage form can be prepared as tablets, capsules by adding suitable ingredients as well as by adding gas generating agent. In this review various techniques used in floating dosage forms along with current & recent developments of stomach specific floating drug delivery system for gastro retention are discussed.
Seymour, L. W.; Fisher, K. D.; Green, N. K.; Hale, S. J.; Lyons, M.; Mautner, V.; Nicum, S.; Onion, D.; Oupický, D.; Stevenson, M.; Ulbrich, Karel
Berlin: Springer Verlag, 2003 - (Rubanyi, G.; Ylä-Herttuala, S.), s. 107-117 ISBN 3-540-00413-0 R&D Projects: GA AV ČR KSK4055109 Keywords : gene delivery * adenovirus * HPMA copolymers Subject RIV: CC - Organic Chemistry
Kim, Y C; Jarrahian, C; Zehrung, D; Mitragotri, S; Prausnitz, M R
Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development. PMID:21472533
Full Text Available Recent advances in chronopharmacology and requirement of an appropriate technology to deliver the drug at specific time and site led to the development of novel type of drug delivery systems as “chronotropic or Pulsatile drug delivery systems”. Rationale behind designing these drug delivery systems is to release the drug at desired time (pathophysiological need of disease, which results into improved therapeutic efficacy and patient-compliance. These systems are meant for treatment of those diseases that are caused due to circadian changes in body like asthma, peptic ulcer, cardiovascular diseases, arthritis and when zero order drug release is not desired. These drug delivery systems are designed to release the drug within a short period of time, immediately after a predetermined lag time. The current article focuses on diseases requiring chronotropic systems and their chronological behavior, various approaches like time controlled chronotropic systems, stimuli induced pulsatile drug delivery systems, externally regulated pulsatile drug delivery systems to design them, recent technologies for chronotherapy and currently available marketed formulations.
O'Hagan, D T
A number of researchers from different scientific disciplines have independently described the uptake of a variety of particulates across the gastrointestinal tract in animal models. The reports of particle uptake are briefly reviewed and the alternative mechanisms and proposed sites of uptake are discussed. Following these observations, some researchers have exploited the phenomenon of particulate uptake by using microparticles and nanoparticles as oral delivery systems for active agents, su...
Patel Harshna; Solanki N S
IN recent years several advancement has been made in research and development of Oral Drug Delivery System. Concept of Novel Drug Delivery System arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations. Purpose of this review is to compile the recent literature with special focus on various gastro retentive approaches that have recently become leading methodologies in the field of site-specific orally administered controlled rel...
Kataria Sahil; Middha Akanksha; Bhardwaj Sudeep; Sandhu Premjeet
The recent scientific and patented literature concluded that an increased interest in novel dosage forms which retained in the stomach for prolong and predictable period of time has been shown. Various technological attempts have been made in the research and development of rate-controlled oral drug delivery systems to overcome physiological diversities, as short gastric residence times and unpredictable gastric emptying times using gastro retentive drug delivery system. It is a well known fa...
Sandhu Premjeet; Kataria Sahil; Bilandi Ajay; Jain Sonam; Rathore Devashish
Conventional drug delivery systems are often not suitable for new protein based and other Therapeutic compounds produced by modern technology. Therefore an alternative Approach to deliver these drugs can be achieved through the skin in the form of transcutaneous drug delivery system. Modern medicine has responded with the development of methods to deliver drug transcutanously (through) the skin for therapeutic use as an alternative to traditional route including oral, intravascular, intramusc...
Harnish Patel; Upendra Patel; Hiren Kadikar; Bhavin Bhimani; Dhiren Daslaniya; Ghanshyam Patel
Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable con...
Bhawandeep Gill; Jatinder Singh; Vikas Sharma; S L Hari Kumar
The oral route is the easiest, cost effective, and most vital method for drug administration. Therefore, improvement of dosage forms mainly for the prolonged release purpose has been a challenge for scientists. Vesicular drug delivery systems are developed with a purpose to overcome problems coupled with the drugs such a poor bioavailability, protection from harsh gastric environment, and from gastric enzymes, which degrade the drug. Vesicular drug delivery systems such as liposomes, emulsion...
Full Text Available 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.
Full Text Available The purpose for this review on pulsatile drug delivery systems (PDDS is to compile the recent literatures with special focus on the different types and approaches involved in the development of the formulation. Pulsatile drug delivery system is the most interesting time and site-specific system. Diseases wherein PDDS are promising include asthma, peptic ulcer, cardiovascular diseases, arthritis,attention deficit syndrome in children, and hypercholesterolemia. PDDS can be classified into time controlled systems wherein the drug release is controlled primarily by the delivery system; stimuli induced PDDS in which release is controlled by the stimuli, like the pH or enzymes present in the Intestinal tract or enzymes present in the drug delivery system and externally regulated system where release is programmed by external stimuli like magnetism, ultrasound, electrical effect and irradiation. Marketed product like Pulsicap®, Ritalin® and Pulsys® are based on pulsatile release system. The aim of this review is to describe several types of drug delivery systems. This review also summarizes some current PDDS already available in the market. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form.
Full Text Available The main goal of any drug delivery system is to achieve desired concentration of the drug in blood or tissue, which is therapeutically effective and non toxic for a prolonged period. Various attempts have been made to develop gastroretentive delivery systems such as high density system, swelling, floating system. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. This review also summarizes the studies to evaluate the performance and application of floating systems, and applications of these systems. Gastric emptying is a complex process and makes in vivo performance of the drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 hours. The floating or hydrodynamically controlled drug delivery systems are useful in such application.
Full Text Available Dhananjayan Dhanasooraj, R Ajay Kumar, Sathish MundayoorMycobacterium Research Group, Rajiv Gandhi Centre for Biotechnology, Kerala, IndiaAbstract: Nano-sized hepatitis B virus core virus-like particles (HBc-VLP are suitable for uptake by antigen-presenting cells. Mycobacterium tuberculosis antigen culture filtrate protein 10 (CFP-10 is an important vaccine candidate against tuberculosis. The purified antigen shows low immune response without adjuvant and tends to have low protective efficacy. The present study is based on the assumption that expression of these proteins on HBc nanoparticles would provide higher protection when compared to the native antigen alone. The cfp-10 gene was expressed as a fusion on the major immunodominant region of HBc-VLP, and the immune response in Balb/c mice was studied and compared to pure proteins, a mixture of antigens, and fusion protein-VLP, all without using any adjuvant. The humoral, cytokine, and splenocyte cell proliferation responses suggested that the HBc-VLP bearing CFP-10 generated an antigen-specific immune response in a Th1-dependent manner. By virtue of its self-adjuvant nature and ability to form nano-sized particles, HBc-VLPs are an excellent vaccine delivery system for use with subunit protein antigens identified in the course of recent vaccine research.Keywords: Mycobacterium tuberculosis, VLP, hepatitis B virus core particle, CFP-10, self-adjuvant, vaccine delivery
Full Text Available The oral route is the easiest, cost effective, and most vital method for drug administration. Therefore, improvement of dosage forms mainly for the prolonged release purpose has been a challenge for scientists. Vesicular drug delivery systems are developed with a purpose to overcome problems coupled with the drugs such a poor bioavailability, protection from harsh gastric environment, and from gastric enzymes, which degrade the drug. Vesicular drug delivery systems such as liposomes, emulsions, niosomes, proniosomes, solid lipid-nano particles, ethosomes, nanoparticles, and pharmacosomes, etc have gained much attention, but emulsomes have rouse as system, which bypasses many disadvantages associated with other systems, developed as novel lipoidal vesicular system with internal solid fat core surrounded by phospholipid bilayer. This technology is designed to act as vehicle for poorly soluble drugs. The drug is enclosed in the emulsomes and provide prolong existence of drug in systemic circulation. Furthermore, emulsomal-based formulations of genetic drugs such as antisense oligonucleotides and plasmids for gene therapy that have clear potential for systemic utility are increasingly available. This review addresses the concept of emulsomal drug delivery system, summarizes the success of emulsomes for the delivery of small molecules, and special attention has been paid to its formulation design, advantages, biopharmaceutical aspects, stability aspects, and various aspects related to drug delivery including future aspects.
Shyam Sunder Mandava et al.
Transdermal drug delivery system (TDS) is not practically for delivery of materials whose final target is skin itself. Application topical agents generally offer many problems such as rashes, skin irritancy and burning sensation etc due to higher percutaneous absorption of drugs on the skin. Some conventional dosage e.g., gels and ointments. Which are often aesthetically unappealing, greasiness and stickiness etc. that often result into lack of patient compliance. For reduce this side effects...
Full Text Available Controlled release local drug delivery systems offer advantages compared to systemic dosage forms for many dental diseases like gingivitis, periodontitis. The objective of this literature survey was to gain knowledge about various dental drug delivery systems for targeted delivery of the drug. The polymer ethyl cellulose was used in the formulation of dental films. The dental film was then evaluated for various parameters like thickness, folding endurance and weight variation and content uniformity, in vitro and in vivo study. There has been a great attention in using iontophoretic technique for the transdermal drug delivery of medications, both ionic and non ionic. This technique of facilitated movement of ions across a membrane under the influence of an externally applied electric potential difference is one of the most promising physical skin penetrations enhancing method. Another novel approach is the use of lasers in dentistry. Lasers can be used in both hard and soft tissue applications including laser bleaching, frenectomy, gingivectomy, caries removal etc. Drugs delivery via the buccal routs using bio adhesive dosage forms offers such a novel route of drugs administration. This route has been used successfully for the systematic delivery of number of drugs candidates. Problems such as high first pass metabolisms and drugs degradation in the gastrointestinal tract can be circumvented by administrating the drug buccal routes.
S. R. Tajane et al.
Full Text Available The purpose for this review on pulsatile drug delivery systems (PDDS is to compile the recent literatures with special focus on the different types and approaches involved in the development of the formulation. Pulsatile drug delivery system is the most interesting time and site-specific system. This system is designed for chronopharmacotherapy. Thus, to mimic the function of living systems and in view of emerging chronotherapeutic approaches, pulsatile delivery, which is meant to release a drug following programmed lag phase, has increasing interest in the recent years. Diseases wherein PDDS are promising include asthma, peptic ulcer, cardiovascular diseases, arthritis, and attention deficit syndrome in children, cancer, diabetes, and hypercholesterolemia. Pulsatile drug delivery system divided into 2 types’ preplanned systems and stimulus induced system, preplanned systems based on osmosis, rupturable layers, and erodible barrier coatings. Stimuli induced system based on electrical, temperature and chemically induced systems. This review also summarizes some current PDDS already available in the market. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form.
Shikha Deshwal et al
Full Text Available Transdermal drug technology specialists are continuing to search for new methods that can effectively and painlessly deliver larger molecules in therapeutic quantities to overcome the difficulties associated with the oral route. Transdermal Drug Delivery System (TDDS is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Skin is an effective medium from which absorption of the drug takes place and enters in to circulatory system. Various types of transdermal patches are used to incorporate the active ingredients into the circulatory system via skin. The patches have been proved effective because of its large advantages over other controlled drug delivery systems. This review article covers a brief outline of various components of transdermal patch, applications of transdermal patch, their advantages, disadvantages, when the transdermal patch are used and when their use should be avoided, types of transdermal patch, recent techniques for enhancing TDDS
Full Text Available Today though the oral drug delivery system is dominant still it is found to be need of ideal transdermal drug delivery system. “A micro emulsion is a system of water, oil and an amphiphile which is a single optically isotropic and thermodynamically stable liquid solution”. Microemulsions offer several advantages as drug delivery systems as these are thermodynamically stable and stability allows for self emulsification of the system with microemulsion acting as supersolvent of the drugs which are poorly or insoluble in water. They are preferred more as compared to conventional emulsions due stability. The dispersed phase mainly acts as the solvent for the water insoluble drug. Microemulsions have been proved to increase the cutaneous absorption of both lipophilic and hydrophilic API’s when compared to conventional vehicles.
Full Text Available Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. These systems are designed according to the circadian rhythm of the body. The principle rationale for the use of pulsatile release is for the drugs where a constant drug release, i.e., a zero-order release is not desired. The release of the drug as a pulse after a lag time has to be designed in such a way that a complete and rapid drug release follows the lag time. Various systems like capsular systems, osmotic systems, single- and multiple-unit systems based on the use of soluble or erodible polymer coating and use of rupturable membranes have been dealt with in the article. It summarizes the latest technological developments, formulation parameters, and release profiles of these systems. Products available as once-a-daily formulation based on Pulsatile release like Pulsincap ®, Ritalin ®, and Pulsys ® are also covered in the review. These systems are beneficial for the drugs having chronopharmacological behaviour where night time dosing is required and for the drugs having high first-pass effect and having specific site of absorption in GIT. Drugs used in asthmatic patients and patients suffering from rheumatoid arthritis are also discussed along with many other examples.
Full Text Available The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.
D. Nagasamy Venkatesh
Full Text Available Lipid based drug delivery systems have been examined in various studies and exhibited their potential in controlled and targeted drug delivery. Pharmacosomes, a novel vesicular drug delivery system, offering a unique advantage over liposomes and niosomes, and serve as potential alternative to these conventional vesicles. They constitute an amphiphilic phospholipid complex with drug bearing an active hydrogen atom covalently that bind to phospholipids. They provide an efficient delivery of drug required at the site of action, which ultimately reduces the drug toxicity with reduced adverse effects and also reduces the cost of therapy by imparting better biopharmaceutical properties to the drug, resulting in increases bioavailability, especially in case of poorly soluble drugs. As the system is formed by binding the drug (pharmakon to carrier (soma, they are termed as pharmacosomes. Depending upon the chemical structure of the drug lipid complex they may exist as ultrafine vesicular, micellar and hexagonal aggregate. Drug having active hydrogen group such as carboxyl, hydroxyl group can be esterified to lipids, resulting in amphiphilic compound. Pharmacosomes are widely used as carriers for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular and antineoplastic drugs. The release of drug from pharmacosomes is generally governed by the process of enzymatic reaction and acid hydrolysis. Here, in the present review paper we have discussed the potential of pharmacosomes as a controlled and targeted drug delivery system and highlighted the method of preparation and characterization.
SERVIR, an automated document delivery system developed by CIN/CNEN, is described. Parametric procedures for reading bibliographic data bases and requesting documents from libraries through computer are specified. Statistical procedures, accounting system and the on-line fulfillment of requests are presented. (Author)
Full Text Available The purpose of writing this review on the floating drug delivery systems (FDDS was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. FDDS is one of the approaches in chronotherapeutic drug delivery. In the past reviews of FDDS the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, their classification and formulation aspects have been covered. This review summarizes the special focus on chronotherapeutics, diseases affected by biological rhythm, its importance, advantages, various approaches in Chronotherapeutic drug delivery and applications of FDDS. These systems are useful for several problems encountered during the development of a pharmaceutical dosage forms.
Shyam Sunder Mandava et al.
Full Text Available Transdermal drug delivery system (TDS is not practically for delivery of materials whose final target is skin itself. Application topical agents generally offer many problems such as rashes, skin irritancy and burning sensation etc due to higher percutaneous absorption of drugs on the skin. Some conventional dosage e.g., gels and ointments. Which are often aesthetically unappealing, greasiness and stickiness etc. that often result into lack of patient compliance. For reduce this side effects, microsponge technology offers many advantage over the conventional drug delivery. The microsponge based drug delivery system is a unique technology for controlled release and enhanced drug deposition in the skin while minimizing transdermal penetration of topically active agents. Drug loaded microsponge consist of microporous beads, typically 10-25 μm in diameter. Microsponge delivery system (MDS can provide increased efficacy for topically active agents with enhanced safety, extended product stability, enhanced formulation flexibility, reduced side effects and improved aesthetic properties in an efficient and novel manner. In addition these are non-irritating, non-allergenic, non-mutagenic, and non-toxic. MDS technology is being used currently in cosmetics, over-the-counter skin care, sunscreen and prescription products.
Garbayo, E; Ansorena, E; Blanco-Prieto, M J
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
Patel DS; Patel MV; Patel KN; Patel BA; Patel PA
Today about 70% of drugs are taken orally and are found not to be as effective as desired. To improvesuch characters transdermal drug delivery system was emerged. Transdermal drug delivery system(TDDS) provides a means to sustain drug release as well as reduce the intensity of action and thusreduce the side effects associated with its oral therapy and differs from traditional topical drug delivery.Transdermal Drug Delivery System is the system in which the delivery of the active ingredients o...
Full Text Available Drug delivered can have significant effect on its efficacy. Some drugs have an optimum concentration range with in which maximum benefit is derived and concentrations above (or below the range can be toxic or produce no therapeutic effect. Various drug delivery and drug targeting systems are currently under development. The main goal for developing such delivery systems is to minimize drug degradation and loss, to prevent harmful side effects and to increase bioavailability. Targeting is the ability to direct the drug loaded system to the site of interest. Among drug carrier one can name soluble polymers, microparticles made of insoluble (or biodegradable natural and synthetic polymers, microcapsules, cells, cell ghosts, lipoproteins, liposomes and micelles. Two major mechanisms can be distinguished for addressing the desired sites for drug release, (a Passive and (b Active targeting. Controlled drug carrier systems such as micellar solutions, vescicles and liquid crystal dispersions, as well as nanoparticle dispersions consisting of small particles of 10 – 400 nm show great promise as drug delivery systems. Hydrogels are three dimensional, hydrophilic, polymer networks capable of imbibing large amounts of water or biological fluids. Buckyballs, a novel delivery system with 60 carbon atoms formed in the shape of hollow ball. They are other type’s namely bucky babies, fuzzy balls, gadofullereness, and giant fullerenes. Nanoparticles can be classified as nano tubes, nano wires, nano cantilever, nanoshells, quantum dots, nano pores. Researchers at north western university using gold particles to develop ultra sensitive detection systems for DNA and protein markers associated with many forms of cancer, including breast and prostrate cancer. Drug loaded erythrocytes is one of the growing and potential systems for delivery of drugs and enzymes.
Xu, Yan; Lyu, Liu
Reduction of intraocular pressure (IOP) by drugs is a major treatment for glaucoma. Clinically, diverse antiglaucoma drugs take effect to decrease the IOP through different mechanisms.However, due to limitations of traditional form of eye drops, the bioavailability of the drug and the patient compliance is lowered, the clinical efficacy is not good and also some toxic and side-effects come out.Otherwise, traditional medication is not suitable for neuroprotective drugs to work on both retina and optic nerve. Drug delivery system has the potential to improve the bioavailability of the drug, prolong the time of drug action, decrease the dosage and frequency of drugs, reduce the side-effects, and improve the patient compliance and efficacy.It is one of the most important studies in glaucoma medication development because it is valuable for patients' neuroprotection.Nowadays, several novel delivery systems have been designed. This review will focus on the progressions of some of the sustained-release antiglaucoma eye drops, polymeric gels, colloidal systems, membrane-controlled drug delivery system, ocular implants, and transscleral drug delivery systems. PMID:25619186
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
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.
Brezániová, I.; Král, V.; Černochová, Zulfiya; Hrubý, Martin
Kathmandu : ICIDN-2015 Conference Secretariat, 2015. s. 52. [International Conference on Infectious Diseases and Nanomedicine /2./ - ICIDN-2015. 15.12.2015-18.12.2015, Kathmandu] R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : polyplex nanoparticles * drug delivery system Subject RIV: EB - Genetics ; Molecular Biology
Full Text Available Gene therapy is an active field that has progressed rapidly into clinical trials in a relatively short time. The key to success for any gene therapy strategy is to design a vector able to serve as a safe and efficient gene delivery vehicle. This has encouraged the development of nonviral DNA-mediated gene transfer techniques such as liposomes. Many liposome-based DNA delivery systems have been described, including molecular components for targeting given cell surface receptors or for escaping from the lysosomal compartment. Another recent technology using cationic lipids has been evaluated and has generated substantial interest in this approach to gene transfer.
Allen, Theresa M.; Cullis, Pieter R.
Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.
De Pintu Kumar
Full Text Available Pharmacosome is a potential approach in the vesicular drug delivery system which exhibit several advantages over conventional vesicular drug delivery systems. Pharmacosomes are amphiphilic lipid vesicular system possessing phospholipid complexes of drugs. Drugs bearing active hydrogen atom can be esterified to the lipid. This type of vesicular system improves permeation of drugs across the biomembranes and thus results in an improvement in the bioavailability and can also improve the pharmacokinetic and pharmacodynamic properties of various types of drug molecules.This vesicular system can be characterized by surface morphology, solubility study, differential scanning calorimrtry, x-ray powder diffraction, in vitro dissolution study. Pharmacosomes are suitable for incorporating both hydrophilic and lipophilic drugs.Preparations of pharmacosomes are basically performed for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular and antineoplastic drugs.
Kumar, Sunny; Tummala, Hemachand
The goal of the present study is to develop a potent and safe vaccine adjuvant that can also stabilize vaccine formulations during lyophilization and storage. Inulin is a safe plant polysaccharide, and in its water soluble isoform, it is known to stabilize protein formulations during storage. However, soluble inulins have never been shown to stimulate the immune system. In this study, for the first time, we showed that water soluble inulins could be developed into vaccine adjuvants by formulating as antigen encapsulated microparticles. A method was developed to prepare soluble inulin microparticles (sIMs) with high encapsulation efficiency (∼75%) and loading (∼75 μg/mg) of the antigen. When immunized in mice, sIMs have generated robust Th2-type antibody titers (IgG1: 500,000) compared to unadjuvanted antigens (IgG1: 17,500) or alum adjuvanted antigens (IgG1: 80,000). In vitro assays showed that a higher proportion of antigen presenting cells (APC's) have taken up the antigen when presented in sIMs versus in solution (99 % vs 22 %). In addition, the amount of antigen taken up per cell has also been enhanced by more than 25 times when antigen was presented in sIMs. Efficient uptake of the antigen by APCs through sIMS was attributed to the observed enhancement in the immune response by antigen loaded sIMs. The sIMs neither caused any granuloma/tissue damage at the injection site in mice nor were they toxic to the APC's in cell culture. In conclusion, the current study has developed a safe, soluble inulin based vaccine adjuvant and delivery system. PMID:23506468
Deepak Sharma et al
Full Text Available Mucoadhesion is a field of current interest in the design of drug delivery systems. Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Mucoadhesive drug delivery system may be designed to enable prolonged residence time of the dosage form at the site of application or absorption and facilitate an intimate contact of the dosage form with the underline absorption surface. Extending the residence time of a dosage form at a particular site and controlling the release of drug from the dosage form are useful especially for achieving controlled plasma level of the drug as well as improving bioavailability. Application of these dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The present review describes mucoadhesion, mucoadhesive polymers and use of these polymers in designing different types of mucoadhesive gastrointestinal, nasal, ocular, vaginal and rectal drug delivery systems. The research on mucoadhesives, however, is still in its early stage, and further advances need to be made for the successful translation of the concept into practical application in controlled drug delivery.
Qiu, Yuqin; Li, Chun; Zhang, Suohui; Yang, Guozhong; He, Meilin; Gao, Yunhua
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
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. (paper)
Bhalla.Neetika; Deep Arsh; Goswami Manish
In recent years scientific and technological advancements have been made in the research and development of oral drug delivery system. Oral sustained drug delivery system is complicated by limited gastric residence times (GRTs). In order to understand various physiological difficulties to achieve gastric retention, we have summarized important factors controlling gastric retention. To overcome these limitations, various approaches have been proposed to increase gastric residence of drug deli...
Kharat, Rekha; Bathe, Ritesh Suresh
Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical administration of therap...
Handrock, J.L.; Malinowski, M.E.; Wally, K. [Sandia National Lab., Livermore, CA (United States)
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.
Full Text Available Vaccines intended to induce a cytotoxic CD8+ T-cell response are highly sought after. However, some of these vaccines can be problematic if they replicate in the host. An alternative strategy is to exploit cross-presentation of exogenous antigens to express peptides on major histocompatibility complex (MHC class I molecules. During cross-presentation, the delivered exogenous antigen can be taken up and processed through diverse mechanisms. Here, we will discuss the recent advances regarding the complex nature of the cross-priming process and the models that reflect its relevance in vivo. Moreover, we summarize current data that explore potential adjuvants and vaccine vectors that deliver antigens to activate CD8+ T cells relying on cross-presentation.
Handrock, J.L. [Sandia National Labs., Livermore, CA (United States)
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.
Vidyavathi Maravajhala et al.
Full Text Available Nanotechnology is science of matter and material that deal with particle size in nanometers. Nanotechnology has received a lot of attention with never-seen-before enthusiasm because of its future potential. It has provided fine lined diagnosis and focus treatment of disease at molecular level. This technology offers the advantage of protecting drugs from degradation; reduce the number of doses required. In this review, a discussion was carried out on different techniques for the preparation of nanodrug delivery systems like nanoparticles, solid lipid nanoparticles, nanocrystals, nanosuspensions, nanoemulsions. The concept of nanotechnology is widely expanded and applied to many drugs to the present. The ultimate application goal of nano drug delivery system is to develop clinically useful formulation for treating diseases in patients.
Sharma Ritika; Rajput Meenu; Prakash Pawan; Sharma Saurabh
Tablet is the most popular among all dosage forms existing today because of its convenience of self administration, compactness and easy manufacturing; however in many cases immediate onset of action is required than conventional therapy. To overcome these drawbacks, immediate release pharmaceutical dosage form has emerged as alternative oral dosage forms. There are novel types of dosage forms that act very quickly after administration. Drug delivery systems are becoming sophisticated day by ...
Dvorak, Rudolf; Eggl, Siegfried; Süli, Áron; Sándor, Zsolt; Galiazzo, Mattia; Pilat-Lohinger, Elke
As part of the national scientific network 'Pathways to Habitable Worlds' the delivery of water onto terrestrial planets is a key question since water is essential for the development of life as we know it. After summarizing the state of the art we show some first results of the transport of water in the early Solar System for scattered main belt objects. Hereby we investigate the questions whether planetesimals and planetesimal fragments which have gained considerable inclination due to the ...
Rathore K. S.; Nema R. K.
Promising management of eye ailments take off effective concentration of drug at the eye for sufficient period of time. Dosage forms are administered directly to eye for localized ophthalmic therapy. Most of the treatments call for the topical administration of ophthalmic active drugs to the tissues around the ocular cavity. Conventional ophthalmic drug delivery systems including eye drops, ophthalmic ointments, are no longer sufficient to encounter eye diseases. This article reviews the cons...
Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita
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.
Full Text Available Conventional drug delivery systems are often not suitable for new protein based and other Therapeutic compounds produced by modern technology. Therefore an alternative Approach to deliver these drugs can be achieved through the skin in the form of transcutaneous drug delivery system. Modern medicine has responded with the development of methods to deliver drug transcutanously (through the skin for therapeutic use as an alternative to traditional route including oral, intravascular, intramuscular, subcutaneous, and sublingual. Transcutaneous drug delivery has many theoretic and practical advantage and disadvantages, and such issues are often a concern for both clinicians and patients. Transcutaneous patches are flexible pharmaceutical preparations of varying sizes, containing one or more active ingredient, intended to be applied to the unbroken skin in order to deliver the active ingredient to the systemic circulation after passing through the skin barriers. A Transcutaneous patch or skin patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Often, this promotes healing to an injured area of the body. In this method, the drug enters the bloodstream directly through skin and it avoid first pass effect. Characterization of Transcutaneous patch are necessary because check it’s quality, size, time of onset & duration, adhesive property, thickness, weight of patch, moisture of content, uniformity & cutaneous toxicological studies. Their requirements for evaluation are HPLC, U.V. spectrophotometer, screw gauge, digital balance, desiccators, thin layer chromatography & K.C. Cell used.
Byeon, Hoyeon; Hur, Jin; Kim, Bo Ram; Lee, John Hwa
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
Shyamal Kumar Kundu
Full Text Available Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole.
Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled
Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems. PMID:26898739
Full Text Available Oral route still remains the favorite route of drug administration in many diseases and till today it is the first wayinvestigated in the development of new dosage forms. Approximately 40 per cent of new drug candidates have poor water solubility and the oral delivery ofsuch drugs is frequently associated with implications of low bioavailability, high intra and inter-subjectvariability, and lack of dose proportionality. Bioavailability problem of lipophillic drugs can be solved byformation of Self Emulsifying Drug Delivery System (SEDDS. SEDDS are isotropicmixtures of oil, surfactant, co-surfactant and drug with a unique ability to form fine oil in water microemulsion upon mild agitation following dilution with aqueous phase. The principal characteristic of thesesystems is their ability to form fine oil-in-water (o/w emulsions or micro-emulsions upon mild agitation followingdilution by an aqueous phase. For lipophilic drugs, which have dissolution rate-limited absorption, SEDDS may be apromising strategy to improve the rate and extent of oral absorption.This review article explains how self-emulsifying drug delivery systems can increase the solubility and bioavailability ofpoorly soluble drug.
Abadi, Danielle; Zderic, Vesna
A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative. PMID:22124008
Full Text Available Transdermal drug delivery system (TDDS is one of the systems lying under the category of controlled drug delivery, in which the aim is to deliver the drug through the skin in a predetermined and controlled rate. It has various advantages, like prolonged therapeutic effect, reduced side-effects, improved bioavailability, better patient compliance and easy termination of drug therapy. The stratum corneum is considered as the rate limiting barrier in transdermal permeation of most molecules. There are three main routes of drug penetration, which include the appendageal, transcellular and intercellular routes. Skin age, condition, physicochemical factors and environmental factors are some factors that are to be considered while delivering drug through this route. Basic components of TDDS include polymer matrix, membrane, drug, penetration enhancers, pressure-sensitive adhesives, backing laminates, release liner, etc. Transdermal patches can be divided into various systems like reservoir system, matrix system and micro-reservoir system, which are used to incorporate the active ingredients into the circulatory system via the skin. After preparation of transdermal patches, consistent methodology are adopted to test the adhesion properties, physicochemical properties, in vitro drug release studies, in vitro skin permeation studies, skin irritation studies and stability studies. According to the duration of therapy, various drugs are commercially available in the form of transdermal patches.
Malakar Jadupati; Das Tanmay; Ghatak Souvik
In this review, the various new and well established technologies relevant to the controlled and targeted drug delivery systems have been precisely discussed. A perfectly designed controlled drug delivery system can be of huge advantage towards solving problems concerning to the targeting of drug to a specific organ or tissue and controlling the rate of drug delivery at the target site. Novel drug delivery systems have various advantages over other conventional drug therapy. In which microenc...
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
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
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
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.
West, Nicholas P; Thomson, Scott A; Triccas, James A; Medveczky, C Jill; Ramshaw, Ian A; Britton, Warwick J
The development of effective anti-Tuberculosis (TB) vaccines is an important step towards improved control of TB in high burden countries. Subunit vaccines are advantageous in terms of safety, particularly in the context of high rates of HIV co-infection, but they must contain sufficient Mycobacterium tuberculosis antigens to stimulate immunity in genetically diverse human populations. We have used a novel approach to develop a synthetic scrambled antigen vaccine (TB-SAVINE), comprised of overlapping, recombined peptides from four M. tuberculosis proteins, Ag85B, ESAT-6, PstS3 and Mpt83, each of which is immunogenic and protective against experimental TB. This polyvalent TB-SAVINE construct stimulated CD4 and CD8T cell responses against the individual proteins and M. tuberculosis in C57BL/6 and Balb/c mice, when delivered as DNA, Fowl Pox Virus or Vaccinia Virus vaccines. In addition, the DNA-TBS vaccine induced protective immunity against pulmonary M. tuberculosis infection in C57BL/6 mice. Co-immunization of Balb/c mice with virally expressed TBS and HIV1-SAVINE vaccine stimulated strong T cell responses to both the M. tuberculosis and HIV proteins, indicating no effects of antigenic competition. Further development of this TB-SAVINE vaccine expressing components from multiple M. tuberculosis proteins may prove an effective vaccine candidate against TB, which could potentially form part of a safe, combined preventative strategy together with HIV immunisations. PMID:21846485
Sakhon, Olivia S; Ross, Brittany; Gusti, Veronica; Pham, An Joseph; Vu, Kathy; Lo, David D
M cells are a subset of mucosal epithelial cells with specialized capability to transport antigens across the mucosal barrier, but there is limited information on antigen transfer in the subepithelial zone due to the challenges in tracking microparticles and antigens that are transcytosed by this unique cell. Using transgenic reporter mice expressing dsRed in the cytoplasm of M cells and EGFP in myeloid cells, we observed that the M cell basolateral pocket hosts a close interaction between B lymphocytes and dendritic cells. Interestingly, we identified a population of previously undescribed M cell-derived vesicles (MCM) that are constitutively shed into the subepithelial space and readily taken up by CX3CR1(+)CD11b(+) CD11c(+) dendritic cells. These MCM are characterized by their cytoplasmic dsRed confirming their origin from the M cell cytoplasm. MCM showed preferential colocalization in dendritic cells with transcytosed bacteria but not transcytosed polystyrene beads, indicating a selective sorting of cargo fate in the subepithelial zone. The size and number of MCM were found to be upregulated by bacterial transcytosis and soluble toll-like receptor 2 (TLR2) agonist, further pointing to dynamic regulation of this mechanism. These results suggest that MCM provide a unique function by delivering to dendritic cells, various materials such as M cell-derived proteins, effector proteins, toxins, and particles found in the M cell cytoplasm during infection or surveillance. PMID:25838974
Jaini, Ritika; Popescu, Daniela C.; Flask, Chris A.; Macklin, Wendy B.; Tuohy, Vincent K.
This study was designed to understand the impact of self-antigen load on manifestation of organ specific autoimmunity. Using a transgenic mouse model characterized by CNS hypermyelination, we show that larger myelin content results in greater severity of experimental autoimmune encephalomyelitis attributable to an increased number of microglia within the hypermyelinated brain. We conclude that a larger self-antigen load affects an increase in number of tissue resident antigen presenting cells...
... 42 Public Health 4 2010-10-01 2010-10-01 false Delivery and utilization control systems. 457.490... State Plan Requirements: Coverage and Benefits § 457.490 Delivery and utilization control systems. A... targeted low-income children, including a description of the proposed methods of delivery and...
Paquette, Gilbert; Rosca, Ioan
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,…
Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R
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
Medina, Luis Alberto
Liposome drug formulations are defined as pharmaceutical products containing active drug substances encapsulated within the lipid bilayer or in the interior aqueous space of the liposomes. The main importance of this drug delivery system is based on its drastic reduction in systemic dose and concomitant systemic toxicity that in comparison with the free drug, results in an improvement of patient compliance and in a more effective treatment. There are several therapeutic drugs that are potential candidates to be encapsulated into liposomes; particular interest has been focused in therapeutic and antineoplastic drugs, which are characterized for its low therapeutic index and high systemic toxicity. The use of liposomes as drug carriers has been extensively justified and the importance of the development of different formulations or techniques to encapsulate therapeutic drugs has an enormous value in benefit of patients affected by neoplastic diseases.
Bindu M Boddupalli
Full Text Available Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity. In this regard, this review covers the areas of mechanisms and theories of mucoadhesion, factors influencing the mucoadhesive devices and also various mucoadhesive dosage forms.
Alexander Jeffrey A; Hearld Larry R
Abstract Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned). This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not) into the operating context of the delivery system. Methods The purpose of this paper is to desc...
Nielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo;
of these studies was to fabricate microcontainers in either SU-8 or biodegradable poly-L-lactic acid (PLLA), and fill the microcontainers with poorly soluble drugs. Furthermore, the application of the microcontainers as an oral drug delivery system was investigated in terms of release, in situ......In oral delivery, it can sometimes be necessary to employ drug delivery systems to achieve targeted delivery to the intestine. Microcontainers are polymeric, cylindrical devices in the micrometer size range (Figure 1), and are suggested as a promising oral drug delivery system ,. The purpose...
Gray, S. T.; Nicholson, C. M.; Bergantino, A. R.
Online, map-based applications have experienced an explosion in popularity over the past decade. The success of these systems is largely due to their ability to provide a spatial framework data exploration, and for the visual context (e.g., satellite images) they offer. Here we detail the development of a new online mapping system for Wyoming that will serve as a portal for the delivery of weather, climate, and water-related data for users across the state. While capitalizing on the success of previous online mapping efforts, this new system also highlights the potential for additional applications and functionality. Known as the Wyoming Internet Map Server (WyoIMS), the system brings together real-time observations and summary products from multiple federal agencies (NOAA-NWS, NRCS, USGS) to provide “one-stop-shopping” for key climatic datasets. Likewise this system is providing a platform for data delivery, archiving, and QC/QA as part of a new statewide hydroclimatic monitoring network. Moving beyond the simple transfer of data, this system also allows users to access information from resources that include state libraries and various databases that contain information related to climate and water resources. Users can, for example, select individual counties, watersheds, irrigation districts, or municipalities and download a wide range of documents and reports specific to those locations. On the whole, WyoIMS has become a catalyst for the development of new climate-related products, and a foundation for decision support with applications in water resources, wildlife management, and agriculture.
Ravi Kant Upadhyay
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 insi...
Full Text Available Novel drug delivery system in the field of medicine had taken a popular attention now a day as it makes the intake, bioavailability and overall therapeutics of a drug easier and in short period of time. In current scenario herbal drugs has been also fascinated a lot of researchers because of their less side effects, cost effectiveness and easy availability. To make herbal drugs more potent newer approaches are going on and current review deals one of the herbal Novel Drug Delivery System (NDDS i.e. Phytosomes.Phytosomes are herbal formulation which has enhanced the therapeutic effect of the plant extracts and herbal lead molecule by increasing bioavailability in the target site. Development of Phytosomes is at its budding stage in India and abroad. It has a lot of potential in the field of medicine, pharmaceutical and cosmetics. These drug phospholipid complexes can be formulated in the form solution suspension, emulsion, pills capsule powder. Current review will give all the information about Phytosomes and their benefits in the recent herbal drug formulations.
Full Text Available Tablet is the most popular among all dosage forms existing today because of its convenience of self administration, compactness and easy manufacturing; however in many cases immediate onset of action is required than conventional therapy. To overcome these drawbacks, immediate release pharmaceutical dosage form has emerged as alternative oral dosage forms. There are novel types of dosage forms that act very quickly after administration. Drug delivery systems are becoming sophisticated day by day as pharmaceutical scientists has acquired a better understanding of the physicochemical and biochemical parameters of drugs and excipients. Over the past three decades, fast disintegrating tablets (FDTs have gained considerable attention and is one of the most widely employed commercial product which is preferred alternative to conventional tablets and capsules especially for the pediatric and geriatric patients and for the patients who are bedridden, those having hand tremors, motion sickness, disphagia and who may not have access to water during traveling or who are uncooperative, on reduced liquid intake plan and also preferred in sudden episodes of allergic attack. Fast-dissolving drug delivery systems may offer a solution for these problems.
Johnson, Noah R.; Wang, Yadong
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.
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
Full Text Available Nanoemulsion has been identified as a promising delivery system for various drugs including biopharmaceuticals. Nanoemulsion is a heterogeneous system composed of one immiscible liquid dispersed as droplets within another liquid. The droplets size of nano emulsion is between 20 to 500 nm. Diameter and surface properties of droplets of nanoemulsion plays an important role in the biological behavior of the formulation. Small droplet sizes lead to transparent emulsions so that product appearance is not altered by the addition of an oil phase. In this paper various aspects of nanoemulsion have been discussed including advantages, disadvantages and methods of preparation. Furthermore new approaches of stability of formulation, effect of types and concentration of surfactant, process variables and method are also discussed to improve the stability of nanoemulsion formulation
Sanders, Jay H.
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.
Pham, Dinh-Duy; Fattal, Elias; Tsapis, Nicolas
Tuberculosis (TB) remains a major global health problem as it is the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus (HIV). Conventional treatments fail either because of poor patient compliance to the drug regimen or due to the emergence of multidrug-resistant tuberculosis. The aim of this review is to give an update on the information available on tuberculosis, its pathogenesis and current antitubercular chemotherapies. Direct lung delivery of anti-TB drugs using pulmonary delivery systems is then reviewed since it appears as an interesting strategy to improve first and second line drugs. A particular focus is place on research performed on inhalable dry powder formulations of antitubercular drugs to target alveolar macrophages where the bacteria develop. Numerous studies show that anti-TB drugs can be incorporated into liposomes, microparticles or nanoparticles which can be delivered as dry powders to the deep lungs for instantaneous, targeted and/or controlled release. Treatments of infected animals show a significant reduction of the number of viable bacteria as well as a decrease in tissue damage. These new formulations appear as interesting alternatives to deliver directly drugs to the lungs and favor efficient TB treatment. PMID:25499020
Full Text Available Novel technologies have been developed recently for drug delivery systems. The use of herbal formulations for novel drug delivery systems is more advantageous and has more benefits compared to others. The use of liposome, ethosome, phytosomes, emulsion, microsphere, solid lipid nanoparticles of herbal formulation has enhanced the therapeutic effects of plant extracts. With the use of all these, targeted delivery of the formulation is achieved, due to which the formulation demonstrates effect on the site, and the bioavailability of the formulation is also increased. With these novel drug delivery systems, the actives and extracts which are used in herbal formulations demonstrate enhancement in stability, sustained release of formulation, protection from toxicity and improved therapeutic efficacy. The main purpose of developing alternative drug delivery technologies is to increase efficiency of drug delivery and safety in the process of drug delivery and provide more convenience for the patient. The present paper includes information about novel formulations of herbal formulations.
Hannan, P A; Khan, J A; Khan, A; Safiullah, S
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
Full Text Available Today about 70% of drugs are taken orally and are found not to be as effective as desired. To improvesuch characters transdermal drug delivery system was emerged. Transdermal drug delivery system(TDDS provides a means to sustain drug release as well as reduce the intensity of action and thusreduce the side effects associated with its oral therapy and differs from traditional topical drug delivery.Transdermal Drug Delivery System is the system in which the delivery of the active ingredients of thedrug occurs by means of skin. Several important advantages of transdermal drug delivery are limitationof hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steadyplasma level of the drug. Various types of transdermal patches are used to incorporate the activeingredients into the circulatory system via skin. This review article covers a brief outline of theprinciples of transdermal permeation, various components of transdermal patch, approaches oftransdermal patch, evaluation of transdermal system, its application with its limitation.
DASH ALOK KUMAR; MISHRA JHANSEE
Several controlled oral drug delivery systems with prolonged gastric residence time have been reported recently. Gastro retentive drug delivery system is an approach to prolong gastric residence time, thereby targeting site-specific drug release in upper gastro intestinal tract improving the oral sustained delivery of drug that have an absorption window in a particular region of the gastrointestinal tract. These systems help in continuously releasing the drug before it reaches the absorption ...
Singh Amit Kumar; Dubey Vivek; Arora Vandana
Floating drug delivery system is the form of gastro-retentive drug delivery system that controls the kinetic release rate of a drug to a specific site for its pharmacological action. These are achieved by use of various polymeric substance including natural polymers such as Guar Gum, Xanthan Gum, Gellan Gum etc. This delivery system prolongs the retention time of the drug in the stomach as compared to conventional dosage forms. The present article highlights the use of polymers for the formul...
L. K. Omray
Gastro retentive drug delivery system of diltiazem hydrochloride was designed and evaluated for its effectiveness for the management of mild to moderate hypertension. Gastro retentive drug delivery system were prepared using polyvinyl alcohol and sodium carboxy methyl cellulose as the polymers and sodium bicarbonate as a gas generating agent for the reduction of floating lag time. Gastro retentive drug delivery system tablets were prepared by wet granulation method by compression in tablet co...
Singh Amit Kumar
Full Text Available Floating drug delivery system is the form of gastro-retentive drug delivery system that controls the kinetic release rate of a drug to a specific site for its pharmacological action. These are achieved by use of various polymeric substance including natural polymers such as Guar Gum, Xanthan Gum, Gellan Gum etc. This delivery system prolongs the retention time of the drug in the stomach as compared to conventional dosage forms. The present article highlights the use of polymers for the formulation of the floating drug delivery system especially with natural polymers.
D. Nagasamy Venkatesh
Full Text Available Proniosomes are solid colloidal particles which may be hydrated immediately before use to yield aqueous niosomes dispersions similar to those produced by more cumbersome conventional methods. The proniosomes minimize the problems associated with niosomes in terms of its physical stability such as aggregation, fusion and leaking. They also offer an additional convenience in transportation, distribution, storage, and dosing. The proniosomes derived niosomes are better than conventional niosomes in terms of their morphology, particle size, particle size distribution, and drug release. A slurry method was commonly used to produce proniosomes using maltodextrin as carrier. The time required to produce proniosomes by this simple method is independent of the ratio of surfactant solution to carrier material and appears to be a scalable process. The encapsulation efficiency of proniosomes is depends upon the amount of maltodextrin used in the process. The present review describes the method of preparation, characterization, applications of proniosomes as a potential drug delivery system.
Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta
There is no doubt that controlled and pulsatile drug delivery system is an important challenge in medicine over the conventional drug delivery system in case of therapeutic efficacy. However, the conventional drug delivery systems often offer a limited by their inability to drug delivery which consists of systemic toxicity, narrow therapeutic window, complex dosing schedule for long term treatment etc. Therefore, there has been a search for the drug delivery system that exhibit broad enhancing activity for more drugs with less complication. More recently, some elegant study has noted that, a new type of micro-electrochemical system or MEMS-based drug delivery systems called microchip has been improved to overcome the problems related to conventional drug delivery. Moreover, micro-fabrication technology has enabled to develop the implantable controlled released microchip devices with improved drug administration and patient compliance. In this article, we have presented an overview of the investigations on the feasibility and application of microchip as an advanced drug delivery system. Commercial manufacturing materials and methods, related other research works and current advancement of the microchips for controlled drug delivery have also been summarized. PMID:24758139
Ritesh Kumar1*, Amrish Chandra2, Pawan Kumar Gautam3
Full Text Available The colon is a site where both local and systemic delivery of drugs can take place. Local delivery allows topicaltreatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeteddirectly into the colon, thereby reducing the systemic side effects. This review mainly describes the primaryapproaches for CDDS (Colon Specific Drug Delivery namely prodrugs, pH and time dependent systems, andmicrobially triggered systems, which achieved limited success and had limitations as compared with newer CDDSnamely pressure controlled colonic delivery capsules. Oral administration of different dosage forms is the mostcommonly used method due to flexibility in design of dosage form and high patient acceptance, but thegastrointestinal tract presents several formidable barriers to drug delivery. In oral colon-specific drug deliverysystem, colon has a large amount of lymphoma tissue (facilitates direct absorption in to the blood, negligible brushboarder membrane activity, and much less pancreatic enzymatic activity as compared with the small intestine.Colon-specific drug delivery has gained increased importance not just for the delivery of the drugs for treatment oflocal diseases associated with the colon but also for its potential for the delivery of proteins and therapeutic peptides.Different approaches are designed based on prodrug formulation, pH-sensitivity, time-dependency (lag time,microbial degradation and osmotic pressure etc to formulate the different dosage forms like tablets, capsules,multiparticulates, microspheres, liposomes for colon targeting. The delivery of drugs to the colon has a number oftherapeutic implications in the field of drug delivery. In the recent times, the colon specific delivery systems are alsogaining importance not only for local drug delivery of drugs but also for the systemic delivery of protein and peptidedrugs. This review updated the research on different approaches formulation and
Gosenca, Mirjam; GAŠPERLIN, MIRJANA
This study examined the suitability of various colloidal systems for ascorbyl palmitate (AP) skin delivery. First, a pseudoternary phase diagram for Tween 80/lecithin/butanol, isopropyl myristate (IPM), and water was constructed and regions of lipophilic (w/o) or hydrophilic (o/w) microemulsions (MEs), and emulsions (EMs) were identified. Afterwards, various phase transition systems on the selected dilution line, as well as liquid crystal (LC) as a delivery system on the same dilution line (b...
DASH ALOK KUMAR
Full Text Available Several controlled oral drug delivery systems with prolonged gastric residence time have been reported recently. Gastro retentive drug delivery system is an approach to prolong gastric residence time, thereby targeting site-specific drug release in upper gastro intestinal tract improving the oral sustained delivery of drug that have an absorption window in a particular region of the gastrointestinal tract. These systems help in continuously releasing the drug before it reaches the absorption window, thus ensuring optimal bioavailability. Various approaches for gastric retention are Floating system, Swelling and expanding system, Bioadhesive systems, Modified-shape systems, High density systems etc.
V Kusum Devi
Full Text Available Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drug delivery system used for administering the herbal medicine to the patient is traditional and out-of-date, resulting in reduced efficacy of the drug. If the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems. However, modern phytopharmaceutical research can solve the scientific needs (such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required etc. of herbal medicines to be incorporated in novel drug delivery system, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. This article summarizes various drug delivery technologies, which can be used for herbal actives together with some examples.
Cordeiro, Ana S; Alonso, María J
The field of vaccination is moving from the use of attenuated or inactivated pathogens to safer but less immunogenic protein and peptide antigens, which require stronger adjuvant compositions. Antigen delivery carriers appear to play an important role in vaccine development, providing not only antigen protection and controlled release but also an intrinsic adjuvant potential. Among them, carriers based on polymers and lipids are the most representative ones. Patent applications in this area have disclosed, either the design and preparation methods for new biocompatible antigen delivery systems or the application of the previously developed systems for the delivery of novel antigens. Some of them have also reported the use of these technologies for modern therapeutic vaccination approaches. PMID:26667309
Batista, Jorge G.S.; Varca, Gustavo H.C.; Ferraz, Caroline C.; Garrido, Gabriela P.; Diniz, Bruna M.; Carvalho, Vinicius S.; Lugao, Ademar B., E-mail: firstname.lastname@example.org [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)
Hydrogels are formed by polymers capable of absorbing large quantities of water. They consist of one or more three-dimensionally structured polymer networks formed by macromolecular chains linked by covalent bonds-crosslinks - and physical interactions. The application of hydrogels, has been widely studied. Biodegradable synthetic or natural polymers such as chitosan, starch and poly-lactic-co-glycolic acid, have properties that allow the development of biodegradable systems for drug and nutraceutics delivery. This study aimed to develop polymeric hydrogels based on polyvinyl alcohol, polyacrylamide and polyvinylpyrrolidone using ionizing radiation in order to develop hydrogels for improved loading and release of compounds. Polymer solutions were solubilized in water and poured into thermoformed packages. After sealing, the material was subjected to γ-irradiation at 25kGy. The samples were assayed by means of mechanical properties, gel fraction and swelling degree. Nanostructure characterization was performed using Flory's equation to determine crosslinking density. The systems developed showed swelling degree and adequate mechanical resistance. The nanostructure evaluation showed different results for each system demonstrating the need of choosing the polymer based on the specific properties of each material. (author)
Sunena Sethi, SL Harikumar* and Nirmala
Full Text Available The colon is the terminal part of the GIT which has gained in recent years as a potential site for delivery of various novel therapeutic drugs, i.e. peptides. However, colon is rich in microflora which can be used to target the drug release in the colon. Colon is a site where both local and systemic drug delivery can take place. Local delivery allows the topical treatment of inflammatory bowel disease. If drug can be targeted directly into the colon, treatment can become more effective and side effects can be minimized. These systemic side effects can be minimized by primary approaches for CDDS (Colon specific drug delivery namely prodrugs, pH and time dependent systems and microbially triggered system which gained limited success and have limitations as compared with recently new CDDS namely pressure controlled colon delivery capsules (PCDCS, CODESTM (Novel colon targeted delivery system osmotic controlled drug delivery system, Pulsincap system, time clock system, chronotropic system. This review is to understand the pharmaceutical approaches to colon targeted drug delivery systems for better therapeutic action without compromising on drug degradation (or its low bioavailability.
Full Text Available Over the past few decades, advances in the in situ gel technologies have spurred development in manymedical and biomedical applications including controlled drug delivery. Many novel in situ gel baseddelivery matrices have been designed and fabricated to fulfill the ever increasing needs of thepharmaceutical and medical fields. In situ gelling systems are liquid at room temperature but undergogelation when in contact with body fluids or change in pH. In situ gel forming drug delivery is a type ofmucoadhesive drug delivery system. The formation of gel depends on factors like temperaturemodulation, pH change, presence of ions and ultraviolet irradiation from which the drug gets released ina sustained and controlled manner. Nasal delivery is a promising drug delivery option where commondrug administrations such as intravenous, intramuscular or oral are inapplicable. Recently, it has beenshown that many drugs have better bioavailability by nasal route than the oral route. This has beenattributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled withavoidance of hepatic first-pass elimination, gut wall metabolism and/or destruction in thegastrointestinal tract. The physiology of the nose presents obstacles but offers a promising route for noninvasivesystemic delivery of numerous therapies and debatably drug delivery route to the brain. Thusthis review focuses on nasal drug delivery, various aspects of nasal anatomy and physiology, nasal drugabsorption mechanisms, various nasal drug delivery systems and their applications in drug delivery.
G T Kulkarni
Full Text Available
Nanoemulsion has been identified as a promising delivery system for various drugs including biopharmaceuticals. Nanoemulsion is a heterogeneous system composed of one immiscible liquid dispersed as droplets within another liquid. The droplets size of nano emulsion is between 20 to 500 nm. Diameter and surface properties of droplets of nanoemulsion plays an important role in the biological behavior of the formulation. Small droplet sizes lead to transparent emulsions so that product appearance is not altered by the addition of an oil phase. In this paper various aspects of nanoemulsion have been discussed including advantages, disadvantages and methods of preparation. Furthermore new approaches of stability of formulation, effect of types and concentration of surfactant, process variables and method are also discussed to improve the stability of nanoemulsion formulation
Izhar Ahmed Syed
Full Text Available The “Liquisolid” technique is a novel and capable addition towards such an aims for solubility enhancement and dissolution improvement, thereby it increases the bioavailability. It contains liquid medications in powdered form. This technique is an efficient method for formulating water insoluble and water soluble drugs. This technique is based upon the admixture of drug loaded solutions with appropriate carrier and coating materials. The use of non-volatile solvent causes improved wettability and ensures molecular dispersion of drug in the formulation and leads to enhance solubility. By using hydrophobic carriers (non-volatile solvents one can modify release (sustained release of drugs by this technique. Liquisolid system is characterized by flow behavior, wettability, powder bed hydrophilicity, saturation solubility, drug content, differential scanning calorimetry, Fourier transform infra red spectroscopy, powder X-ray diffraction, scanning electron microscopy, in-vitro release and in-vivo evaluation. By using this technique, solubility and dissolution rate can be improved, sustained drug delivery systems be developed for the water soluble drugs.
American Psychologist, 2013
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…
Singh, Deependra; Pradhan, Madhulika; Nag, Mukesh; Singh, Manju Rawat
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
Shaji Jessy; Shinde Amol B
Pulsatile drug delivery aims to release drugs in a planned pattern i.e. at appropriate time and/or at a suitable site of action. Pharmaceutical invention and research are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. However, in recent pharmaceutical applications involving pulsatile delivery, multiparticulate dosage forms are gaining much favour over single-unit dosage forms because of their potential benefits like pred...
We have developed a multiportal compensator system for IMRT delivery, comprising a rotational compensator mount for a linac head, cylindrical compensator enclosures positioned in the mount, a vacuum-formed thermoplastic sheet with heavy alloy granules inside the enclosure, and a vacuum thermoforming device. The mount rotates like a revolver by a stepping motor, thus allowing automatic multiportal IMRT without exchanging compensators by human operators during treatment. The thermoforming device has servo-motor-driven 10x10 metal rod elements to actualize an arbitrary intensity profile. The thermoplastic sheet is preheated by a built-in biplanar heater and then it is placed over the rod elements. Subsequently, vacuum forming is performed through corner cut-outs of the rod elements. After forced cooling down, the heavy alloy granules are fed into the formed sheet. Preliminary experiment using solid water phantoms and an x-ray film has shown that the intensity profile on the film agrees reasonably well with the desired profile
Matias J. Cardoso
Full Text Available Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.
Cardoso, Matias J; Costa, Rui R; Mano, João F
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
India, Israel, Pakistan, and south Africa are today each capable of building nuclear arms and if they have not done so already, could well be prepared to deploy such weapons in any future war. Although attention has been focused over the years on how these and other emerging nuclear nations have progressed toward the acquisition of nuclear weapons capabilities, it is becoming increasingly important to understand how such capabilities, once acquired, may be militarized---that is, transformed into small nuclear forces. An early and essential first step in this process is the mating of nuclear weapons with the mean for delivering them to enemy targets. Over the next decade, the delivery systems potentially available to the new nuclear states will fall into two principal categories: manned aircraft and ballistic missiles. (Cruise missiles are a third possibility, but one that appears more remote at present.) This paper reports on a number of the de facto nuclear-weapons states, along with several other industrializing countries, are today producing jet combat aircraft and military missiles
Dvorak, Rudolf; Süli, Áron; Sándor, Zsolt; Galiazzo, Mattia; Pilat-Lohinger, Elke
As part of the national scientific network 'Pathways to Habitable Worlds' the delivery of water onto terrestrial planets is a key question since water is essential for the development of life as we know it. After summarizing the state of the art we show some first results of the transport of water in the early Solar System for scattered main belt objects. Hereby we investigate the questions whether planetesimals and planetesimal fragments which have gained considerable inclination due to the strong dynamical interactions in the main belt region around 2 AU can be efficient water transporting vessels. The Hungaria asteroid group is the best example that such scenarios are realistic. Assuming that the gas giants and the terrestrial planets are already formed, we monitor the collisions of scattered small bodies containing water (in the order of a few percent) with the terrestrial planets. Thus we are able to give a first estimate concerning the respective contribution of such bodies to the actual water content i...
Full Text Available Abstract Background The accurate quantification of antigens at low concentrations over a wide dynamic range is needed for identifying biomarkers associated with disease and detecting protein interactions in high-throughput microarrays used in proteomics. Here we report the development of an ultrasensitive quantitative assay format called immunoliposome polymerase chain reaction (ILPCR that fulfills these requirements. This method uses a liposome, with reporter DNA encapsulated inside and biotin-labeled polyethylene glycol (PEG phospholipid conjugates incorporated into the outer surface of the liposome, as a detection reagent. The antigenic target is immobilized in the well of a microplate by a capture antibody and the liposome detection reagent is then coupled to a biotin-labeled second antibody through a NeutrAvidin bridge. The liposome is ruptured to release the reporter DNA, which serves as a surrogate to quantify the protein target using real-time PCR. Results A liposome detection reagent was prepared, which consisted of a population of liposomes ~120 nm in diameter with each liposome possessing ~800 accessible biotin receptors and ~220 encapsulated reporters. This liposome detection reagent was used in an assay to quantify the concentration of carcinoembryonic antigen (CEA in human serum. This ILPCR assay exhibited a linear dose–response curve from 10-10 M to 10-16 M CEA. Within this range the assay coefficient of variance was Conclusions The ILPCR assay has several advantages over other immuno-PCR methods. The reporter DNA and biotin-labeled PEG phospholipids spontaneously incorporate into the liposomes as they form, simplifying preparation of the detection reagent. Encapsulation of the reporter inside the liposomes allows nonspecific DNA in the assay medium to be degraded with DNase I prior to quantification of the encapsulated reporter by PCR, which reduces false-positive results and improves quantitative accuracy. The ability to
Rossi, Filippo; Masi, Maurizio
This book offers a state-of-the-art overview of controlled drug delivery systems, covering the most important innovative applications. The principles of controlled drug release and the mechanisms involved in controlled release are clearly explained. The various existing polymeric drug delivery systems are reviewed, and new frontiers in material design are examined in detail, covering a wide range of polymer modification techniques. The concluding chapter is a case study focusing on use of a drug-eluting stent. The book is designed to provide the reader with a complete understanding of the mechanisms and design of controlled drug delivery systems, and to this end includes numerous step-by-step tutorials. It illustrates how chemical engineers can advance medical care by designing polymeric delivery systems that achieve either temporal or spatial control of drug delivery and thus ensure more effective therapy that eliminates the potential for both under-and overdosing.
Alexander Jeffrey A
Full Text Available Abstract Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned. This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1 modeling intervention context; (2 measuring readiness for change; (3 assessing intervention fidelity and sustainability; (4 assessing complex, multicomponent interventions; and (5 incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ, US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on
Paulsen, G.; Yoon, S.; Zacny, K.; Wettergreeng, D.; Cabrol, N. A.
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
Yalin, Azer; Willson, Bryan; Defoort, Morgan; Joshi, Sachin; Reynolds, Adam
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.
Etrych, Tomáš; Chytil, Petr; Šírová, Milada; Hoffman, S.; Müller, T.; Mäder, K.; Říhová, Blanka; Ulbrich, Karel
Roč. 6, Proceedings (2015), s. 67. ISSN 2153-2435. [International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems /5./ - Pharmaceutica 2015. 16.03.2015-18.03.2015, Dubai ] R&D Projects: GA MŠk(CZ) EE2.3.30.0029 Institutional support: RVO:61389013 ; RVO:61388971 Keywords : drug delivery * polymer Subject RIV: CE - Biochemistry
Full Text Available This paper reviews constructed drug delivery systems applying osmotic principles for controlled drugrelease from the formulation. Osmotic devices which are tablets coated with walls of controlled porosityare the most promising strategy based systems for controlled drug delivery. In contrast to commontablets, these pumps provide constant (zero order drug release rate. When these systems are exposed towater, low levels of water soluble additive is leached from polymeric material i.e. semipermeablemembrane and drug releases in a controlled manner over an extended period of time. The main clinicalbenefits of oral osmotic drug delivery system are their ability to improve treatment tolerability andpatient compliance. These advantages are mainly driven by the capacity to deliver drugs in a sustainedmanner, independent of the drug chemical properties, of the patient’s physiological factors or followingfood intake. This review brings out the theoretical concept of drug delivery, history, advantages anddisadvantages of the delivery systems, types of oral osmotic drug delivery systems, factors affecting thedrug delivery system and marketed products.
Wang, Yuehui; Ghoshal, Sarbani; Ward, Martin; de Villiers, Willem; Woodward, Jerold; Eckhardt, Erik
Background A small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate m...
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
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
Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric
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
Full Text Available Niosomes are non-ionic surfactant vesicles inclosing an aqueous phase and a wide range of molecules could be encapsulated within aqueous spaces of lipid membrane vesicles. They are microscopic lamellar structures formed on the admixture of a non-ionic surfactant, cholesterol and phosphate with subsequent hydration in aqueous media. Niosomes belongs to novel drug delivery system which offers a large number of advantages over other conventional and vesicular delivery systems. Namely they are the targeted drug delivery system which showing reduction of dose, stability and compatibility of non-ionic surfactants, easy modification, delayed clearance, suitability for a wide range of Active Pharmaceutical Agents.
Jaimini Manish; Joshi Vishalkumar
The purpose of this review on floating drug delivery systems is the recent literature with mechanism to achieve gastric retention by floatation. Gastroretentive drug delivery system have advantages besides providing better bioavailability to poorly absorbed drugs and a required release profile thus attracting interest of pharmaceutical formulation. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form. The objectives of the review disc...
Alexander Amit; Sharma Sharad; Ajazuddin,; Khan Mohammed Junaid; Swarna
Bioadhesion is an interfacial phenomenon in which two materials, at least one of which is biological, are held together by means of interfacial forces. When the associated biological system is mucous, it is called mucoadhesion. This property of certain polymeric systems have got place in the drug delivery research in order to prolong contact time in the various mucosal route of drug administration, as the ability to maintain a delivery system at a particular location for an extended period of...
Some gas delivery systems used in pulmonary ventilation scanning are unable to satisfactorily supply 133Xe gas to bed-ridden patients. A mechanical gas valve assembly to control the flow of gas in such systems was constructed. A commercially produced 133Xe gas delivery system when fitted with the new assembly was able to ventilate almost all patients whereas previously this could be achieved with approximately only 50% of patients
Dhanasooraj, Dhananjayan; Kumar, R Ajay; Mundayoor, Sathish
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
Full Text Available Conventional drug delivery systems have little control over their drug release and almost no control over the effective concentration at the target site. The major problem associated with conventional drug delivery system is unpredictable plasma concentrations. Controlled drug delivery systems offer spatial control over the drug release. Osmotic pumps are most promising systems for controlled drug delivery. These systems are used for both oral administration and implantation. The present review is concerned with the study of drug release systems which are tablets coated with walls of controlled porosity. . Osmotic pump uses the basic principle of osmosis for release of drug(s. Osmotic pumps consist of an inner core containing drug and osmogens, coated with a semi permeable membrane. As the core absorbs water, it expands in volume, which pushes the drug solution out through the delivery ports. Osmotic pumps release drug at a rate that is independent of the pH and hydrodynamics of the dissolution medium. Various patents available for osmotic drug delivery system like Rose-Nelson pump, Higuchi-leeper pump, higuchi-theeuwes pump and elementary osmotic pump. In this paper, various types of osmotic pump and the basic components of osmotic system tablets have been discussed briefly. Keywords: Osmosis, component of osmotic system, Osmotic pump
Kadam Shashikant M; Kadam.S.R; Patil.U.S; Ratan G N; Jamkandi.V.G.
Controlled release (CR) dosage forms have been extensively used to improve therapy with many important drugs. Several approaches are currently utilized in prolongation of gastric residence time, including floating drug delivery system, swelling and expanding system, polymeric bioadhesive system, modified shape system, high density system and other delayed gastric emptying devices. However, the development processes are faced with several physiological difficulties such as the inability to res...
Brayden, David J; Oudot, Emilie J M; Baird, Alan W
Delivery of biologically active agents to animals is often perceived to be the poor relation of human drug delivery. Yet this field has a long and successful history of species-specific device and formulation development, ranging from simple approaches and devices used in production animals to more sophisticated formulations and approaches for a wide range of species. While several technologies using biodegradable polymers have been successfully marketed in a range of veterinary and human products, the transfer of delivery technologies has not been similarly applied across species. This may be due to a combination of specific technical requirements for use of devices in different species, inter-species pharmacokinetic, pharmacodynamic and physiological differences, and distinct market drivers for drug classes used in companion and food-producing animals. This chapter reviews selected commercialised and research-based parenteral and non-parenteral veterinary drug delivery technologies in selected domestic species. Emphasis is also placed on the impact of endogenous drug transporters on drug distribution characteristics in different species. In vitro models used to investigate carrier-dependent transport are reviewed. Species-specific expression of transporters in several tissues can account for inter-animal or inter-species pharmacokinetic variability, lack of predictability of drug efficacy, and potential drug-drug interactions. PMID:20204584
Chen, Wei; Li, Hui; Shi, De; Liu, Zhenguo; Yuan, Weien
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
Vahid Bagheri; Hossein Motamedi; Masoud Reza Seifiabad Shapouri
Objective:To produce high quantities of recombinant protective antigen (rPA) for human vaccine and diagnosis.Methods: ThePAgene was amplified byPCR with pXO1 plasmid as template. ThePCR product was cloned into pMAL-c2X vector using theBamHI andSalI restriction enzymes. The recombinant plasmid was transformed intoEscherichia coliDH5α strain and then screened for transformation. The expression of protective antigen was analyzed bySDS-PAGE and Western blotting after isopropyl β-D-thiogalactopyranoside(IPTG) induction.Results:The full-length PA gene (2.2kb) was cloned into pMAL vector system. The recombinant vector was confirmed by restriction enzyme andPCRanalysis. The expression of cytoplasmic maltose-binding protein-protective (MBP-P) antigen fusion protein was detected bySDS-PAGE and Western blotting, and obtained a125 kDa protein band, which was similar to expected size of fusion protein.Conclusions: This expression system can be used in the high production of rPA. After purification and immunization studies, the purified rPA may be used in the development of the human recombinant anthrax vaccine and also in diagnosis of anthrax disease.
Li, Zhenyu; Wu, Qinghua; Salamatian, Kavé; Xie, Gaogang
Video delivery performance is the main factor that affects Internet video quality. Characterizing the video delivery performance, especially the delivery throughput, can help content providers as well as Internet service providers (ISPs) in system optimization and network planning. Based on a unique dataset consisting of 20 million video download speed measurements , this paper comprehensively studies the video delivery throughput of a large-scale commercial video-on- demand (VoD) system. We ...
Full Text Available The reason of writing this research article on gastro retentive drug delivery systems was to gather the recent literature with special focus on various gastro retentive approaches that have recently become leading methodologies in the field of site-specific orally administered controlled release drug delivery. In order to identify with various physiological difficulties to achieve gastric retention, we have summarized important factors controlling gastric retention. Afterwards, we have reviewed various gastro retentive approaches designed and developed until now, i.e. microspheres, microcapsules, floating gel beads, floating matrix tablets and in-situ gel, with advantages and limitations of gastro retentive drug delivery systems in detail.
Rajiv Chintaman Yeravdekar
Conclusions: The collective responses obtained could provide the basis for a policy formulation. The policy formulation in turn could be the basis of a national consensus for health care delivery systems operational at higher educational institutions in India.
Elk, M. van
Nanosized drug delivery systems are developed to improve the therapeutic efficacy and to reduce unwanted side effects of existing drugs as well as drug candidates. Liposomes are the most intensively studied drug delivery systems and a number of studies showed that encapsulation of doxorubicin (DOX) in liposomes resulted in an increased therapeutic index particularly due to a significant reduction in unwanted side effects. Nevertheless, the concentration of free drug in the tumor is relatively...
Taksande Jayshree B; Trivedi Rashmi V; Mahore Jayashri G; Wadher Kamlesh J; Umekar Milind J.
Oral delivery of poorly water-soluble drugs creates critical problem for their formulation as 35- 40% of new active pharmaceutical ingredients have poor water solubility and frequently associated with low bioavailability. Recently much attention has been given to lipid-based formulation with particular emphasis on self emulsifying drug delivery system (SEDDS) to improve the oral bioavailability. These can exist in either liquid or solid states. Self-emulsifying system formulation mainly depen...
Mertz, Elizabeth A.; Finocchio, Len
The objective of this paper is to describe the purpose, rationale and key elements of the special issue, Improving Oral Healthcare Delivery Systems through Workforce Innovations. The purpose of the special issue is to further develop ideas presented at the 2009 Institute of Medicine (IOM) workshop, Sufficiency of the U.S. Oral Health Workforce in the Coming Decade. Using the IOM discussions as their starting point, the authors evaluate oral health care delivery system performance for specific...
Pallavi Pal; Vijay Sharma; Lalit Singh
Oral controlled release delivery systems are programmed to deliver the drug in predictable time frame that will increase the efficacy and minimize the adverse effects and increase the bioavailability of drugs. Oral route is considered mostnatural, uncomplicated, convenient and safe due to its ease of administration, patient acceptance, and cost-effective manufacturing process.Floating Drug delivery system are designed to prolong the gastric residence time after oral administration, at particu...
Reshmy Rajan; Shoma Jose; V P Biju Mukund; Deepa T Vasudevan
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 a...
Highlights significance of designing service delivery system, explains the integral role of customer in service production process, stresses the importance of customer-organisation interface, lists important ingredients of service package to be considered while designing customer interface, enumerates various dimensions of customer interface which can be positively made use of in design of service production and delivery system, discusses various ways and means of inducing and enhancing custo...
Tayal Ayushi; Jamil Faraz; Sharma Ritika; Sharma Saurabh
Oral route still remains the favorite route of drug administration in many diseases and till today it is the first wayinvestigated in the development of new dosage forms. Approximately 40 per cent of new drug candidates have poor water solubility and the oral delivery ofsuch drugs is frequently associated with implications of low bioavailability, high intra and inter-subjectvariability, and lack of dose proportionality. Bioavailability problem of lipophillic drugs can be solved byformation of...
Janaswamy, Srinivas; Youngren, Susanne R.
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 GRAS status. Iota-carrageen and curcumin have been chosen as models of hydrocolloid and nutraceutical compound, res...
Ortiz-Mellet, Carmen; García Fernández, José M.; Benito, Juan M.
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...
Bansal, Vivek; Kumar, Manoj; Bhardwaj, Arun; Brahmne, H G; Singh, Harpal
Delivery of antigen through admixture formulation containing poly caprolactone (PCL) and aluminum phosphate was studied as a promising strategy to generate antigen specific immune response. The present study demonstrates the synergistic effect of admixture formulation of PCL with reduced aluminum (PCL-Al 0.2 mg-TT and PCL-PEG-Al 0.2 mg-TT) as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. On evaluation of the magnitude of efficacy for the proposed formulation by ELISA as well as challenge method, persistent and strong antibody response was obtained throughout the 180 day study period on storage at 5 ± 3 °C. In comparison to the aluminum phosphate based conventional tetanus vaccine, higher levels of IFN-γ and IL-4 were obtained with PCL-Al 0.2 mg-TT and PCL-PEG-Al 0.2 mg-TT, indicating the presence of cell mediated as well as humoral immune responses. Histopathology and serum biochemistry profile in mice further indicated the suitability of the proposed formulation. Percent adsorption/encapsulation of the antigen also increased to nearly 95% in the admixture formulation compared to 55% adsorption in the conventional tetanus vaccine. The present study established a useful baseline for designing biocompatible and effective delivery system for toxoid vaccines through judicious use of PCL based biodegradable nanoparticles in combination with aluminum phosphate. PMID:26343498
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...
Full Text Available Novel drug delivery systems present an opportunity for formulation scientists to overcome the many challenges associated with antihypertensive drug therapy, thereby improving the management of patients with hypertension. Currently available Anti-hypertensive drugs can be classified into these categories: ACE inhibitors, angiotensin antagonist, calcium channel blocker, diuretics, central sympathomimetics, á- adernergic blocker, vasodilator, â-adernergic blocker. Most of these drugs bear some significant drawbacks such as relatively short half-life, low bioavailability, poor permeability and undesirable side effects. Efforts have been made to design drug delivery systems for anti hypertensive drugs to: a reduce the dosing frequency, b increase the bioavailability, c deliver them to the target cells selectively with minimal side effects. This paper provides a comprehensive review of the various anti hypertensive drug delivery systems that have been developed for achieving sustained drug release kinetics, and for addressing formulation difficulties such as poor solubility, stability and drug entrapment. The physicochemical properties and the in vitro/in vivo performances of various system such as such as sustained release tablets, ceramic implants, nanoparticles, nanocontainers, liposomes, emulsomes, aspasomes, microemulsions, nanopowders and PheroidTM are summarised. This review highlights the significant potential that novel drug delivery systems have for the future effective treatment of hypertensive patients on anti-hypertensive drug therapy.
Simulation modelling is a powerful analysis tool used to evaluate complex systems or processes. The modeling concept was utilized to evaluate the performance of the Waste Isolation Pilot Plant (WIPP) transportation and delivery system. The model will assist in analyzing the responsiveness of the components in the system to the variations in waste generation schedule, system failures, and material handling options. (author)
Boks, M.A.; Bruijns, Sven C.M.; Ambrosini, Martino; Kalay, Hakan; Bloois, van Louis; Storm, G.; Gruijl, de T.D.; Kooyk, van Y.
Dendritic cells (DCs) have an important role in tumor control via the induction of tumor-specific T-cell responses and are therefore an ideal target for immunotherapy. The human skin is an attractive site for tumor vaccination as it contains various DC subsets. The simultaneous delivery of tumor ant
Boks, Martine A.; Bruijns, Sven C M; Ambrosini, Martino; Kalay, Hakan; Van Bloois, Louis; Storm, G; De Gruijl, Tanja; Van Kooyk, Yvette
Dendritic cells (DCs) have an important role in tumor control via the induction of tumor-specific T-cell responses and are therefore an ideal target for immunotherapy. The human skin is an attractive site for tumor vaccination as it contains various DC subsets. The simultaneous delivery of tumor ant
Milan Agrawal et al
Full Text Available The parenteral administration route is the most effective and common form of delivery for active drug substances with poor bioavailability and the drugs with a narrow therapeutic index. Drug delivery technology that can reduce the total number of injection throughout the drug therapy period will be truly advantageous not only in terms of compliance, but also to improve the quality of the therapy and also may reduce the dosage frequency. Such reduction in frequency of drug dosing is achieved by the use of specific formulation technologies that guarantee the release of the active drug substance in a slow and predictable manner. The development of new injectable drug delivery system has received considerable attention over the past few years. A number of technological advances have been made in the area of parenteral drug delivery leading to the development of sophisticated systems that allow drug targeting and the sustained or controlled release of parenteral medicines.
Snook, Adam E.; Li, Peng; Stafford, Benjamin J.; Elizabeth J. Faul; Huang, Lan; Birbe, Ruth C; Bombonati, Alessandro; Schulz, Stephanie; Schnell, Matthias J.; Eisenlohr, Laurence C.; Waldman, Scott A.
Cancer mucosa antigens comprise an emerging category of self-antigens expressed normally in immunologically privileged mucosal compartments and universally by their derivative tumors (1, 2). These antigens leverage the established immunological partitioning of systemic and mucosal compartments (3, 4), limiting tolerance opposing systemic antitumor efficacy (5). An unresolved issue surrounding self-antigens as immunotherapeutic targets is autoimmunity following systemic immunization (6-8). In ...
Lahoti S.R.; Syed Iftequar; Sabina M; Dehghan M.H.; Shoaib S; Mohiuddin S
The reason of writing this research article on gastro retentive drug delivery systems was to gather the recent literature with special focus on various gastro retentive approaches that have recently become leading methodologies in the field of site-specific orally administered controlled release drug delivery. In order to identify with various physiological difficulties to achieve gastric retention, we have summarized important factors controlling gastric retention. Afterwards, we have review...
Modi Kushal; Modi Monali; Mishra Durgavati; Panchal Mittal; Sorathiya Umesh; Shelat Pragna
Oral drug delivery is the most preferred and convenient option as the oral route provides maximum active surface area among all drug delivery system for administration of various drugs. The attractiveness of these dosage forms is due to awareness to toxicity and ineffectiveness of drugs when administered by oral conventional method in the form of tablets and capsules. Usually conventional dosage form produces wide range of fluctuation in drug concentration in the bloodstream and tissues with ...
Jose S; Dhanya K; Cinu T; Aleykutty N
Targeted delivery of drugs to colon has the potential for local treatment of a variety of colonic diseases. The main objective of the study was to develop a multiparticulate system containing chitosan microspheres for the colon targeted delivery of ondansetron for the treatment of irritable bowel syndrome. This work combines pH-dependent solubility of eudragit S-100 polymers and microbial degradability of chitosan polymers. Chitosan microspheres containing ondansetron were prepared by emulsio...
Misak, Heath E; Asmatulu, Ramazan; Gopu, Janani S; Man, Ka-Poh; Zacharias, Nora M; Wooley, Paul H; Yang, Shang-You
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
A. S. Chudasama
Full Text Available Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation. However, HIV/AIDS patients experience a variety of functional and anatomical abnormalities in gastrointestinal tract that result in diarrhoea and nutrient malabsorption. Medium chain triglycerides are readily absorbed from the small bowel under conditions in which the absorption of long chain triglycerides is impaired. Therefore, nevirapine self-emulsifying drug delivery system containing medium chain fatty acid, caprylic acid and a solubilizer, Soluphor ® P (2-pyrrolidone was developed and found to be superior to the marketed conventional suspension with respect to in vitro diffusion and ex vivo intestinal permeability. This self-emulsifying drug delivery system has now been further investigated for in vivo absorption in an animal model. The contribution of caprylic acid and Soluphor ® P on in vivo absorption of nevirapine was also studied in the present study. The bioavailability of nevirapine from self-emulsifying drug delivery system, after oral administration, was 2.69 times higher than that of the marketed suspension. The improved bioavailability could be due to absorption of nevirapine via both portal and intestinal lymphatic routes. The study indicates that medium chain or structured triglycerides can be a better option to develop self-emulsifying drug delivery system for lipophilic and extensively metabolised drugs like nevirapine for patients with AIDS-associated malabsorption.
Chudasama, A S; Patel, V V; Nivsarkar, M; Vasu, Kamala K; Shishoo, C J
Nevirapine is a highly lipophilic and water insoluble non-nucleoside reverse transcriptase inhibitor used for the treatment of HIV-1 infection. Lymphoid tissue constitutes the major reservoir of HIV virus and infected cells in HIV-infected patients. Self-emulsifying drug delivery system, using long chain triglycerides, is a popular carrier of drugs due to their ability to transport lipophilic drugs into the lymphatic circulation. However, HIV/AIDS patients experience a variety of functional and anatomical abnormalities in gastrointestinal tract that result in diarrhoea and nutrient malabsorption. Medium chain triglycerides are readily absorbed from the small bowel under conditions in which the absorption of long chain triglycerides is impaired. Therefore, nevirapine self-emulsifying drug delivery system containing medium chain fatty acid, caprylic acid and a solubilizer, Soluphor(®) P (2-pyrrolidone) was developed and found to be superior to the marketed conventional suspension with respect to in vitro diffusion and ex vivo intestinal permeability. This self-emulsifying drug delivery system has now been further investigated for in vivo absorption in an animal model. The contribution of caprylic acid and Soluphor(®) P on in vivo absorption of nevirapine was also studied in the present study. The bioavailability of nevirapine from self-emulsifying drug delivery system, after oral administration, was 2.69 times higher than that of the marketed suspension. The improved bioavailability could be due to absorption of nevirapine via both portal and intestinal lymphatic routes. The study indicates that medium chain or structured triglycerides can be a better option to develop self-emulsifying drug delivery system for lipophilic and extensively metabolised drugs like nevirapine for patients with AIDS-associated malabsorption. PMID:25035533
Yadav Nisha R.
Full Text Available Probiotic are bacteria that help to maintain the natural balance of the microorganism in the intestine. Probiotic is gaining its popularity as an alternate approach for the healthcare management and till now has proofed its therapeutic indication in many simple to complex diseases. Diverse mechanism of action and being a living organism are two main advantages. However there are several drawbacks also associated with this new emerging therapeutic area. Probiotic strain identification, characterization, screening, understanding its mechanism of action for particular disease which is seeking much attention. The primary aim associated with the probiotic delivery is maintaining bacteria viability during product manufacturing and during storage. Several approaches such as microencapsulation and use of suitable biocompatible material have been studied and still under continuous exploration. Along with the regulatory aspect associated with the probiotics in this review details on current research in the area of exploring indication and advancement in delivery technologies has been covered. Review concluded with rational recommendations of each aspect of probiotics.
Full Text Available With the discovery of insulin in 1922, identification and commercialization of potential protein and peptide drugs have been increased. Since then, research and development to improve the means of delivering protein therapeutics to patients has begun. The research efforts have followed two basic pathways: One path focused on noninvasive means of delivering proteins to the body and the second path has been primarily aimed at increasing the biological half-life of the therapeutic molecules. The search for approaches that provide formulations that are stable, bioavailable, readily manufacturable, and acceptable to the patient, has led to major advances in the development of nasal and controlled release technology, applicable to every protein or peptide. In several limited cases, sustained delivery of peptides and proteins has employed the use of polymeric carriers. More successes have been achieved by chemical modification using amino acid substitutions, protein pegylation or glycosylation to improve the pharmacodynamic properties of certain macromolecules and various delivery systems have been developed like the prolease technology, nano-particulate and microparticulate delivery systems, and the mucoadhesive delivery of peptides. The needle and syringe remain the primary means of protein delivery. Major hurdles remain in order to overcome the combined natural barriers of drug permeability, drug stability, pharmacokinetics, and pharmacodynamics of protein therapeutics. In our present review we have tried to compile some recent advances in protein and peptide drug delivery systems.
This document defines the systems engineering processes and products planned by the Waste Feed Delivery Program to develop the necessary and sufficient systems to provide waste feed to the Privatization Contractor for Phase 1. It defines roles and responsibilities for the performance of the systems engineering processes and generation of products
Janaswamy, Srinivas; Youngren, Susanne R. (Purdue)
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.
Pichichero, Michael E
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
Full Text Available 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.
Yavuz, Burçin; Pehlivan, Sibel Bozdağ; Unlü, Nurşen
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