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International Journal of Pharmacy and Biological Sciences , 2011,
Abstract: Nanaocochleate represent a new technology for oral and systemic delivery of drugs. It is a novel lipid-based system which represent a unique technology platform suitable for the oral and systemic administration of a wide variety of molecules with important therapeutic biological activities, including drugs, genes, and vaccine antigens. Nanocochleate formulation technology is particularly applicable to macromolecules as well as small molecule drugs that are hydrophobic, positively charged, negatively charged, and that possess poor oral bioavailability. Proof-of-principle studies for cochleate-mediated oral delivery of macromolecules as well as small molecule drugs is being carried out in appropriate animal models with well established, clinically important drugs, which currently can only be effectively delivered by injection.
Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism  [PDF]
Greice Krautz-Peterson,Yongrong Zhang,Kevin Chen,George A. Oyler,Hanping Feng,Charles B. Shoemaker
Journal of Toxicology , 2012, DOI: 10.1155/2012/760142
Abstract: Botulinum neurotoxins (BoNTs) deliver a protease to neurons which can cause a flaccid paralysis called botulism. Development of botulism antidotes will require neuronal delivery of agents that inhibit or destroy the BoNT protease. Here, we investigated the potential of engineering Clostridium difficile toxin B (TcdB) as a neuronal delivery vehicle by testing two recombinant TcdB chimeras. For AGT-TcdB chimera, an alkyltransferase (AGT) was appended to the N-terminal glucosyltransferase (GT) of TcdB. Recombinant AGT-TcdB had alkyltransferase activity, and the chimera was nearly as toxic to Vero cells as wild-type TcdB, suggesting efficient cytosolic delivery of the AGT/GT fusion. For AGT-TcdB-BoNT/A-Hc, the receptor-binding domain (RBD) of TcdB was replaced by the equivalent RBD from BoNT/A (BoNT/A-Hc). AGT-TcdB-BoNT/A-Hc was >25-fold more toxic to neuronal cells and >25-fold less toxic to Vero cells than AGT-TcdB. Thus, TcdB can be engineered for cytosolic delivery of biomolecules and improved targeting of neuronal cells. 1. Introduction Clostridial toxins in nature are remarkably efficient cell cytosol delivery vehicles with highly evolved cell-specific delivery features that may be ideal for therapeutic applications. Specifically these toxins (1) gain entry to animals; (2) survive in blood; (3) bind to target cells expressing a specific receptor; (4) penetrate the target cells; (5) deliver an enzymatically active cargo to the cytosol. C. difficile toxins A and B (TcdA and TcdB) contain a receptor-binding domain (RBD) that binds to receptors that are broadly expressed on cells and then enters by endocytosis. Once in the endosome, the toxins employ a translocation domain (TD) to deliver a glucosyltransferase (GT) to the cytosol which inactivates Rho GTPases and leads to cell death [1]. The toxins also contain a cysteine protease (CPD), located between GT and TD, that cleaves the GT enzymatic “cargo” from the “delivery vehicle” at the endosomal membrane and liberates it into the cytosol [2–4]. C. difficile bacteria generally reside in the gut where the released toxins intoxicate intestinal epithelial cells and cause the disruption of tight junctions of epithelium and its barrier function. It is likely that in severe cases of the infection, the toxins penetrate into the submucosa and disseminate systemically [5]. We recently identified C. difficile toxins in the blood of the experimentally infected animals [6, 7], suggesting that the toxins may be reasonably stable in serum. Recent developments have enabled the application of TcdA and TcdB as therapeutic
Microemulsions : As Novel Drug Delivery Vehicle  [cached]
Mrunali R. Pate Mrunali R. Patel,Mr. Rashmin B. Patel,Dr Jolly R Parikh,Dr Kashyap K. Bhatt
Pharmaceutical Reviews , 2007,
Abstract: The design and development of new drug delivery systems with the intention of enhancing the efficacy of existing drugs is an ongoing process in pharmaceutical research. It is necessary for a pharmaceutical solution to contain a therapeutic dose of the drug in a volume convenient for administration.-1Dispersions of oil and water are commonly employed in the pharmaceutical industry. These dispersions can be classified in three major categories: 2 1. Microemulsions 2. Micellar Solutions 3. Conventional Emulsions (or) Macroemulsions
Centrifugal spun ultrafine fibrous web as a potential drug delivery vehicle
V. R. Giri Dev,L. Amalorpava Mary,T. Senthilram,S. Suganya
eXPRESS Polymer Letters , 2013, DOI: 10.3144/expresspolymlett.2013.22
Abstract: Centrifugal spinning (C-spin) is one of the emerging techniques for the production of ultrafine fibrous web which mimics Extracellular matrix (ECM). Due to its unique characteristic features it is widely used in bio-medical applications such as tissue engineered scaffolds, wound dressing materials and drug delivery vehicles. In the present study tetracycline loaded polycaprolactone (PCL) blended polyvinyl pyrrolidone (PVP) fibers were fabricated using in-house built C-spin system. The developed ultrafine fibers were morphologically characterized by Scanning Electron Microscope (SEM) before and after drug release and the results showed that the developed webs were highly porous and the pores were evenly distributed. Fourier Transform Infrared (FTIR) spectroscopy results confirmed that the drug was incorporated on the fibers. The antibacterial activity and drug releasing strategy were examined and the results showed that the developed webs can effectively act as a drug delivery vehicle.
Preeti K Suresh*,Satish K Suryawani,Divya Dewangan
Pharmacie Globale : International Journal of Comprehensive Pharmacy , 2011,
Abstract: Multicomponent drug delivery systems have found several potential diagnostic and therapeutic applications. Among these the interpenetrating polymeric network (IPN) has emerged as one of the most useful novel biomaterial, which is entanglement of polymer networks with at least one network synthesized and/or cross-linked in the presence of the other. The development of IPN is attractive because they provide free volume space for the easy encapsulation of drugs in the three-dimensional network structure which are obtained by cross-linking of two or more polymer network. This review focuses on the IPN hydrogels based on chitosan for oral drug delivery applications. Chitosan is a natural, biodegradable, nontoxic, mucoadhesive and biocompatible polymer and has found diverse pharmaceutical applications. Chitosan based IPN hydrogels have garnered immense attention as a vehicle for oral drug delivery. The suitability of chitosan based IPN hydrogels as potential oral delivery vehicle stems from their capability of imbibing large amount of body fluid without solubilisation and potential for encapsulation of large amount of drugs, adaptability to be combined with specific responsive polymer(s). This review also summarizes IPN and various multicomponent polymeric materials for developing drug delivery vehicle.
Non-Aqueous Emulsion : Versatile Vehicle For Drug Delivery  [cached]
Mr.Santosh Payghan,Mr.Mahesh Bhat,Dr.D.N.Shrivastava,Mr.Emmanuel Toppo
Pharmaceutical Reviews , 2008,
Abstract: The delivery of poorly water-soluble drugs has been the subject of much research, as approximately 40% of new chemical entities are hydrophobic in nature. One area in which published literature is lacking is the field of non-aqueous emulsions. This review gives a conceptual idea about non-aqueous system. Non-aqueous systems are well known as solvents for drugs, suspension vehicles, oleogels, soft gelatin or magnoresponsive drug delivery system. It provides reservoir vehicles for transdermal systems and controlled drug delivery systems or hydrolytically unstable drugs.
Entrapment of ketorolac tromethamine in polymeric vehicle for controlled drug delivery  [cached]
Paliwal S,Chauhan Rajani,Sharma Veena,Majumdar D
Indian Journal of Pharmaceutical Sciences , 2009,
Abstract: The most common method for applying a drug in to the eye is to formulate the drug in the form of an eye drop, but this method is not considered ideal for ocular delivery of drug because of poor bioavailability arising from precorneal loss processes, this loss of drug from the precorneal area is a net effect of drainage, tear secretion and noncorneal absorption. Following the above lead we tried to improve the ocular bioavailability by increasing the corneal contact time and the feasible way was to formulate a drug with mucoadhesive/viscosity imparting agents. The adhesive strength of various polymers on corneal surface was studied with the help of self modified Franz diffusion cell and freshly excised goat/bovine cornea. The polymers hydroxypropylmethylcellulose, carboxymethylcellulose sodium, Eudragit type E/RL/RS, Carbopol ETD 2020 and Carbopol 934 National Formulary were formulated with drug, ketorolac tromethamine. The adhesive strength of polymers on corneal surface and permeation characteristics of drug through cornea were investigated by using above said formulations. Eudragit type E/RL/RS did not show any improvement in mucoadhesion, but the formulations containing Carbopol ETD 2020 and Carbopol 934 national formulary showed good mucoadhesion on corneal surface in the concentration as low as 0.75%. The mucoadhesive strength was also evaluated using the combination of Carbopol acrylates/C 10-30 alkylacrylate with allylpentaerithrital and preservative benzalkonium chloride, which also resulted in good mucoadhesion with improved corneal permeation. Observations made in this study indicate the potentiality of the ophthalmic formulations containing mucoadhesive/viscosity imparting agents.
Surface engineering of macrophages with nanoparticles to generate a cell–nanoparticle hybrid vehicle for hypoxia-targeted drug delivery
Christopher A Holden, Quan Yuan, W Andrew Yeudall, et al
International Journal of Nanomedicine , 2010, DOI: http://dx.doi.org/10.2147/IJN.S8339
Abstract: rface engineering of macrophages with nanoparticles to generate a cell–nanoparticle hybrid vehicle for hypoxia-targeted drug delivery Original Research (6733) Total Article Views Authors: Christopher A Holden, Quan Yuan, W Andrew Yeudall, et al Published Date December 2009 Volume 2010:5 Pages 25 - 36 DOI: http://dx.doi.org/10.2147/IJN.S8339 Christopher A Holden1, Quan Yuan1, W Andrew Yeudall2,3, Deborah A Lebman3,4, Hu Yang1 1Department of Biomedical Engineering, School of Engineering, 2Philips Institute of Oral and Craniofacial Molecular Biology, School of Dentistry, 3Massey Cancer Center, 4Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA Abstract: Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluoresceinlabeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.
Effect of Surface-Modified Paclitaxel Nanowires on U937 Cells In Vitro: A Novel Drug Delivery Vehicle
Mohamed H. Abumaree,Salem Al-Suwaidan,Rabih O. Al-Kaysi
Journal of Nanomaterials , 2012, DOI: 10.1155/2012/328520
Abstract: We have fabricated surface-modified paclitaxel nanowires (SM-PNs) with a precise diameter and an average length of 50 μm. The surface of these nanowires is coated with a monolayer of octadecylsiloxane (ODS), which prevents aggregation and enhances dispersivity in aqueous media. This system constitutes a novel drug delivery vehicle based on one-dimensional (1D) nanostructures with a large drug to vehicle ratio. We assayed the cytotoxicity of different diameter SM-PNs (200, 80, 35, and 18 nm) with U937 cells and compared their activity to microcrystalline paclitaxel. SM-PNs reduced U937 cell proliferation in culture followed by cell death. For the same amount of paclitaxel, different diameter SM-PNs displayed different cytotoxic effect at the same incubation time period. SM-PNs with 35 nm diameters were the most efficient in completely halting cell proliferation following the first 24 hours of treatment, associated with 42% cell death. SM-PNs with 18 nm diameters were least effective. These SM-PNs can be tailored to fit a certain treatment protocol by simply choosing the appropriate diameter.
Bacterial Growth Kinetics under a Novel Flexible Methacrylate Dressing Serving as a Drug Delivery Vehicle for Antiseptics  [PDF]
Christina Forstner,Johannes Leitgeb,Rupert Schuster,Verena Dosch,Axel Kramer,Keith F. Cutting,David J. Leaper,Ojan Assadian
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms140510582
Abstract: A flexible methacrylate powder dressing (Altrazeal ?) transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth kinetics in combination with three antiseptics was investigated in an in vitro porcine wound model. Standardized in vitro wounds were contaminated with Staphylococcus aureus (MRSA; ATCC 33591) and divided into six groups: no dressing (negative control), methacrylate dressing alone, and combinations with application of 0.02% Polyhexamethylene Biguanide (PHMB), 0.4% PHMB, 0.1% PHMB?+ 0.1% betaine, 7.7 mg/mL Povidone-iodine (PVP-iodine), and 0.1% Octenidine-dihydrochloride (OCT) + 2% phenoxyethanol. Bacterial load per gram tissue was measured over five days. The highest reduction was observed with PVP-iodine at 24 h to log 10 1.43 cfu/g, followed by OCT at 48 h to log 10 2.41 cfu/g. Whilst 0.02% PHMB resulted in a stable bacterial load over 120 h to log 10 4.00 cfu/g over 120 h, 0.1% PHMB + 0.1% betaine inhibited growth during the first 48 h, with slightly increasing bacterial numbers up to log 10 5.38 cfu/g at 120 h. These results indicate that this flexible methacrylate dressing can be loaded with various antiseptics serving as drug delivery system. Depending on the selected combination, an individually shaped and controlled antibacterial effect may be achieved using the same type of wound dressing.
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