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Polymeric Carriers (polymeric + carrier)
Selected AbstractsSwelling characteristics and drug delivery properties of nifedipine-loaded pH sensitive alginate,chitosan hydrogel beadsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2008Ya-Ni Dai Abstract The aim of the present work was to investigate the swelling behavior and in vitro release of nifedipine from alginate,chitosan hydrogel beads. Structure and surface morphology of the hydrogel were characterized by FTIR and SEM, respectively. Alginate,chitosan mixed beads and alginate,chitosan coated beads were prepared by ionic gelation method. The swelling ability of the beads and in vitro release of nifedipine in simulated gastric fluid (pH 1.5) and different phosphate buffer solutions (pH 2.5, 5.0, 6.8, 7.4, and 8.0) were found to be dependent on the presence of the polyelectrolyte complex between chitosan and alginate. The amount of nifedipine released from the mixed beads at pH 1.5 was relatively low (42%), whereas this value approached to 99% at pH 6.8. In comparison with the mixed beads, the released nifedipine from the coated beads was minimal at pH 1.5 (18%), whereas ,99% nifedipine was released at pH 6.8. The results suggested that the coated beads can hold drug better at low pH than the mixed beads and show excellent pH sensitivity. Therefore, the alginate,chitosan coated beads could be a suitable polymeric carrier for drug delivery in the intestinal tract. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008 [source] Review: physical chemistry of solid dispersionsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2009Sandrien Janssens Abstract Objectives With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state. Key findings After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life. Conclusions Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development. [source] C. botulinum inactivation kinetics implemented in a computational model of a high-pressure sterilization processBIOTECHNOLOGY PROGRESS, Issue 1 2009Pablo Juliano Abstract High-pressure, high-temperature (HPHT) processing is effective for microbial spore inactivation using mild preheating, followed by rapid volumetric compression heating and cooling on pressure release, enabling much shorter processing times than conventional thermal processing for many food products. A computational thermal fluid dynamic (CTFD) model has been developed to model all processing steps, including the vertical pressure vessel, an internal polymeric carrier, and food packages in an axis-symmetric geometry. Heat transfer and fluid dynamic equations were coupled to four selected kinetic models for the inactivation of C. botulinum; the traditional first-order kinetic model, the Weibull model, an nth-order model, and a combined discrete log-linear nth-order model. The models were solved to compare the resulting microbial inactivation distributions. The initial temperature of the system was set to 90°C and pressure was selected at 600 MPa, holding for 220 s, with a target temperature of 121°C. A representation of the extent of microbial inactivation throughout all processing steps was obtained for each microbial model. Comparison of the models showed that the conventional thermal processing kinetics (not accounting for pressure) required shorter holding times to achieve a 12D reduction of C. botulinum spores than the other models. The temperature distribution inside the vessel resulted in a more uniform inactivation distribution when using a Weibull or an nth-order kinetics model than when using log-linear kinetics. The CTFD platform could illustrate the inactivation extent and uniformity provided by the microbial models. The platform is expected to be useful to evaluate models fitted into new C. botulinum inactivation data at varying conditions of pressure and temperature, as an aid for regulatory filing of the technology as well as in process and equipment design. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Evaluation of the potential of polymeric carriers based on chitosan- grafted -polyacrylonitrile in the formulation of drug delivery systemsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 3 2010A. A. Sarhan Abstract Graft copolymerization of chitosan with acrylonitrile (AN) was carried out by free radical polymerization using KMnO4 and oxalic acid as a combined redox initiator system. Graft copolymerization was confirmed by Fourier transform infrared spectra (FTIR), proton nuclear magnetic resonance spectra (1H-NMR), thermal gravimetric analysis (TGA) measurements, and wide angle X-ray diffraction (WAXD). In addition, further modification of the cyano groups of the grafted copolymers was performed by partial hydrolysis into carboxylic function groups with various extents. The extent of hydrolysis was monitored using FTIR spectroscopy. The potential of the hydrolyzed and unhydrolyzed grafted copolymers as polymeric carriers for drug delivery systems was extensively studied by preparation of tablets incorporated with methyl orange (MO) as a drug model. In vitro drug release was carried out in simulated gastric and intestinal conditions. The effects of grafting percentage (GP) and the extent of hydrolysis on the release kinetics were evaluated. Release continued up to 24 h for both hydrolyzed and unhydrolysed chitosan- g -PAN copolymers. The nature of drug transport through the polymer matrices was studied by comparing with power law or Kormeyer-Peppas equation. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] Efficacy of chitosan microspheres for controlled intra-articular delivery of celecoxib in inflamed jointsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004Hetal Thakkar The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. In this study, we aimed to prepare celecoxib-loaded chitosan microspheres for intra-articular administration and to compare the retention of the celecoxib solution and chitosan microspheres in the joint cavity. The microspheres were characterized for entrapment efficiency, particle size and surface morphology by scanning electron microscopy. In-vitro drug release studies of microspheres revealed that the microspheres are able to control the release of celecoxib over a period of 96 h. Biodistribution studies of celecoxib and chitosan microspheres were performed by radiolabelling with 99mTc and injecting intra-articularly in rats. The study indicated that following intra-articular administration the distribution of the drug to the organs, like liver and spleen, is very rapid compared with that of the microspheres. Compared with the drug solution, a 10-fold increase in the concentration of the drug in the joint was observed 24 h post intra-articular injection (P < 0.005) when drug was encapsulated in microspheres. [source] ,Smart' delivery systems for biomolecular therapeuticsORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 3 2005PS Stayton Structured Abstract Authors ,, Stayton PS, El-Sayed MEH, Murthy N, Bulmus V, Lackey C, Cheung C, Hoffman AS Objective ,, There is a strong need for drug delivery systems that can deliver biological signals from biomaterials and tissue engineering scaffolds, and a particular need for new delivery systems that can efficiently deliver biomolecules to intracellular targets. Viruses and pathogens have evolved potent molecular machinery that sense the lowered pH gradient of the endosomal compartment and become activated to destabilize the endosomal membrane, thereby enhancing protein or DNA transport to the cytoplasmic compartment. A key feature of many of these biological delivery systems is that they are reversible, so that the delivery systems are not directly toxic. These delivery systems have the ability to change their structural and functional properties and thus display remarkable ,smart' material properties. The objective of this presentation is to review the initial development of smart polymeric carriers that mimic these biological delivery systems and combine similar pH-sensitive, membrane-destabilizing activity for the delivery of therapeutic biomolecules. Design ,, We have developed new ,smart' polymeric carriers to more effectively deliver and broaden the available types of biomolecular therapeutics. The polymers are hydrophilic and stealth-like at physiological pH, but become membrane-destabilizing after uptake into the endosomal compartment where they enhance the release of therapeutic cargo into the cytoplasm. They can be designed to provide a range of pH profiles and membrane-destabilizing activities, allowing their molecular properties to be matched to specific drugs and loading ranges. A versatile set of linker chemistries is available to provide degradable conjugation sites for proteins, nucleic acids, and/or targeting moieties. Results ,, The physical properties of several pH-responsive polymers were examined. The activity and pH profile can be manipulated by controlling the length of hydrophobic alkyl segments. The delivery of poly(propyl acrylic acid) (PPAA)-containing lipoplexes significantly enhanced wound healing through the interconnected effects of altered extracellular matrix organization and greater vascularization. PPAA has also been shown to enhance cytoplasmic delivery of a model protein therapeutic. Polymeric carriers displaying pH-sensitive, membrane-destabilizing activity were also examined. The pH profile is controlled by the choice of the alkylacrylic acid monomer and by the ratio of the carboxylate-containing alkylacrylic acid monomer to alkylacrylate monomer. The membrane destabilizing activity is controlled by the lengths of the alkyl segment on the alkylacrylic acid monomer and the alkylacrylate monomer, as well as by their ratio in the final polymer chains. Conclusion ,, The molecular mechanisms that proteins use to sense and destabilize provide interesting paradigms for the development of new polymeric delivery systems that mimic biological strategies for promoting the intracellular delivery of biomolecular drugs. The key feature of these polymers is their ability to directly enhance the intracellular delivery of proteins and DNA, by destabilizing biological membranes in response to vesicular compartment pH changes. The ability to deliver a wide variety of protein and nucleic acid drugs to intracellular compartments from tissue engineering and regenerative scaffolds could greatly enhance control of important processes such as inflammation, angiogenesis, and biomineralization. [source] Inhibition of LPS-induced chemokine production in human lung endothelial cells by lipid conjugates anchored to the membraneBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2002G Ch Beck In acute respiratory distress syndrome (ARDS) induced by endotoxins, a high production of inflammatory mediators by microvascular lung endothelial cells (LMVEC) can be observed. Activation of cells by endotoxins may result in elevated secretion of phospholipase A2 (sPLA2) which is thought to contribute to tissue damage. The present study was undertaken to investigate the role of sPLA2 in chemokine production in human lung microvascular endothelial cells (LMVEC) stimulated with the endotoxins lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In particular, we investigated the effects of sPLA2 inhibitors, specifically, the extracellular PLA2 inhibitors (ExPLIs), composed of N-derivatized phosphatidyl-ethanolamine linked to polymeric carriers, and LY311727, a specific inhibitor of non-pancreatic sPLA2. ExPLIs markedly inhibited LPS and LTA induced production and mRNA expression of the neutrophile attracting chemokines IL-8, Gro-, and ENA-78, as well as of the adhesion molecules ICAM-1 and E-selectin. Concomitantly, ExPLIs inhibited the LPS-induced activation of NF-,B by LPS but not its activation by TNF-, or IL-1. Endotoxin mediated chemokine production in LMVEC seems not to involve PLA2 activity, since LPS stimulation was not associated with activation of intracellular or secreted PLA2. It therefore seems that the inhibitory effect of the ExPLIs was not due to their PLA2 inhibiting capacity. This was supported by the finding that the LPS-induced chemokine production was not affected by the selective sPLA2 inhibitor LY311727. It is proposed that the ExPLIs may be considered a prototype of potent suppressors of specific endotoxin-induced inflammatory responses, with potential implications for the therapy of subsequent severe inflammation. British Journal of Pharmacology (2002) 135, 1665,1674; doi:10.1038/sj.bjp.0704618 [source] | |||||||||||||