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Evaluation of microencapsulated gentamicin on Escherichia coli in gram negative sepsis

Posted on:2006-12-15Degree:Ph.DType:Dissertation
University:Mercer UniversityCandidate:Haswani, Dinesh KFull Text:PDF
GTID:1454390008462559Subject:Health Sciences
Abstract/Summary:
Biodegradable Microspheres (MS) showing targeting ability, prolonged release, sustained action has opened a new field in drug delivery. The first biodegradable and biocompatible albumin MS were formulated in 1970's, earlier used for diagnostic purposes in detecting abnormalities of reticuloendothelial system (RES) and estimation of the activation of macrophages, now their importance in drug delivery systems is well understood and documented. Albumin MS are easily metabolized and the factors influencing its metabolism are the size of particles, degree of stabilization and the site of metabolism (Bernard et al.).; Gentamicin is one of the aminoglycosides and an important group of antibiotic used against bacterial infection especially in severe sepsis. Gentamicin is usually administered in the IV solution form, it has several disadvantages such as systemic toxicity due to high dose administration; need to be frequently administered due to short half-life. Gentamicin in solution form has a poor penetration into the macrophages or the endothelial cell membrane hence it is unable to treat the intracellular infection which may be caused by the organism such as an internalized Escherichia coli or S.aureus in the endothelial cell, which may eventually damage the endothelium and may lead to severe septic shock condition and cause death of the patient. A biodegradable carrier system in the form of microspheres, liposomes etc. obviates the need to administer high doses and also offers the benefits of less frequent administration, these parentally administered microparticles represent foreign particulate material to the body which can be phagocytosed by the endothelial cell or the macrophages, thus help in treating intracellular infection.; The objective of this study was to prepare biodegradable microspheres of gentamicin with bovine serum albumin as a natural polymer using nebulization or spray drying technique. Spray drying is commonly used in the pharmaceutical industry for preparing slow release formulations of antibiotics, vitamins, vaccines, proteins and enzymes (Masters, 1991; Broadhead et al., 1992); another aim was to evaluate the properties of microspheres prepared using spray drying. Eventually these microspheres were tested in peritonitis rats and there efficacy in reducing bacteremia was compared to the traditional solution form.
Keywords/Search Tags:Microspheres, Gentamicin, Solution form
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