الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
This thesis comes in 201 pages, and includes lists of contents, figures (70 figure), tables (6 tables), and references (226 references), in addition to an Arabic and an English summaries. It describes the encapsulation of prednisolone into biodegradable controlled-release microspheres. Two biodegradable polymers were selected to prepare the microspheres, namely poly lactide, and poly lactide-co-glycolide. The aim of this work was to obtain microspheres formulations, with suitable injectable size, high encapsulation efficiency, and sustained drug release over a long period, with minimal burst release. In addition, this work also aimed at applying the prepared microspheres formulation in an animal model, with a chronic inflammatory disease. The thesis was divided into an introduction, in addition to three chapters. Chapter 1 ”Preparation and Characterization of Prednisolone-Loaded Biodegradable PLA Microspheres” dealt with the production of prednisolone-loaded microspheres using poly (DL-lactide) by the O/W emulsion solvent evaporation technique. The formulation parameters effects on the produced microspheres characteristics were studied. The produced microspheres were characterized by scanning electron microscopy, particle size analysis, encapsulation efficiency, drug release study, and physical state study. Scanning electron microscopy results showed that most microspheres formulations had smooth and intact surfaces. However, the surface became corrugated or perforated when formulation parameters were varied. Size analysis, in addition to encapsulation efficiency percent and release rates showed marked dependence on formulation parameters. Fitting the release results to Peppas equation, Higuch, and Baker-Lonsdale spherical models was carried out. A comparative study using Baker-Lonsdale model showed that drug diffusion is believed to be through capillaries in the polymeric matrix. In chapter 2 ”Preparation and Characterization of Prednisolone-Loaded PLGA Microspheres”, the more degradable poly (DL-lactide-co-glycolide) was used instead. Formulation parameters were adjusted, so that EE% efficiencies as high as 68% were obtained. In addition, sustained, almost-steady drug release rates could be achieved for up to 28 days, which suits in vivo application. The microspheres degradation was also studied. Chapter 3 ”Animal Study”, aimed at evaluation of the produced microspheres in an animal model, involving a chronic inflammatory lesion, such as rheumatoid arthritis. Freund’s Complete Adjuvant (FCA) was used to induce mono-arthritis in mice, and the anti-inflammatory efficiency of two microsphere formulations was tested. Methodologies used to evaluate the induced arthritis along with the effect of the used microspheres included joint diameter measurement, x-ray examination, and histological evaluation. Arthritis was characterized by moderate to severe redness and swelling of the injected limb, with no sign of inflammation on the contra-lateral paw. Also, diameter of the FCA-injected limb increased dramatically. In addition, histological examination showed inflammatory infiltration, synovial hyperplasia, and cartilage and bone erosion. The application of the microsphere formulation on the induced arthritis model efficiently reduced redness and swelling of the affected limb. In addition and most importantly, histopathological investigation showed that the bone and cartilage appeared intact and preserved.