Synthesis and Evaluation of Some Polymeric Drug Delivery Systems

Abstract

This thesis deals with the investigations carried out by the writer on the synthesis, characterization and evaluation of some polymeric pro-drugs. The first chapter of the thesis deals with a brief introduction to controlled drug delivery systems, passive drug targeting and specific tissue targeting, cellular uptake of polymers, site specific drug release, polymer conjugates, incorporation of spacers in pro-drug conjugates, PEG chemistry and use of Dextran in drug delivery. The use of antiviral drug namely, zidivudine, problems associated with its use and a literature survey on the investigations that have been carried out on polymeric drug conjugates of zidovudine are briefly given. The Second chapter of the thesis deals with the scope and objective of the present investigations in detail. It explains, in particular, how when zidovudine is linked covalently to biocompatible polymers through succnic spacer should lead to a better drug delivery system capable of releasing of the drug in a sustained manner. The Third chapter of the thesis deals with the experimental procedures that are adopted in the preparation of the polymeric pro-drugs, estimation of the drug content, in vitro drug release studies, enzymatic hydrolysis, stability studies and bioavailability studies. The Fourth chapter of the thesis deals with the results obtained in the present study along with a detailed discussion of the results supported by chemical equations, tables, figures, etc. The following are some of the important findings in the present study: Two macromolecular pro-drugs of the known antiviral drug zidovudine were synthesized by conjugating it with poly (ethylene glycol) 1500, and detrain through succinic spacer. The pro-drugs were thoroughly characterized in terms of IR, and H1NMR. Stability studies carried out for the pro-drugs for a period of three months as per ICH guidelines indicate that no major physical and chemical changes occur in the polymeric pro-drugs during storage period indicating the stability of the pro-drugs. newline