Preparation Of Functionalized Poly(ε-Caprolactone) Microspheres And Study On Their Drug Release Properties

Controlled drug delivery technology has grown and diversified rapidly in recent years. Drug delivery systems (DDS) offer numerous advantages compared to conventional dosage forms, such as improved efficacy, reduced toxicity, and convenience. The delivery systems using macromolecules as drug carriers are the most important type of DDS. Of the different dosage forms reported, nanoparticles and microparticles attained much importance because their injectable property which can avoid the inconvenient surgical insertion of large implants.In the research background section of this thesis, we review the advantages, classification, mechanism and polymer matrices of drug delivery systems, the applications of poly (ε-caprolactone) (PCL) in drug controlled release field, and the preparation approaches of microsphere drug delivery systems.The research carried out is divided into two parts. In the first part, end-functionalized poly/oligo(ε-caprolactone)s were synthesized through the ring-opening polymerization of ε-caprolactone initiated by cholesterol with a hydroxyl group. Using the end-functionalized poly/oligo(ε-caprolactone)s with different molecular weights, the microsphere drug delivery systems with narrow size distributions were fabricated using a convenient melting-emulsion method. The drug release properties of microspheres were investigated with the presence of an enzyme, Pseudomonas cepacia lipase, as well as in the absence of the enzyme. The release profiles can be fitted nicely by the classical empirical exponential expression. Under the hydrolytic condition, the drug release is mainly controlled by Fickian diffusion, and the high molecular weight of the matrix results in a slower drug release rate. Under the enzymatic condition, the drug release is dominated by combined degradation and diffusion mechanism, and the high molecular weight sample exhibits a faster release rate which is mainly caused by the higher degradation rate of the sample with lower cholesteryl moiety content.In the second part, a series of star-like biodegradable polymers/oligomers based on ε-caprolactone (CL) containing cholic acid moieties were studied. The functionalized polymers/oligomers, CA-(CL)n, were synthesized through ring-opening polymerization initiated by cholic acid with hydroxyl groups. The functionalizedpolymers/oligomers were characterized by lK nuclear magnetic resonance spectroscopy ('H NMR), Fourier transform infrared (FTIR) and polarizing light microscopy (PLM). Incorporation of cholic acid moiety to the polymer chain results in liquid crystallinity for the resultant oligomers with particular molecular weights. The molecular weight of the CA-(CL)n polymers/oligomers can be controlled by adjusting the feed ratio of the initiator cholic acid to the monomer CL. The in vitro enzymatic degradation of CA-(CL)n polymers/oligomers was studied. Comparing with linear poly(s-caprolactone), incorporation of cholesteryl moiety to the polymer chain leads to a slower enzymatic degradation rate.