| Summary: | 碩士 === 國立臺灣大學 === 藥學研究所 === 92 === Biomaterials have been explored in recent years, especially aliphatic polyesters. Poly(��-caprolactone) (PCL) exhibits certain desirable characteristics for drug delivery applications. However, high crystallinity and hydrophobicity result in its long degradation time. Therefore, hydrophilic groups are introduced into the PCL structure in this study to solve theses problems and make PCL more effective as a drug delivery carrier.
Amphiphilic diblock copolymer composing methoxy poly(ethylene glycol) (MEPEG) and PCL was synthesized via a ring-opening polymerization without a catalyst. The molecular structure and average molecular weight were determined by 1H-NMR and GPC. A dialysis method was used to prepare the polymeric micelles containing indomethacin as a hydrophobic model drug. The drug loading efficiency was up to 86.61±8.21%. The particle size of micelles measured by transmission electron microscope was 82.17±32.17 nm. After subcutaneous administering micelles, the plasma concentration profile showed the sustained release of drug from micelles. The AUCs of drug in liver, kidney, and lung after administration of micelles were significantly higher than drug solution. The degradation behavior of diblock copolymer was studied in rat plasma at 37℃. It was found that the weight of the copolymer was lost with time, and the decrease of MEPEG peak intensity was shown in NMR spectrum. The chromatography of GPC also showed the increase of polydispersity during the degradation process. The melting points of degradation products measured by DSC increased with time. These results indicated that the hydrophilic block of the copolymer could be the degradation position to cause this outcome.
Modification of PCL with galactose was another approach to improve the specificity of drug delivery. We used the benzyl ether to protect the hydroxyl group of galactose. The anomeric hydroxyl group in the presence of stannous octoate was used to attack the acyl carbon of ��-caprolactone to evoke the coordination-insertion reaction. The characteristics of the polymer conjugated galactose were identified by 1H-NMR, GPC, and DSC. Each gram of product contained 0.695 mg galactose. The micro-nanoparticles prepared by PCL conjugated galactose were loaded with indomethacin and the drug loading efficiency was up to 76.86±7.78%. The particle size of micro-nanoparticles measured by inverted microscopy was 3.51±3.36 �慆. Although the plasma concentration profile displayed the sustained drug release after subcutaneous administration of micro-nanoparticles, the drug accumulation in organs except kidney was not significantly different from dru
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