聚[碳酸(亚丁酯-co-ε-己内酯)酯]的制备及其载药微球性能的研究

采用阴离子配位聚合方法, 合成了二氧化碳、1,2-环氧丁烷与ε-己内酯的三元共聚物: 聚碳酸(亚丁酯-co-ε-己内酯)酯](PBCL). 并采用复相乳液(W/O/W)溶剂挥发法制备了包裹抗菌药物甲磺酸帕珠沙星的可降解微球. 对聚合物进行了FTIR, ¹H NMR, ¹³C NMR, DSC, TGA和WAXD等表征, 以及降解性能和载药微球特性的研究. 结果表明, PBCL热稳定性及降解性能优于聚碳酸亚丁酯(PBC). 所得PBCL微球球形规整、表面光滑. 大部分微球粒径在0.5～1 μm的范围内, 载药量和包封率分别达到38.21%和87.9%. 微球的体外释药性能研究在pH 7.4的磷酸缓冲溶液中进行, 释放21 d后, PBCL微球的累积释药量为84.74%, PBC微球的释药量仅为17.29%. 药物的体外释放行为符合Higuchi方程. PBCL载药微球具有长效缓释作用.

Preparation of Poly(butylene-co-ε-caprolactone carbonate) and Properties of Its Drug-Loaded Microspheres

Poly(butylene-co-ε-caprolactone carbonate) (PBCL) was synthesized by anionic coordination polymerization of carbon dioxide, 1,2-butylene oxide and ε-caprolactone (CL). PBCL microspheres containing pazufloxacian mesilate were elaborated by solvent evaporation method based on the formation of double W/O/W emulsion. The resulting polymers were characterized by FTIR, ¹H NMR, ¹³C NMR, DSC, TGA and WAXD measurements, and the degradability of polymers and the properties of drug-loaded polymeric microspheres were studied. The results showed that the thermal properties and degradability of poly(butylene carbonate) (PBC) were improved via introduction of CL during copolymerization. The polymeric microspheres had smooth and spherical surface, and the size of most microspheres was in the range of 0.5～1 μm. The drug loading and drug encapsulation efficiency of PBCL microspheres were 38.21% and 87.9%, respectively. In vitro drug release of these microspheres was performed in a pH 7.4 phosphate-buffered solution. The drug released from PBCL microspheres was found to reach 84.74% after 21 d, and that of PBC microspheres was just 17.29%. The re-lease profile obeyed the Higuchi equation. It was suggested that PBCL was suitable for long-term sustained-release drug delivery system.