氟尿嘧啶聚丙交酯微球的制备及体外特性

Preparation and Characterization of Fluorouracil-loaded Poly(d,l-lactide) Microspheres

目的:制备缓释1月以上的氟尿嘧啶(Fu)聚丙交酯微球。方法:溶剂挥发法制备Fu聚丙交酯微球,比较外水相Fu饱和与否,有机相Fu/聚丙交酯投料比对载药量及包封率的影响。光学及电子显微镜下对微球的外观形态进行考察,并对其体外释放进行初步探讨。结果:制得的微球光滑圆整。Fu饱和外水相后可以提高其载药量及包封率,投料比对载药量、微球的粒径和跨距影响不大,包封率随投料比增大而减小。Fu从聚丙交酯微球中4周时约释放总量的65％,符合一级动力学,没有明显的突释效应。结论:外水相Fu饱和后可减少Fu向外水相的逸失,制得的微球可作为每月1次的给药系统。

Objective: To prepare fluorouracil-loaded ploy(d, 1-lactide) microspheres( Fu-PL-MS) which slowly release Fu for more than one month. Methods; O/W emulsification/solvent evaporation technique was used to prepare Fu-PL-MS and the effect of the outer aqueous phase, with or without Fu saturation, and the Fu to PL ratio in the organic phase on drug loading and encapsulation rate investigated. The appearence of Fu-PL-MS was observed under optical and electronic microscopes, and their release in vitro primarily expolred. Results: All prepared microspheres appeared spherical with smooth surface. The drug loading and encapsulation rate of the microspheres were increased after Fu saturation in the outer aqueous phase. The effect of Fu/PL ratio on durg loading, diameter and span of the microspheres was insignificant, while the encapsulation rate declined as the Fu/PL ratio in-creaed. Total release rate of Fu from Fu-PL-MS was about 65% after four weeks, following first kinetics without obvious burst effect. Conclusion: The preparation technology proved successful and charaterization of Fu-PL-MS satisfactory. The prepared micro-spheres showed a sustained release charateristic in vitro for over one month, so they can be potentially used as an once-a-month drug delivery system.