Ozalp Y, Ozdemir N, Kocagöz S, Hasirci V
Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara University, Turkey.
J Microencapsul. 2001 Jan-Feb;18(1):89-110. doi: 10.1080/026520401750038638.
Poly D,L-lactic acid (PLA) and its copolymers with glycolide PLGA 90:10 and 70:30 were polymerized under various conditions to yield polymers in the molecular weight range 12000-40000 daltons, as determined by gel permeation chromatography. Vancomycin hydrochloride was the hydrophilic drug of choice for the treatment of methicillin resistant Staphyloccoccal infections. It was microencapsulated in the synthesized polymers using water-oil-water (w/o/w) double emulsion and solvent evaporation. The influence of microcapsule preparation medium on product properties was investigated. An increase in polymer-to-drug ratio from 1:1 to 3:1 caused an increase in the encapsulation efficiency (i.e. from 44-97% with PLGA). An increase in the emulsifier (PVA) molecular weight from 14-72 kD caused an increase in encapsulation efficiency and microcapsule size. The in vitro release of vancomycin from microcapsules in phosphate buffer saline (pH 7.4) was found to be dependent on molecular weight and copolymer type. The kinetic behaviour was controlled by both diffusion and degradation. Sterilization with 60Co (2.5 Mrad) also affected the degradation rate and release profiles. Degradation of microcapsules could be seen by scanning electron microscopy, by the increase in the release rate from PLA and by the decrease in the Tg values of microcapsules. In vitro bactericidal effects of the microcapsule formulations on S. aureus were determined with a special diffusion cell after the preparations had been sterilized, and were found to have bactericidal effects lasting for 4 days.
聚D，L-乳酸（PLA）及其与乙交酯的共聚物PLGA 90:10和70:30在各种条件下聚合，以产生分子量范围为12000 - 40000道尔顿的聚合物，这是通过凝胶渗透色谱法测定的。盐酸万古霉素是治疗耐甲氧西林葡萄球菌感染的首选亲水性药物。使用水 - 油 - 水（w/o/w）双乳液和溶剂蒸发法将其微囊化在合成聚合物中。研究了微囊制备介质对产品性能的影响。聚合物与药物的比例从1:1增加到3:1会导致包封效率提高（即PLGA的包封效率从44 - 97%）。乳化剂（PVA）分子量从14 - 72 kD增加会导致包封效率和微囊尺寸增加。发现万古霉素在磷酸盐缓冲盐水（pH 7.4）中从微囊中体外释放取决于分子量和共聚物类型。动力学行为受扩散和降解两者控制。用60Co（2.5兆拉德）进行灭菌也会影响降解速率和释放曲线。通过扫描电子显微镜可以看到微囊的降解，表现为PLA释放速率增加以及微囊玻璃化转变温度（Tg）值降低。在制剂灭菌后，使用特殊的扩散池测定微囊制剂对金黄色葡萄球菌的体外杀菌效果，发现其具有持续4天的杀菌作用。
