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首页> 外文期刊>Acta biomaterialia >Hydrolytic degradation and drug release properties of ganciclovir-loaded biodegradable microspheres.
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Hydrolytic degradation and drug release properties of ganciclovir-loaded biodegradable microspheres.

机译：更昔洛韦负载的可生物降解微球的水解降解和药物释放特性。

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摘要

The in vitro hydrolytic degradation of ganciclovir (GCV)-loaded biodegradable microspheres of poly(d,l-lactide) and poly(d,l-lactide-co-glycolide) polymers were studied. Microspheres of size 120+/-40mum were prepared using an oil-in-water emulsification/solvent evaporation technique. The effects of polymer molecular weight, lactide (LA) to glycolide (GA) ratio and GCV payload on the degradation and drug release profiles were investigated in vitro in phosphate-buffered solution (pH 7.0) at 37 degrees C. GCV accelerated the hydrolysis process of the low (5-7wt.%) GCV-loaded microspheres due to a basic catalytic effect, giving a larger degradation rate, k', compared with blank and high (18-20wt.%) GCV-loaded microspheres. In the high GCV-loaded microspheres, hydrolysis of the polymer backbone occurred with little and/or no autocatalytic effect, resulting in a smaller k' compared with low GCV-loaded microspheres. This was due to pores and microchannels created at the surface following the initial burst release, which increased water uptake and the dissolution and diffusion of GCV and degradation products from the matrix. The rate of hydrolytic degradation was also affected by the LA to GA ratio. For polymers of similar LA to GA ratio, those with a higher degree of blockiness had faster hydrolytic degradation rates irrespective of the initial molecular weight. The release profile had a biphasic pattern, which closely followed the degradation profile of the polymer. The time taken for the complete release of GCV was controlled by the diffusion phase and was dependent on the hydrolytic degradation rate of the polymers.
机译：研究了更昔洛韦（GCV）负载的聚（d，l-丙交酯）和聚（d，l-丙交酯-乙交酯）聚合物的生物可降解微球的体外水解降解。使用水包油乳化/溶剂蒸发技术制备尺寸为120 +/-40μm的微球。在37°C的磷酸盐缓冲溶液（pH 7.0）中体外研究了聚合物分子量，丙交酯（LA）与乙交酯（GA）的比率以及GCV有效负载对降解和药物释放曲线的影响.GCV加速了水解过程低（5-7wt。％）的GCV的微球具有碱性催化作用，与空白和高（18-20wt。％）的GCV的微球相比，降解速率k'更大。在高GCV负载的微球中，聚合物骨架的水解几乎没有和/或没有自催化作用，与低GCV负载的微球相比，k'较小。这是由于最初的爆炸释放后在表面形成了孔和微通道，这些孔和微通道增加了水的吸收以及GCV和基质降解产物的溶解和扩散。水解降解速率也受LA与GA之比的影响。对于LA与GA之比相似的聚合物，具有较高嵌段度的那些聚合物具有更快的水解降解速率，而与初始分子量无关。释放曲线具有两相模式，其紧密跟随聚合物的降解曲线。完全释放GCV所花费的时间由扩散阶段控制，并取决于聚合物的水解降解速率。

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