Duvvuri Sridhar, Janoria Kumar Gaurav, Mitra Ashim K
Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005, Rockhill road, Kansas City, MO 64110, USA.
J Control Release. 2005 Nov 28;108(2-3):282-93. doi: 10.1016/j.jconrel.2005.09.002. Epub 2005 Oct 17.
The purpose of this work is to develop empirical equations for describing the in vitro ganciclovir (GCV) release from PLGA microspheres and also to develop and characterize a formulation containing GCV loaded PLGA microspheres dispersed in thermogelling PLGA-PEG-PLGA polymer gel. Effect of polymer chain length and polymer blending on GCV entrapment and release from PLGA microspheres is also examined. PLGA microspheres of GCV were prepared from two polymers PLGA 6535 (d,l-lactide:glycolideColon, two colons65:35, Mw=45,000-75,000 Da) and Resomer RG 502H (d,l-lactide:glycolideColon, two colons50:50, Mw=8000 Da) and a 3:1 mixture. PLGA-PEG-PLGA polymer was synthesized and characterized. In vitro GCV release studies were conducted with microspheres and microspheres dispersed in 23% w/v PLGA-PEG-PLGA solution. Polymer blended microspheres entrap more GCV (72.67+/-2.49%) than both PLGA 6535 (51.37+/-2.7%) and Resomer RG 502H (47.13+/-1.13%) microspheres. In vitro drug release data was fit to sigmoid equations and release parameters were estimated by nonlinear regression analysis. These equations effectively describe three different phases in GCV release from PLGA microspheres, initial diffusion, matrix hydration and degradation. The amount of drug release during the initial phase decreased for the blend microspheres indicating efficient packing between the PLGA 6535 and Resomer RG 502H in the microsphere matrix. Moreover, upon dispersion into the polymer gel, the rate of drug release during initial diffusion phases slowed relative to microspheres alone. In conclusion, this study reports the development of PLGA microspheres with high payloads and their PLGA-PEG-PLGA gel based formulations. Drug release equations have been developed that effectively describe the triphasic GCV release.
这项工作的目的是建立用于描述更昔洛韦（GCV）从聚乳酸-羟基乙酸共聚物（PLGA）微球中体外释放的经验方程，同时开发和表征一种含有分散在热凝胶化PLGA-聚乙二醇（PEG）-PLGA聚合物凝胶中的载GCV的PLGA微球的制剂。还研究了聚合物链长和聚合物共混对GCV包封率以及从PLGA微球中释放的影响。由两种聚合物PLGA 6535（d，l-丙交酯：乙交酯，65:35，Mw = 45,000 - 75,000 Da）和Resomer RG 502H（d，l-丙交酯：乙交酯，50:50，Mw = 8000 Da）以及3:1混合物制备了载GCV的PLGA微球。合成并表征了PLGA-PEG-PLGA聚合物。对微球以及分散在23% w/v PLGA-PEG-PLGA溶液中的微球进行了体外GCV释放研究。聚合物共混微球比PLGA 6535（51.37±2.7%）和Resomer RG 502H（47.13±1.13%）微球包封更多的GCV（72.67±2.49%）。体外药物释放数据拟合为S型方程，并通过非线性回归分析估计了释放参数。这些方程有效地描述了GCV从PLGA微球中释放的三个不同阶段，即初始扩散、基质水合和降解。共混微球在初始阶段的药物释放量减少，表明在微球基质中PLGA 6535和Resomer RG 502H之间的有效堆积。此外，分散到聚合物凝胶中后，初始扩散阶段的药物释放速率相对于单独的微球减慢。总之，本研究报告了高载药量PLGA微球及其基于PLGA-PEG-PLGA凝胶的制剂的开发。已经建立了能够有效描述GCV三相释放的药物释放方程。
