Adsorption determines in-vitro protein release rate from biodegradable microspheres: Quantitative analysis of surface area during degradation
Adsorption determines in-vitro protein release rate from biodegradable microspheres: Quantitative analysis of surface area during degradation
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DOI：
10.1016/s0168-3659(96)01624-0
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发表时间：
1997-07-07
影响因子：
10.8
通讯作者：
Park, TG
中科院分区：
文献类型：
--
作者：
Crotts, G;Sah, H;Park, TG
采用多重乳化溶剂挥发技术，将模型蛋白羧甲基化牛血清白蛋白(CM-BSA)包裹在降解较快和较慢的聚(D，L-丙交酯-乙交酯共聚物)微球中。考察了微球在降解过程中的比表面积、孔隙率、相对分子质量变化和质量侵蚀与非特异性蛋白质吸附和体外蛋白质释放动力学的关系。对由50/50和75/25的PLGA组成的微球进行的氮吸附分析表明，在1个月和3个月的孵化过程中，聚合物降解和随后的质量侵蚀使微球的比表面积分别增加了约30和36倍。研究发现，两种微球膨胀的聚合物表面对包裹的蛋白质分子的非特异性吸附严重限制了可供释放的蛋白质的量，导致缓慢和不完整的释放曲线。当在释放介质中加入5 mM十二烷基硫酸钠(SDS)抑制蛋白质吸附时，快降解和慢降解微球分别以65%和77%的释放脉冲孵育21d和60d时，蛋白质呈现脉冲式释放。在十二烷基硫酸钠存在下脉冲释放的开始时间与降解微球的表面积值的增加很好地对应。这项研究表明，非特异性蛋白质吸附是控制PLGA微球中蛋白质释放动力学的关键因素。
A model protein, carboxymethylated bovine serum albumin (CM-BSA), was encapsulated within relatively fast degrading and slow degrading poly(D,L-lactide-co-glycolide, PLGA) microspheres using st multiple emulsion solvent evaporation technique. The specific surface area (sigma), porosity, molecular weight change, and mass erosion of the microspheres during the degradation period were examined in relation to non-specific protein adsorption and the in-vitro protein release kinetics. Nitrogen sorption analysis of the microspheres composed of the 50/50 and 75/25 PLGA revealed that polymer degradation and subsequent mass erosion increased the specific surface area values of the microspheres by approximately 30- and 36-fold throughout 1 month and 3 months of incubation, respectively. It was found that a non-specific adsorption of encapsulated protein molecules onto the expanding polymeric surface of both microspheres severely limited the amount of protein available for release, resulting in slow and incomplete release profiles. When the protein adsorption was suppressed with the addition of 5 mM sodium dodecyl sulfate (SDS) in the release medium, a pulse-type release of the protein was exhibited from the fast degrading and slow degrading microspheres by 21 and 60 days of incubation with 65% and 77% release pulses, respectively. The onset timings of the pulsed releases in the presence of SDS corresponded well with the increases in the surface area values of degrading microspheres. This study suggests that non-specific protein adsorption is a critical factor in controlling protein release kinetics from PLGA microspheres.