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首页> 外文期刊>Journal of pharmaceutical sciences. >BSA degradation under acidic conditions: A model for protein instability during release from PLGA delivery systems.
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BSA degradation under acidic conditions: A model for protein instability during release from PLGA delivery systems.

机译：BSA在酸性条件下的降解：从PLGA输送系统释放蛋白质过程中蛋白质不稳定的模型。

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Acidification of the internal poly(lactide-co-glycolide) (PLGA) microenvironment is considered one of the major protein stresses during controlled release from such delivery systems. A model protein, bovine serum albumin (BSA), was incubated at 37 degrees C for 28 days to simulate the environment within the aqueous pores of PLGA during the release phase and to determine how acidic microclimate conditions affect BSA stability. Size-exclusion high performance liquid chromatography (SE-HPLC), SDS-PAGE, and infrared spectroscopy were used to monitor BSA degradation. BSA was most stable at pH 7, but rapidly degraded via aggregation and hydrolysis at pH 2. These simulated degradation products were nearly identical to that of unreleased BSA found entrapped within PLGA 50/50 millicylinders. At pH 2, changes in BSA conformation detected by various spectroscopic techniques were consistent with acid denaturation of the protein. By contrast, at pH 5 and above, damage to BSA was insufficient to explain the instability of the protein in the polymer. Thus, these data confirm the hypothesis that acid-induced unfolding is the basis of BSA aggregation in PLGA and the acidic microclimate within PLGA is indeed a dominant stress for encapsulated BSA. To increase the stability of proteins within PLGA systems, formulations must protect against potentially extreme acidification such that native structure is maintained. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1626-1639, 2006.
机译：内部聚（丙交酯-共-乙交酯）（PLGA）微环境的酸化被认为是从此类递送系统控制释放过程中的主要蛋白质压力之一。将模型蛋白牛血清白蛋白（BSA）在37摄氏度下孵育28天，以模拟释放阶段PLGA水性孔内的环境，并确定酸性微气候条件如何影响BSA稳定性。使用尺寸排阻高效液相色谱（SE-HPLC），SDS-PAGE和红外光谱法监测BSA降解。 BSA在pH值为7时最稳定，但在pH 2时会通过聚集和水解迅速降解。这些模拟的降解产物与PLGA 50/50毫微柱内截留的未释放BSA几乎相同。在pH为2时，通过各种光谱技术检测到的BSA构象变化与蛋白质的酸变性一致。相反，在pH 5或更高时，对BSA的破坏不足以解释聚合物中蛋白质的不稳定性。因此，这些数据证实了以下假设：酸诱导的解折叠是PLGA中BSA聚集的基础，而PLGA中的酸性微气候确实是封装BSA的主要压力。为了增加PLGA系统中蛋白质的稳定性，制剂必须防止潜在的极端酸化，以保持天然结构。 （c）2006 Wiley-Liss，Inc.和美国药师协会J Pharm Sci 95：1626-1639，2006。

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