The microclimate pH in poly(D,L-lactide-co-hydroxymethyl glycolide) microspheres during biodegradation.
The microclimate pH in poly(D,L-lactide-co-hydroxymethyl glycolide) microspheres during biodegradation.
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DOI：
10.1016/j.biomaterials.2012.06.013
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发表时间：
2012-10
期刊：
影响因子：
14
通讯作者：
Schwendeman, Steven P.
中科院分区：
文献类型：
--
作者：
Liu, Yajun;Ghassemi, Amir H.;Hennink, Wim E.;Schwendeman, Steven P.
关键词：
可生物降解聚合物如聚(D，L-乳酸-乙醇酸)(PLGA)50/50的小气候pH(µpH)在生物降解过程中通常会下降到有害的酸性水平，导致包裹的不稳定酸分子。测定了亲水性较强的聚(D，L-丙交酯-羟甲基乙交酯)(PLHMGA)微球的pH分布，并与相同分子量和降解时间的PLGA50/50微球进行了比较。在生理条件下孵育后，使用先前验证的比率共焦激光扫描显微镜(CLSM)方法进行聚合物中的PH值测绘。共聚焦微pH图显示，与PLGA微球相比，PLHMGA微球在4周的孵育过程中产生的酸性微球远低于PLGA微球。CLSM观察到一种与pH无关的聚合物基质扩散荧光探针标记BODIPY在PLHMGA中的扩散速度是PLGA微球的3-7倍，这与在生物侵蚀过程中观察到的亲水性聚合物更快的酸释放相一致。因此，与类似的PLGA制剂相比，PLHMGA微球在降解过程中不容易酸化，因此PLHMGA可能更适合于输送不稳定酸的分子，如蛋白质。
The microclimate pH (µpH) in biodegradable polymers, such as poly(D,L-lactic-coglycolic acid) (PLGA) 50/50, commonly falls to deleterious acidic levels during biodegradation, resulting in instability of encapsulated acid-labile molecules. The µpH distribution in microspheres of a more hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA), was measured and compared to that in PLGA 50/50 of similar molecular weight and degradation time scales. pH mapping in the polymers was performed after incubation under physiological conditions by using a previously validated ratiometric confocal laser scanning microscopic (CLSM) method. Confocal µpH maps revealed that PLHMGA microspheres, regardless of copolymer composition, developed a far less acidic µpH during 4 weeks of incubation compared with microspheres from PLGA. A pH-independent fluorescent probe marker of polymer matrix diffusion of µpH-controlling water-soluble acid degradation products, bodipy, was observed by CLSM to diffuse ~3–7 fold more rapidly in PLHMGA compared to PLGA microspheres, consistent with much more rapid release of acids observed from the hydrophilic polymer during bioerosion. Hence, PLHMGA microspheres are less susceptible to acidification during degradation as compared to similar PLGA formulations, and therefore, PLHMGA may be more suitable to deliver acid labile molecules such as proteins.
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