Acidic microclimate pH distribution in PLGA microspheres monitored by confocal laser scanning microscopy.
Acidic microclimate pH distribution in PLGA microspheres monitored by confocal laser scanning microscopy.
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DOI：
10.1007/s11095-008-9594-3
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发表时间：
2008-09
影响因子：
3.7
通讯作者：
Schwendeman, Steven P.
中科院分区：
文献类型：
--
作者：
Ding, Amy G.;Schwendeman, Steven P.
关键词：
在酸性范围内定量监测聚乳酸-羟基乙酸共聚物（PLGA）微球内的微气候pH（μpH）分布，作为几个制剂变量的函数。采用Lysosensor yellow/blue®葡聚糖通过共聚焦激光扫描显微镜的比率计量法改编自先前报道的方法，并在生理条件下孵育4周期间检查PLGA微球内的μpH分布动力学。考察了聚合物分子量、乳酸/乙醇酸比、微球粒径、制备方法以及聚合物与聚乙二醇共混等因素对微球性能的影响。μpH动力学通过染料在宽酸性范围（2.8 < μpH < 5.8）内准确地感测，以补充我们先前报道的检测中性μpH的方法。在孵育4周期间，发现PLGA内部的μpH值更酸性且变化较大，分子量和乳酸/乙醇酸比较低。一个更酸性的环境中发现，在较大尺寸的微球与较低分子量的聚合物，但微球尺寸的影响，乳酸丰富的聚合物在4周内并不显着。重要的是，通过油包油乳液法制备的PLGA 50/50微球的酸性低于通过双重乳液制备的那些微球，并且将PLGA 50/50与20%PEG共混显著增加μpH，其中大多数水性孔在整个孵育期间表现出pH > 5。因此，将该方法与先前用中性pH敏感染料SNARF-葡聚糖（5.8 - 8.0）开发的方法相结合，将来应该为我们提供在整个有用的pH范围（2.8-8.0）上的微气候pH映射，以优化pH敏感生物活性物质的PLGA递送。
The microclimate pH (μpH) distribution inside poly(lactic-co-glycolic acid) (PLGA) microspheres was monitored quantitatively over an acidic range as a function of several formulation variables. A ratiometric method by confocal laser scanning microscopy with Lysosensor yellow/blue® dextran was adapted from those previously reported, and μpH distribution kinetics inside PLGA microspheres was examined during incubation under physiologic conditions for 4 weeks. The effects of polymer molecular weight (MW) and lactic/glycolic acid ratio, microspheres size and preparation method, and polymer blending with poly(ethylene glycol) (PEG) were evaluated. The μpH kinetics was accurately sensed by the dye over a broadly acidic range (2.8 < μpH < 5.8) to compliment our previously reported method detecting neutral μpH. μpH was found be more acidic and variable inside PLGA with lower MW and lactic/glycolic acid ratio during incubation for 4 weeks. A more acidic environment was found in larger size microspheres with lower MW polymers, but microsphere size effects for lactic-rich polymers were not significant during 4 weeks. Importantly, PLGA 50/50 microspheres prepared by the oil-in-oil emulsion method were less acidic than those microspheres prepared by double emulsion, and blending PLGA 50/50 with 20% PEG increased μpH significantly with most aqueous pores exhibiting a pH > 5 throughout the incubation period. Hence, coupling this method with that previously developed with a neutral pH-sensitive dye, SNARF-dextran (5.8 – 8.0), should provide us in the future with microclimate pH mapping over the entire useful pH range (2.8–8.0) for optimization of PLGA delivery of pH-sensitive bioactive substances.
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