Mapping neutral microclimate pH in PLGA microspheres
- 作者：Li ; Lei ; Schwendeman ; Steven P.
- 关键词：Microclimate pH ; PLGA microsphere ; Laser scanning confocal microscope ; Ratiometric imaging ; Protein stability
- 刊名：Journal of Controlled Release
- 出版年：2005
- 期刊代码：25_01683659
- 类别：pha
- 出版时间：January 3, 2005
- 卷：101
- 期：1-3
- 页码：163-173
- 文件大小：659 K
摘要
A quantitative ratiometric method based on laser scanning confocal microscopic imaging was developed to create a pixel-by-pixel neutral microclimate pH (5.8芒芒芒8.0) map inside poly(lactic-co-glycolic acid) (PLGA) microspheres. The method was accurate to within 芒芒0.2 pH units. PLGA microspheres with encapsulated bovine serum albumin and the pH-sensitive dye, SNARF-1芒芒 dextran (MW=10 kDa), were prepared by a water-in-oil-in-water solvent evaporation method. The imaging method was used to monitor the pH changes in PLGA microspheres with or without co-encapsulation of acid-neutralizing MgCO3, and for three different microsphere sizes (2.0芒芒0.3, 40芒芒10 and 137芒芒32 芒芒m) during incubation under physiological conditions. The pH of microspheres was significantly higher with co-encapsulated base compared to base-free microspheres, whose microclimate pH was predominantly below the dye detection limit of pH=5.8. The small microspheres displayed a more neutral pH during incubation probably due to their much shorter diffusion path for polymer-dissolved acids compared with medium- and large-size microspheres. The pH mapping technique discussed here may be useful in routine formulation development and for elucidation of mechanisms of microclimate pH development and polymer erosion.