Mapping neutral microclimate pH in PLGA microspheres

摘要

A quantitative ratiometric method based on laser scanning confocal microscopic imaging was developed to create a pixel-by-pixel neutral inicroclimate pH (5.8-8.0) map inside poly(lactic-co-glycolic acid) (PLGA) microspheres. The method was accurate to within +/- 0.2 pH units. PLGA microspheres with encapsulated bovine serum albumin and the pH-sensitive dye, SNARF-1 (R) 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 +/- 0.3, 40 +/- 10 and 137 +/- 32 mu m) during incubation under physiological conditions. The pH of microspheres was significantly higher with co-encapsulated base compared to base-free microspheres, whose inicroclimate pH was predominantly below the dye detection limit of pH=5.8. The small inicrospheres displayed a more neutral pH during incubation probably due to their much shorter diffusion path for polymer-dissolved acids compared with medium-and lame-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. (c) 2004 Elsevier B.V. All rights reserved.