Mapping neutral microclimate pH in PLGA microspheres.
A quantitative ratiometric method based on laser scanning confocal microscopic imaging was developed to create a pixel-by-pixel neutral microclimate 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 microm) 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.
Li
Lei
L
Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48019-1065, USA.
Schwendeman
Steven P
SP
D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000008:administration & dosage*; D018613:Microscopy, Confocal; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid