Journal
PHARMACEUTICAL RESEARCH
Volume 25, Issue 9, Pages 2041-2052Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-008-9594-3
Keywords
confocal laser scanning microscopy; microclimate pH; microspheres; pH distribution; Poly(ethylene glycol); Poly(lactic-co-glycolic acid)
Funding
- NIH HL [68345]
- Univ, of Michigan Barbour Fellowship
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Purpose. The acidic microclimate pH (mu pH) distribution inside poly(lactic-co-glycolic acid) (PLGA) microspheres was monitored quantitatively as a function of several formulation variables. Methods. A ratiometric method by confocal laser scanning microscopy with Lysosensor yellow/blue (R) dextran was adapted from those previously reported, and mu pH distribution kinetics inside microspheres was examined during incubation under physiologic conditions for 4 weeks. Effects of PLGA molecular weight (MW) and lactic/glycolic acid ratio, microspheres size and preparation method, and polymer blending with poly(ethylene glycol) (PEG) were evaluated. Results. mu pH kinetics was accurately sensed over a broadly acidic range (2.8 5 throughout incubation). Conclusions. Coupling this method with that previously developed (SNARF-1 (R) dextran for mu pH 5.8-8.0) should provide 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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