Acidic microclimate pH distribution in PLGA microspheres monitored by confocal laser scanning microscopy.
OBJECTIVE
The acidic microclimate pH (micropH) 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 dextran was adapted from those previously reported, and micropH 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
micropH kinetics was accurately sensed over a broadly acidic range (2.8 < micropH < 5.8) and was more acidic and variable inside PLGA with lower MW and lactic/glycolic acid ratio. Lower micropH was found in larger microspheres of lower MW polymers, but size effects for lactic-rich polymers were insignificant during 4 weeks. Microspheres prepared by the oil-in-oil emulsion method were less acidic than those prepared by double emulsion, and blending PLGA 50/50 with 20% PEG increased micropH significantly (micropH > 5 throughout incubation).


CONCLUSIONS
Coupling this method with that previously developed (SNARF-1 dextran for micropH 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.
Ding
Amy G
AG
Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
Schwendeman
Steven P
SP
D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004655:Emulsions; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents / Q000737:chemistry; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D018613:Microscopy, Confocal; D008863:Microspheres; D008970:Molecular Weight; D009821:Oils / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012815:Signal Processing, Computer-Assisted; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry
C120434:2-(4-pyridyl)-5-((4-(2-dimethylaminoethylaminocarbamoyl)methoxy)phenyl)oxazole; D004337:Drug Carriers; D004655:Emulsions; D007202:Indicators and Reagents; D009821:Oils; D010080:Oxazoles; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols