Acidic Microclimate pH Distribution in PLGA Microspheres Monitored by Confocal Laser Scanning Microscopy

Authors:
Publisher website
Google Scholar
Abstract
Purpose The acidic microclimate pH (µpH) 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 µpH 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 µpH kinetics was accurately sensed over a broadly acidic range (2.8 < µpH < 5.8) and was more acidic and variable inside PLGA with lower MW and lactic/glycolic acid ratio. Lower µpH 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 µpH significantly (µpH > 5 throughout incubation). Conclusions Coupling this method with that previously developed (SNARF-1® dextran for µpH 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.

This publication has 34 references indexed in Scilit: