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

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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.

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Acknowledgements

This work was supported by NIH HL 68345 and a Univ. of Michigan Barbour Fellowship to A.G. Ding.

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Author notes

  1. Amy G. Ding

    Present address: Impax Laboratories, Inc., Hayward, California, 94544, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan, 48109-1065, USA

    Amy G. Ding & Steven P. Schwendeman

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Correspondence to Steven P. Schwendeman.

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Ding, A.G., Schwendeman, S.P. Acidic Microclimate pH Distribution in PLGA Microspheres Monitored by Confocal Laser Scanning Microscopy. Pharm Res 25, 2041–2052 (2008). https://doi.org/10.1007/s11095-008-9594-3

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  • DOI: https://doi.org/10.1007/s11095-008-9594-3

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