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Mapping microclimate pH distribution inside protein-encapsulated PLGA microspheres using confocal laser scanning
Yajun Liu1, Steven P Schwendeman
1Department of Pharmaceutical Sciences, University of Michigan, 428 Church Street, Ann Arbor, Michigan 48109, United States.
Molecular Pharmaceutics
|March 21, 2012
Summary
The microclimate pH (μpH) within poly(lactide-co-glycolide) microspheres was measured and controlled. Formulation strategies like adding magnesium carbonate or acetate buffer improved protein stability by managing μpH.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Polymer Chemistry
Background:
- The microclimate pH (μpH) within poly(lactide-co-glycolide) (PLGA) microspheres is critical for encapsulated protein stability but often uncontrolled.
- Accurate μpH measurement in PLGA matrices is challenging due to probe interference from encapsulated proteins.
Purpose of the Study:
- To quantitatively evaluate μpH distribution in protein-encapsulated PLGA microspheres.
- To develop and validate a method for correcting protein-induced fluorescence interference in μpH mapping.
- To investigate formulation strategies for controlling μpH and enhancing protein stability.
Main Methods:
- Confocal laser scanning microscopy was used to map μpH using Lysosensor yellow/blue dextran.
- A correction method was developed to account for protein interference with the fluorescent probe.
- PLGA microsphere formulations were incubated under physiological conditions for 4 weeks to study μpH kinetics.
Main Results:
- Protein presence interfered with μpH measurements, necessitating a correction method based on protein concentration.
- μpH generally became more acidic over time, with acidity appearing within 3 weeks.
- Magnesium carbonate prolonged the time to detectable acidity; acetate buffer controlled μpH around 4.7.
- Lower polymer concentration resulted in higher μpH due to reduced diffusional resistance.
- Protein stability was enhanced by magnesium carbonate, acetate buffer, or lower polymer concentration.
Conclusions:
- The developed μpH imaging technique allows for accurate quantification and control of the microenvironment within PLGA microspheres.
- Formulation modifications, including the addition of magnesium carbonate or acetate buffer, can effectively manage μpH and improve protein stability.
- This technique offers a valuable tool for optimizing PLGA microsphere formulations for enhanced protein delivery and stability.
