Potentiometric Method for Determination of Microclimate pH in Poly(lactic-co-glycolic acid) Films
2004-12-28T00:00:00Z (GMT) by
The acidic microclimate pH (μpH) in poly(lactide-co-glycolide) (PLGA) devices has been identified as a major source of instability of encapsulated proteins and acid labile small molecules. A fast and reliable potentiometric technique for μpH measurement in thin PLGA films was developed and validated. Standard glass pH electrodes were coated with PLGA films, and the zero-current potential was measured with respect to a calomel reference electrode. The measurement was independent of external media pH but responsive to addition to the polymer films buffering salts from lyophilized solutions of various pH values. The contribution of additional diffusion and interfacial potentials in the electrochemical cell due to the presence polymer coating was determined to be roughly ≤0.2 pH units by two independent measurements and slightly pH dependent. A highly acidic μpH (μpH <3) developed in PLGA 50/50 films (∼30−100 μm thick) after 1 day of incubation in a physiological buffer at 37 °C and remained acidic for 4 weeks. The μpH varied significantly with the thickness of the coating during extended incubation. The μpH of a 7 μm thick coating rose to a neutral value (pH 6.5) after 1 week of incubation, but it remained acidic (pH 2−3.5) for 250 and 30 μm thick coatings. Hence, the microclimate pH measurement described here may be useful for mechanistic evaluation and μpH control of biodegradable polymer systems encapsulating labile molecules.
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