Non-invasive in vivo characterization of release processes in biodegradable polymers by low-frequency electron paramagnetic resonance spectroscopy

Biomaterials
Karsten MäderH M Swartz

Abstract

Using stable free radicals (nitroxides) whose spectra reflect microviscosity and pH, low-frequency electron paramagnetic resonance (EPR) spectroscopy was used to characterize the release pattern of subcutaneous implants of poly(D,L-lactide-co-glycolide) (PLGA) continuously and non-invasively in living mice. No significant changes occurred during the first days after implantation. After about 1 week, the recorded EPR spectra gave direct evidence for the formation of compartments with high mobility and increasing acidity in the delivery system. The contribution of the mobile part of the spectrum increased with time, but no remarkable decay of the overall signal intensity was observed during the second week. The EPR signals decayed rapidly after 3 weeks. The experimental data are consistent with bulk hydrolysis as the dominating mechanism of release and are not consistent with a surface-controlled pattern of degradation. The formation of acidic compartments in the delivery system may have significant effects on drug stability, drug solubility, bioavailability, pharmacokinetics, and ultimately on therapeutic efficiency. In particular, the finding of areas of low pH within the polymer raise the possibility that hydrolysable drugs ma...Continue Reading

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