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Combinatorial Synthesis of and High-throughput Protein Release from Polymer Film and Nanoparticle Libraries
Published on: September 6, 2012
pH-Dependent Protein Chemical Degradation as a Representation of Effective pH Around Proteins Within Polymer-Based
Caroline Black1, Sean McCarthy2, Milad Khorrami1
1Drug Delivery Sciences, AbbVie Inc., Irvine, CA 92612, USA.
Abstract:
Protein-based therapeutics are prone to pH-dependent intramolecular chemical degradation reactions. Knowledge of the pH around protein-based therapeutics inside sustained release (SR) formulations is necessary for assessing their suitability for sustained delivery applications. Herein, we have taken advantage of the pH-sensitive chemical reactions of a model antibody, mAb1, to infer the pH around proteins in two representative SR formulations: PLGA microspheres and hyaluronic acid hydrogel. Distinct chemical changes in mAb1 retrieved from the two SR formulations at various stages of in vitro release were measured and compared with the chemical changes in mAb1 exposed to aqueous buffers of known pH to infer the pH around mAb1 in the SR formulations. The monomer content, charge variants, and residue level chemical degradation in mAb1 were quantified using SEC, icIEF, and peptide mapping, respectively. The results suggest that mAb1 was exposed to pH 4-7 in PLGA microspheres and to pH 6-7 in hyaluronic acid hydrogels. The approach presented here will be universally applicable for characterizing pH in the vicinity of proteins inside any SR formulation.
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