Effect of inner pH on peptide acylation within PLGA microspheres.

Polymer degradation within the controlled-release depots comprising of lactide and glycolide (PLGA) forms an acidic microenvironment, in which severe acylation of the peptide by the polymer degradation products takes place. The aim of this study was to make out the role of the inner μpH on peptide acylation within the microspheres and how could it influence the reaction. The effects of pH on the acylation reaction within microspheres were composed of two aspects. Firstly, the inherent effect of pH on the acylation reaction itself was figured out: with the pH environment going up from acid to neutral, a model peptide (octreotide acetate) acylation became more and more serious. Then, the multivariate effect of pH on the dynamic microsphere delivery system especially the state of the acylation substrates (drug and oligomer) was investigated. When the inner pH was neutralized by Ca(OH)2 to varying degrees, polymer degradation rate, drug release rate, polymer degradation mechanism and oligomer accumulation state within the microspheres all changed. These changes highly affected the mass transfer of the acylation substrates to the external release medium. Neutralization of the μpH prolonged the retention time of drug and oligomer within the microspheres. Water absorption and single microsphere swelling experiments all showed a higher retention amount of acylation substrates during the critical period for peptide acylation. Generally, when the inner μpH was neutralized, except that the neutral environment itself promoted acylation reaction, the effects of pH on the dynamic system were also highly responsible for the serious acylation within the microspheres.