Autocatalytic Acidification in Poly(Lactic-Co-Glycolic Acid) Nanoparticles: Effects on the Chemical Stability of the Encapsulated Substance and Control by Alkaline Excipients

Abstract

This article analyzes the process of autocatalytic acidification occurring in poly(lactide-co-glycolide) (PLGA) nanoparticles and its effect on the chemical stability of encapsulated substances. Based on a literature review, the study examines the decrease in internal pH of nanoparticles caused by the accumulation of carboxyl groups during PLGA degradation, as well as the impact of this process on the stability of proteins, peptides, and acid-sensitive substances. In addition, the effects of factors such as particle size, glycolide content, molecular weight, terminal group type, and matrix porosity on the kinetics of acidification were evaluated. The effectiveness of alkaline additives in stabilizing internal pH and their potential effects on matrix morphology and drug release kinetics were comparatively analyzed. The findings demonstrate the need to monitor internal pH in PLGA nanoparticles and to consider autocatalytic acidification at the early stages of formulation design.