Positive Charge of "Sticky" Peptides and Proteins Impedes Release From Negatively Charged PLGA Matrices.

The influence of electrostatic interactions and/or acylation on release of charged ("sticky") agents from biodegradable polymer matrices was systematically characterized. We hypothesized that release of peptides with positive charge would be hindered from negatively charged poly(lactic-co-glycolic acid) (PLGA) microparticles. Thus, we investigated release of peptides with different degrees of positive charge from several PLGA microparticle formulations, with different molecular weights and/or end groups (acid- or ester-terminated).

A systems approach to modeling drug release from polymer microspheres to accelerate in vitro to in vivo translation.

Mathematical models of controlled release that span the in vitro to in vivo transition are needed to speed the development and translation of clinically-relevant controlled release drug delivery systems. Fully mechanistic approaches are often challenged due to the use of highly-parameterized mathematically complex structures to capture the release mechanism. The simultaneous scarcity of in vivo data to inform these models and parameters leads to a situation where overfitting to capture observed phenomena is common.