Transport of ionizable drugs and proteins in crosslinked poly(acrylic acid) and poly(acrylic acid-co-2-hydroxyethyl methacrylate) hydrogels. II. Diffusion and release studies

Abstract

The goal of this research was to define the controlling parameters affecting transport of drugs and proteins through poly(acrylic acid), PAA, and poly(acrylic acid-co-2-hydroxyethyl methacrylate), P(AA-co-HEMA). The hydrogel formulation variables investigated included the amount of crosslinking agent and non-ionizable comonomer (i.e. HEMA), which ultimately defined the mesh size available for solute diffusion. The solutes selected for this study represent a broad range in molecular size and included theophylline, oxprenolol HCl, insulin, lysozyme, albumin, and fibrinogen. These hydrogels ranged from non-porous to microporous based on the characteristic mesh sizes of 13–140 Å for P(AA-co-HEMA) and 100–400 Å for PAA, respectively. Accordingly, solute diffusion and release studies were performed and analyzed using the commonly applied (free volume and hydrodynamic) theories for each gel porosity regime. The observed deviations from theory were attributed to hindered diffusion of oxprenolol and insulin caused by solute/polymer interactions. The results demonstrated that at the lowest ratio of solute radius to polymer mesh size, solute/polymer interactions were a dominant factor in hindering the diffusion process.