Mechanisms controlling diffusion and release of model proteins through andfrom partially esterified hyaluronic acid membranes

The effects of polymer percent esterification and protein molecular weight on the diffusion of two model proteins, deoxyribonuclease (DNase) and ribon uclease A (RNase A), through and from partially esterified hyaluronic acid membranes were compared. The permeability of the polymer membranes was inve rsely related to the degree of polymer esterification and the molecular wei ght of the protein. Transport rates of proteins through the membranes decre ased dramatically over narrow ranges of polymer esterification. As expected , the apparent diffusivity of the larger protein in the polymer matrix was more sensitive to changes in membrane hydration than that of the smaller pr otein. These observations demonstrated the dependence of the mobility of la rge molecular weight proteins on polymer hydration and chain relaxation. Th e relationship between protein diffusion through and release from the modif ied hyaluronate matrices was also investigated using RNase A as a model. Th e release profiles from fully esterified membranes showed lag behavior and varied with protein load and hyaluronate hydrolysis rates, while release fr om less esterified membranes was rapid and independent of polymer esterific ation or hydrolysis. Potential applications of modified hyaluronate matrice s in the controlled delivery of proteins are discussed. (C) 1999 Elsevier S cience B.V. All rights reserved.