EFFECT OF ELECTROSTATIC INTERACTIONS ON POLYLYSINE RELEASE RATES FROMCOLLAGEN MATRICES AND COMPARISON WITH MODEL PREDICTIONS

Collagen was investigated as a drug delivery matrix because it is inje ctable, biocompatible and is naturally resorbed in the body. This work focuses on understanding the effect of electrostatically mediated bin ding interactions on release kinetics of charged polypeptides from col lagen matrices. The charge distribution on collagen molecules can be m odified by specific chemical reactions to yield net negative or net po sitive charges at physiological pH. These electrostatic charges are fa vorable in binding oppositely charged polypeptides. An ESR based techn ique was utilized to measure adsorption isotherms in order to characte rize the strength of binding interactions. Adsorption isotherm measure ments indicate that increasing the charge density of collagen enhances binding interactions. Enhanced binding interactions are also observed when the degree of charge modification is increased as well as when t he prevailing ionic strength of the matrix is lowered. Charged polypep tides show slower release rates from higher charge density collagen ma trices. Release kinetics have been modeled via coupled desorption and diffusion mechanisms and comparisons based on independent measurements of desorption (kinetic and equilibrium) and diffusional parameters wi th experimentally measured release rates are in good agreement.