Correlation between drug release kinetics from proteineous matrices and protein folding: elasticity and compressibility study.

Naproxen sodium (NS) release mechanism from proteineous matrices based on egg albumin (EA) and bovine serum albumin (BSA) was investigated by several physico-chemical methods. The gel strength, modulus of elasticity and erosion properties of the matrices were studied and correlated with drug release kinetics. The results revealed that NS release rate from EA and BSA matrices was markedly different, indicating the significant role of protein nature and conformation on matrix behavior. Unexpectedly it was found that incorporation of NS to EA matrix increased gel strength and modulus of elasticity and decreased matrix erosion. This effect was dependent on NS concentration in the matrix. In contrast to EA, BSA behaved as a non-gelling matrix and was unable to retard drug release because of its high solubility. The influence of NS on protein folding and compressibility in protein solutions was studied using densitometric and ultrasonic techniques. Adiabatic compressibility measurements revealed that NS caused unfolding of EA, an effect which led to a decrease in EA intrinsic compressibility and the exposure of atomic side groups buried in protein interior. Unfolding of EA led to an increase of modulus of elasticity in solution (measured by ultrasonic velocimetry technique) which is in correlation with the modulus of elasticity measurements of gelled tablets (measured by Instron). In concentrated EA solutions, the results showed a large increase in EA compressibility and ultrasonic absorption in the presence of NS indicating a strong aggregation of the denatured state of EA. Regarding BSA, the results suggested that NS affected the packing of the protein interior, transforming it to a molten globule intermediate state, an effect that led to an increase in BSA compressibility. At high BSA concentrations, aggregation of the molten globule state was observed as indicated by an increase of BSA compressibility and ultrasonic absorption values.