Preparation and in vitro characterization of poly(acrylic acid)-cysteine microparticles

The purpose of the present study was to prepare and characterize a novel mucoadhesive microparticulate drug delivery system. Microparticles were prepared by the solvent evaporation emulsion technique using a poly(acrylic acid)-cysteine conjugate of an average molecular mass of 450 kDa with an amount of 308 mumol thiol groups per gram polymer. The crosslinking of thiol groups via the formation of disulfide bonds during this preparation process was pH-controlled. The resulting microparticles were characterized with regard to the degree of cross-linking and the amount of remaining free thiol groups, shape, size distribution and stability. Furthermore, the drug release behaviour using bromelain as model drug and the mucoadhesive properties were evaluated. Results demonstrated that the higher the pH of the aqueous phase was during the preparation process, the higher was the degree of cross-linking within the particles. However, even at pH 9, 8.9 +/- 2.2% of free thiol groups remained on the microparticles. Particles were of spherical and partially porous structure and had a main size in the range of 20-60 mum with a center at 35 mum. Because of the formation of disulfide bonds within the particles, they did not disintegrate under physiological conditions within 48 h. In addition, a controlled drug release of bromelain was achieved. Due to the immobilization of thiol groups on poly(acrylic acid), the mucoadhesive properties of the corresponding microparticles were improved threefold. These features should render poly(acrylic acid)-cysteine conjugate microparticles useful as drug delivery system providing a prolonged residence time on mucosal epithelia. (C) 2003 Elsevier B.V. All rights reserved.