Development and in vitro evaluation of a mucoadhesive vaginal delivery system for progesterone.

The purpose of the present study was to design a novel carrier system based on a mucoadhesive polymer exhibiting improved properties concerning drug delivery to the vaginal mucosa. This was reached by the covalent attachment of L-cysteine to commercially available polyacrylic acid (Carbopol 974P). Mediated by a carbodiimide, increasing amounts of L-cysteine were covalently linked to the polymer. The resulting thiolated polyacrylic acid conjugates (NaC974P-Cys) displayed between 24.8 and 45.8 micromol thiol groups per gram of polymer. Because of the formation of intra- and/or intermolecular disulfide bonds, the viscosity of an aqueous thiolated polymer gel (3%) increased about 50% at pH 7.0 within 1 h. In oscillatory rheological measurements, it was shown that this increase in viscosity is mainly due to the increase in elasticity. Tensile studies carried out on freshly excised cow vagina demonstrated a significant (P<0.05) increase in the total work of adhesion (TWA) compared to the unmodified polymer. An amount of 24.8 micromol thiol groups per gram of polymer resulted in a 1.45-fold increase in the TWA, whereas an amount of 45.8 micromol showed an even 2.28-fold increase. These improved mucoadhesive properties can be explained by the formation of disulfide bonds between the thiolated polymer and cysteine rich subdomaines of the mucus layer. The release rate of the model drug progesterone from tablets based on microcrystalline cellulose serving as the reference was approximately 1% per hour, whereas it was 0.58% per hour for the unmodified polymer (NaC974P) and 0.12% per hour for the thiolated polymer (NaC974P-Cys). Therefore, this thiolated polymer is a promising carrier for progesterone providing a prolonged residence time and a controlled drug release.

[Endothelium protective effect of the high viscosity substances hyaluronic acid and methylcellulose in mechanical damage]. / Experimentelle Untersuchungen zur endothelschützenden Wirkung der hochviskösen Substanzen Hyaluronsäure und Methylzellulose gegenüber mechanischen Schädigungen.

We investigated the protective effect of the high-viscosity substances sodium hyaluronate (1%) and methylcellulose (2%) on corneal endothelium in the face of severe mechanical insult. An intraocular lens was drawn across the endothelium of porcine corneas with standardized conditions. We used different compression forces. Methylcellulose and sodium hyaluronate were used as lubricating substances in the experimental groups, while balanced salt solution (BSS PLUS) was used in the control group. In this study no significant protective effect of high-viscosity substances against strong direct mechanical damage was generally demonstrable. Only one group in which a moderately strong compression force was applied showed significantly less smaller endothelial cell loss when methylcellulose was used. The most important function of viscous substances is therefore to prevent a collapse of the anterior chamber and to prevent any contact of the intraocular lens or of instruments with the endothelium. Any mechanical contact with the endothelium means an irreversible endothelial cell loss.