PERMEABILITY OF ARTICULAR-CARTILAGE TO MATRIX METALLOPROTEASE INHIBITORS

Purpose. To develop an in vitro cartilage permeation model for cartila ge permeability study and to evaluate the effects of molecular hydroph ilicity and cartilage location on the permeability of articular cartil age to matrix metalloprotease inhibitors. Methods. An in vitro cartila ge permeation model was developed and utilized to determine the permea bility of articular cartilage to the matrix metalloprotease inhibitors of different hydrophilicity. Permeability coefficients were obtained by measuring the steady-state flux of the inhibitor compounds. HPLC me thods were also developed and employed for the analysis of drug levels in assay media. Results. The relationship between permeability and hy drophilicity of drug molecules was examined. Results indicated that th e permeability coefficient increased with increasing hydrophilicity of the molecule. Additionally, the relationship between the permeability and the location of the cartilage section within the animal joint was investigated. Our results showed that the drug molecules penetrated f aster in the surface laver cartilage than in the deep layer cartilage. Conclusions. Increasing the hydrophilicity of a molecule would increa se its permeability across articular cartilage. The ill vitro cartilag e permeation model developed could be used to rank order drug compound s according to their cartilage permeability profiles and ca aid in dru g selection and development.