Peng S X, VonBargen E C, Bornes D M, Pikul S
The Procter & Gamble Company, Health Care Research Center, Mason, Ohio 45040, USA.
Pharm Res. 1998 Sep;15(9):1414-8. doi: 10.1023/a:1011905806123.
To develop an in vitro cartilage permeation model for cartilage permeability study and to evaluate the effects of molecular hydrophilicity and cartilage location on the permeability of articular cartilage to matrix metalloprotease inhibitors.
An in vitro cartilage permeation model was developed and utilized to determine the permeability 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 methods were also developed and employed for the analysis of drug levels in assay media.
The relationship between permeability and hydrophilicity of drug molecules was examined. Results indicated that the 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 faster in the surface layer cartilage than in the deep layer cartilage.
Increasing the hydrophilicity of a molecule would increase its permeability across articular cartilage. The in vitro cartilage permeation model developed could be used to rank order drug compounds according to their cartilage permeability profiles and to aid in drug selection and development.
建立用于软骨通透性研究的体外软骨渗透模型，并评估分子亲水性和软骨位置对关节软骨对基质金属蛋白酶抑制剂通透性的影响。
建立并利用体外软骨渗透模型来测定关节软骨对不同亲水性基质金属蛋白酶抑制剂的通透性。通过测量抑制剂化合物的稳态通量获得通透系数。还开发了高效液相色谱法并用于分析测定介质中的药物水平。
研究了药物分子通透性和亲水性之间的关系。结果表明，通透系数随分子亲水性的增加而增加。此外，研究了通透性与动物关节内软骨切片位置之间的关系。我们的结果表明，药物分子在表层软骨中的渗透速度比在深层软骨中快。
增加分子的亲水性会增加其跨关节软骨的通透性。所建立的体外软骨渗透模型可用于根据药物化合物的软骨通透性概况对其进行排序，并有助于药物的选择和开发。
