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Effect of epidermal/dermal separation methods and ester chain configuration on the bioconversion of a homologous series of methotrexate dialkyl esters in dermal and epidermal homogenates of hairless mouse skin


Effect of epidermal/dermal separation methods and ester chain configuration on the bioconversion of a homologous series of methotrexate dialkyl esters in dermal and epidermal homogenates of hairless mouse skin



International Journal of Pharmaceutics (Amsterdam) 102(1-3): 241-247



A comparison has been made regarding various methods of hairless mouse skin dermal/ epidermal separation techniques using criteria such as soluble protein yield and rate of hydrolysis per unit soluble protein, as well as effectiveness of separation, in which histological techniques were employed. Also compared were the relative esterase activities of dermal and epidermal layers, in which the dermis exhibited higher activity. A homologous series of methotrexate dialkyl esters were studied as to their pseudo-first order degradation in homogenates of dermis and epidermis of hairless mouse skin. A logarithmic relationship between pseudo-first order rate constant and alkyl chain length was observed for both dermal and epidermal homogenates. The degree of bioconversion of the diesters was also studied and the enzymatic reaction failed to proceed beyond the level of the monoalkyl esters. Examination of the selectivity for the formation of alpha- and gamma-monoalkyl products revealed that y-monoester appeared to predominate over alpha-monoester in the case of the branched-chain dialkyl ester.

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Effects of epidermal/dermal separation methods and ester chain configuration on the bioconversion of a homologous series of methotrexate dialkyl esters in dermal and epidermal homogenates of hairless mouse skin. International Journal of Pharmaceutics 102(1-3): 241-247, 1994

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