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Physicochemical Characterization of Methotrexate—Bovine Serum Albumin Conjugates

Gavin Halbert, Alexander T. Florence

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Abstract

Physiochemical parameters have been determined for a series of methotrexate-bovine serum albumin conjugates produced using a water-soluble carbodiimide. Drug coupling produces a heterogeneous product consisting of mixtures of albumin and albumin polymers with varying quantities of covalently bound drug. Due to this heterogeneity, the measurement of absolute physiochemical values was not possible but two factors producing change were evident. The water soluble carbodiimide is responsible for major changes by producing polymers that dominate the properties of the conjugates. The changes induced by the covalently attached drug are less dramatic but still appreciable. The results emphasize that both the attached drug and the method of coupling are significant factors in altering the physiochemical properties of proteinaceous drug carriers.

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Physiochemical parameters have been determined for a series of methotrexate-bovine serum albumin conjugates produced using a water-soluble carbodiimide. Drug coupling produces a heterogeneous product consisting of mixtures of albumin and albumin polymers with varying quantities of covalently bound drug. Due to this heterogeneity, the measurement of absolute physiochemical values was not possible but two factors producing change were evident. The water soluble carbodiimide is responsible for major changes by producing polymers that dominate the properties of the conjugates. The changes induced by the covalently attached drug are less dramatic but still appreciable. The results emphasize that both the attached drug and the method of coupling are significant factors in altering the physiochemical properties of proteinaceous drug carriers.

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Available abstract

Physiochemical parameters have been determined for a series of methotrexate-bovine serum albumin conjugates produced using a water-soluble carbodiimide. Drug coupling produces a heterogeneous product consisting of mixtures of albumin and albumin polymers with varying quantities of covalently bound drug. Due to this heterogeneity, the measurement of absolute physiochemical values was not possible but two factors producing change were evident. The water soluble carbodiimide is responsible for major changes by producing polymers that dominate the properties of the conjugates. The changes induced by the covalently attached drug are less dramatic but still appreciable. The results emphasize that both the attached drug and the method of coupling are significant factors in altering the physiochemical properties of proteinaceous drug carriers.

Key concepts: Carbodiimide, Conjugate, Bovine serum albumin, Chemistry, Albumin, Serum albumin, Covalent bond, Methotrexate

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