Reducing the Impact of Binding of UCN-01 to Human α_1-Acid Glycoprotein by Encapsulation in Liposomes(Biopharmacy)

概要

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A liposomal formulation of UCN-01 was studied to prevent binding of drug to human α_1-acid glycoprotein (hAGP). The release of drug from liposomes added to various media was investigated by monitoring the concentration of UCN-01 in different fractions. Protein bound UCN-01 was separated from liposomal UCN-01 and free UCN-01 by gel chromatography and the drug content in the fractions was measured by high-performance liquid chromatography. Also, the blood levels of hAGP bound drug and drug retained in liposomes were assessed after intravenous administration to rats of UCN-01 liposomes together with hAGP. In media containing hAGP, but not rat AGP, UCN-01 was released from liposomes. When UCN-01 liposomes were mixed with rat plasma plus hAGP, the UCN-01 in the liposomes was only gradually released so that some drug remained in the liposomes, and therefore not bound to hAGP, for up to 24h. After the mixture of liposomal UCN-01 and hAGP was injected into rats, some UCN-01 was retained in liposomes for several hours. Encapsulation of UCN-01 into liposomes is an effective method of preventing binding of UCN-01 to hAGP.
公益社団法人日本薬学会の論文
2005-07-01