Controlled release of a protein kinase inhibitor UCN-01 (cas 112953-11-4) from liposomes influenced by the particle size
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Add time:08/04/2019 Source:sciencedirect.com
A protein kinase inhibitor UCN-01 (cas 112953-11-4) binds with high affinity to human α1-acid glycoprotein (hAGP) which may compromise the drugs therapeutic effectiveness. Liposomal formulations of UCN-01 have been evaluated as a means of reducing the impact of binding to hAGP. However, in an initial study, UCN-01 was released rapidly from liposomes added to rat plasma containing hAGP. The purpose of this study was to develop a liposomal formulation of UCN-01 that only slowly released drug. Liposomes composed of lipids with a high phase transition temperature and having an average particle size of 120 nm and above reduced leaking of UCN-01 when the formulations were evaluated by adding to rat plasma containing hAGP. Furthermore, formulations composed of larger liposomes were also more effective in vivo; in tests in which liposomal preparations were injected together with hAGP into rats, more UCN-01 was retained in liposomes for 24 h after administration of 155 nm liposomes as compared to 112 nm liposomes.
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