Artificial Lipids Stabilized Camptothecin Incorporated in Liposomes(Miscellaneous)

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概要

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• Camptothecin (CPT) has anticancer activity. While only the lactone form of CPT is biologically active, this form exhibits poor aqueous solubility. Pharmaceutical formulation of CPT incorporated in liposomes is of significant importance to develop the therapeutic utilization of CPT. The aim of this study was to increase incorporation efficiency and stability of CPT in liposomes composed of hydrogenated soybean phosphatidylcholine, cholesterol, and oleic acid (7:3:1, molar ratio), by incorporating three kinds of artificial lipids (DBs) (DB-liposome); 4-n-(M12B), 3,5-bis(B12B) and 3,4,5-tris(dodecyloxy)benzoic acid (T12B). The interaction of CPT with DB in the state of liposomes, was examined. In DB-liposomes presenting mean diameters of 150 nm, incorporation efficiency of CPT up to 55% and final drug to lipid molar ratio up to 0.07 were obtained when the liposomes were prepared at a feeding ratio of 1/30 (w/w) CPT/total lipid. However, in the optimal formulations, incorporated DB mol% was different; T12B and D12B were incorporated about one third and half mol% of M12B, respectively. Moreover, we demonstrated that T12B stabilized CPT in liposomes significantly compared with other DBs as measured by CPT release, and by steady state fluorescence polarization degree of CPT using intrinsic fluorescence of CPT. These findings suggested that in addition of contribution of phenyl group of DB, dodecyloxy group may interact strongly with lactone ring of CPT. The capacity to contain CPT interacted with DBs may be limited in liposomes. T12B may be incorporated in the interior of the bilayers, resulting in increase of incorporation stability of CPT. This finding demonstrates a potential application of the novel liposome formulation of CPT in drug delivery.

• 公益社団法人日本薬学会の論文
• 2008-05-01

著者

• Maitani Yoshie

  Institute Of Medicinal Chemistry Hoshi University

• TOMA KAZUNORI

  The Noguchi Institute

• KAWANO Kumi

  Institute of Medicinal Chemistry Hoshi University

• KATAYAMA Sayaka

  Institute of Medicinal Chemistry, Hoshi University

• HAYAMA Akihiro

  Institute of Medicinal Chemistry, Hoshi University

• Hayama Akihiro

  Institute Of Medicinal Chemistry Hoshi University

• Katayama Sayaka

  Institute For Chemical Research Kyoto University

• Katayama Sayaka

  Institute Of Medicinal Chemistry Hoshi University

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