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A study of the interaction of drugs with liposomes with isothermal titration calorimetry

Journal of Biophysical Chemistry 2013年第1期4卷 11-21页

作者： Hiroko Osanai Tastuya Ikehara seiji Miyauchi Kazumi shimono Jun Tamogami Toshifumi Nara Naoki Kamo College of Pharmaceutical sciences Matsuyama University Matsuyama Japan Faculty of Pharmaceutical sciences Toho University Funabashi Japan Graduate school of Pharmaceutical sciences Hokkaido University Sapporo Japan

Isothermal titration calorimetry (ITC) was applied to investigate the interaction of drugs with liposomes. Two types of titration are possible. One type is when the liposome suspension in the cell is titrated by aliquots of drug solution, and the other is when the drug and liposome solutions take the opposite roles. In this paper, we employed the latter type because the disturbance of liposomes may be minimal in this titration type. We derived an equation in which the accumulated heat-flow is expressed as a function of the added lipid concentration. In the derivation, the uniform binding model was used although there may be various binding sites. This equation contains a parameter n, the number of binding sites per lipid molecule. In addition, we derive the relation between the dissociation constant (Kd), partition coefficient (Pm) and n. Binding parameters such as Kd, n, the Gibbs energy change, enthalpy change and entropy change were estimated for ANs (1-anilino-8-naphtarenesulfonate), TPB (tetraphenylborate), amlodipine, nifedipine, amitriptyline, nortriptyline, imipramine, desipramine, propranolol, chlorpromazine, promethazine, miconazole, indomethacin, diclofenac and diflunisal. For some drugs, the enthalpy change was the major binding affinity instead of the classical hydrophobic interaction in which entropy takes the essential role. We proved an approximate rule that for drugs with smaller n (the number of binding sites per lipid molecule), the entropy change contributes more than the enthalpy change.

关键词： TC Drug Binding Liposome Dissociation Constant ΔH and δs Change

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