UC781, a very potent HIV-1 non-nucleoside reverse transcriptase inhibitor with extreme hydrophobicity and poor water solubility, is under development as a topical vaginal microbicide product to prevent HIV transmission. In this study, the thermodynamic behavior of the interaction between UC781 with three cyclodextrins (CDs): β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD) and methyl-β-cyclodextrin (MβCD), was investigated using a reversed-phase HPLC method. A mobile phase consisting of acetonitrile: H2O (30:70) solution containing various CD concentrations was used. The retention time at different temperatures was determined to evaluate the inclusion process. The influence of βCDs on the solubility and hydrophobicity of UC781 was characterized by retention time values. The results showed that the inclusion capacity of cyclodextrins follows the order MβCD > βCD > HPβCD. An enthalpy–entropy compensation effect was also observed. In addition, the results revealed that the change of ΔH is greater than that of ΔS. These results suggested that the complexation of UC781 with βCDs is an enthalpy driven process. The modification on β-cyclodextrin will influence the inclusion process.

中文翻译：

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使用 HPLC 方法对环糊精-UC781 包合物进行热力学研究

UC781 是一种非常有效的 HIV-1 非核苷逆转录酶抑制剂，具有极强的疏水性和较差的水溶性，正在开发作为一种外用阴道杀菌剂产品，以防止 HIV 传播。在这项研究中，UC781 与三种环糊精 (CD) 之间相互作用的热力学行为：β-环糊精 (βCD)、羟丙基-β-环糊精 (HPβCD) 和甲基-β-环糊精 (MβCD)，使用反向-液相 HPLC 法。使用由乙腈组成的流动相：H2O (30:70) 溶液，其中含有不同浓度的 CD。确定在不同温度下的保留时间以评估夹杂过程。βCDs 对 UC781 的溶解度和疏水性的影响通过保留时间值来表征。结果表明，环糊精的包合能力大小为MβCD>βCD>HPβCD。还观察到焓-熵补偿效应。此外，结果显示ΔH的变化大于ΔS的变化。这些结果表明 UC781 与 βCDs 的复合是一个焓驱动的过程。β-环糊精的改性会影响包合过程。