Yang Haitao, Parniak Michael A, Hillier Sharon L, Rohan Lisa C
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
J Incl Phenom Macrocycl Chem. 2012 Apr;72(3-4):459-465. doi: 10.1007/s10847-011-0019-2.
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: HO (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.
UC781是一种极具效力的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，目前正作为一种局部阴道杀菌剂产品进行开发，用于预防HIV传播。在本研究中，采用反相高效液相色谱法研究了UC781与三种环糊精（CDs）：β-环糊精（βCD）、羟丙基-β-环糊精（HPβCD）和甲基-β-环糊精（MβCD）之间相互作用的热力学行为。使用由含有不同CD浓度的乙腈：水（30:70）溶液组成的流动相。测定不同温度下的保留时间以评估包合过程。通过保留时间值表征βCDs对UC781溶解度和疏水性的影响。结果表明，环糊精的包合能力顺序为MβCD > βCD > HPβCD。还观察到焓-熵补偿效应。此外，结果表明ΔH的变化大于ΔS的变化。这些结果表明，UC781与βCDs的络合是一个焓驱动的过程。β-环糊精的修饰会影响包合过程。
