A thermodynamic study of the cyclodextrin-UC781 inclusion complex using a HPLC method

作者：Yang Haitao; Parniak Michael A; Hillier Sharon L; Rohan Lisa C^*

来源：Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2012, 72(3-4): 459-465.

DOI：10.1007/s10847-011-0019-2

• UC781
• beta-Cyclodextrin inclusion complex
• Non-nucleoside reverse transcriptase inhibitor (NNRTI)
• Thermodynamics
• HPLC
• Enthalpy

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): beta-cyclodextrin (beta CD), hydroxypropyl-beta-cyclodextrin (HP beta CD) and methyl-beta-cyclodextrin (M beta CD), 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 beta CDs 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 M beta CD > beta CD > HP beta CD. An enthalpy-entropy compensation effect was also observed. In addition, the results revealed that the change of Delta H is greater than that of Delta S. These results suggested that the complexation of UC781 with beta CDs is an enthalpy driven process. The modification on beta-cyclodextrin will influence the inclusion process.

• 出版日期2012-4