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• W2026943911 abstract "The highly potent anti-HIV agent UC781 is being evaluated for use in topical microbicides to prevent HIV transmission. However, UC781 is extremely hydrophobic with poor water solubility, a property that may complicate appropriate formulation of the drug. In this study, we examined the ability of several cyclodextrins, beta-cyclodextrin (beta CD), methyl-beta-cyclodextrin (M beta CD), and 2-hydroxylpropyl-beta-cyclodextrin (HP beta CD), to enhance the aqueous solubility of UC781. Each of the cyclodextrins provided dramatic increases in UC781 aqueous solubility, the order being M beta CD>HP beta CD>beta CD. The complexation constants (K (1:1)) of the inclusion complexes were determined via a phase solubility technique using high-performance liquid chromatography and showed that UC781 solubility increased linearly as a function of cyclodextrin concentration. Ultraviolet spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and 2D (1)H ROESY NMR spectroscopy were used to further characterize these UC781/cyclodextrin complexes. The inhibitory potency of UC781 and its HP beta CD inclusion complex were evaluated using an in vitro HIV-1 reverse transcriptase inhibition assay The inhibitory potency of the UC781/HP beta CD complex was 30-fold greater than that of UC781 alone, showing that the complexed drug is able to provide substantial inhibition of its target. The enhancement of UC781 aqueous solubility is essential for the development of a useful vaginal microbicide dosage form, and our data suggest that UC781/cyclodextrin inclusion complexes may be useful in this context." @default.
• W2026943911 created "2016-06-24" @default.
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• W2026943911 date "2008-12-01" @default.
• W2026943911 modified "2023-10-16" @default.
• W2026943911 title "Characterization of Cyclodextrin Inclusion Complexes of the Anti-HIV Non-Nucleoside Reverse Transcriptase Inhibitor UC781" @default.
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• W2026943911 doi "https://doi.org/10.1208/s12248-008-9070-3" @default.
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