Physicochemical evaluation and pharmacodynamics of itraconazole-loaded liquid crystal precursor for vaginal delivery.

PURPOSE: To develop a liquid crystal (LC) precursor that can be used as a novel vaginal delivery system for Itraconazole (ITZ) and evaluate its pharmacodynamics.

METHODS

The LC precursor was prepared by using phytantriol (PYT) as lipid matrix and N, N-dimethylformamide (DMAC) as solvent. Swelling studies were performed to assess the phase conversion ability. The formulations were characterized by crossed polarized light microscopy (CPLM), small-angle X-ray scattering (SAXS). Moreover, the rheological and in vitro drug release behavior were investigated. Then the vaginal retention time of ITZ in the optimal prescription was evaluated. Finally, the pharmacodynamics studies of the ITZ-loaded LC precursor were performed in a mouse model of vulvovaginal candidiasis (VVC).

RESULTS

The LC precursor could transform to LC gels after administration into the vagina. Based on PLM and SAXS, the LC gels, formed after phase-conversion, were cubic LC. The LC precursor was non-Newtonian, while the LC gels exhibited a pseudo-plastic fluid behavior. In vitro release results revealed that F2 (68.0%) had a higher cumulative drug release than that of F1 (59.17%) at 72 h. Most of the LC gels could be retained in the vagina of mice for 24-36 h. Pharmacodynamics studies showed that there was only mild inflammation or no inflammatory stimulation in the control group. The ITZ-loaded LC precursor significantly improved the symptoms of vaginitis in mice and had a better therapeutic effect than that of the positive control group.

CONCLUSIONS

The ITZ-loaded LC precursor would be a promising formulation for vaginal drug delivery.