Development and anti-Candida evaluation of the vaginal delivery system of amphotericin B nanosuspension-loaded thermogel.

Vulvovaginal candidiasis (VVC) is a typical kind of vaginal mucosal infection. Herein, we developed a novel vaginal delivery system of amphotericin B (AmB) nanosuspension-loaded thermogel (AmB NPs/thermogel) utilising pharmaceutical technique of high-pressure homogenisation and Poloxamer P407/P188 hydrogel. The stabiliser and hydrogel materials of the formulation were tested to maintain proper sol-gel transition as well as the relative stability of the particle size of AmB nanosuspension in the thermogel. The particle size of AmB nanosuspensions in the hydrogel was ∼247 nm. Transmission electron microscopy images confirmed the round-shape morphology of AmB nanoparticles in AmB NPs/thermogel, while that of irregular morphology of merely AmB nanosuspensions without stabiliser and hydrogel materials. AmB could be sustained release for ∼12 h in vitro. In vivo drug content in the vaginal tissue was also evaluated with 87, 47, 33 and 6.7% drug remaining after 1, 3, 6 and 12 h, respectively. The in vivo anti-Candida test was conducted on candidiasis-infected mice model. In the same drug dose of 2.5 mg/kg, AmB NPs/thermogel showed better anti-Candida efficiency compared with commercial AmB effervescent tablet. This delivery system might show some insights for the vaginal formulation development of other hydrophobic antifungal drugs.