Composite Thermoresponsive Hydrogel with Auranofin‐Loaded Nanoparticles for Topical Treatment of Vaginal Trichomonad Infection

Abstract

Trichomonas vaginalis is responsible for the most common non-viral sexually transmitted disease worldwide. Standard treatment is with oral metronidazole or tinidazole, but resistance is emerging and adverse effects can be problematic. Topical treatment offers potential benefits for increasing local drug concentrations while reducing systemic exposure, but none are currently approved for trichomoniasis. The anti-rheumatic drug, auranofin (AF), was recently discovered to have significant trichomonacidal activity, but has a long plasma half-life and significant adverse effects. Here, this drug is used as a model to develop a novel topical formulation composed of AF-loaded nanoparticles (NP) embedded in a thermoresponsive hydrogel for intravaginal administration.

Nanotechnology for virus treatment

“…Various tissue-targeted nanoparticle formulations, such as those for vaginal delivery or topical application [ [125] , [126] , [127] , [128] , [129] ], as well as those for brain delivery to treat neuroAIDS [ [130] , [131] , [132] , [133] , [134] ], have been synthesized to better manage and prevent HIV infections at those tissue sites. For topical mucosal application in the vagina, maraviroc, an entry inhibitor that acts on the CCR5 receptor, and tenofovir disoproxil fumarate have been loaded into hydrogel nanoparticles with a lipid shell [ 135 ].…”

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

“…Furthermore, no profound alteration was observed in the activity of hepatic thioredoxin reductase, an enzyme targeted by AF, and the estrus cycle in female mice. The findings illustrated that the formulation did not cause apparent systemic or topical toxicity [ 119 ].…”

Nanomedicine Approaches to Negotiate Local Biobarriers for Topical Drug Delivery

“…Overall intravaginal administration of AF‐NP outperforms oral delivery when treating vaginal trichomonad and does not induce toxicity at the local or systemic level. [ 256 ] Chlamydia infection of vaginal epithelial cells can be addressed using poly(ethylenimine)‐condensed PDGFR‐β siRNA within PLGA‐PEG diblock copolymer NPs. This formulation can prevent the acquisition and reoccurrence of the infection by inducing autophagy in the epithelial cells.…”

“…The antirheumatic drug, auranofin (AF), has significant trichomonacidal activity, but its oral delivery induces several adverse effects due to long plasma half-life. [255,256] AF-loaded NPs (PLGA functionalized with PEG) embedded into a chitosanbased hydrogel matrix can be used for intravaginal administration in BALB/c mice. This method has excellent NPs retention in the vaginal tissue (>6 h) and also remarkably increases local AF levels.…”