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Background  Vulvovaginal candidiasis (VVC) is a common infection in need of more effective treatment. Formation of epithelium-associated  Candida  biofilms and the presence of persister cells are among the major contributing factors to the recurrence of this condition. We have previously developed RAFT-derived polymethacrylates that are effective in killing  C. albicans  biofilms  in vitro . This study aimed to examine the clinical potential of polymethacrylates as antifungals for treatment of recurrent VVC (RVVC).    Methods  A mouse model of VVC was used to establish vaginal epithelium-associated biofilms, using  C. albicans  isolates from VVC/RVVC patients. A comparison was made of the efficacies of polymethacrylates and conventional antifungals, clotrimazole and nystatin, in killing  Candida  in epithelium-associated biofilms  in vivo .  Ex vivo  biofilms were used for  Candida  population profiling and to quantify persister cells in vaginal epithelia. The potency of polymethacrylates and conventional antifungals against persister cells, either as sole agents or in combination, was assessed.    Results  Polymethacrylates showed negligible local toxicity, resistance to vaginal acidity, and outstanding  in vivo  activity against vaginal epithelium-associated  C. albicans  biofilms.  In vivo  tests polymethacrylates outperformed the conventional antifungals, nystatin and clotrimazole at concentrations 50 times below the over-the-counter concentrations. Using polymethacrylates was associated with fewer persister cells, and better eradication of persister cells pre-selected by conventional antifungals.    Conclusion  This study systematically assessed the clinical potential of RAFT-derived polymethacrylates as an effective treatment for VVC/RVVC in a mouse model. Polymethacrylates effectively killed vaginal epithelium-related  C. albicans in vivo  by specially targeting biotic biofilms and persister cells. Treatment presented negligible local toxicity.

RAFT-Derived Polymethacrylates as a Superior Treatment for Recurrent Vulvovaginal Candidiasis by Targeting Biotic Biofilms and Persister Cells