title: Co-delivery of antiviral and antifungal therapeutics for the treatment of sexually transmitted infections using a moldable, supramolecular hydrogel.
abstract: In this investigation, a therapeutic co-delivery hydrogel system is developed to provide effective HIV prophylaxis, alongside the prevention and/or treatment of candidiasis. Two components-a HIV reverse transcriptase inhibitor, tenofovir, and a cationic macromolecular antifungal agent derived from a vitamin D-functionalized polycarbonate (VD/BnCl (1:30))-are formulated into biodegradable vitamin D-functionalized polycarbonate/PEG-based supramolecular hydrogels. The hydrogels exhibit thixotropic properties and can be easily spread across surfaces for efficient drug absorption. Sustained release of tenofovir from the hydrogel is observed, where approximately 85% tenofovir is released within 3 h. VD/BnCl (1:30) does not impede drug diffusion from the hydrogel as the drug release profiles are similar with and without the polycation. Antimicrobial efficacy studies indicate that the hydrogels kill C. albicans efficiently with a minimum bactericidal concentration (MBC) of 0.25-0.5 g L(-1) . These hydrogels also eradicate C. albicans biofilm effectively at 4× MBC. When human dermal fibroblasts (as model mammalian cells) are treated with these hydrogels, cell viability remains high at above 80%, demonstrating excellent biocompatibility. When applied topically, this dual-functional hydrogel can potentially prevent HIV transmission and eliminate microbes that cause infections in the vulvovagina region.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Ashlynn L Z
authors.initials: AL
authors.lastname: Lee
authors.forename: Victor W L
authors.initials: VW
authors.lastname: Ng
authors.forename: Ghim Lee
authors.initials: GL
authors.lastname: Poon
authors.forename: Xiyu
authors.initials: X
authors.lastname: Ke
authors.forename: James L
authors.initials: JL
authors.lastname: Hedrick
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D011076:Polycarboxylate Cement / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D012749:Sexually Transmitted Diseases / Q000188:drug therapy; D015229:Sexually Transmitted Diseases, Viral / Q000188:drug therapy; D000068698:Tenofovir / Q000008:administration & dosage / Q000737:chemistry; D014807:Vitamin D / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D000998:Antiviral Agents; D020100:Hydrogels; D011076:Polycarboxylate Cement; D014807:Vitamin D; C005506:polycarbonate; D011092:Polyethylene Glycols; D000068698:Tenofovir
keywords: antifungal; antiviral; hydrogels; polycarbonate; vitamin D