f66e0dbd81bf93602544f61417942c0f pmc_10223105.pdf e01549bbd453e521094e2bc22615dcc8709bf215 pmc_10223105.pdf dbb8eabf4b4e0356f4e8f27ab3a1c24328e99746123806e472ed5325a5125e90 pmc_10223105.pdf Title: Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel Subject: Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative to treat vaginal candidiasis. The aim of the current study was to develop and optimize a mucoadhesive drug delivery system for the local administration of disulfiram. Such formulations were composed of polyethylene glycol and carrageenan to improve the mucoadhesive and mechanical properties and to prolong the residence time in the vaginal cavity. Microdilution susceptibility testing showed that these gels had antifungal activity against Candida albicans, Candida parapsilosis, and Nakaseomyces glabratus. The physicochemical properties of the gels were characterized, and the in vitro release and permeation profiles were investigated with vertical diffusion Franz cells. After quantification, it was determined that the amount of the drug retained in the pig vaginal epithelium was sufficient to treat candidiasis infection. Together, our findings suggest that mucoadhesive disulfiram gels have the potential to be an effective alternative treatment for vaginal candidiasis. Keywords: disulfiram; Candida spp.; mucoadhesion; ATP-binding cassette; resistant; vaginitis Author: Maria Lajarin-Reinares, Iria Naveira-Souto, Mireia Mallandrich, Joaquim Suñer-Carbó, Montserrat Llagostera Casas, Maria Angels Calvo and Francisco Fernandez-Campos Creator: LaTeX with hyperref Producer: MiKTeX pdfTeX-1.40.21 CreationDate: Tue May 9 08:16:25 2023 CEST ModDate: Tue May 9 08:21:02 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2761962 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- TOYVEE+VnURWPalladioL Type 1 Custom yes yes no 10 0 UMYAXG+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 NRLLQE+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 UVLVIS+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 SOZKOC+VnURWPalladioL-Bold Type 1 Custom 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HAJJHG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 364 0 HAJKLB+PalatinoLinotype TrueType MacRoman yes yes no 367 0 HAJNDC+CambriaMath CID TrueType Identity-H yes yes yes 370 0 HAJOBP+Calibri CID TrueType Identity-H yes yes yes 387 0 HAJJHC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 393 0 HAJJHD+PalatinoLinotype CID TrueType Identity-H yes yes yes 396 0 HAJJHE+PalatinoLinotype TrueType WinAnsi yes yes no 402 0 HAJJHG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 405 0 HAJKLB+PalatinoLinotype TrueType MacRoman yes yes no 408 0 HAJOBP+Calibri CID TrueType Identity-H yes yes yes 421 0 HAJJHC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 427 0 HAJJHD+PalatinoLinotype CID TrueType Identity-H yes yes yes 430 0 HAJJHE+PalatinoLinotype TrueType WinAnsi yes yes no 436 0 HAJJHG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 439 0 HAJKLB+PalatinoLinotype TrueType MacRoman yes yes no 442 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-13 02:28:46 CEST 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of the Gels Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Viscosity of the Mucoadhesive Gels Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Mucoadhesive Properties Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Optimization of the Mucoadhesive Gels Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Final Rheological Properties Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Syringeability of the Formulations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: In Vitro Release Tests of the Disulfiram Gel Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Pig Vagina Permeation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Determination of the Concentration Retained in the Pig Vagina Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Results and Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Children: Item: Title: Antifungal Susceptibility Testing Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Preparation and Statistical Design to Evaluate the Effect of Experimental Variables on the Mucoadhesive Gel Properties Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Optimization of the Mucoadhesive Gels Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Rheological Properties Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Syringeability of the Formulations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: In Vitro Release of Disulfiram from the Gel Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Pig Vagina Permeation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Disulfiram Concentration Retained in the Pig Vagina Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Info: Title: Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel Author: Maria Lajarin-Reinares, Iria Naveira-Souto, Mireia Mallandrich, Joaquim Suñer-Carbó, Montserrat Llagostera Casas, Maria Angels Calvo and Francisco Fernandez-Campos Subject: Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative to treat vaginal candidiasis. The aim of the current study was to develop and optimize a mucoadhesive drug delivery system for the local administration of disulfiram. Such formulations were composed of polyethylene glycol and carrageenan to improve the mucoadhesive and mechanical properties and to prolong the residence time in the vaginal cavity. Microdilution susceptibility testing showed that these gels had antifungal activity against Candida albicans, Candida parapsilosis, and Nakaseomyces glabratus. The physicochemical properties of the gels were characterized, and the in vitro release and permeation profiles were investigated with vertical diffusion Franz cells. After quantification, it was determined that the amount of the drug retained in the pig vaginal epithelium was sufficient to treat candidiasis infection. Together, our findings suggest that mucoadhesive disulfiram gels have the potential to be an effective alternative treatment for vaginal candidiasis. 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