Publicação
Development and dermatological validation of vaginal gel capsules containing antisense oligomers to control Candida albicans filamentation
| Resumo: | Vulvovaginal candidiasis (VVC) is an increasingly prevalent public health concern that poses significant clinical, social, and economic challenges due to its difficulty to treat. This infection is primarily caused by the fungus Candida albicans, whose ability to shift from yeast to filamentous forms contributes to its pathogenicity. Emerging therapeutic strategies include antisense oligonucleotides (ASOs), which offer a promising alternative to conventional therapies. In this context, chitosan-coated alginate capsules formulated as gels serve as localized drug delivery systems, ensuring controlled drug release and targeted action within the vaginal environment. The main objective of this research was to develop and evaluate such capsules incorporating a cationic lipid-encapsulated 2'-O-MethylRNA EFG1 oligomer—an ASO known to inhibit C. albicans filamentation—alongside Aloe vera, using an ionotropic gelation method. The resulting capsules, coated with medium molecular weight chitosan and containing 10 % low-viscosity Aloe vera, measured approximately 1.59 mm in diameter and weighed around 1.85 mg. Further, a comprehensive physicochemical characterization – including Fourier-transform infrared, differential scanning calorimetry, and scanning electron microscopy analyses- confirmed effective polymer interactions and revealed a uniform, porous surface suitable for enabling ASOs release. In vitro cytotoxicity evaluation confirmed the biocompatibility of the capsules, showing no significant signs of toxicity. Importantly, in vitro testing against C. albicans indicated a significant reduction in fungal filamentation, correlating with increased of the capsules with free ASO at 6 and 24 hours, achieving a reduction up to 100 % and 50 % at synthetic vaginal fluid pH 4 and 80 % and 50 % at synthetic vaginal fluid pH 7, respectively. However, the capsules with lipoplex with ASO showed an increase in release at 24 hours, with a filamentation reduction up to 60 % at synthetic vaginal fluid pH 7 and at 48 hours, achieving up to 80 % of reduction at synthetic vaginal fluid pH 4. In summary, this study highlights the potential of chitosan-coated alginate capsules as a safe, biocompatible, and effective therapeutic approach for the treatment of VVC, offering an innovative strategy to control of C. albicans filamentation. |
|---|---|
| Autores principais: | Costa, Joana Beatriz Lobo Marinho |
| Assunto: | Antisense oligonucleotides (ASO) Candida albicans Chitosan Filamentation Vulvovaginal candidiasis (VVC) Candidíase vulvovaginal (CVV) Filamentação Oligonucleótidos antisense (OA) Quitosano |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade do Minho |
| Idioma: | português |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Vulvovaginal candidiasis (VVC) is an increasingly prevalent public health concern that poses significant clinical, social, and economic challenges due to its difficulty to treat. This infection is primarily caused by the fungus Candida albicans, whose ability to shift from yeast to filamentous forms contributes to its pathogenicity. Emerging therapeutic strategies include antisense oligonucleotides (ASOs), which offer a promising alternative to conventional therapies. In this context, chitosan-coated alginate capsules formulated as gels serve as localized drug delivery systems, ensuring controlled drug release and targeted action within the vaginal environment. The main objective of this research was to develop and evaluate such capsules incorporating a cationic lipid-encapsulated 2'-O-MethylRNA EFG1 oligomer—an ASO known to inhibit C. albicans filamentation—alongside Aloe vera, using an ionotropic gelation method. The resulting capsules, coated with medium molecular weight chitosan and containing 10 % low-viscosity Aloe vera, measured approximately 1.59 mm in diameter and weighed around 1.85 mg. Further, a comprehensive physicochemical characterization – including Fourier-transform infrared, differential scanning calorimetry, and scanning electron microscopy analyses- confirmed effective polymer interactions and revealed a uniform, porous surface suitable for enabling ASOs release. In vitro cytotoxicity evaluation confirmed the biocompatibility of the capsules, showing no significant signs of toxicity. Importantly, in vitro testing against C. albicans indicated a significant reduction in fungal filamentation, correlating with increased of the capsules with free ASO at 6 and 24 hours, achieving a reduction up to 100 % and 50 % at synthetic vaginal fluid pH 4 and 80 % and 50 % at synthetic vaginal fluid pH 7, respectively. However, the capsules with lipoplex with ASO showed an increase in release at 24 hours, with a filamentation reduction up to 60 % at synthetic vaginal fluid pH 7 and at 48 hours, achieving up to 80 % of reduction at synthetic vaginal fluid pH 4. In summary, this study highlights the potential of chitosan-coated alginate capsules as a safe, biocompatible, and effective therapeutic approach for the treatment of VVC, offering an innovative strategy to control of C. albicans filamentation. |
|---|