Hidrogéis e filmes nanocompósitos de polissacarídeos contendo substâncias do gergelim para o tratamento de doenças vaginais

Abstract

Trichomoniasis and cervical cancer are gynecological diseases relevant to public health. This study focused on researching new potential therapeutical agents and improving the pharmaceutical dosage forms used for their vaginal release, aiming greater clinical efficiency. Xanthan (XG) and ƙ-carrageenan gums (CG) were used in the design of mucoadhesive films and hydrogels for the administration of sesame oil (SO) and sesamol (SES), both components obtained from sesame. The films were produced by the solvent evaporation technique and the hydrogels by directly thickening the gums, considering physiological vaginal conditions. A sesame oil nanoemulsion (SONE) was prepared using the spontaneous emulsification method to enable its inclusion in the hydrophilic polysaccharide film. Subsequently, SES was associated with SONE, obtaining the sesame oil nanoemulsion containing sesamol (SONESES) for inclusion in the hydrogel. The film composed of the XG and CG blend (at 2 %, ratio 1:3) and plasticized with glycerol (SONE-XCF) proved to be more promising for vaginal administration than the films obtained through the isolated use of the gums. SONE was adequately converted into the film (SONE-XCF), and the nanodroplets remained unchanged in the SONE-XCF polysaccharide matrix. SONE-XCF showed a homogeneous appearance, hydrophilic characteristic (θ = 56 ± 3), high swelling capacity (2427.22 ± 109.57 %), mucoadhesiveness (5773 ± 952 dyne/cm²), and long disintegration time (> 8 h), which contributes to the absorption of excessively produced fluids during vaginal infections and provides greater retention time at the site of action. For the first time, the anti-Trichomonas vaginalis activity of SO in vitro was demonstrated (IC50 of 5.935 mg/mL), and SONE potentiated this effect (IC50 of 1.8549 mg/mL), indicating an inherent activity against T. vaginalis for SONE-XCF and potential for incorporating other valuable drugs in this infection treatment. In turn, SONE-SES presented an encapsulation efficiency of 67.41%. SES showed in vitro cytotoxic effect on the HeLa cell line (IC50 > 75 µg/mL), and a better response was achieved through SONE-SES (IC50 of 42.06 µg/mL). SONE-SES was converted into a hydrogel (HG SONE-SES) composed of XG and CG blend at a 3.5% and 2:1 ratio, which provided adequate coverage, retention, and mucoadhesion to the bovine vaginal mucosa. The content was close to 100 %, and the average diameter of SONE-SES was maintained. HG SONE-SES had a spreadability factor of 5.48 mm²/g, pseudoplastic non-Newtonian flow, and high mucoadhesive strength (12619 ± 324 dyne/cm²). Part of the SES was retained in the mucosa in the ex vivo permeation assay, justifying its topical proposition in cervical cancer therapy. Finally, the hemocompatibility and chorioallantoic membrane assays (HET-CAM) attested on a preliminary basis the biocompatibility of both formulations (film and hydrogel). Thus, the important nanoemulsion’s role in improving the biological effect was evidenced, and nanocomposite formulations of natural polysaccharides were obtained with the desired properties for vaginal application and promising character for treating trichomoniasis and cervical cancer.