Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal

Abstract

Trichomoniasis is a sexually transmitted infection (IST) whose vector is the parasite Trichomonas vaginalis. Conventional therapies have, in most cases, low efficacy and high toxicity, making the search for new therapies relevant. Diphenyl diselenide (PhSe)2, is an organic selenium compound with antioxidant, anti-inflammatory properties, in addition to activity against some microorganisms. However, this compound has high lipophilicity and toxic effects, which makes its clinical use difficult. In this sense, polymeric nanocapsules become an interesting alternative to overcome its limitations. Therefore, this dissertation aimed to develop nanocapsule suspensions of Eudragit® RS100 and coconut oil containing (PhSe)2 and to evaluate, in an unprecedented way, its anti-trichomonas activity, in addition to investigating the feasibility of preparing a hydrogel with this suspension, using locust bean gum as a gel-forming agent, aiming at vaginal application for the treatment of trichomoniasis. The nanocapsule suspensions were prepared by the preformed polymer interfacial deposition method and characteristics compatible with nanostructured drug delivery systems were observed, such as average particle size in the nanometric range (193-206 nm), adequate polydispersion index (0.19-0.22), positive zeta potential, pH in the acidic range (4.97-5.04), compound content close to theoretical value (1.04 mg/mL), and high encapsulation efficiency (99.92 %). In the evaluation of the in vitro activity in cells infected by T. vaginalis, (PhSe)2 nanoencapsulated at intermediate concentrations reduced the viability of the trophozoite more significantly compared to the free form of the active, due to controlled release provided by the nanocarrier system. The antioxidant capacity of nanoencapsulated (PhSe)2 was superior to the free form. The mucoadhesion evaluation of the nanocapsules, with change in the average diameter and the inversion of the zeta potential, confirmed their mucoadhesive potential, attributed to the cationic polymer. The hydrogels were prepared by thickening the nanocapsule suspensions with locust bean gum (3%). The developed formulations presented physicochemical characteristics suitable for vaginal application, maintaining the nanometer size in the range of 237-295 nm (photon correlation spectroscopy), active content close to the theoretical value (1mg/g of (PhSe)2) (HPLC), pH values in the neutrality range 6.16-6.20 (potentiometry), as well as non-Newtonian pseudo-plastic behavior (rotational viscometer). The evaluation of the irritation potential by the chorioallantoic membrane method indicated the absence of hemorrhage, coagulation or lysis, demonstrating that the formulations are considered non-irritating. The mucoadhesive strength of hydrogels was improved for the nanoencapsulated active compared to the free (PhSe)2, demonstrating the correct choice of gum. Permeation through the bovine vaginal mucosa using Franz cells showed that the formulations remained on the surface of the vaginal mucosa, which is ideal for the treatment of superficial vaginal infections. Therefore, based on the results obtained, the development of the hydrogel met the proposed therapeutic purpose and could be a promising alternative for the treatment of trichomoniasis.