Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos

Abstract

The skin is constantly exposed to external stimuli, such as irritants substances and ultraviolet radiation type B (UVB), which can trigger an inflammatory response. Indole-3-carbinol (I3C) and 3-3'-diindolmethane (DIM) are obtained by the hydrolysis of glycobrassicin, present in plants of the genus Brassica, and its anti-inflammatory effects have already been reported. However, they present physicochemical limitations that hinder their therapeutic use. Thus, in studies carried out in our research group, nanocapsule suspensions containing I3C or DIM were developed. Nanotechnology within the scope of topical application has provided numerous benefits such as: modulation of permeation/penetration/retention of substances in the cutaneous tissue. Aimed at cutaneous application, this dissertation aimed to develop hydrogels as a vehicle for nanocapsules containing I3C or DIM and check their potential against two models of skin inflammation. The hydrogels were prepared from the thickening of the nanocapsule suspensions with locust bean gum (3%). The formulations developed presented physicochemical characteristics suitable for cutaneous application, maintaining the nanometer size in the range of 138-231 nm (photon correlation spectroscopy), active content close to the theoretical value (0.5 mg/g for I3C hydrogels and 1.0 mg/g for DIM hydrogels (CLAE), pH values in the neutral range 6.69-7.43 (potentiometry), as well as non-Newtonian pseudoplastic behavior (rotational viscometer). For the release studies of the active from the hydrogel and skin permeation through human skin, Franz cell apparatus was used. The in vitro release demonstrated that the nanocapsules can easily leave the semisolid vehicle, whereas the study of skin permeation showed that nanoencapsulation promoted a greater retention of the active in the stratum corneum and epidermis, suggesting that the stratum corneum can act as deposit for their release. The evaluation of the irritation potential by the HET-CAM method indicated no bleeding, coagulation or lysis of the vessels present in the membrane, demonstrating that the formulations are considered non-irritating. Furthermore, nanoencapsulation protected the I3C from photodegradation induced by UVC radiation. Finally, the performance of the formulations was evaluated in two in vivo models of cutaneous inflammation, one induced by croton oil and the other by UVB radiation. In the croton oil model both the hydrogels containing the nanocapsules and the hydrogels containing the free actives were able to act by expressively reducing ear edema and inflammatory cells. The UVB radiation experiment demonstrated that formulations containing the free or nanoencapsulated actives were effective in reducing mouse ear edema and leukocyte infiltration within 24 h. In 48 h, only the hydrogels containing the nanoencapsulated actives maintained the antidematogenic effect, indicating a prolonged effect of the nanocapsules. Thus, it can be concluded that the developed hydrogels are promising in the treatment of inflammatory skin disorders, modulating the cutaneous distribution of the active substances in the layers of interest, besides being considered non-irritating for dermatological use.