Hidrogel de base nanotecnológica contendo silibinina com ação anti-inflamatória no modelo de óleo de cróton

Abstract

Currently, irritant contact dermatitis is the most prevalent dermatitis among the others and is triggered by the activation of innate immunity after skin contact with irritants. Silibinin (SB), a naturally occurring active, has beneficial activities for the cutaneous tissue, among which the anti-inflammatory action can be highlighted. Thus, in studies conducted in our research group, nanocapsule suspensions containing pomegranate oil as oily core and silibinin as active have been developed. Aiming at the skin application, this dissertation aimed to develop an innovative bioadhesive hydrogel for the delivery of this NC suspension and to verify its potential in the treatment of irritative contact dermatitis. The hydrogel was prepared from the polymer Pemulen® TR2, which has bioadhesive characteristics. The formulations were characterized in terms of SB content, pH, particle size and distribution, as well as spreadability and rheology, important characteristics mainly in the development of new products for dermal administration. For the studies of SB release from the hydrogels and cutaneous permeation of the active in human skin Franz cells were used. The bioadhesiveness test was performed using a texturometer and, in order to guarantee the safety of the formulations, the cutaneous biometry assay was performed, evaluating the parameters of erythema, pH, transepidermal loss of water and skin hydration. Also, considering the ability of SB to regulate inflammatory events, the viability of these hydrogels in the inflammation treatment was studied in an animal model induced by croton oil. The proposed formulations presented physico-chemical characteristics compatible with topical administration, maintaining the nanometric size after incorporation into the hydrogels (184 ± 26 nm), adequate pH range (6.70 ± 0.15), SB concentration close to concentration (0.99 ± 0.01 mg/g), as well as non-Newtonian pseudoplastic behavior. The in vitro release evidenced that the hydrogels containing the nanocapsules provided less silibinin retention in the dosage form for both media: phosphate buffer pH 5.5 plus ethanol and the buffer alone (4.73 ± 0.50 μg / mL for HP-NCSB and 1.14 ± 0.18 μg/mL for HP-SB and 2.25 ± 0.25 μg/mL from HP-NCSB and 0.49 ± 0.05 μg/mL for HP-SB, respectively). Permeation studies on human skin have indicated that the nanoencapsulation of silibinin increases its retention in the stratum corneum, which can act as a deposit for gradual release of this active. Evaluating the bioadhesive potential of the formulations, it was verified that the HP-NCSB stands out against the other formulations tested. In the in vivo study, the hydrogels containing the silibinin nanocapsules and pomegranate oil were able to act by expressively reducing ear edema and inflammatory cells. In the cutaneous biometry test, for all the parameters tested the formulations did not alter the normal skin conditions of the volunteers. Therefore, based on the results obtained, the hydrogel development was successful and the formulation has met the proposed therapeutic purpose, and may be a therapeutic alternative for the treatment of irritant contact dermatitis, using the natural source active silibinin allied to nanotechnology, since it was possible to demonstrate that the hydrogel containing silibinin nanocapsules had satisfactory results against the hydrogel containing non-nanoencapsulated silibinin, as well as it was possible to demonstrate the contribution of Pemulen® TR2 in the performance of the formulations.