Hidrogel de goma guar contendo nanocápsulas de sesamol: do desenvolvimento da formulação à avaliação em modelos animais de inflamação cutânea

Abstract

The use of corticosteroid drugs for the treatment of inflammatory skin diseases is associated with adverse effects. Sesamol, a phenolic compound present in sesame oil, has antiinflammatory and antioxidant properties. The development of nanocapsules has been recognized as an alternative to modulate the cutaneous permeation of substances through the skin and circumvent the physicochemical limitations. Therefore, the present study aimed to develop hydrogels containing sesamol nanocapsules to obtain a formulation with potential application in treating inflammatory skin diseases. Nanocapsule suspensions (ethylcellulose as polymer and medium-chain triglyceride as the oily core) containing sesamol (1 mg/mL) were prepared. The nanocapsules had an average diameter exclusively in the nanometer range (127 nm), polydispersity index values below 0.2, negative zeta potential (-20.4 mV), and slightly acidic pH values (5.2). The sesamol content in the hydrogels was close to the theoretical value, and an encapsulation efficiency of 65% was achieved. Nanoencapsulation attenuated photodegradation induced by exposure to UVC radiation and increased the scavenging capacity of synthetic free radicals of sesamol. Besides, nanoencapsulation reduces sesamols’ cytotoxicity in fibroblasts. Subsequently, hydrogels containing sesamol (1 mg/g) were prepared by thickening the nanocapsule suspensions with guar gum at 2.5%. The hydrogel containing sesamol-loaded nanocapsules had an average diameter of 127 nm, sesamol content close to theoretical, pseudoplastic behavior, and was classified as non-irritating by the HET-CAM test. The hydrogel containing sesamol in nanoencapsulated form prolonged the sesamol release profile and decreased the compound permeation rate through the skin's layers in unimpaired and UVB radiation-injured human skin. Furthermore, the hydrogel containing sesamol in nanoencapsulated form exhibited the best anti-inflammatory effect in acute models of irritant contact dermatitis induced by croton oil and sunburn induced by UVB radiation in mice, similar to dexamethasone (reference drug). In sequence, the developed hydrogels were optimized by adding a preservative solution. The microbiological stability study demonstrated that total aerobic microbial and yeast/mold counts were <10 CFU/mL over 60 days. Physicochemical stability assessments did not show significant changes for 60 days. Furthermore, the hydrogel containing sesamol-loaded nanocapsules exhibited the best anti-inflammatory effect through repeated administrations in the croton oil-induced irritant contact dermatitis model in mice. Therefore, the hydrogel containing sesamol-loaded nanocapsules form is promising for treating inflammatory skin lesions.