RHEOLOGICAL CHARACTERIZATION AND BIOPHARMACEUTICAL EVALUATION OF VITAMIN D3-ORGANOGELS FOR SKIN HEALING

Several pharmaceutical formulations, such as ointments, are used to treat skin lesions. However, physico-chemical limitations lead to the development of new formulations with enhanced skin adhesion and penetration. Poloxamer-based organogels (PLO) have emerged as new strategies due to their incorporation of permeation enhancers into oil phase and aqueous phase thermosensitivity. Due to the lipophilic characteristic of Vitamin D3 (VD), the organogel becomes an interesting vehicle for its topical delivery. This study aimed to characterize and to evaluate the pharmacological effects of PLO containing VD in a skin wound healing model. PLO were composed of PL407 (20 or 30 % m/v) and oleic acid (5 % v/v) as aqueous and oil phases, respectively. The VD3 total concentration was 5 mg/g gel. Physico-chemical characterization was performed by rheological analysis for determining the sol-gel transition temperature (Tsol-gel), viscous (G”) and elastic (G’) moduli, and viscosity (η). In vivo experiments (FMABC/CEUA 08/2022) were carried out by using a skin wound healing animal model at 3, 7 and 14 days-treatment. Skin samples were then analyzed by morphology and morphometry. PLO showed Tsol-gel from 12.6 to 15.4 °C before and after VD3 incorporation. All formulations presented viscoelastic behavior with G’>G” (>10-times) and η values from 10.5 to 25.9 x 10⁴ mPas.s, at 32.5 °C. Skin lesion area was reduced after PLO-VD3 treatments (at 7 to 14 days, 16.5 to 11.6 mm²) when compared to commercially available formulation (20.1 mm²). PLO 20% and 30% formulations showed enhanced healing properties when compared to their controls, since thin collagen fibers were observed, indicating the remodeling phase with predominance of collagen III fibers. All those results pointed out PLO as promising strategies for wound healing applications.