Trans-resveratrol solid dispersions incorporated into polyvinylpyrrolidone membranes for cutaneous application: development, characterization and biological evaluation in vitro and in vivo

Abstract

Cutaneous inflammation is related to the inflammatory mediators synthesis, when produced in exacerbated quantities and in its chronic form, they can lead to skin diseases such as atopic dermatitis. Trans-resveratrol (TR) is a non-flavonoid polyphenol from the class of stilbenes obtained from vegetal sources such as grapes, and it is shown to be effective as an anti-inflammatory agent due to the reduction or inhibition of mediators such as histamine, cytokines and cyclooxygenase-2 (COX-2), but its low solubility in water becomes a limiting factor for their incorporation into pharmaceutical forms. The development of solid dispersions (DS) of TR in chitosan (QS) containing Poloxamer® 407 (P407), TPGS and Aersosil® arises with an innovative strategy to improve the solubility of TR. In order to make DS administration viable, a use of polyvinylpyrrolidone (PVP) films with bioadhesive properties may be of interest, since these systems allow a longer local retention time of the drug. The present study aims to develop, characterize and evaluate an in vitro cytotoxicity and in vivo anti-inflammatory activity of TR DS incorporated into PVP membranes for dermal administration. The DS were obtained by the solvent casting method and characterized by granulometric analysis, solubility study, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM-FEG) and in vitro dissolution. Subsequently, the DS incorporated in PVP membranes are capable of measuring the intensity, X-ray intensity, heat transfer rays, differential scanning calorimetry, X-ray diffraction, infrared spectroscopy with Fourier (FTIR) and field emission scanning electron microscopy. Release and in vitro skin emission assays are performed for DS and free and drug-associated membranes. Biological and in vivo assay to evaluate the anti-inflammatory effect of formulations on animals of ear edema induced by chroton oil. Therefore, it is expected an innovative selection that allows the delivery of a way to make its use viable as an anti-inflammatory in cutaneous diseases. (AU)