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

Author(s)

Bruno Vincenzo Fiod Riccio

• Document type: Master's Dissertation
• Press: Araraquara. 2021-12-04.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara
• Defense date: 2021-11-19
• Advisor: Marlus Chorilli; Priscileila Colerato Ferrari

Abstract

Cutaneous inflammation is related to the synthesis of inflammatory mediators that, when in exacerbated amounts and chronically produced, can generate diseases such as atopic dermatitis. Trans-resveratrol proves to be an effective anti-inflammatory agent due to the reduction or inhibition of mediators such as histamine, cytokines and cyclooxygenase-2. The development of solid dispersions containing trans-resveratrol can improve its solubility. In order to enable the cutaneous administration of solid dispersions, polyvinylpyrrolidone (PVP) membranes can be interesting, since it is a polymer capable of preventing the recrystallization of trans-resveratrol, being something unprecedented from a technological point of view. The study aimed to develop, characterize and evaluate the in vitro cytotoxicity and in vivo anti-inflammatory activity of solid dispersions incorporated in PVP membranes for cutaneous administration. Solid dispersions containing trans-resveratrol constituted by chitosan and surfactant (Poloxamer® 407 or TPGS) were developed, as well as two formulations without surfactants, which were characterized using morphological and physicochemical analyses. An analytical method by high performance liquid chromatography (HPLC) was developed for the quantification of trans-resveratrol. After choosing the best performing formulations, two were incorporated into polymeric PVP membranes and two others were also made without the drug as a control. The membranes were characterized regarding their barrier and physicochemical properties, as well as in vitro and in vivo analyses. According to the results, it was possible to reach up to 56% yield in the production of solid dispersions containing trans-resveratrol using spray drying. According to the X-ray diffraction (XRD) it was possible to verify that the solid dispersions were able to amorphize the trans-resveratrol successfully. Solid dispersions also increased the drug's solubility in water, with some formulations doubling its solubility.The membranes managed to maintain trans-resveratrol without recrystallizing for more than two months, as evidenced by the XRD, in addition to presenting bioadhesion, favorable for cutaneous administration. According to the in vitro release assay, the membranes obtained did not fully release the drug in 24 h, obtaining values from 82.27±2.60 to 92.81±2.50%, thus being a profile of extended release. The in vitro retention assays showed that the amounts of trans-resveratrol retained in the dermis and epidermis layers within 24 h ranged from 42.88 to 53.28%, being available to promote the pharmacological effect. It was also observed that the cytotoxicities of the formulations were not expressive. Finally, in the in vivo test, it was possible to observe that the formulations presented an anti-inflammatory effect favorable to the proposed pharmacological treatment, obtaining a reduction of up to 66% in mouse ear inflammation model. The results demonstrate that the developed system is capable of being used as an anti-inflammatory agent for the treatment of atopic dermatitis. (AU)

• FAPESP's process: 19/00164-0 - Trans-resveratrol solid dispersions incorporated into polyvinylpyrrolidone membranes for cutaneous application: development, characterization and biological evaluation in vitro and in vivo
• Grantee: Bruno Vincenzo Fiod Riccio
• Support Opportunities: Scholarships in Brazil - Master