Nanobioformulações do tipo SNEDDS à base de Anacardium occidentale L. e avaliações farmacológicas

Abstract

Colloidal systems increase the bioavailability of drugs and are largely used as an important strategy in the protection and directed delivery of bioactives compounds from synthetic or natural origin. In this sense, the therapeutic efficacy of the medicinal species Anacardium occidentale Linn. (AO) was evaluated in a nanobiotechnological study in which in vitro (antioxidant) and in vivo (pulmonary anti-inflammatory evaluation) experimental models were accessed. In that, the hydroalcoholic extract (EHA-AO) and a fraction rich in water soluble tannins (FT-AO), obtained from the stem bark of this vegetable, were loaded into a colloidal carrier SNEDDS-type system (selfnanoemulsion drug delivery system). In this context, stands out the reduction of administered therapeutic doses, reduction of toxicological risks, maintenance of the constant level of the drug in the blood (by controlled release), and prolonged efficacy of therapeutic effects, widely attributed to the colloidal systems. The choice of the carrier SNEDDS-type, consist in the fact that SNEDDS systems shows stability under water dilutions, variations of temperature and/or pH, and are effective in the controlled release (slow and prolonged), samples loaded at low concentrations, for example, can be administered orally and keep its activities. The experimental part of the study was carried out in different stages, such as: i) bromatological and microbiological analyses of the regional raw material (stem barks of A. occidentale); ii) phytochemical procedures for obtaining the EHA-AO and FT-AO samples; iii) solubility analyses and development of the polar colloidal nanosystem O/A (oil in water) with characteristic SNEDDS, cosurfactant free; iv) application of the formulations SNEDDS-EHA-AO and SNEDDS-FT-AO in the experimental in vitro oxidation tests, as well as in an in vivo experimental model of inflammation (pulmonary emphysema in Rattus norvegicus through orotracheal papain instillation), via oral administration. The SNEDDS carrier was prepared with Tween 80 (surfactant phase), a food-based vegetable oil containing the following constituents: vitamin E, polyunsaturated, saturated fat, and a mixture of the acids oleic, linoleic and linolenic. The SNEDDS-white system (free from the samples of the vegetable A. occidentale), after physicochemical characterization (pH, surface tension, CMC, viscosity and droplet diameter), satisfactorily solubilized the samples EHA-AO and FT-AO. The antioxidant potential of the nanoproducts SNEDDS-EHA-AO (10 mg mL-1 ) and SNEDDS-FT-AO (2.5 mg mL-1 and 5.0 mg mL-1 ) was evaluated by using in vitro experiments with significant results observed by the following tests: reducing activity equivalent to the ascorbic acid, chelating activity of the ions iron and copper, as well as the sequestration of hydroxyl and superoxide radical. The SNEDDS-FT-AO system did not show cytotoxicity to healthy cells of the RAW, Vero and L-929 strains. The in vivo pharmacological study of the SNEDDSEHA-AO and SNEDDS-FT-AO systems, in an experimental model of lung inflammation, as well as subsequent evaluation of histopathological analyses, showed that the SNEDDS-FT-AO formulation presents the best anti-inflammatory result. These findings, together with preliminary results of the medicinal potential of Anacardium occidentale Linn., which has proven immunomodulatory, anti-inflammatory, and antiviral action, will enable the phytotherapeutic validation of the SNEDDS-EHA-AO and SNEDDS-FT-AO formulations against the Sars-CoV-2 virus, and, therefore, may contribute against the therapy against COVID-19.