Desenvolvimento de nanoemulsão multifuncional a base dos óleos de Caryocar coriaceum (pequi) e Lippia origanoides (alecrim-pimenta): atividade repelente (Aedes Aegypti) e anti-inflamatória tópica para o controle da dengue

Abstract

Dengue is a tropical arbovirus of high relevance to global public health, especially in tropical and subtropical countries such as Brazil, where viral circulation is endemic. It is estimated that more than 390 million people are infected annually in the world. The growing resistance of Aedes aegypti to insecticides and their safety limitations, make essential the development of new sustainable strategies for vector control and management of skin inflammation present in the disease cycle. Previous studies have determined the anti-inflammatory and/or repellent effect of Caryocar coriaceum oil (OFCC) and thymol, a major constituent of Lippia origanoides essential oil (OELO). However, vegetable oils have physical-chemical limitations that compromise their use as topical repellent and/or anti-inflammatory products, which justifies the need for nanostructured systems that optimize their stability and effectiveness. The present work had as objective the development, characterization and biological evaluation of nanoemulsions containing oils of Pequi and Rosemary-pepper, aiming to obtain a nanostructured system with larvicidal, repellent and anti-inflammatory activities for topical application. Initially, different proportions of surfactants and oils were tested, being selected the nanoemulsion concentration at 3% pequi as a function of favorable physico-chemical parameters, such as average particle size less than 200 nm (130.8 4.6 nm), low polydispersity index (PDI <0.2) and zeta potential (23.8 0.8), contributing to prolonged colloidal stability. The encapsulation efficiency of nanoemulsion 3% OFCC+1% OELO was greater than 98%. The in vitro release profile, evaluated by membrane diffusion, demonstrated controlled release of essential oil over 24 hours, with kinetics compatible with sustained topical formulations. In vitro cutaneous permeation assays in porcine skin showed significant penetration and predominant retention in the epidermal and dermal layers. The formulations showed absence of cytotoxicity in human fibroblasts (L929) and neutrophils. The anti-inflammatory activity was demonstrated by a significant reduction in the production and release of inflammatory markers (human neutrophil and open wound model in mice). The nanoemulsion showed larval mortality (Ae. aegypti) of 87% after 24 h and 95% in 48 h, surpassing the free OELO. The formulation also demonstrated deterrent activity on oviposition (Aedes aegypti and Aedes albopictus). In the evaluation of the repellent activity in humans, the nanoemulsion showed an effective protection greater than 90% against bites of Aedes aegypti during the period of 4 hours after application, with favorable sensory acceptability and absence of skin reactions. The novel nanoemulsion based on OFCC as a carrier system of OELO potentiated the bioactivity of vegetable oils as repellent and topical anti-inflammatory, making its use possible as a promising option in integrated dengue control. Keywords: dengue; Caryocar coriaceum; Lippia origanoides; vegetable oils; nanotechnology.