Anti-Inflammatory Activity of Bullfrog Oil Polymeric Nanocapsules: From the Design to Preclinical Trials

Lucas Amaral-Machado,1 Wógenes N Oliveira,1 Manoela Torres-Rêgo,2 Allanny A Furtado,3 Éverton N Alencar,1 Matheus F Fernandes-Pedrosa,3 Hugo AO Rocha,1 Eryvaldo Sócrates Tabosa Egito1,3 1Graduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; 2Chemistry Institute, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; 3Graduate Program of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, BrazilCorrespondence: Eryvaldo Sócrates Tabosa EgitoFederal University of Rio Grande do Norte, Rua Jaguarari, 4985 – Apt. 1603D - 59054-500, Natal, Rio Grande do Norte, BrazilTel +55-84-994-31-88-16Fax +55-84-3342-9817; +55-84-3342-9817-9808Email socratesegito@gmail.comBackground: Although bullfrog oil (BFO) exerts anti-inflammatory effects, it has undesirable properties limiting its use.Methodology: BFO nanocapsules (BFONc) were produced through nanoprecipitation, and their physicochemical and morphological properties were characterized. To evaluate the biocompatibility of the formulation, a mitochondrial activity evaluation assay was conducted, and cell uptake was assessed. The in vitro anti-inflammatory activity was evaluated by measuring reactive oxygen species (ROS), nitric oxide (NO), type-6 interleukin (IL-6), and tumor necrosis factor (TNF) levels. The in vivo anti-inflammatory effect was assessed by quantifying myeloperoxidase (MPO) levels using the carrageenan-induced paw edema model.Results: BFONc showed a particle size of 233 ± 22 nm, a polydispersity index of 0.17 ± 0.03, and a zeta potential of − 34 ± 2.6mV. BFONc revealed remarkable biocompatibility and did not induce changes in cell morphology. Furthermore, BFONc decreased ROS levels by 81 ± 4%; however, NO level increased by 72 ± 18%. TNF and IL-6 levels were reduced by approximately 10% and 90%, respectively. Significant in vivo anti-inflammatory activity was observed compared to dexamethasone. MPO levels were reduced up to 2 MPOs/mg.Conclusion: Taken together, the results pointed out the remarkable biocompatibility and anti-inflammatory effects of BFONc.Keywords: polyunsaturated fatty acids, bullfrog oil, nanocapsules, anti-inflammatory activity