Nanoemulsion composed of 10-(4,5-dihydrothiazol-2-yl)thio)decan-1-ol), a synthetic analog of 3-alkylpiridine marine alkaloid : development, characterization, and antimalarial activity.

Abstract

Malaria treatment is based on a reduced number of antimalarial drugs, and drug resistance has emerged, leading to the search for new antimalarial drugs incorporated into pharmaceutical formulations. In this study, 10-(4,5- dihydrothiazol-2-yl)thio)decan-1-ol) (thiazoline), a synthetic analog of 3-alkylpiridine marine alkaloid, and a potent antimalarial substance, was incorporated into O/W nanoemulsion. This formulation was prepared by a 23 factorial design. It was characterized by globule diameter, polydispersity index, zeta potential, encapsulation efficiency, in vitro thiazoline release at pH 2 and 6.86, and accelerated stability. In vitro and in vivo antimalarial activity was determined against P. falciparum and P. berghei, respectively. Thiazoline nanoemulsion showed 248.8 nm of globule diameter, 0.236 of polydispersity index, -38.5 mV of zeta potential, 96.92% encapsulation efficiency, and it was stable for 6 months. Thiazoline release profiles differed in acidic and neutral media, but in both cases, the nanoemulsion controlled and prolonged the thiazoline delivery. Thiazoline nanoemulsion exerted in vitro antimalarial activity against the parasite (IC50 = 1.32 µM), and it significantly reduced the in vivo parasitemia for 8 days without increasing the survival time of animals. Therefore, the thiazoline nanoemulsion represents a strategy to treat malaria combining an antimalarial candidate and a new nanocarrier.