Preparation of Thymol Nanoliposome and Solid Lipid Nanoparticle and Evaluation of their Inhibitory Effects on Leishmania Major Promastigotes

Introduction: Thymol has an antiprotozoal effect. Nanoparticulate systems are useful carriers for both small and large drug molecules, which can protect them from some chemical and biological damages as well as target drug delivery to specific organs or receptors. In this work, the nano-liposomal system and solid lipid nanoparticles loaded by thymol were prepared and the effectiveness of them were evaluated on Leishmania major promastigotes. Methods: Several formulations of nano-liposomes and solid lipid nanoparticles were prepared, and the amount of thymol loading, in-vitro release profile, particle size, and zeta potential were evaluated. Finally, the best formulations were serially diluted and incubated for ۲۴, ۴۸, and ۷۲ hours on Leishmania major promastigotes, which cultured on Novy–MacNeal–Nicolle medium, and the results were analyzed. Results: The highest loading of thymol in nano-liposomes (۹۲%) was seen in the formulations made with phosphatidylcholine (Called L۳), and among the solid lipid nanoparticles, the formulation prepared with glycerol monostearate (S۱) had the most entrapment efficiency of thymol (۸۷%). These formulations were selected to evaluate the release rate of thymol. The results showed that S۱ has a slower release rate than L۳; this may be due to the presence of Glycerol monostearate in solid lipid nanoparticles structure. The best formulations, L۳ and S۱, were chosen for anti-Leishmaniosis assessment; which showed that all three forms of free thymol, nanoliposomes, and solid lipid nanoparticles inhibited Leishmania major. The half maximal inhibitory concentration (IC۵۰) of free thymol, nanoliposome, and solid lipid nanoparticles for a ۲۴-hour incubation are ۷.۸, ۶۲.۵, and ۱۲۵, respectively, which decrease to ۷.۸, ۷.۸, and ۱۵.۶ for ۴۸ hours and ۷.۸, ۰.۴۹, and ۰ for ۷۲ hours of incubation. Conclusion: Thymol has a significant effect on the inhibition of Leishmania major promastigotes and usage of thymol in the form of liposomes or solid lipid nanoparticles can sustain the drug release and have a lower IC۵۰ during the longer incubation time.