Intestinal Permeability of Artesunate-Loaded Solid Lipid Nanoparticles Using the Everted Gut Method

Abstract

Background. Artesunate is one of the most potent, rapidly acting and therapeutically versatile antimalarial drugs. Its efficacy is hampered by poor aqueous solubility and stability resulting in low oral bioavailability. Recent efforts to nanoformulate artesunate have shown great potential of improving its dissolution profile and bioavailability. However, no study has yet been done to investigate the intestinal permeability of these nanoformulations, which is a critical determinant of systemic absorption. Objective of the Study. The main aim of the study was to determine the intestinal permeability of artesunate-loaded solid lipid nanoparticles (SLN). Method. The microemulsion dilution technique was used to fabricate artesunate-loaded solid lipid nanoparticles. In vitro drug release studies were performed at pH 1.2 and 6.8 using the dialysis membrane method. The everted gut sac method was used to assess the intestinal permeability of the prepared nanoparticles. Results. The average particle size was 1109 nm and the polydispersity index (PDI) was 0.082. The zeta potential was found to be −20.7 mV. The encapsulation efficiency of the solid lipid nanoparticles obtained was 51.7%. At both pH 1.2 and 6.8, pure artesunate was rapidly released within the first 30 mins while the SLN showed a biphasic release pattern with an initial burst release during the first hour followed by a prolonged release over time. The rate of drug release increased with increasing pH. The apparent permeability (Papp) of SLN was found to be greater (0.169 mg/cm2) as compared to that of pure artesunate (0.117 mg/cm2) at the end of the experiment. Conclusion. The results obtained in this study showed that the microemulsion dilution technique can be used to formulate artesunate solid lipid nanoparticles. The formulation exhibited a sustained drug release profile. The intestinal permeability of artesunate could be enhanced by the nanoformulation.