(525e) Formulation and Recovery of Fast-Acting Lumefantrine Nanoparticles for Oral Malaria Therapy

Malaria is a major source of mortality in developing tropical regions and new low-cost therapies are needed. Lumefantrine is a Biopharmaceutics Classification System class II drug, and increasing the bioavailability of lumefantrine has the potential to reduce the dose and number of required administrations per treatment, thus reducing the financial burden of malaria therapy. Formulating therapeutics into nanoparticles can increase their bioavailability by reducing drug crystallinity and increasing surface area, thereby resulting in faster dissolution kinetics. In this study, we use Flash Nanoprecipitation to encapsulate lumefantrine into nanoparticles with low-cost stabilizers (zein/casein, HPMCAS, and lecithin) and assess the release of lumefantrine in simulated gastric and intestinal fluids. For the low-melting-point lumefantrine, a feasible spray-drying protocol is further developed to dry lumefantrine-encapsulated nanoparticles into powders, while maintaining the physical state of the drugs. The release experiments show that lumefantrine formulations with all stabilizers showed superior dissolution compared to crystalline lumefantrine release in simulated fasted and fed intestinal media. Remarkably, particles synthesized with zein/casein and HPMC exhibited near complete release in under one hour. These cheap and efficient formulations have the potential to be developed into future therapies for malaria.