Oral Delivery of Clofazimine in Zein Nanoparticles

Abstract

Clofazimine, a lipophilic riminophenazine antibiotic, has been used to treat leprosy as well as other diseases caused by Mycobacteria. It has also been screened for use against cryptosporidiosis, which requires rapid treatment, a requirement that does not lend itself to current formulations of clofazimine. In this work, clofazimine is encapsulated into zein nanoparticles for oral delivery, co-stabilized with sodium caseinate, through the process of Flash NanoPrecipitation (FNP). Zein, a maize-based protein, is low-cost, generally regarded as safe (GRAS), and shows good taste-masking potential. The nanoparticles exhibited excellent size stability over a 24-hour period and high encapsulation efficiency (> 95%). Solid nanoparticles were formed by lyophilization, with sugars used as cryoprotectants. The optimal condition was determined to be a 1:1 drug:mannitol ratio. Dissolution tests were conducted in simulated gastrointestinal fluids to determine release kinetics. The nanoparticles improved the dissolution rate, and produced approximately 100-fold increase in the extent of supersaturation of clofazimine in simulated gastric fluids, compared to free powder. In simulated intestinal fluids, the drug release percentage rapidly reached complete release (~90%) in 15 minutes in the feasted state, but more slowly in the fasted state. The results suggest that these new clofazimine zein nanoparticles, created with affordable materials, show promise to increase bioavailability and absorption in order to be used as a fast-acting treatment.