Engineering sodium alginate microparticles with different crystallinities for niclosamide repositioning and solubilization to improve solubility and oral bioavailability in rats

Abstract

Niclosamide is a commonly used anthelmintic; however, its poor aqueous solubility limits its oral bioavailability. Enhancing its solubility and oral bioavailability is crucial for its repositioning as an anticancer agent. Here, we aimed to develop new sodium alginate–poloxamer microparticles with different crystallinities to increase drug solubility and oral bioavailability. Sodium alginate and poloxamer were used as the polymer and surfactant, respectively, to prepare niclosamide-loaded microparticles via spray drying. The optimized amorphous and crystalline microparticles were prepared with niclosamide/sodium alginate/poloxamer weight ratios of 1:2.5:3 and 1:1.125:0.375, respectively. Their solubilities, dissolution rates, physicochemical properties, and oral bioavailabilities were compared with those of drug powder in rats. Physicochemical characterization of the developed particles revealed changed structure from crystalline to amorphous, with no irregular crystalline characteristics but decreased particle size. Compared to the pure drug powder, crystalline microparticles retained their crystalline nature with no significant changes in particle size. Both microparticles showed significantly higher aqueous solubilities, dissolution rates, and oral bioavailabilities than niclosamide powder in rats. Amorphous microparticles showed higher solubility (approximately 1775-fold) and oral bioavailability (approximately 5.6-fold) than niclosamide powder due to the crystalline-to-amorphous change and decreased particle size. The developed amorphous microparticles can be used to improve niclosamide solubility and oral bioavailability. © 2024 Elsevier B.V.