Beta-casein nanovehicles for oral delivery of chemotherapeutic drugs

Abstract

Bovine β-casein (β-CN) is an abundant milk protein that is highly amphiphilic and self-assembles into stable micellar structures in aqueous solutions. Here we introduce a drug-delivery system comprising a model hydrophobic anticancer drug, mitoxantrone (MX), entrapped within β-CN–based nanoparticles. This novel drug-delivery system allows hydrophobic drugs to be thermodynamically stable in aqueous solutions for oral-delivery applications aimed at treatment of various disorders. The gastric digestibility of β-CN suggests possible targeting to stomach tumors. Dimethyl sulfoxide (DMSO)-dissolved MX was entrapped in β-CN nanoparticles by stirring this solution into phosphate-buffered β-CN solution. High-affinity MX–β-CN association was found (Ka = [2.15 ± 0.30] × 106 M-1). The optimal nanovehicle formation conditions were 1 mg/mL β-CN, ≤6% (vol/vol) DMSO in phosphate-buffer solution, 10 mM MX in DMSO, and a MX:β-CN molar-ratio of 4:1. Under these conditions, particles of 100 to 300-nm diameter were formed. β-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs.