β-casein–based nanovehicles for oral delivery of chemotherapeutic drugs: drug-protein interactions and mitoxantrone loading capacity

Abstract

β-casein (β-CN), a major milk protein, is amphiphilic and self-associates into micelles in aqueous solutions. We have recently introduced a novel oral drug delivery system based on β-CN nanoparticles. The current research builds on and complements this work by studying the interactions of mitoxantrone (MX) and β-CN as they co-assemble into nanoparticles, using absorption and emission spectra, static and dynamic light scattering, and fluorescent emission of both MX and tryptophan 143 (Trp143) of β-CN. The optimal loading molar ratio was 3.3 MX/β-CN at 1 mg/mL β-CN, and the association constant was (2.45 ± 1.76) × 10 5 M –1 based on β-CN Trp143 fluorescence; independent MX fluorescence results provided supporting values. In these conditions a bimodal particle distribution was obtained (174.4 nm, 45.9%; 485.1 nm, 54.1%). The gastric digestibility of β-CN suggests possible targeting to stomach tumors. Hence, β-CN nanoparticles have potential to serve as effective vehicles of hydrophobic drugs for oral delivery preparations. From the Clinical Editor Beta-casein (b-CN) is an amphiphilic milk protein that self-associates into micelles in aqueous solutions and can be utilized as a novel oral drug delivery system. This study investigates the basic properties of a mitoxantrone delivery system based on the above principles.