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

Beta-casein (beta-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 beta-CN nanoparticles. The current research builds on and complements this work by studying the interactions of mitoxantrone (MX) and beta-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 beta-CN. The optimal loading molar ratio was 3.3 MX/beta-CN at 1 mg/mL beta-CN, and the association constant was (2.45 +/- 1.76) x 10(5) M(-1) based on beta-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 beta-CN suggests possible targeting to stomach tumors. Hence, beta-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.