Beta-Casein Based Nano-Vehicles for Oral Delivery of Chemotherapeutic Drugs: Drug-Protein Interactions and Mitoxantrone Loading Capacity

Beta-casein (β-CN), a major milk protein, is amphiphilic and self-associates into micelles in aqueous solutions. We have recently introduced (Shapira A. et al, Nanomedicine 2009 (in press)) a novel oral drug delivery system based on β-CN nanoparticles. The current research builds up 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 by fluorescent emission of both MX and Trp-143 of β-CN. The optimal loading molar-ratio was 3.3 MX:β-CN at 1mg/ml β-CN and the association constant was (2.45±1.76)x105M-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 may serve as effective vehicles of hydrophobic drugs for oral-delivery preparations.