RESUMO
PURPOSE: To develop a novel oral drug delivery system comprising a hydrophobic chemotherapeutic drug entrapped within beta casein (ß-CN), a major milk protein, which self-associates into micelles in aqueous solutions. The efficient gastric digestibility of ß-CN suggests possible targeting to gastric cancers. METHODS: Antitumor drug entrapment was performed by stirring its dimethyl-sulfoxide solution into a phosphate-buffered saline containing ß-CN. The association of drugs to ß-CN was characterized by spectrophotometry and Trp143 fluorescence quenching; particle-size by dynamic light scattering, and colloidal stability by zeta potential. RESULTS: The optimal drug-to-ß-CN molar loading-ratios for paclitaxel and vinblastine at 1 mg/ml ß-CN were found to be 7.3 ± 1.2 and 5.3 ± 0.6 and the association constants were (6.3 ± 1.0) x 10(3) M(-1) and (2.0 ± 0.3) x 10(4) M(-1), respectively. Zeta potential analysis suggested that nanoencapsulation by ß-CN stabilized all studied drugs in aqueous solution. The initial drug-ß-CN association was apparently governed by hydrophobic interactions and at higher drug concentrations, also by electrostatic interactions. Up to the optimal drug:ß-CN loading-ratio, ~80% of the particles were below 100 nm in diameter. At higher drug concentrations, particle diameter increased, and bi- or tri-modal particle distributions were observed. CONCLUSIONS: Beta-CN forms colloidally-stable nanovehicles of hydrophobic anticancer drugs, and may be used for oral-delivery of chemotherapeutics.
