Alina Shapira

Beta-casein nanovehicles for oral delivery of chemotherapeutic drugs ,

UNLABELLED Bovine beta-casein (beta-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 beta-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 beta-CN suggests possible targeting to stomach tumors. Dimethyl sulfoxide (DMSO)-dissolved MX was entrapped in beta-CN nanoparticles by stirring this solution into phosphate-buffered beta-CN solution. High-affinity MX-beta-CN association was found (K(a) = [2.15 +/- 0.30] x 10(6) M(-1)). The optimal nanovehicle formation conditions were 1 mg/mL beta-CN, <or=6% (vol/vol) DMSO in phosphate-buffer solution, 10 mM MX in DMSO, and a MX:beta-CN molar-ratio of approximately 4:1. Under these conditions, particles of 100 to 300-nm diameter were formed. beta-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs. FROM THE CLINICAL EDITOR Bovine beta-casein (beta-CN) is an abundant milk-protein that is highly amphiphilic and self-assembles into stable micellar-structures in aqueous solutions. beta-CN nanoparticles may serve as effective oral-delivery nanovehicles for solubilization and stabilization of hydrophobic drugs, as demonstrated in this study utilizing methotrexate.

β-Casein nanoparticle-based oral drug delivery system for potential treatment of gastric carcinoma: Stability, target-activated release and cytotoxicity

We studied a potential drug delivery system comprising the hydrophobic anticancer drug paclitaxel entrapped within β-casein (β-CN) nanoparticles and its cytotoxicity to human gastric carcinoma cells. Paclitaxel was entrapped by stirring its dimethyl sulfoxide (DMSO) solution into PBS containing β-CN. Cryo-TEM analysis revealed drug nanocrystals, the growth of which was blocked by β-CN. Entrapment efficiency was nearly 100%, and the nanovehicles formed were colloidally stable. Following encapsulation and simulated digestion with pepsin (2 hours at pH=2, 37 °C), paclitaxel retained its cytotoxic activity to human N-87 gastric cancer cells; the IC(50) value (32.5 ± 6.2 nM) was similar to that of non-encapsulated paclitaxel (25.4 ± 2.6 nM). Without prior simulated gastric digestion, β-CN-paclitaxel nanoparticles were non-cytotoxic, suggesting the lack of untoward toxicity to bucal and esophageal epithelia. We conclude that β-CN shows promise to be useful for target-activated oral delivery of hydrophobic chemotherapeutics in the treatment of gastric carcinoma, one of the leading causes of cancer mortality worldwide.

β-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.