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 beta-casein (beta-CN) nanoparticles and its cytotoxicity to human gastric carcinoma cells. Paclitaxel was entrapped by stirring its dimethyl sulfoxide (DMSO) solution into PBS containing beta-CN. Cryo-TEM analysis revealed drug nanocrystals, the growth of which was blocked by beta-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 degrees C), paclitaxel retained its cytotoxic activity to human N-87 gastric cancer cells; the IC50 value (32.5 +/- 6.2 nM) was similar to that of non-encapsulated paclitaxel (25.4 +/- 2.6 nM). Without prior simulated gastric digestion, beta-CN-paclitaxel nanoparticles were non-cytotoxic, suggesting the lack of untoward toxicity to bucal and esophageal epithelia. We conclude that beta-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. (C) 2011 Elsevier B.V. All rights reserved.