title: β-Casein nanoparticle-based oral drug delivery system for potential treatment of gastric carcinoma: stability, target-activated release and cytotoxicity.
abstract: 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.
authors.affiliation: Russell Berrie Nanotechnology Institute, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Shapira
authors.forename: Irit
authors.initials: I
authors.lastname: Davidson
authors.forename: Noa
authors.initials: N
authors.lastname: Avni
authors.forename: Yehuda G
authors.initials: YG
authors.lastname: Assaraf
authors.forename: Yoav D
authors.initials: YD
authors.lastname: Livney
mesh_terms: D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D002364:Caseins / Q000737:chemistry; D045744:Cell Line, Tumor; D003460:Crystallization; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D046529:Microscopy, Electron, Transmission / Q000379:methods; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002364:Caseins; D017239:Paclitaxel; D004121:Dimethyl Sulfoxide