title: Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles.
abstract: β-casein is an amphiphilic protein that self-organizes into well-defined core-shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads >100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which >95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration.
authors.affiliation: Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Bachar
authors.forename: Amitai
authors.initials: A
authors.lastname: Mandelbaum
authors.forename: Irina
authors.initials: I
authors.lastname: Portnaya
authors.forename: Hadas
authors.initials: H
authors.lastname: Perlstein
authors.forename: Simcha
authors.initials: S
authors.lastname: Even-Chen
authors.forename: Yechezkel
authors.initials: Y
authors.lastname: Barenholz
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
mesh_terms: D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002364:Caseins / Q000737:chemistry*; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical; D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D015195:Drug Design; D005612:Freeze Drying; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002364:Caseins; D004337:Drug Carriers; D008823:Micelles; D011720:Pyrazoles; D013449:Sulfonamides; D013501:Surface-Active Agents; D000068579:Celecoxib