title: Effect of temperature and loading on the structure of β-casein/ibuprofen assemblies.
abstract: β-Casein is a 24 kDa amphiphilic and unstructured protein that self-assembles into small core-shell micelles at a wide range of concentrations, pH values and temperatures. We recently developed the micelles as nanocarriers for oral delivery of hydrophobic drugs. In this paper we examined the effect of the hydrophobic non-steroidal anti-inflammatory drug (NSAID) ibuprofen on the micellar structure, as a function of temperature and loading. Using cryo-transmission electron microscopy (cryo-TEM) we find two routes of organization – mixed micellization and co-assembly (aggregation). The time-dependent events that characterize the second routes has been examined in detail. At 25 °C we find coexistence of small assemblies and larger aggregates of irregular (but defined) structures that contain the drug. Increasing the drug loading increases the relative number of the larger aggregates and their dimensions, leading eventually to the formation of long then branched structures, like in amphiphilic block copolymer solutions. Similar trends were identified for changes in the temperature. Combined, our results suggest that ibuprofen acts as a co-surfactant that possibly is localizes to the interface rather than being encapsulated in the micellar core as other NSAID hydrophobic drugs.
authors.affiliation: Russell-Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Tanya
authors.initials: T
authors.lastname: Turovsky
authors.affiliation: Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Irina
authors.initials: I
authors.lastname: Portnaya
authors.affiliation: Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Ellina
authors.initials: E
authors.lastname: Kesselman
authors.affiliation: Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Ionita-Abutbul
authors.affiliation: Department of Chemical and Biological Engineering, Drexel University, 3141 Chestnut St., Philadelphia, PA 19104, USA. Electronic address: dan@coe.drexel.edu.
authors.forename: Nily
authors.initials: N
authors.lastname: Dan
authors.affiliation: Russell-Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel; Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel. Electronic address: dganitd@tx.technion.ac.il.
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002364:Caseins / Q000737:chemistry*; D002417:Cattle; D004337:Drug Carriers / Q000737:chemistry*; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry; D008823:Micelles; D008958:Models, Molecular; D066329:Protein Aggregates
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002364:Caseins; D004337:Drug Carriers; D008823:Micelles; D066329:Protein Aggregates; D007052:Ibuprofen
keywords: Drug-delivery; Nanomedicine; Protein micelles; Self-assembly; β-Casein