title: Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude.
abstract: Amphiphilic chitosan-based polymers (Mw < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the degree of lipidic derivatization and molecular weight of the carbohydrate. The extent of drug incorporation by these novel micellar clusters is 1 order of magnitude higher than is seen with triblock copolymers, with molar polymer/drug ratios of 1:48 to 1:67. On intravenous injection, the pharmacodynamic activity of a carbohydrate propofol formulation is increased by 1 order of magnitude when compared to a commercial emulsion formulation, and on topical ocular application of a carbohydrate prednisolone formulation, initial drug aqueous humor levels are similar to those found with a 10-fold dose of prednisolone suspension.
authors.affiliation: Department of Pharmaceutical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, U.K.
authors.forename: Xioazhong
authors.initials: X
authors.lastname: Qu
authors.forename: Vitaliy V
authors.initials: VV
authors.lastname: Khutoryanskiy
authors.forename: Ailsa
authors.initials: A
authors.lastname: Stewart
authors.forename: Samina
authors.initials: S
authors.lastname: Rahman
authors.forename: Brigitte
authors.initials: B
authors.lastname: Papahadjopoulos-Sternberg
authors.forename: Christine
authors.initials: C
authors.lastname: Dufes
authors.forename: Dave
authors.initials: D
authors.lastname: McCarthy
authors.forename: Clive G
authors.initials: CG
authors.lastname: Wilson
authors.forename: Robert
authors.initials: R
authors.lastname: Lyons
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Carter
authors.forename: Andreas
authors.initials: A
authors.lastname: Schätzlein
authors.forename: Ijeoma F
authors.initials: IF
authors.lastname: Uchegbu
mesh_terms: D001682:Biological Availability; D002240:Carbohydrate Sequence; D002241:Carbohydrates; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D008823:Micelles; D008969:Molecular Sequence Data; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011241:Prednisone; D015742:Propofol; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012995:Solubility
chemical_list: D002241:Carbohydrates; D004337:Drug Carriers; D008823:Micelles; D004364:Pharmaceutical Preparations; D000644:Quaternary Ammonium Compounds; D048271:Chitosan; D011241:Prednisone; D015742:Propofol