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Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude

Qu, Xioazhong and Khutoryanskiy, Vitaliy V. and Stewart, Ailsa and Rahman, Samina and Papahadjopoulos-Sternberg, Brigitte and Dufès, Christine and McCarthy, Dave and Wilson, Clive G. and Lyons, Robert and Carter, Katharine C. and Schätzlein, Andreas and Uchegbu, Ijeoma F. (2006) Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. Biomacromolecules, 7 (12). pp. 3452-3459. ISSN 1525-7797

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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.