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

Xioazhong Qu, Vitaliy V. Khutoryanskiy, Ailsa Stewart, Samina Rahman, Brigitte Papahadjopoulos-Sternberg, Christine Dufès, Dave McCarthy, Clive G. Wilson, Robert Lyons, Katharine C. Carter, Andreas Schätzlein, Ijeoma F. Uchegbu

Research output: Contribution to journalArticle

  • 75 Citations

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.
LanguageEnglish
Pages3452-3459
Number of pages7
JournalBiomacromolecules
Volume7
Issue number12
DOIs
StatePublished - 2006

Fingerprint

Micelles
Carbohydrates
Prednisolone
Pharmacodynamics
Pharmaceutical Preparations
Polymers
Chitosan
Block copolymers
Emulsions
Propofol
Molecular weight
Suspensions
Biological Availability

Keywords

  • oside polymer
  • bioavailability
  • corticosteroid
  • prednisolone
  • central nervous system
  • binding capacity
  • micellar solution
  • aqueous solution
  • propofol
  • amphiphilic polymer
  • hydrophobic group
  • chitosan derivatives
  • pharmacology

Cite this

Qu, X., Khutoryanskiy, V. V., Stewart, A., Rahman, S., Papahadjopoulos-Sternberg, B., Dufès, C., ... Uchegbu, I. F. (2006). Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. Biomacromolecules, 7(12), 3452-3459. DOI: 10.1021/bm0604000
Qu, Xioazhong ; Khutoryanskiy, Vitaliy V. ; Stewart, Ailsa ; Rahman, Samina ; Papahadjopoulos-Sternberg, Brigitte ; Dufès, Christine ; McCarthy, Dave ; Wilson, Clive G. ; Lyons, Robert ; Carter, Katharine C. ; Schätzlein, Andreas ; Uchegbu, Ijeoma F./ Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. In: Biomacromolecules. 2006 ; Vol. 7, No. 12. pp. 3452-3459
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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.",
keywords = "oside polymer, bioavailability, corticosteroid, prednisolone, central nervous system, binding capacity, micellar solution, aqueous solution, propofol, amphiphilic polymer, hydrophobic group, chitosan derivatives, pharmacology",
author = "Xioazhong Qu and Khutoryanskiy, {Vitaliy V.} and Ailsa Stewart and Samina Rahman and Brigitte Papahadjopoulos-Sternberg and Christine Duf{\`e}s and Dave McCarthy and Wilson, {Clive G.} and Robert Lyons and Carter, {Katharine C.} and Andreas Sch{\"a}tzlein and Uchegbu, {Ijeoma F.}",
year = "2006",
doi = "10.1021/bm0604000",
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Qu, X, Khutoryanskiy, VV, Stewart, A, Rahman, S, Papahadjopoulos-Sternberg, B, Dufès, C, McCarthy, D, Wilson, CG, Lyons, R, Carter, KC, Schätzlein, A & Uchegbu, IF 2006, 'Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude' Biomacromolecules, vol. 7, no. 12, pp. 3452-3459. DOI: 10.1021/bm0604000

Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. / Qu, Xioazhong; Khutoryanskiy, Vitaliy V.; Stewart, Ailsa; Rahman, Samina; Papahadjopoulos-Sternberg, Brigitte; Dufès, Christine; McCarthy, Dave; Wilson, Clive G.; Lyons, Robert; Carter, Katharine C.; Schätzlein, Andreas; Uchegbu, Ijeoma F.

In: Biomacromolecules, Vol. 7, No. 12, 2006, p. 3452-3459.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude

AU - Qu,Xioazhong

AU - Khutoryanskiy,Vitaliy V.

AU - Stewart,Ailsa

AU - Rahman,Samina

AU - Papahadjopoulos-Sternberg,Brigitte

AU - Dufès,Christine

AU - McCarthy,Dave

AU - Wilson,Clive G.

AU - Lyons,Robert

AU - Carter,Katharine C.

AU - Schätzlein,Andreas

AU - Uchegbu,Ijeoma F.

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - oside polymer

KW - bioavailability

KW - corticosteroid

KW - prednisolone

KW - central nervous system

KW - binding capacity

KW - micellar solution

KW - aqueous solution

KW - propofol

KW - amphiphilic polymer

KW - hydrophobic group

KW - chitosan derivatives

KW - pharmacology

UR - http://dx.doi.org/10.1021/bm0604000

U2 - 10.1021/bm0604000

DO - 10.1021/bm0604000

M3 - Article

VL - 7

SP - 3452

EP - 3459

JO - Biomacromolecules

T2 - Biomacromolecules

JF - Biomacromolecules

SN - 1525-7797

IS - 12

ER -

Qu X, Khutoryanskiy VV, Stewart A, Rahman S, Papahadjopoulos-Sternberg B, Dufès C et al. Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. Biomacromolecules. 2006;7(12):3452-3459. Available from, DOI: 10.1021/bm0604000