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Loading of doxorubicin into liposomes by forming Mn2+ drug complexes

University of British Columbia

Doxorubicin has been encapsulated into liposomes with a transmembrane pH gradient. In this thesis, a new procedure for loading doxorubicin into large unilamellar vesicles (LUVs) is characterized and compared to loading using the ionophore A23187 with MnSO₄ containing liposomes. It is shown that doxorubicin can be loaded into LUVs composed of sphingomyelin/cholesterol (55/45 mole/mole) in response to a transmembrane MnSO₄ gradient in the absence of a transmembrane pH gradient. Complex formation between doxorubicin and Mn²⁺ is found to be a driving force for doxorubicin uptake. Uptake levels approaching 100 % can be achieved up to a drug-tolipid molar ratio of 0.5 utilizing an encapsulated MnSO₄ concentration of 0.30 M. In vitro leakage assays show excellent retention properties over a 24 hour period. The possible advantages of a liposomal formulation of doxorubicin loaded in response to entrapped MnSO₄ are discussed.

Thesis/Dissertation

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2009-05-21

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http://hdl.handle.net/2429/8037

Biochemistry and Molecular Biology

University of British Columbia

UBCV

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