Loading of doxorubicin into liposomes by forming Mn2+ drug complexes
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 d...
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| Language: | English |
| Published: |
2009
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| Online Access: | http://hdl.handle.net/2429/8037 |
| Summary: | 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. |
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