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UBC Theses and Dissertations
Comparison of pharmacokinetics and biodistribution of doxorubicin loaded in PEGylated liposomes and a phospholipid-free small unilamilar vesicle Zhang, Wunan
Abstract
The thesis focuses on the development and characterization of an innovative phospholipid-free small unilamellar vesicle (PFSUV) for drug delivery. The optimal PFSUVs composed of Tween80/cholesterol (1/5 molar ratio) were fabricated by microfluidics, exhibiting a mean diameter of 60-80 nm. The PFSUVs displayed a single bilayer spherical structure, similar to that of a standard liposomal formulation. Doxorubicin could be actively loaded into the aqueous core of PFSUVs at a drug-to-lipid ratio of 1/20 (w/w) via an ammonium sulfate gradient, and was stably retained for 6 days when incubated in 50% serum. In the presence of serum, DOX loaded PFSUVs were internalized by EMT6 murine breast tumor cells 2-fold more efficiently compared to the serum-free conditions due to LDL endocytosis pathway, while PEGylated liposomal doxorubicin (PLD, DSPC/Chol/DSPE-PEG2000) displayed little cellular uptake in both conditions. The results suggest that serum component(s) triggered cellular internalization of the PFSUVs. As a result, the in vitro potency of PFSUVs-DOX against EMT6 cells was comparable as free DOX and was significantly increased compared to the PLD. In mice, PFSUVs-DOX displayed rapid clearance from the blood (
Item Metadata
Title |
Comparison of pharmacokinetics and biodistribution of doxorubicin loaded in PEGylated liposomes and a phospholipid-free small unilamilar vesicle
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2018
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Description |
The thesis focuses on the development and characterization of an innovative phospholipid-free small unilamellar vesicle (PFSUV) for drug delivery. The optimal PFSUVs composed of Tween80/cholesterol (1/5 molar ratio) were fabricated by microfluidics, exhibiting a mean diameter of 60-80 nm. The PFSUVs displayed a single bilayer spherical structure, similar to that of a standard liposomal formulation. Doxorubicin could be actively loaded into the aqueous core of PFSUVs at a drug-to-lipid ratio of 1/20 (w/w) via an ammonium sulfate gradient, and was stably retained for 6 days when incubated in 50% serum. In the presence of serum, DOX loaded PFSUVs were internalized by EMT6 murine breast tumor cells 2-fold more efficiently compared to the serum-free conditions due to LDL endocytosis pathway, while PEGylated liposomal doxorubicin (PLD, DSPC/Chol/DSPE-PEG2000) displayed little cellular uptake in both conditions. The results suggest that serum component(s) triggered cellular internalization of the PFSUVs. As a result, the in vitro potency of PFSUVs-DOX against EMT6 cells was comparable as free DOX and was significantly increased compared to the PLD. In mice, PFSUVs-DOX displayed rapid clearance from the blood (
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Genre | |
Type | |
Language |
eng
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Date Available |
2019-09-30
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0372090
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2018-11
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International