dc.contributor.author |
Xu, Hongtao |
|
dc.contributor.author |
Li, Yan |
|
dc.contributor.author |
Paxton, James W |
|
dc.contributor.author |
Wu, Zimei |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2021-11-03T04:44:09Z |
|
dc.date.available |
2021-11-03T04:44:09Z |
|
dc.date.issued |
2021-7 |
|
dc.identifier.issn |
0724-8741 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/57212 |
|
dc.description.abstract |
<h4>Purpose</h4>PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were investigated for the potential application in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) treatment. Curcumin was employed as an inhibitor of the efflux transporter, multidrug resistance protein 5 (MRP5) in PDAC cells.<h4>Methods</h4>Liposomes were prepared with gemcitabine in the core and curcumin in the bilayers. The effects of curcumin on pH-sensitivity and 'endosome escape' of PSL with different PEGylation were investigated using a calcein self-quench assay. The effects of curcumin on intracellular gemcitabine concentrations, and cytotoxicity to a MIA PaCa-2 PDAC cell line was evaluated. The pharmacokinetics were investigated in rats following intravenous injection.<h4>Results</h4>The addition of curcumin to the PSL bilayers (0.2-1 mol%)slightly decreased the pH-sensitivity of PSL, but to a less extent than PEGylation (0-5 mol%). Co-treatment with curcumin increased gemcitabine cellular accumulation in a concentration-dependent manner, and resulted in synergistic cytotoxicity towards MIA PaCa-2cells.Both these effects were augmented by the use of PSL, particularly when the two drugs were co-loaded in PSL. In rats, the dual-drug loaded PSL produced significantly reduced (p < 0.05) plasma clearance (CL) and volume of distribution (V<sub>d</sub>) for both drugs, alongside 3 to 4-fold increases in the area-under-the-concentration-time curves compared to the free drugs. Additionally, curcumin slightly increase the plasma concentrations of gemcitabine possibly also via the MRP5 inhibition effect.<h4>Conclusion</h4>Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration thus cytotoxicity to MIA PaCa-2 cells but also significantly improved the pharmacokinetic profiles for both drugs. Graphical Abstract. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Science and Business Media LLC |
|
dc.relation.ispartofseries |
Pharmaceutical research |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.subject |
curcumin |
|
dc.subject |
cytotoxicity |
|
dc.subject |
dual drug loaded liposomes |
|
dc.subject |
efflux transporter |
|
dc.subject |
gemcitabine |
|
dc.subject |
pharmacokinetics |
|
dc.subject |
Science & Technology |
|
dc.subject |
Physical Sciences |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Chemistry, Multidisciplinary |
|
dc.subject |
Pharmacology & Pharmacy |
|
dc.subject |
Chemistry |
|
dc.subject |
curcumin |
|
dc.subject |
cytotoxicity |
|
dc.subject |
dual drug loaded liposomes |
|
dc.subject |
efflux transporter |
|
dc.subject |
gemcitabine |
|
dc.subject |
pharmacokinetics |
|
dc.subject |
MULTIDRUG-RESISTANCE |
|
dc.subject |
PEGYLATED LIPOSOMES |
|
dc.subject |
INTRACELLULAR DELIVERY |
|
dc.subject |
RAT PLASMA |
|
dc.subject |
DRUG |
|
dc.subject |
EXPRESSION |
|
dc.subject |
NANOPARTICLES |
|
dc.subject |
CYTOTOXICITY |
|
dc.subject |
CIRCULATION |
|
dc.subject |
DOXORUBICIN |
|
dc.subject |
1115 Pharmacology and Pharmaceutical Sciences |
|
dc.title |
Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1007/s11095-021-03072-2 |
|
pubs.issue |
7 |
|
pubs.begin-page |
1209 |
|
pubs.volume |
38 |
|
dc.date.updated |
2021-10-28T21:08:11Z |
|
dc.rights.holder |
Copyright: The author |
en |
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/34189639 |
|
pubs.end-page |
1219 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
|
pubs.elements-id |
858498 |
|
dc.identifier.eissn |
1573-904X |
|
dc.identifier.pii |
10.1007/s11095-021-03072-2 |
|
pubs.online-publication-date |
2021-6-29 |
|