In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs

Eliezar, Jeaniffer, Scarano, Wei, Boase, Nathan R. B., Thurecht, Kristofer J. and Stenzel, Martina H. (2015) In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs. Biomacromolecules, 16 2: 515-523. doi:10.1021/bm501558d

Author Eliezar, Jeaniffer
Scarano, Wei
Boase, Nathan R. B.
Thurecht, Kristofer J.
Stenzel, Martina H.
Title In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs
Journal name Biomacromolecules   Check publisher's open access policy
ISSN 1526-4602
Publication date 2015-02-09
Year available 2015
Sub-type Article (original research)
DOI 10.1021/bm501558d
Open Access Status
Volume 16
Issue 2
Start page 515
End page 523
Total pages 9
Place of publication Washington, DC United States
Publisher American Chemical Society
Collection year 2016
Language eng
Abstract The biodistribution of micelles with and without folic acid targeting ligands were studied using a block copolymer consisting of acrylic acid (AA) and polyethylene glycol methyl ether acrylate (PEGMEA) blocks. The polymers were prepared using RAFT polymerization in the presence of a folic acid functionalized RAFT agent. Oxoplatin was conjugated onto the acrylic acid block to form amphiphilic polymers which, when diluted in water, formed stable micelles. In order to probe the in vivo stability, a selection of micelles were cross-linked using 1,8-diamino octane. The sizes of the micelles used in this study range between 75 and 200 nm, with both spherical and worm-like conformation. The effects of cross-linking, folate conjugation and different conformation on the biodistribution were studied in female nude mice (BALB/c) following intravenous injection into the tail vein. Using optical imaging to monitor the fluorophore-labeled polymer, the in vivo biodistribution of the micelles was monitored over a 48 h time-course after which the organs were removed and evaluated ex vivo. These experiments showed that both cross-linking and conjugation with folic acid led to increased fluorescence intensities in the organs, especially in the liver and kidneys, while micelles that are not conjugated with folate and not cross-linked are cleared rapidly from the body. Higher accumulation in the spleen, liver, and kidneys was also observed for micelles with worm-like shapes compared to the spherical micelles. While the various factors of cross-linking, micelle shape, and conjugation with folic acid all contribute separately to prolong the circulation time of the micelle, optimization of these parameters for drug delivery devices could potentially overcome adverse effects such as liver and kidney toxicity.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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