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J Control Release. 2009 Jul 1;137(1):8-14. doi: 10.1016/j.jconrel.2009.02.023. Epub 2009 Mar 12.

Oxaliplatin encapsulated in PEG-coated cationic liposomes induces significant tumor growth suppression via a dual-targeting approach in a murine solid tumor model.

Author information

1
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.

Abstract

We recently designed a PEG-coated cationic liposome targeted to angiogenic vessels and showed, in a murine dorsal air sac model, potent anti-angiogenic activity of an oxaliplatin (l-OHP) formulation of this liposome. In the present study, we extended the l-OHP formulation to a murine tumor-xenograft model. Following three injections, l-OHP containing PEG-coated cationic liposomes showed substantial tumor growth suppression and increased survival time of tumor-bearing mice without apparent side effects, compared with other l-OHP containing PEG-coated neutral liposomes and free l-OHP. In vivo imaging showed a preferential tumor accumulation and a broader distribution of PEG-coated cationic liposomes, compared with PEG-coated neutral liposomes. In addition, PEG-coated cationic liposomes delivered larger amounts of l-OHP into the tumor tissue than other l-OHP formulations, correlating with its antitumor efficiency. In vitro studies indicated that PEG-coated cationic liposomes were internalized not only by tumor cells but also by endothelial cells, and consequently its l-OHP formulation displayed higher cytotoxicity towards both cell types as compared with l-OHP containing PEG-coated neutral liposomes. In summary, l-OHP containing PEG-coated cationic liposomes induced significant tumor growth suppression, presumably by delivering encapsulated l-OHP into both tumor endothelial cells and tumor cells. Such dual targeting approach, i.e. vascular-targeting and tumor-targeting with a single liposomal l-OHP formulation, may have great potential for overcoming some major limitations in conventional chemotherapy.

PMID:
19285528
DOI:
10.1016/j.jconrel.2009.02.023
[Indexed for MEDLINE]

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