Journal
JOURNAL OF DRUG TARGETING
Volume 19, Issue 1, Pages 14-24Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10611861003733953
Keywords
Drug delivery; folate receptor; KB tumor; ligand-targeting
Categories
Funding
- NIH [RO1 GM061851]
- PhRMA Foundation
- UNCF-Merck
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM061851] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The effect of folate-targeted liposomal doxorubicin (FTL-Dox) has been well characterized in folate receptor (FR) overexpressing tumors in vitro, particularly in KB human carcinoma cells. However, there are few studies evaluating the in vivo efficacy of FTL-Dox in KB murine xenograft models. In this study, we investigated the antitumor activity of FTL-Dox injected intravenously in mice bearing KB tumors. Folate ligands comprising of folate-polyethyleneglycol-distearoylphosphatidylethanolamine (FA-PEG-DSPE) were synthesized with different MW PEG. To design an optimum FTL-Dox formulation for therapeutic studies, we prepared various FTLs and characterized their in vitro targeting and in vivo tissue biodistribution. Mice were administered a single intravenous injection of free Dox, nontargeted PEGylated liposomal Dox (PL-Dox), or FTL-Dox. FTLs and PLs accumulated similarly in tumor tissue, despite FTLs' faster clearance from circulation. Mice treated with FTL-Dox 20 mg/kg had a slightly greater tumor growth inhibition and almost a 50% increase in life span than mice receiving PL-Dox 20 mg/kg (P = 0.0121; log-rank test). We conclude that FTLs administered systemically have the potential to enhance the delivery of anticancer drugs in vivo; however, their removal by FR expressing normal tissues may have to be blocked if the benefits of tumor targeting are to be realized.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available