Antitumor effect of folate-targeted liposomal doxorubicin in KB tumor-bearing mice after intravenous administration
| Autor: | Francis C. Szoka, Kareen Riviere, Nichole Macaraeg, Katherine Jerger, Zhaohua Huang |
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| Rok vydání: | 2010 |
| Předmět: |
Biodistribution
Pharmaceutical Science Mice Nude macromolecular substances Pharmacology KB Cells Article Polyethylene Glycols Mice Drug Delivery Systems Folic Acid In vivo PEG ratio medicine polycyclic compounds Animals Humans Doxorubicin Tissue Distribution Liposome Mice Inbred BALB C Antibiotics Antineoplastic Chemistry organic chemicals Phosphatidylethanolamines Folate Receptors GPI-Anchored technology industry and agriculture Xenograft Model Antitumor Assays In vitro carbohydrates (lipids) Folate receptor Drug delivery Injections Intravenous Liposomes medicine.drug |
| Zdroj: | Journal of drug targeting. 19(1) |
| ISSN: | 1029-2330 |
| Popis: | The effect of folate-targeted liposomal doxorubicin (FTL-Dox) has been well characterized in folate receptor (FR) over-expressing 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, non-targeted 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. |
| Databáze: | OpenAIRE |
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