Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study.

Abstract

A range of antitumor agents for cancer treatment is available; however, they show low specificity, which often limit their use. Recently, we have reported the preparation of folate-coated long-circulating and pH-sensitive liposomes (SpHL-folate-PTX) loaded with paclitaxel (PTX), an effective drug for the treatment of solid tumors, including breast cancer. The purpose of this study was to prepare and characterize SpHL-PTX and SpHL-folate-PTX radiolabeled with technetium-99m (99mTc). Biodistribution studies and scintigraphic images were performed after intravenous administration of 99mTc-PTX, 99mTc-SpHL-PTX and 99mTc-SpHL-folate-PTX into healthy and tumor-bearing mice. High radiochemical purity (>98%) and in vitro stability (>90%) were achieved for both liposome formulations. The pharmacokinetic properties of 99mTc-SpHL-DTPA-PTX and 99mTc-SpHL-folate-DTPA-PTX decreased in a monophasic manner showing half-life of 400.1 and 541.8min, respectively. Scintigraphic images and biodistribution studies showed a significant uptake in liver, spleen and kidneys, demonstrating these routes as way for excretion. At 8h post-injection, the liposomal tumor uptake was higher than 99mTc-PTX. Interesting, 4h after administration, the liposome folate coated showed higher tumor-to-muscle ratio than 99mTc-SpHL-DTPA-PTX and 99mTc-PTX. In conclusion, the liposomal systems, showed high tumor uptake by scintigraphic images, especially the 99mTc-SpHL-folate-DTPA-PTX that showed a sustained and higher tumor-to-muscle ratio than non-functionalized liposome, which indicate its feasibility as a PTX delivery system to folate positive tumors.

• Authors: Liziane O F Monteiro, Renata S Fernandes, Caroline M R Oda, Sávia C Lopes, Danyelle M Townsend, Valbert N Cardoso, Mônica C Oliveira, Elaine A Leite, Domenico Rubello, André L B de Barros
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 97 Pg. 489-495 (Jan 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29091899 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Drug Carriers
• Liposomes
• Technetium
• Folic Acid
• Paclitaxel

Topics

• Animals
• Breast Neoplasms (blood, diagnostic imaging, drug therapy)
• Cell Line, Tumor
• Drug Carriers (administration & dosage, metabolism)
• Drug Delivery Systems (methods)
• Female
• Folic Acid (administration & dosage, blood)
• Humans
• Liposomes
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Paclitaxel (administration & dosage, blood)
• Technetium (administration & dosage, blood)
• Tissue Distribution