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

• Published in: Biomedicine & pharmacotherapy 2018-01, Vol.97, p.489-495
• Main Authors: Monteiro, Liziane O.F., Fernandes, Renata S., Oda, Caroline M.R., Lopes, Sávia C., Townsend, Danyelle M., Cardoso, Valbert N., Oliveira, Mônica C., Leite, Elaine A., Rubello, Domenico, de Barros, André L.B.
• Format: Article
• Language: English
• Subjects: Animals; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - drug therapy; Cell Line, Tumor; Drug Carriers - administration & dosage; Drug Carriers - metabolism; Drug Delivery Systems - methods; Female; Folate; Folic Acid - administration & dosage; Folic Acid - blood; Humans; Liposomes; MDA-MB-231 tumor; Mice; Mice, Inbred BALB C; Mice, Nude; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - blood; pH-sensitive liposomes; Scintigraphic images; Technetium - administration & dosage; Technetium - blood; Tissue Distribution
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2017.10.135

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.