Folic acid-modified liposomal drug delivery strategy for tumor targeting of 5-fluorouracil

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Eskandar Moghimipour, Mohsen Rezaei, Zahra Ramezani, Maryam Kouchak, Mohsen Amini, Kambiz Ahmadi Angali, Farid Abedin Dorkoosh, Somayeh Handali
The aim of this study was to develop a liposomal formulation to selectively target cancer cells. Liposomes were prepared using thin layer method and folic acid (FA) was applied for targeted delivery of 5FU to cancer cells. Liposomes prepared were characterized for encapsulation efficiency (EE%), morphology and their particle size. Cellular uptake, cytotoxicity study and ROS production were evaluated using CT26 cell line. Hemolysis test was performed on rat red blood cells (RBCs). Moreover, the efficacy of targeted liposomes were investigated by in vivo antitumor activity and tissue toxicities were studied by histological examination. The EE% and average particle size of liposomes were 67.88±1.84% and 114.00±4.58nm, respectively. TEM image revealed that liposomes were spherical in shape. Targeted liposomes showed higher cellular uptake, lower IC50 (12.02μM compared to 39.81μM for liposomal 5FU and 39.81μM for free 5FU) and higher ROS production than free drug (62,271.28 vs 2369.55 fluorescence intensity) on cancer cells. Results of hemolysis assay confirmed the blood biocompatibility of the liposomes. Moreover, folate targeted liposomes showed better tumor inhibition than free drug (88.75mm³ tumor volume vs 210.00mm³) and no tissue abnormalities were found in histological examination. It can be concluded that folate targeted liposomes provide an effective and safe strategy for colon cancer targeted chemotherapy.

Graphical abstract

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