Folate-chitosan Coated Quercetin Liposomes for Targeted Cancer Therapy

Abstract

Background: Although quercetin exhibits promising anti-tumor properties, its clinical application is limited due to inherent defects and a lack of tumor targeting.

Objectives: This study aimed to prepare and characterize active targeting folate-chitosan modified quercetin liposomes (FA-CS-QUE-Lip), and its antitumor activity in vitro and in vivo was also studied.

Materials and methods: Box-Behnken Design (BBD) response surface method was used to select the optimal formulation of quercetin liposomes (QUE-LP). On this basis, FA-CS-QUE-LP was obtained by connecting folic acid chitosan complex (FA-CS) and QUE-LP. The release characteristics in vitro of QUE-LP and FA-CS-QUE-LP were studied. Its inhibitory effects on HepG2 cells were studied by the MTT method. The pharmacokinetics and pharmacodynamics in vivo were studied in healthy Wistar mice and S180 tumor-bearing mice, respectively.

Results: The average particle size, zeta potential and encapsulation efficiency of FA-CS-QUELP were 261.6 ± 8.5 nm, 22.3 ± 1.7 mV, and 98.63 ± 1.28 %, respectively. FA-CS-QUE-LP had a sustained release effect and conformed to the Maloid-Banakar release model (R2=0.9967). The results showed that FA-CS-QUE-LP had higher inhibition rates on HepG2 cells than QUE-Sol (P < 0.01). There was a significant difference in AUC, t_1/2, CL and other pharmacokinetic parameters among QUE-LP, FA-CS-QUE-LP, and QUE-Sol (P < 0.05). In in vivo antitumor activity study, the weight inhibition rate and volume inhibition rate of FA-CS-QUE-LP were 30.26% and 37.35%, respectively.

Conclusion: FA-CS-QUE-LP exhibited a significant inhibitory effect on HepG2 cells, influenced the pharmacokinetics of quercetin in mice, and demonstrated a certain inhibitory effect on S180 tumor-bearing mice, thus offering novel avenues for cancer treatment.

Keywords: Box-Behnken design.; Tumor targeting; chitosan; folic acid; liposomes; quercetin.