Folate-chitosan Coated Quercetin Liposomes for Targeted Cancer Therapy

Background:: Although quercetin exhibits promising anti-tumor properties, its clinical application is limited due to inherent defects and a lack of tumor targeting. background: The anti-tumor activity of quercetin (QUE) had attracted much attention, but the rapid metabolism in vivo and lack of targeting lesion site severely hindered its therapeutic effect and clinical application. Objective:: 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. objective: The purpose of this study was to prepare and characterize an active targeting liposome FA-CS-QUE-LP, with quercetin (QUE) as the model drug and folic acid (FA) as the targeting molecular. The antitumor activity of FA-CS-QUE-LP in vitro and in vivo was also studied. 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. method: In this study, quercetin liposomes (QUE-LP) were prepared by thin film evaporation-ultrasonic dispersion method. The particle size and entrapment rate were taken as indicators, the optimal formulation was selected by using the single factor investigation and Box-Behnken Design (BBD) response surface method. On this basis, the self-made folic acid chitosan complex (FA-CS) was modified onto the QUE-LP surface to obtain FA-CS-QUE-LP. The release characteristics of QUE-LP and FA-CS-QUE-LP were studied by in vitro drug release test. The inhibitory effects of quercetin solution (QUE-Sol), QUE-LP and FA-CS-QUE-LP on HepG2 cells were studied by MTT method. The pharmacokinetics of QUE-Sol, QUE-LP and FA-CS-QUE-LP in healthy Wistar rats was studied. The growth inhibition of QUE-Sol, QUE-LP and FA-CS-QUE-LP on solid tumor was studied with S180 tumor bearing mice as the animal model. 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, t1/2, 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. conclusion: The QUE-LP and FA-CS-QUE-LP prepared in this study had small particle size, high entrapment efficiency, a certain sustained-release effect in vitro, a good inhibitory effect on HepG2 cells, affected the pharmacokinetics of quercetin in rats, and showed a certain inhibitory effect on S180 tumor bearing mice model. This study could provide new ideas for the treatment of liver cancer.