Preparation of flavonoid liposomes from lingonberry leaves and their inhibitory effect on growth of HepG2 cells
The highest flavonoid fraction(L6)in lingonberry leaves was obtained from ultrasound-assisted extraction and purification with AB-8 macroporous resin,with its main components analyzed by HPLC-MS.Carboxymethyl chitosan-L6-liposome(CMCS-L6-Lips)were then prepared from CMCS aqueous solution with different mass fraction modification of L6-liposomes,which were synthesized using L6 as core material via ethanol injection method,and characterized by FTIR,particle size analysis,Zeta potential and dialysis method.Its in vitro release ability at different pH and inhibitory ability on HepG2 cells were further analyzed and evaluated.The results showed that the flavonoid content of L6 could reach 899.44 mg/g,mainly containing 7 components such as rutin,quercetin,quercetin 3-O-β-D-glucuronide,quercetin 3-O-rhamnosid-7-O-glucoside,eriodictyol 7-O-glucoside,catechin and chlorogenic acid.The mass fraction of CMCS was correlated with the particle size,encapsulation rate,and Zeta potential of CMCS-L6-Lips.The surface modification effect of liposomes was optimal when 0.4%(mass fraction)CMCS solution was added,with a Zeta potential of-35.65 mV,indicating successful attachment of CMCS to the surface of L6-Lips and stronger repulsion forces between CMCS-L6-Lips particles,resulting in higher stability.The CMCS-L6-Lips exhibited pH sensitivity,with the highest in vitro release capacity at pH=4.0.The kinetic equation conformed to the Weibull model,indicating a skeleton erosion release mechanism.CMCS-L6-Lips could effectively inhibit the proliferation of HepG2 cells,slow down cell migration,and block cells from staying in the S and G2 phases.The encapsulation of liposomes effectively improved the solubility of lingonberry leaves flavonoid,enhancing the cell's ability to uptake the drug.Furthermore,the modification of CMCS increased the targeting ability of liposomes,which was beneficial for tumor treatment.
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