Preparation And Cytotoxicity Investigation Of Hyaluronic Acid Targeted Curcumin Liposomes

Objective: To prepare hyaluronic acid targeted curcumin liposomewith curcumin as antitumor drug and investigate the technology ofpreparation. To investigate the cytotoxicity of HA-CUR-L on A549cellsover-expressing HA receptor and HepG2cells lower-expressing HAreceptor.Methods: Reverse phase evaporation was used to prepare HA-CUR-L.The orthogonal experimental design was applied to screen the optimumformula of liposomes. CUR entrapment efficiency and HA-DOPE bindingrate were applied to assess the stability of liposomes at differentenvironment. MTT assay was applied to investigate the cytotoxicity ofCUR、CUR-L and HA-CUR-L on A549cells and HepG2cells.Results: The optimum formula was as follows:phosphatide:cholesterol was3:1, the ratio of drug to lipid was1:60,incubation temperature was45℃,ultrasonic time was5min, HA-DOPE was2mg.The average entrapment efficiency for curcumin was88.56%, bindingrate for HA-DOPE was71.69%. The liposome observed through transmission electron microscopy presents uniform distribution of size, andthe average diameter is about160nm. The cytotoxicity test showed that theproliferation inhibition effect of HA-CUR-L on A549cells wasCUR<CUR-L<HA-CUR-L. On HepG2cells it wasCUR<CUR-L≈HA-CUR-L.Conclusions: The method of using UV detection to evaluate thecontents and the entrapment rate of HA-CUR-L was easy, accurate andconvenient. The stability result showed that liposomes stored in4℃wouldkeep more stable. The drug releasing experiment in vitro indicated that theliposomes exhibited better sustained-release efficacy. MTT assay showedthat HA-CUR-L had the best proliferation inhibition effect on A549cells.All pointed out that HA-CUR-L can actively deliver drugs to tumor cellswith HA binding to its receptor specifically and enhance its proliferationinhibition effect on tumor cells.