Preparation of Celastrol-loaded Liposomes by Microfluidic Method and Its Preliminary Study on Anti-colon Cancer
Objective:Based on the unique advantage of the microfluidic method to precisely control the particle size and size distribution of liposomes in liposome preparation,and in order to overcome the shortcomings such as poor water solubility of Celastrol,Cel-LPs were prepared and the therapeutic effect of Cel-LPs on colorectal cancer was investigated with the aim of providing a safe and effective platform.Methods:Cel-LPs were prepared by the microfluidic method and the formulations were optimized by one-way testing;the morphology,particle size,polydispersity index(PDI),Zeta potential,in vitro release and stability of the optimized formulations of Cel-LPs were investigated;the toxicity of Cel and Cel-LPs on human colon cancer cells(HCT116)was determined by the CCK-8 method;coumarin 6(coumarin 6,Cou6)was used as a fluorescent substance to prepare coumarin 6 liposomes(Cou6-LPs).The uptake behavior of Cou6-LPs by HCT116 cells was investigated by inverted fluorescence microscopy.Results:The optimized formulation was as follows:aqueous phase to oil phase flow rate ratio of 4.5∶1;drug to phospholipid ratio of 1:4;cholesterol to phospholipid ratio of 1:5.Cel-LPs prepared according to the optimized prescription had a spherical appearance and uniform distribution,with particle sizes and PDIs of(85.02±0.43)nm and 0.12±0.01,respectively,a Zeta potential of(-11.4±0.25)mV,and an encapsulation rate of(95.42±0.12)％.The prepared liposomes had good stability and showed a good slow release effect in the in vitro release experiments.Cel-LPs showed good cytotoxicity against HCT116 cells,and inhibited their proliferation more than Cel,with a half inhibitory concentration(IC50)of 6.26 µg/mL.The in vitro cellular uptake experiments showed that HCT116 cells had a better uptake effect of Cou6-LPs in the in vitro cellular uptake experiments.Conclusion:A stable,homogeneous,well-dispersed liposome of tretinoin with a high encapsulation rate was successfully prepared by the microfluidic method,confirming its unique characteristics and promising prospects as a liposome preparation method.The study showed that the liposome could be well taken up and slowly released by HCT116 cells,effectively inhibited the proliferation of HCT116 cells,and demonstrated good anti-tumor effect.
CelastrolLiposomeMicrofluidic methodColorectal cancer
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