Preparation of novel Tubeimoside Ⅰ liposomes and its anti-pancreatic cancer research
Objective To determine the potential anti-tumor effect of new Tubeimoside Ⅰ liposomes(Tub Ⅰ-LPs)in vitro and in vivo.Methods Liposomes were prepared with the thin film hydration method.The particle size and potential were analyzed by a particle size analyzer,while the morphology was observed with a transmission electron microscope.The encapsulation efficiency and in vitro stability were also determined.To compare the hemolytic properties of Tubeimoside Ⅰ monomer,Tubeimoside Ⅰ ordinary cholesterol liposomes,and novel Tub Ⅰ-LPs,mouse whole blood was taken.The cell proliferation inhibitory effect of the new Tub Ⅰ-LPs on Panc 02 cells and MIA PaCa 02 cells was detected with the CCK-8 method,and the apoptosis effect was determined by flow cytometry.The cellular uptake ability of the two liposomes by Panc 02 cells and MIA PaCa 02 cells was qualitatively and quantitatively assessed with inverted fluorescence microscopy and flow cytometry,respectively.Additionally,changes in the mitochondrial membrane potential were detected with the JC-1 assay.Furthermore,the anti-tumor effect of both liposomes were evaluated with in vivo experiments.The safety of the formulation was assessed by HE staining.Results The particle sizes of the two prepared liposomes were uniformly dispersed and approximately spherical.The average particle size of the Tub Ⅰ-LPs was(112.8±0.2)nm,and the Zeta potential was(-2.6±0.2)mV.The average particle size of the C-Tub Ⅰ-LPs was(185.2±0.2)nm,and the Zeta potential was(-3.1±0.2)mV.The encapsulation rates of the Tub Ⅰ-LPs and the C-Tub Ⅰ-LPs were 98.22％and 48.39％respectively.The stabilities of two preparations were similar,but the Tub Ⅰ-LPs significantly reduced plastid hemolysis.They exhibited a more significant effect in inhibiting the cell proliferation and inducing cancer cell apoptosis.The cell uptake flow cytometry demonstrated that cancer cells took up the Tub Ⅰ-LPs three time more than the C-LPs.The Tub Ⅰ-LPs caused a more pronounced decrease in the mitochondrial membrane potential of cancer cells.The C57 orthotopic pancreatic cancer model confirmed that the Tub Ⅰ-LPs had a more significant tumor inhibitory effect.HE staining showed no obvious toxic or side effects were found in the new preparation.Conclusion Tubeimoside Ⅰ as a membrane material greatly enhances its cellular uptake capacity and effectively improves the overall anti-tumor effect.This finding provides a basis for future utilization of this film material for encapsulating anti-tumor drugs,thereby promoting the development of innovative traditional Chinese medicine drugs for tumor treatment.
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