Primary Study On Liposomes Constructed By Poly(2-Methyl-2-Oxazoline)-Cholesteryl Methyl Carbonate For Docetaxel Delivery

In the article,poly(2-methyl-2-oxazoline)(PMOZ)was synthesized by using2-methyl-2-oxazoline(MOZ)as polymerizable monomer through a cationic ring-opening polymerization.Subsequently,a novel amphiphilic[poly(2-methyl-2-oxazoline)-cholesteryl methyl carbonate,PMOZ-CHMC]was synthesized through esterification between PMOZ(with molecular weight 2000)and cholesteryl chloroformate(CHM).The structure of PMOZ-CHMC was confirmed by Infrared spectroscopy(IR)and Nuclear Magnetic Resonance Spectroscopy(~1H-NMR),and the p H-sensitive property was approved by acid-base titration.The detection methods of two kinds of model drug of docetaxel(DOC)and coumarin-6(C6) were established with high performance liquid chromatography(HPLC)and fluorescence spectrophotometric.Furthermore,a systematic study on methodology of the analysis method was also conducted.Conventional liposome(CL),docetaxel liposome(DOC-L)and coumarin-6 liposome(C6-L)were prepared by thin-film dispersion method.Afterwards,PMOZ-CHMC or PEG-distearoyl phosphatidyl ethanolamine(PEG-DSPE)was modified on the surface of the liposome through the post-insertion method,respectively.The encapsulation efficiency(EE)of DOC-L and C6-L were measured by sephadex G-50 mini-column centrifugation method,and the EE were(89.59±2.61)%and(75.63±1.47)%,respectively.The results showed that the particle size of DOC-L and C6-L were(78.67±0.22)nm and(117.07±0.12)nm,and the zeta potentials were(-5.77±0.47)mv and(-6.43±0.32)mv,respectively.We can draw the conclusion that the polymers-modified liposome had no obvious change of the particle size but appeared tiny increase of zeta potential.The variation of light transmittance was detected after the liposomes were incubated in 10% fetal bovine serum.The results showed that the stability of liposomes increased after modified by PMOZ-CHMC or PEG-DSPE than that of CL.Under different p H values,the change of particle size and in vitro release were investigated,and the results showed that both liposomes modified by PMOZ-CHMC and PEG-DSPE could significantly improve the stability of liposomes.In addition,PMOZ showed some different phenomenon that there was a relatively large variation of particle size and cumulative release rate under p H 6.4,which displayed the p H sensitivity.The qualitative and quantitative analysis was conducted by fluorescence eliasa and fluorescent microscope.The experimental results showed that the colon cancer cellular uptake of liposomes is in the following order:PMOZ-C6-L>C6-L>PEG-C6-L.Moreover,there was a significantly increase of cellular uptake increase in PMOZ-C6-L with the p H decrease,which displayed the p H-sensitive sensitivity of PMOZ.The MTT results indicated that all three kinds of DOC-L had some toxicity on colon cancer cell under different concentrations,and cell viability rate reduced significantly with the drug concentration increase.When the p H drop to 6.4,only PMOZ-DOC-L group could significantly reduce the cell viability rate,which demonstrated that PMOZ-CHMC endow a certain acid sensitivity with liposomes successfully.