不同粒径多西他赛固体脂质纳米粒制剂及其细胞毒活性

Pharmacy characters and cytotoxic activity of docetaxel-loaded solid lipid nanoparticles with different sizes

目的制备不同粒径的多西他赛(docetaxel,DTX)固体脂质纳米粒,考察多西他赛固体脂质纳米粒理化性质,研究粒径对体外释放行为以及细胞毒作用的影响。方法通过热熔超声法制备不同粒径多西他赛固体脂质纳米粒,观察纳米粒形态,测定其包封率、粒径、Zeta电位。考察粒径因素对固体脂质纳米粒体外释放行为、体外细胞毒性的影响。结果制备的纳米粒均为球形及类球形,3种粒径的多西他赛固体脂质纳米粒平均粒径分别为(83.7±8.4)、(162.7±11.9)、(232.1±26.4)nm;Zeta电位分别为-24.19、-23.67、-23.19 mV;包封率分别为98.03%、97.84%、97.92%。60 h粒径分别为83、16、232 nm的多西他赛固体脂质纳米粒在释放介质中分别累计释放86.34%、76.98%、67.14%。3种不同粒径多西他赛固体脂质纳米粒(DTX-SLN-83,DTX-SLN-162,DTX-SLN-232),多西他赛原料药(DTX solutions)以及空白SLN溶液与多西他赛的混合溶液(physi-calm ixture)对MCF-7细胞作用24 h的IC50值分别为3.36、6.20、9.74、13.15、12.92 mg.L-1;48 h的IC50值分别为0.93、2.01、4.35、9.48、9.21 mg.L-1;72 h的IC50值分别为0.30、0.91、1.67、7.36、7.82 mg.L-1。随着多西他赛固体脂质纳米粒粒径的减小,其肿瘤细胞杀伤力逐渐增强。结论热熔超声法可用于制备不同粒径多西他赛固体脂质纳米粒。降低固体脂质纳米粒粒径有利于药物更完全地释放,同时增强其对肿瘤细胞的杀伤能力。

Objective To prepare different sizes of docetaxel-loaded solid lipid nanoparticles,study their physico-chemical properties and investigate the effect of paricle size on drug release in vitro and cytotoxic effect.Methods The different sizes of docetaxel-loaded solid lipid nanoparticles were prepared by melt-emulsification-ultrasound method.The shape of SLN,entrapment efficiencies,particle size and Zeta potential were evaluated.The drug release and cytotoxicity in vitro were investigated among different sizes of docetaxel-loaded solid lipid nanoparticles.Results The results showed that the solid lipid nanoparticles were sphere and sphere-like.The particle sizes of the three kinds of docetaxel-loaded solid lipid nanoparticles were（83.7±8.4）nm,（162.7±11.9）nm,（232.1±26.4）nm,respectively.Zeta potential,entrapment efficiency and the cumulative release during 60 h of the DTX-SLN-83,DTX-SLN-162 and DTX-SLN-232 seperately were-24.19,-23.67,-23.19 mV;98.03%,97.84%,97.92%;86.34%,76.98%,67.14%,ND.After incubation for 24 h,the IC50 values of DTX-SLN-80,DTX-SLN-160,DTX-SLN-230,DTX solution and physical mixture were 3.36,6.20,9.74,13.15,12.92 mg·L-1;after incubation for 48 h,the IC50 values were 0.93,2.01,4.35,9.48,9.21 mg·L-1,after incubation for 72 h,the IC50 values were 0.30,0.91,1.67,7.36,7.82 mg·L-1.The results showd that the reduction of particle size could improve inhibitory action on tumor cells.Conclusions Using the melt-enmulsification-ultrasound method,the preparation of docetaxel-loaded solid lipid nanoparticles is highly feasible.The particle size of SLN has a significant influence on the drug release and cytotoxicity in vitro.There was a higher efficiency in killing MCF-7 cells in vitro and a faster drug release of docetaxel-loaded solid lipid nanoparticles with a decrease of particle size.