纳米递药系统胚胎毒性研究进展

Progress in studies on embryo toxicity of nano drug delivery system

纳米递药系统（NDDS）是指药物与药物载体形成的、粒径在1 000 nm以内的药物输送系统,一般是以聚合物胶束、脂质体、纳米囊、微乳以及有机或无机纳米粒子为载体,将药效物质以一定的方式与载体结合制成新型控/缓释制剂,或直接将原药加工制成纳米粒子.NDDS的胚胎毒性是评价其非临床安全性的重要内容.体外研究显示,NDDS的胚胎毒性与纳米粒子的理化性质如尺度和表面修饰物、纳米粒子暴露时间和剂量相关.已有的研究显示,氧化锌纳米粒子胚胎毒性明显,二氧化钛、二氧化硅、氧化镁纳米粒子和碲化镉量子点也有不同程度的胚胎毒性,而聚苯乙烯基纳米粒子无胚胎毒性.体内研究结果显示,氧化锌纳米粒子、含镉或硒量子点和高浓度纳米银对大鼠、小鼠、斑马鱼、海胆、爪蟾和紫贻贝等动物中的一种或几种胚胎有毒性作用;不同剂量、不同尺寸的二氧化钛、二氧化硅、壳聚糖纳米粒子和碳纳米管对不同种属动物胚胎发育的影响不同.NDDS的胚胎毒性反应主要表现为发育停滞、流产和畸形,其胚胎毒性机制主要与氧化应激和炎症有关.NDDS的胚胎毒性研究虽然在模型、方法和内容方面都有待进一步探索和深入,但已开展的研究为后续的纳米药物胚胎毒性研究提供了重要的参考依据.

Nano drug delivery system （NDDS） is a kind of drug delivery system which are made up of drugs and drug carriers and their particle sizes are less than 1 000 nm.In general,polymeric micelles,liposome,nano capsule,microemulsion,and organic or inorganic nanoparticles are used as carriers in NDDS,pharmacodynamic substance and carriers are combined into new type of controlled/slow release preparations or the drugs are directly processed into nanoparticles.Embryo toxicity is an important index for non-clinic safety evaluation of NDDS.The in vitro studies showed that embryo toxicity of NDDS is related to physical and chemical properties of nanoparticles,such as size and modification materials on surface,exposure time of nanoparticles,and dosage.It has been shown that zinc oxide nanoparticles have embryo toxicity,titanium dioxide,silica,magnesium oxide,and quantum dots have different degrees of embryo toxicity,and polystyrene based nanoparticles have no embryo toxicity.The in vivo studies showed that zinc oxide nanoparticles,quantum dots containing cadmium or selenium,and high concentrations of nano silver have embryo toxicity in one or several animal models,such as rat,mouse,zebrafish,Paracentrotus lividus,Xenopus laevis,and Mytilus Galloprovincialis.Silica,titanium dioxide,chitosan nanoparticles and singlewalled carbon nanotubes at different dose and size showed different effects on embryonic development of different animal models.Embryotoxic or teratogenic effects of NDDS include stagnation,miscarriage,and deformity,and the mechanism of toxicity is mainly related to oxidative stress and inflammation.Though embryo toxicity of NDDS in models,methods and content need further exploration and research,studies which have been carried out provide important references for further research.