文献：Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid–polymer hybrid nanoparticles

文献链接：https://www.tandfonline.com/doi/full/10.2147/DDDT.S172199#d1e176

作者：Jia Liu,Hao Cheng,Le Han ,Zhun Qiang ,Xinwei Zhang ,Wei Gao ,Kun Zhao ,Yangrong Song

相关产品：DSPE-PEG5000-FITC 磷脂-聚乙二醇5000-荧光素

原文摘要：

Purpose: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer. Lipid–polymer hybrid nanoparticles (LPNs) combine the advantages of both polymeric nanoparticles and liposomes into a single delivery platform. In this study, we engineered LPNs as the co-delivery system of paclitaxel (PTX) and triptolide (TL) to achieve synergistic therapeutic effect and reduced drug resistance.

Materials and methods: In this study, PTX- and TL-coloaded LPNs (P/T-LPNs) were fabricated by nanoprecipitation method using lipid and polymeric materials. The P/T-LPNs combination effects on human lung cancer cells were studied. Therapeutic potentials of P/T-LPNs were further determined using lung cancer cells-bearing mice model.

Results:The average particle sizes of LPNs were around 160 nm, with narrow size distribution below 0.2. The zeta potential value of LPNs was about -30 mV. The encapsulating efficiency (EE) of PTX and TL loaded in LPNs was over 85%. The cytotoxicity of dual drug loaded LPNs was higher than single drug loaded LPNs. The combination therapy showed synergistic when PTX:TL weight ratio was 5:3, indicating the synergy effects of the LPNs. In vivo tumor growth curve of the experimental group was more gentle opposed to the control group, and tumor volumes of P/T-LPNs and control group were 392 and 1,737 mm3, respectively. The inhibition rate on day 20 was 77.4% in the P/T-LPNs group, which is higher than the free drugs solution.

Conclusion: The in vivo and in vitro results proved the synergetic effect of the two drugs coloaded in LPNs on the lung cancer xenografts, with the least systemic toxic side effect.

DSPE-PEG5000-FITC由DSPE（1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺）、PEG（聚乙二醇，5000分子量）和FITC（荧光素异硫氰酸酯）三部分组成。DSPE-PEG5000-FITC中的PEG链能够增加脂质体的水溶性和稳定性，防止脂质体在制备和存储过程中发生聚集或降解。PEG链具有良好的生物相容性，可以减少脂质体被体内免疫系统的识别和清除，从而延长脂质体在体内的循环时间和作用时间。DSPE-PEG5000-FITC的应用较广，比如DSPE-PEG5000-FITC在P/T-LPNs的制备中发挥着多重作用。

图为：PTX和TL联合装载LPN（P/T-LPN）示意图

P/T-LPNs的制备：

采用纳米共沉淀法制备了P/t-lpn。将DSPE-mPEG5000和ISL分散在蒸馏水（水相）中。将PTX、TL和PLGA溶解在丙酮（油相）中。将油相滴加入到水相中，在室温下搅拌，直到丙酮完全蒸发。将混合物离心，除去未卸载的PTX和/或TL一段时间，然后通过注射器过滤器过滤过滤。采用相同的方法，将PTX和PLGA溶解在丙酮中，得到含有PTX的LPNs（P-LPNs）的油相。采用相同的方法，将TL和PLGA在丙酮中溶解生产TL（T-LPNs）产生油相。用同样的方法将PLGA溶解在丙酮中生成油相，得到空白lpn。采用相同的方法制备FITC负载的lpn，用DSPE-PEG5000-FITC取代DSPE-mPEG5000。将 PTX溶解在L溶剂1中制备PTX溶液（P溶液）。将TL溶解在溶剂1中制备TL溶液（T溶液）。将 PTX和 TL溶解在溶剂1中，制备了PTX和TL混合溶液（P/T溶液）。

图为：药物负载lpn和药物溶液的体外PTX (A)和TL (B)释放行为

结论：纳米颗粒的存储稳定性评估对于确认其结构特性的保存至关重要，因为dds中纳米载体的破坏可能会影响其Treatment 潜力。对于各种lpn，颗粒大小在一段时间几乎保持不变。在lpn中装载的两个粉尘的EE也保留了下来，在研究中测试的所有时间点都很稳定，表明lpn是稳定的，在一段时间内不会拆卸或聚集。用DSPE-mPEG10000、DSPE-mPEG5000、DSPE-mPEG2000和DSPE-mPEG550进行了试验，DSPE-mPEG5000能形成具有均匀粒径和多分散性指数的纳米颗粒。还尝试了大豆卵磷脂、卵磷脂和油相胆固醇；有些在制备后立即沉淀或储存稳定性不会持续一周。只有大豆卵磷脂才能获得良好的稳定性。