Milk-derived exosomes for oral delivery of paclitaxel
Milk-derived exosomes for oral delivery of paclitaxel
复制标题
DOI：
10.1016/j.nano.2017.03.001
复制
发表时间：
2017-07-01
影响因子：
5.4
通讯作者：
Gupta, Ramesh C.
中科院分区：
文献类型：
--
作者：
Agrawal, Ashish K.;Aqil, Farrukh;Gupta, Ramesh C.
在本报告中，研究了乳源性外泌体用于口服化疗药物紫杉醇（PAC），作为常规静脉内治疗的替代方案，以提高疗效并降低毒性。发现装载PAC的外泌体（ExoPAC）具有类似于108 nm的粒度、窄粒度分布（PDI类似于0.190）、ζ电位（类似于-7 mV）和类似于8%的实际装载效率。外泌体和ExoPAC在模拟胃肠液的存在下以及在-80 ℃下储存期间表现出优异的稳定性。使用PBS（pH 6.8）在体外也观察到PAC的持续释放长达48 h。重要的是，口服ExoPAC对裸鼠中的人肺肿瘤异种移植物显示出显著的肿瘤生长抑制（60%; P < 0.001）。然而，以与ExoPAC相同的剂量腹腔内PAC处理显示出适度但统计学上不显著的抑制（31%）。此外，ExoPAC显示出与静脉内PAC相比显著更低的全身和免疫毒性。爱思唯尔公司出版
In this report milk-derived exosomes have been investigated for oral delivery of the chemotherapeutic drug paclitaxel (PAC) as an alternative to conventional i.v. therapy for improved efficacy and reduced toxicity. PAC-loaded exosomes (ExoPAC) were found to have a particle size of similar to 108 nm, a narrow particle size distribution (PDI similar to 0.190), zeta potential (similar to -7 mV) and a practical loading efficiency of similar to 8%. Exosomes and ExoPAC exhibited excellent stability in the presence of simulated-gastrointestinal fluids, and during the storage at -80 degrees C. A sustained release of PAC was also observed up to 48 h in vitro using PBS (pH 6.8). Importantly, ExoPAC delivered orally showed significant tumor growth inhibition (60%; P < 0.001) against human lung tumor xenografts in nude mice. Treatment with i.p. PAC at the same dose as ExoPAC, however, showed modest but statistically insignificant inhibition (31%). Moreover, ExoPAC demonstrated remarkably lower systemic and immunologic toxicities as compared to i.v. PAC. Published by Elsevier Inc.