期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 13, 期 5, 页码 1627-1636出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2017.03.001
关键词
Exosomes; Taxol; Antitumor efficacy; Lung cancer; Systemic toxicity; Immunological responses
资金
- USPHS grant [R41-CA-189517, KSTC-184-512-15-209]
- Agnes Brown Duggan Endowment
- Helmsley Trust Fund
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.
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