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Aerosol delivery of biocompatible dihydroergotamine-loaded PLGA-PSPE polymeric micelles for efficient lung cancer therapy

Cited 13 time in Web of Science Cited 12 time in Scopus
Authors
Qiao, Jian-Bin; Jang, Yoonjeong; Fan, Qian-Qian; Chang, Seung-Hee; Xing, Lei; Cui, Peng-Fei; He, Yu-Jing; Lee, Soomin; Hwang, Sunghyun; Cho, Myung-Haing; Jiang, Hu-Lin
Issue Date
2017-01
Citation
Polymer Chemistry, Vol.8 No.9, pp.1540-1554
Abstract
Safe and efficient drug delivery systems have received great attention for cancer therapy due to their enhanced cancer-targeting efficiency and reduced undesirable side effects. Administration, safety, and effectiveness are the main issues for clinical trials in nanomedicine. Here, we develop a series of poly (lactic-co-glycolic acid)-co-polyspermine (PLGA-PSPE) copolymers via a simple polymerization reaction between activated carboxyl groups of poly(lactic-co-glycolic acid) (PLGA) and amine groups of polyspermine (PSPE) with different molecular weights (Mw) for safe and efficient lung cancer drug delivery. PLGA-PSPE can self-assemble into polymeric micelles with a low critical micelle concentration. PLGA-PSPE had very low cytotoxicity and hemolytic activity. In addition, PLGA-PSPE also had no potential systemic toxicity after aerosol delivery to mice. Dihydroergotamine tartrate (DHE), which could suppress lung cancer cell survival by induction of apoptosis and mitophagy in the latest study, was employed as the model hydrophobic drug and encapsulated into PLGA-PSPE polymeric micelles (PLGA-PSPE/DHE). PLGA-PSPE/DHE could be stored at 25 degrees C for 7 days, and showed a controlled and sustained drug release, and time and dose dependent cellular uptake. Moreover, PLGA-PSPE/DHE efficiently increased apoptosis and mitophagy in A549 lung cancer cells. Furthermore, PLGA-PSPE/DHE significantly reduced tumor sizes and numbers, and efficiently suppressed lung tumorigenesis in K-ras(LA1) lung cancer model mice after aerosol delivery. These results indicate that PLGA-PSPE polymeric micelles have a potential as an anticancer drug delivery carrier for lung cancer therapy.
ISSN
1759-9954
URI
https://hdl.handle.net/10371/172505
DOI
https://doi.org/10.1039/c7py00024c
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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