Fabrication of psoralen-loaded lipid-polymer hybrid nanoparticles and their reversal effect on drug resistance of cancer cells

Yuan,Yueling; Chiba,Peter; Cai,Tiange; Callaghan,Richard; Bai,Li; Cole,Susan  P.C.; Cai,Yu

doi:10.3892/or.2018.6492

Fabrication of psoralen-loaded lipid-polymer hybrid nanoparticles and their reversal effect on drug resistance of cancer cells

Authors:
- Yueling Yuan
- Peter Chiba
- Tiange Cai
- Richard Callaghan
- Li Bai
- Susan P.C. Cole
- Yu Cai
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Affiliations: College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Institute of Medical Chemistry, Medical University of Vienna, 1090 Vienna, Austria, College of Life Science, Liaoning University, Shenyang, Liaoning 110000, P.R. China, Research School of Biology, Australian National University, Canberra 2601, Australia, Guangzhou Jiayuan Pharmaceutical Technology Co., Ltd., Guangzhou, Guangdong 510663, P.R. China, Division of Cancer Biology and Genetics, Queen's University, Kingston, ON K7L 3N6, Canada
Published online on: June 14, 2018 https://doi.org/10.3892/or.2018.6492
Pages: 1055-1063

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Abstract

In the present study, a lipid-polymer hybrid drug carrier system was developed to encapsulate psoralen (PSO), a multidrug resistance reversal agent and traditional Chinese medicine. Emphasis was focused the parameters that influence physicochemical characteristics, and then the drug release profile, stability, cytotoxicity and drug resistance reversal effect of the lipid-polymer hybrid nanoparticles (LPNs) were investigated. It was found that various formulation parameters affected NP size, drug loading (DL) and release characteristics. Hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-carboxy(polyethylene glycol)2000 increased the ζ potential and thus the stability of the NPs, but also enlarged their diameter. The amount of PSO influenced their DL and encapsulation efficiency, but did not show any effect on drug release kinetics. Next, the stability of the LPNs in different media and their storage characteristics were assessed. Finally, the cytotoxicity and multidrug resistance reversal effect was studied in the K562 and HepG2 cell lines. The analysis of half maximal inhibitory concentration values demonstrated that combination therapy with doxorubicin (DOX) and PSO-loaded LPNs (P-LPNs) was 14- and 23-fold more effective than a single-dose DOX treatment in resistant K562 and HepG2 cells, respectively, and 2.2- and 2.1-fold more effective than a single-dose combination regimen of DOX and PSO in solution, respectively. These data indicate that the LPNs have superior properties compared with a combination therapy in solution.

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