College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
Institute of Medical Chemistry, Medical University of Vienna, 1090 Vienna, Austria.
Oncol Rep. 2018 Aug;40(2):1055-1063. doi: 10.3892/or.2018.6492. Epub 2018 Jun 14.
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.
在本研究中，开发了一种载药脂质-聚合物杂化纳米载体系统来包裹补骨脂素（PSO），这是一种多药耐药逆转剂和传统中药。重点研究了影响物理化学特性的参数，然后考察了载药脂质-聚合物杂化纳米粒（LPNs）的释放特性、稳定性、细胞毒性和耐药逆转作用。结果发现，各种制剂参数影响 NP 的粒径、载药量（DL）和释放特性。亲水性 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-羧基（聚乙二醇）2000 增加了 NP 的 ζ 电位，从而提高了 NP 的稳定性，但也增大了 NP 的粒径。PSO 的用量影响其 DL 和包封效率，但对药物释放动力学没有影响。接下来，研究了 LPNs 在不同介质中的稳定性及其储存特性。最后，在 K562 和 HepG2 细胞系中研究了 LPNs 的细胞毒性和多药耐药逆转作用。半数最大抑制浓度值的分析表明，与 DOX 单剂量治疗相比，DOX 和 PSO 负载 LPNs（P-LPNs）联合治疗在耐药 K562 和 HepG2 细胞中的疗效分别提高了 14 倍和 23 倍，与 DOX 和 PSO 的单剂量组合治疗相比，分别提高了 2.2 倍和 2.1 倍。这些数据表明，与溶液中的联合治疗相比，LPNs 具有更好的性能。
