Anti-lung cancer effect of paclitaxel solid lipid nanoparticles delivery system with curcumin as co-loading partner in vitro and in vivo

被引:43
作者
Pi, Chao [1 ,2 ,3 ]
Zhao, Wenmei [1 ,2 ,3 ]
Zeng, Mingtang [1 ,2 ,3 ]
Yuan, Jiyuan [2 ,4 ]
Shen, Hongping [2 ,4 ]
Li, Ke [1 ,2 ,3 ]
Su, Zhilian [1 ,2 ,3 ]
Liu, Zerong [5 ,6 ]
Wen, Jie [1 ,2 ,3 ]
Song, Xinjie [7 ,8 ]
Lee, Robert J. [9 ]
Wei, Yumeng [1 ,3 ]
Zhao, Ling [2 ,3 ]
机构
[1] Southwest Med Univ, Key Lab Med Electrophysiol, Sch Pharm, Minist Educ, 1,Sect 1,Xianglin Rd, Luzhou 646000, Sichuan, Peoples R China
[2] Southwest Med Univ, Luzhou Key Lab Tradit Chinese Med Chron Dis Joint, Affiliated Tradit Chinese Med Hosp, Luzhou, Sichuan, Peoples R China
[3] Southwest Med Univ, Cent Nervous Syst Drug Key Lab Sichuan Prov, Luzhou, Sichuan, Peoples R China
[4] Southwest Med Univ, Clin Trial Ctr, Affiliated Tradit Chinese Med Hosp, Luzhou, Sichuan, Peoples R China
[5] Sichuan Credit Pharmaceut CO Ltd, Cent Nervous Syst Drug Key Lab Sichuan Prov, Luzhou, Sichuan, Peoples R China
[6] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing, Shapingba, Peoples R China
[7] Zhejiang Univ Sci & Technol, Sch Biol & Chem Engn, Hangzhou, Zhejiang, Peoples R China
[8] Yeungnam Univ, Dept Food Sci & Technol, Gyongsan, South Korea
[9] Ohio State Univ, Coll Pharm, Div Pharmaceut & Pharmacol, 500 W 12Th Ave, Columbus, OH 43210 USA
关键词
Paclitaxel; curcumin; solid lipid nanoparticles; combination therapy; DRUG-DELIVERY; LUNG-CANCER; ANTITUMOR; CHEMOTHERAPY; DOXORUBICIN; MECHANISM; EFFICACY; MICELLES; RELEASE; PATHWAY;
D O I
10.1080/10717544.2022.2086938
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The main aim of this study was to improve the therapeutic potential of a paclitaxel (PTX) and curcumin (CU) combination regimen using solid lipid nanoparticles (SLNs). PTX and CU were successfully co-encapsulated at a predetermined ratio in SLNs (PC-SLNs) with high encapsulation efficiency (CU: 97.6%, PTX: 95.8%), appropriate particle size (121.8 +/- 1.69 nm), small PDI (0.267 +/- 0.023), and negative zeta potential (-30.4 +/- 1.25 mV). Compared with PTX or the combination of CU and PTX (CU + PTX), PC-SLNs can greatly reduce the dose of PTX while still achieving the same therapeutic effect on four cancer cell lines, among which the inhibitory effect on A549 lung cancer cells was the strongest. PC-SLNs improved the area under the curve (CU: 1.40-fold; PTX: 2.88-fold), prolonged the residence time (CU: 6.94-fold; PTX: 2.51-fold), and increased the half-life (CU: 5.62-fold; PTX: 6.46-fold), achieving long circulation. PC-SLNs were used to treat lung cancer in a nude mouse xenograft tumor model and the tumor suppression rate reached 78.42%, while those of PTX and (CU + PTX) were 40.53% and 51.56%, respectively. As PC-SLNs can prevent P-glycoprotein efflux, reverse MDR and downregulate the NF-kappa B pathway. PC-SLNs are a potential antineoplastic agent that is more effective and less toxic in treating lung cancer.
引用
收藏
页码:1878 / 1891
页数:14
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