A Promising Emodin-Loaded Poly (Lactic-Co-Glycolic Acid)-d-α-Tocopheryl Polyethylene Glycol 1000 Succinate Nanoparticles for Liver Cancer Therapy.
OBJECTIVE
Emodin (EMO) has multi-targets and multi-way antitumor effect, which was limited by the instability and poor solubility of EMO. The aim of this study was to formulate EMO-loaded poly (lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (EPTN) to increase the liver targeting of EMO for cancer therapy.


METHODS
EMO/coumarin-6-loaded PLGA-TPGS nanoparticles (ECPTN) and EMO-loaded PLGA nanoparticles (EPN) were also prepared as comparison. The cellular uptake of ECPTN by HepG2 and HCa-F cells was investigated using Confocal laser scanning microscopy. The apoptosis of HepG2 cells handled with EPTN was assayed by flow cytometry. The liver targeting property of ECPTN in mice was evaluated using the drug concentration determined by RP-HPLC and the freezing slices were investigated via fluorescence inversion microscopy. The blood samples were obtained from vein intubation to illustrate the pharmacokinetics process of EPTN. The tumor-bearing mice model was established to elucidate the in vivo therapeutic effect of EPTN.


RESULTS
The results demonstrated that ECPTN could be internalized by HepG2 and HCa-F cells respectively. The ratio of apoptosis cells was increased after dealing with EPTN. The detection indexes of drug concentration and fluorescence inversion microscopy images indicated ECPTN had an excellent effect on liver targeting property than EMO solutions (EMS). The pharmacokinetics process of EPTN showed obvious sustained-release effect than EMS. Compared with EPN, the in vivo antitumor activity of EPTN against tumor cells were better.


CONCLUSIONS
In conclusion, EPTN could be used in the treatment of liver cancer acted as a kind of promising intravenous dosage forms.
College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
Hongyan
H
Liu
College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
Meng
M
Gao
College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.
Hong
H
Xu
College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
Xin
X
Guan
College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
Li
L
Lv
College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
Sa
S
Deng
College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.
Chenghong
C
Zhang
College of Pharmacy, Dalian Medical University, Dalian, 116044, China. tiany2004@126.com.
Yan
Y
Tian
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004642:Emodin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D024502:alpha-Tocopherol / Q000737:chemistry*
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D024502:alpha-Tocopherol; D004642:Emodin
Emodin; PLGA-TPGS; liver cancer; liver targeting property; nanoparticles