[Preparation of doxorubicin encapsulated in amphiphilic polysaccharide nanoparticles and anti-hepatocarcinoma effect thereof].
OBJECTIVE
To investigate the sustained release rule of doxorubicin/polylactide-grafted dextran copolymer (DOX/DEX-PLA) nanoparticles and the effect thereof in killing hepatocarcinoma cells.


METHODS
DOX/DEX-PLA nanoparticles were prepared by method of emulsification & evaporation of organic solvent. Its morphology was observed by transmission electron microscopy and the encapsulating efficiency of DOX was determined by ultraviolet spectrophotometry. DOX/DEX-PLA was put in a dialysis bag to observe the releasing characteristics of DOX from DOX/DEX-PLA nanoparticles in vitro. Human liver carcinoma cells of the line HepG2 were cultured with DOX/DEX-PLA of different concentrations or the original drug of DOX as control group for 24, 36, or 48 h. MTT method was used to observe the cancer inhibition rate. BALB/c nude mice underwent subcutaneous injection of HepG2 cells at the right scapula and then randomly divided into 4 groups to undergo intravenous injection of DOX/DEX-PLA (excremental group), original drug of DOX (naked drug group), DEX-PLA (nanovector group), or normal saline (blank control group) once every 5 days for 3 times. Twenty-one days later the mice were killed with the tumors taken out to measure the weight to analyze the inhibitory effect against hepatocarcinoma cells.


RESULTS
The DOX/DEX-PLA nanoparticles were of round or elliptical shape with the diameter of about 83 nm, and the DOX entrapment efficiency was about 67.1%. The releasing test in vitro manifested a sustained release of over 50% of DOX encapsulated in DOX/DEX-PLA nanoparticles for about 7 days. Both the DOX/DEX-PLA nanoparticles and naked drug DOX inhibited the growth of HepG2 cells with a similar inhibitory rate (51.3% vs 50.7%, P > 0.05), meanwhile the DEX-PLA nanovector failed to inhibit the HepG2 cells. In-vivo experiment showed an inhibitory rate of DOX/DEX-PLA nanoparticles on hepatocellular carcinoma xenografts of 68.56%, significantly higher than that of the naked drug DOX (48.17%).


CONCLUSIONS
DOX/DEX-PLA nanoparticles can effectively inhibit the growth of hepatocarcinoma cells.
Huang
Ying-Feng
YF
Department of Surgery, First Municipal People's Hospital of Guangzhou, Guangzhou 510018, China.
Gu
Wei-Li
WL
Li
Zhi-Hua
ZH
Chen
Ru-Fu
RF
Zhou
Jia-Jia
JJ
Zhou
Quan-Bo
QB
Guo
Ning
N
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*
D004337:Drug Carriers; D004317:Doxorubicin