Polymeric micelles with citraconic amide as pH-sensitive bond in backbone for anticancer drug delivery.
A novel pH-sensitive polymeric micelle was reported. Methoxy poly(ethylene glycol)-b-poly(ϵ-caprolactone) copolymer with citraconic amide as pH-sensitive bond was synthesized (mPEG-pH-PCL). The copolymers self-assembled into micelles to encapsulate anticancer drug doxorubicin (DOX). The morphology, size and size distribution, drug release profile and in vitro anticancer activity of the DOX loaded mPEG-pH-PCL micelles were studied. The results showed that the mean size of the micelles was around 120 nm, the drug loading content and encapsulation efficiency of the mPEG-pH-PCL micelles were 6.8% and 54.3%, respectively. The mean diameter and size distribution of the mPEG-pH-PCL micelles increased significantly when soaking in medium with pH 5.5. The drug release of micelles in pH 5.5 was much faster than that in pH 7.4. The confocal laser microscopy and flow cytometry measurements indicated that the weak acidity of endosomes broke the citraconic amide bonds in the copolymer backbones and triggered the fast release of DOX. The in vitro IC50 of the drug loaded mPEG-pH-PCL micelles was lower than that of drug loaded polymeric micelles without pH-sensitivity to both HepG2 and 4T1 cancer cells.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 China.
Jun
J
Cao
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 China.
Ting
T
Su
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 China.
Longgui
L
Zhang
College of Medical and Nursing,Chengdu University, Chengdu 610106 China.
Rong
R
Liu
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 China. Electronic address: wgskyer@163.com.
Gang
G
Wang
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 China.
Bin
B
He
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064 China.
Zhongwei
Z
Gu
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005650:Fumarates / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008298:Maleates / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D018613:Microscopy, Confocal; D015394:Molecular Structure; D008970:Molecular Weight; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013499:Surface Properties
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005650:Fumarates; D008298:Maleates; D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); C073341:citraconic acid; D011092:Polyethylene Glycols; D004317:Doxorubicin
Citraconic anhydride; Doxorubicin; Drug delivery; Polymeric micelle; pH-sensitive