title: Preparation and in vitro evaluation of novel poly(anhydride-ester)-based amphiphilic copolymer curcumin-loaded micelles.
abstract: Novel poly(anhydride-ester)-b-poly(ethylene glycol) copolymers (PAE-b-PEGs) were synthesized by esterization of methyl poly(ethylene glycol) and poly(anhydride-ester), which were obtained by the melt polycondensation of alpha,omega-acetic anhydride-terminated poly(L-lactic acid), and characterized by 1H-NMR and gel permeation chromatography. The two poly(anhydride-ester)-b-poly(ethylene glycols) (denoted as PAE-b-PEG2k and PAE-b-PEG5k) thus obtained can self-assemble in water to form micelles with hydrodynamic diameters of 92.5 and 97.5 nm above their critical micelle concentrations of 3.78 and 2.36 microg/mL, respectively. The curcumin-loaded PAE-b-PEG2k and PAE-b-PEG5k micelles were prepared by the solid dispersion method, and they could encapsulate approximately 7% (w/w) curcumin. The diameters of the micelles were stable for 5 days. Curcumin is released faster from the micelles at pH 5.0 than at pH 7.4. Curcumin is released from the micelles at a fast rate during the initial 12 h, followed by a zero-order release during the subsequent 200 h, both at pH 5.0 and 7.4. The IC50 values of the curcumin-loaded PAE-b-PEG2k and PAE-b-PEG5k micelles against HeLa cells are 12.41 and 15.31 microg/mL, respectively, which is lower than that of free curcumin (25.90 microg/mL). The PAE-b-PEG2k micelles are taken up faster than the PAE-b-PEG5k micelles by HeLa cells. Curcumin-loaded micelles can induce G2/M phase cell cycle arrest and apoptosis of HeLa cells.
authors.forename: Li
authors.initials: L
authors.lastname: Lv
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shen
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Shengrong
authors.initials: S
authors.lastname: Guo
authors.forename: Shengtang
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057446:Hydrodynamics; D007700:Kinetics; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D049388:Polyanhydrides / Q000138:chemical synthesis* / Q000737:chemistry; D011091:Polyesters; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004952:Esters; D008823:Micelles; D049388:Polyanhydrides; D011091:Polyesters; D011108:Polymers; D013501:Surface-Active Agents; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D003474:Curcumin