title: Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers.
abstract: In this work, racemic hybrid polypeptides poly(ethylene glycol) (PEG)-b-poly(racemic-leucine) (PRL) copolymers with different leucine residues have been synthesized and characterized. Using docetaxel as a model molecule, the high drug-loaded spherical micelles based on PEG-PRL were prepared successfully using dialysis, with a tunable particle size from 170 nm to 250 nm obtained by changing the length of the hydrophobic blocks. Facilitated drug-loading behavior (higher drug-loading ability and easier drug-loading process) of PEG-PRL compared with their corresponding levo forms (PEG-b-poly[levo leucine]) was observed and clarified for the first time. With this facilitation, the highest drug-loading content and efficiency of PEG-PRL micelles can achieve 11.2% ± 0.4% and 67.2% ± 2.4%, respectively. All drug-loaded PEG-PRL micelles exhibit a similar release behavior with a sustained release up to 72 hours. The PEG-PRL was shown to be nontoxic against MCF-7 and human umbilical vein endothelial cells up to a concentration of 100 μg/mL, displaying a good biocompatibility. Also, the docetaxel-loaded PEG-PRL micelles were more toxic than the free drug against MCF-7 human breast cancer cells - both dose and time dependent. Therefore, these high docetaxel-loaded micelles based on racemic hybrid polypeptides appear to be a novel promising nanomedicine for anticancer therapy.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No 103, Wenhua Road, Shenyang, People’s Republic of China.
authors.forename: Peng Fei
authors.initials: PF
authors.lastname: Gu
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Bo Wen
authors.initials: BW
authors.lastname: Sui
authors.forename: Jing Xin
authors.initials: JX
authors.lastname: Gou
authors.forename: Ling Kuo
authors.initials: LK
authors.lastname: Meng
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Xiu Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Qi
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hai Bing
authors.initials: HB
authors.lastname: He
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008823:Micelles; D008968:Molecular Conformation; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D013237:Stereoisomerism; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; D043823:Taxoids; D000077143:Docetaxel; C027819:polyleucine; D011092:Polyethylene Glycols