title: Degradation behavior and biosafety studies of the mPEG-PLGA-PLL copolymer.
abstract: In a previous study, a novel biodegradable multiblock copolymer, monomethoxy(poly-ethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine) (PEAL), was developed as a new drug carrier material. It is imperative to study the biocompatibility and degradation behavior of PEAL to pave the way for clinical applications. Here, we systematically demonstrated that the PEAL copolymer has the appropriate hydrophilicity and biosafety. The degradation rate of the PEAL films was obtained by observing changes in mass, molecular weight (Mw), Mw distribution and degradation products. The degradation rate was observed to have a highly positive correlation with the pH of the medium and negative correlation with the ratio of lactic acid to glycolic acid (LA/GA). Cytotoxicity tests indicated that the degradation products of the copolymer were non-toxic to cells. In zebrafish embryos, the PEAL nanoparticles had no obvious impact on heart rate, production of reactive oxygen species, mortality, or cell apoptosis, and they were observed to have a long circulation time. Therefore, the PEAL copolymer has great potential for use as a drug carrier material.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20003, China. yrduan@shsci.com and The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Western Road, Wenzhou 325027, China.
authors.forename: Zelai
authors.initials: Z
authors.lastname: He
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20003, China. yrduan@shsci.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Dahua Hospital, Xuhui District, Shanghai 200237, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 20003, China. yrduan@shsci.com.
authors.forename: Yourong
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D003167:Complement Activation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D011107:Polylysine / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D015027:Zebrafish
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D017382:Reactive Oxygen Species; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011107:Polylysine; D011092:Polyethylene Glycols