title: The biocompatibility evaluation of mPEG-PLGA-PLL copolymer and different LA/GA ratio effects for biocompatibility.
abstract: Biomaterial poly(lactic-co-glycolic acid) (PLGA), a FDA-approved material for clinical application, showed broad prospects in the past, but gradually can no longer meet present clinical developments and requirements, which we synthesized monomethoxy(polyethylene glycol)-poly(D,L-lactic-co-glycolic acid)-poly(L-lysine) (mPEG-PLGA-PLL) (PEAL) and have had some relevant reports. But studies on biocompatibility and the impacts of LA and GA ratio (LA/GA=60/40, 70/30, and 80/20) in main material have not yet been reported. Hemolysis experiment indicates that the hemolysis rate of PEAL extraction medium is less than 5%. Whole blood clotting time (CT), plasma recalcification time, activated partial thromboplastin time, prothrombin time evaluations, and dynamic CT assay show that the anticoagulant time of PEAL copolymer for blood is longer than that under negative and positive control. Protein adsorption assay indicates that PEAL films adsorb less protein than PLGA films (p<0.01); but comparing with expanded polytetrafluoroethylene, the aforementioned difference is not significant (p>0.05). Complement activation test shows that PEAL surface does not induce complement activation. CCK8 measurement shows that the relative growth rates of Huh7, L02, and L929 cells co-incubated with PEAL nanoparticles (NPs) are more than 90%. PEAL NPs co-incubated with 5% foetal bovine serum or 2% bovine serum albumin, through dynamic light scattering assay, remain stable. Different concentrations of PEAL NPs co-incubated with zebrafish embryos at 6-72 h post fertilization show that comparing with negative control, 10, 100, or 500 μM of NPs for embryos development has no significant effects (p>0.05), only 1000 or 2000 μM of NPs has some effects (p<0.05). It is concluded that the PEAL copolymer, with excellent biocompatibility, proves to be a high-safety dose as drug carrier and implant candidate in vivo.
authors.affiliation: a State Key Laboratory of Oncogenes and Related Genes , Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032 , China.
authors.forename: Zelai
authors.initials: Z
authors.lastname: He
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhu
authors.forename: Malin
authors.initials: M
authors.lastname: Gu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yourong
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000327:Adsorption; D000818:Animals; D001780:Blood Coagulation Tests; D002460:Cell Line; D003165:Complement System Proteins / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006016:Glycolates / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D015027:Zebrafish / Q000196:embryology
chemical_list: D006016:Glycolates; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); C031149:glycolic acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D003165:Complement System Proteins
keywords: biocompatibility; copolymer; cytotoxicity; nanoparticles; zebrafish embryos