title: In vitro evaluation of the genotoxicity of a family of novel MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer and PLGA nanoparticles.
abstract: Despite the booming development of nanoparticle materials for pharmaceutical applications, studies on their genotoxicity are few. In our previous efforts to develop an intravenous nanoparticle material, a family of novel monomethoxy(polyethylene glycol)-poly(D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) polymers was synthesized. The cytotoxicity and genotoxicity of nine kinds of selected blank PELGE and PLGA (poly(D,L-lactic and glycolic acid)) nanoparticles were evaluated using methyl thiazolyl tetrazolium (MTT), micronucleus (MN) and sister chromatid exchange (SCE) assays with or without the addition of a metabolic activation system (S9 mix), using Chinese hamster ovary (CHO) cells. The cytotoxicity of nanoparticles exhibited a dose-dependent response, with a concentration of 5 mg ml(-1) being the turning point. The frequencies of MN observed in samples treated with various nanoparticles were not statistically different from those seen in the negative controls in the presence or absence of the S9 mix. Also, no cell cycle delay was observed. The numbers of SCE per cell observed in samples treated with five kinds of PELGE nanoparticles were significantly greater than those found in the negative controls with or without the S9 mix. The discrepancies found in the two assays suggest that the five kinds of nanoparticles may produce only a weakly clastogenic response.
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: He
authors.forename: Likai
authors.initials: L
authors.lastname: Yang
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D015162:Micronucleus Tests; D053758:Nanoparticles / Q000633:toxicity*; D036103:Nanotechnology; D011091:Polyesters / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013778:Tetrazolium Salts
chemical_list: D011091:Polyesters; D013778:Tetrazolium Salts; C525451:methylpoly(ethylene glycol)-oly(lactic acid-co-glycolic acid)-poly(ethylene glycol); D011092:Polyethylene Glycols