title: Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats.
abstract: Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, Sichuan, People's Republic of China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Liao
authors.forename: Mengtian
authors.initials: M
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: Xuanmiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhaolu
authors.initials: Z
authors.lastname: Xie
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage / Q000138:chemical synthesis / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D014022:Tissue Survival / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D011091:Polyesters; C525451:methylpoly(ethylene glycol)-oly(lactic acid-co-glycolic acid)-poly(ethylene glycol); D011092:Polyethylene Glycols