title: Toxicity and in vivo biological effect of the nanoparticular self-supported hydrogel of a thermosensitive copolymer for non-invasive drug delivery.
abstract: Injectable thermosensitive hydrogels provide local non-invasive platforms for sustained drug release,tissue engineering and cellular immunity. As a long-term implant, the toxicity and in vivo biological effect should be concerned.Previously we developed a novel type of injectable nanoparticular self-supported hydrogel (PECT NPs(Gel))of PEG and pendent cycle ethers modified poly(ε-caprolactone) triblock copolymer (PECT), which could sustainedly release PECT or drug-loaded PECT nanoparticles with the hydrogel disassembly and provided efficient antitumor activity and significant decrease of side effects. Herein, the aim of this work was to reveal the toxicity and in vivo biological effect of PECT nanoparticles and PECT NPs(Gel). In vitro cytotoxicity indicated no cell cytotoxicity was observed when the concentration of PECT nanoparticle was up to 500 µg/mL, and also nomutagenic effect and no genotoxicity were observed.In vivo intravenous injection of PECT nanoparticles demonstrated that the LD50 was approximate high to 2.564 g/kg, and compared with the control mice, the mice treated with daily administration of PECT nanoparticles showed no difference in the physical or behavioral alterations, body weight changes, biochemical and hematological parameters as well as organ coefficients. The in vivo chronic effect of PECT NPs(Gel)confirmed no toxic lesions to animals in a whole period of three months even the dosage was high to 20 g/kg. These findings indicated PECT nanoparticles and PECT NPs(Gel) were of well biocompatibility and did not provoke any side effect to body, which represented a new class of injectable and non-invasive systemic or site-specific delivery carrier.
authors.affiliation: Department of polymer science and engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Liandong
authors.initials: L
authors.lastname: Deng
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Huang
authors.forename: Shuxin
authors.initials: S
authors.lastname: Xu
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Lv
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Renjie
authors.initials: R
authors.lastname: Hu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000379:methods; D020100:Hydrogels / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry
chemical_list: D020100:Hydrogels
keywords: biological effect; injectable hydrogel; nanoparticles; thermosensitiveamphiphilic copolymer; toxicity