title: PEGylated poly(trimethylene carbonate) nanoparticles loaded with paclitaxel for the treatment of advanced glioma: in vitro and in vivo evaluation.
abstract: The aim of this study was to investigate the antitumor effect of paclitaxel (PTX)-loaded poly(ethylene glycol)-poly(trimethylene carbonate) (MPEG-PTMC) nanoparticles (NP) against gioblastoma multiforme (GMB). PTX-loaded NP (NP/PTX) were prepared with synthesized MPEG-PTMC by the emulsion/solvent evaporation technique. In vitro physiochemical characterization of those NP/PTX showed satisfactory encapsulation efficiency and loading capacity and size distribution. Cytotoxicity assay revealed that encapsulation in nanoparticles did not compromise the antitumor efficacy of PTX against U87MG cells. Pharmacokinetic study in rats demonstrated that the polymer micellar nanoparticles significantly enhanced the bioavailability of PTX than Taxol. In intracranial xenograft tumor-bearing mice, the accumulation of nanoparticles in tumor tissues increased distinctly after 12 h post i.v. More importantly, in vivo anti-tumor effect exhibited the median survival time of NP/PTX treated mice (27 days) was significantly longer than those of mice treated with Taxol (24 days), physiological saline (21 days) and blank MPEG-PTMC NP (21 days). Therefore, our results suggested that PTX-loaded MPEG-PTMC nanoparticles significantly enhanced the anti-glioblastoma activity of PTX and may be a potential vehicle in the treatment of high-grade glioma.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Rd., Shanghai 201203, People's Republic of China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Jiang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.forename: Xianyi
authors.initials: X
authors.lastname: Sha
authors.forename: Jijin
authors.initials: J
authors.lastname: Gu
authors.forename: Ye
authors.initials: Y
authors.lastname: Jiang
authors.forename: Kitki
authors.initials: K
authors.lastname: Law
authors.forename: Yanzuo
authors.initials: Y
authors.lastname: Chen
authors.forename: Liangcen
authors.initials: L
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004146:Dioxanes / Q000737:chemistry / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004146:Dioxanes; D004337:Drug Carriers; C515872:monomethoxy poly(ethylene glycol)-block-poly(trimethylene carbonate); D011092:Polyethylene Glycols; D017239:Paclitaxel