title: Treatment of glioblastoma with poly(isohexyl cyanoacrylate) nanoparticles.
abstract: Glioblastomas belong to the most devastating cancer diseases. For this reason, polysorbate 80 (Tween 80)-coated poly(isohexyl cyanoacrylate) (PIHCA) (Monorex) nanoparticles loaded with doxorubicin were developed and tested for their use for the treatment of glioblastomas. The preparation of the nanoparticles resulted in spherical particles with high doxorubicin loading. The physico-chemical properties and the release of doxorubicin from the PIHCA-nanoparticles were analysed, and the influence on cell viability of the rat glioblastoma 101/8-cell line was investigated. In vitro, the empty nanoparticles did not show any toxicity, and the anti-cancer effects of the drug-loaded nanoparticles were increased in comparison to doxorubicin solution, represented by IC(50) values. The in vivo efficacy was then tested in intracranially glioblastoma 101/8-bearing rats. Rats were treated with 3 × 1.5mg/kg doxorubicin and were sacrificed 18 days after tumour transplantation. Histological and immunohistochemical analyses were carried out to assess the efficacy of the nanoparticles. Tumour size, proliferation activity, vessel density, necrotic areas, and expression of glial fibrillary acidic protein demonstrated that doxorubicin-loaded PIHCA-nanoparticles were much more efficient than the free drug. The results suggest that poly(isohexyl cyanoacrylate) nanoparticles hold great promise for the non-invasive therapy of human glioblastomas.
authors.affiliation: Institute of Pharmaceutical Technology, Goethe-University, Max-von-Laue-Straße 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wohlfart
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Khalansky
authors.forename: Christian
authors.initials: C
authors.lastname: Bernreuther
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003487:Cyanoacrylates / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D023041:Xenograft Model Antitumor Assays
chemical_list: D003487:Cyanoacrylates; D004337:Drug Carriers; C057532:polyisohexylcyanoacrylate; D004317:Doxorubicin