Influence of surfactants, polymer and doxorubicin loading on the anti-tumour effect of poly(butyl cyanoacrylate) nanoparticles in a rat glioma model.
Poly(n-butyl cyanoacrylate) nanoparticles coated with polysorbate-80 can enable the transport of bound drugs across the blood-brain barrier (BBB) after i.v. injection. In the present study the influence of different formulation parameters on the anti-tumoural effects of doxorubicin nanoparticles against glioblastoma 101/8 was investigated. The manufacturing parameters of poly(alkyl cyanoacrylate) doxorubicin-loaded nanoparticles were optimized concerning drug loading. The nanoparticles were coated with different surfactants and injected intravenously on days 2, 5 and 8 after intra-cranial implantation of glioblastoma 101/8 to rats. The survival times of all doxorubicin containing preparations, including a doxorubicin solution, increased the survival times significantly compared to untreated tumour-bearing rats. The most pronounced increase in survival was obtained with the poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80 and 35% of these animals survived for over 180 days (termination of the experiments). The other nanoparticle preparations yielded lower survival times. Poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80-coated proved to be very efficient against glioblastoma 101/8. The data suggest that the interaction of nanoparticles with the blood after injection as well as the enhanced permeability and retention effect (EPR effect) contributed differently to the anti-tumoural efficacy depending on nanoparticle formulation and surface properties.
Ambruosi
Alessandra
A
Institute of Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
Gelperina
Svetlana
S
Khalansky
Alexander
A
Tanski
Sandra
S
Theisen
Alf
A
Kreuter
Jörg
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D004339:Drug Compounding / Q000379:methods; D004659:Enbucrilate / Q000737:chemistry*; D005909:Glioblastoma / Q000188:drug therapy*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D013501:Surface-Active Agents; D004317:Doxorubicin; D004659:Enbucrilate