title: Brain tumor targeting of magnetic nanoparticles for potential drug delivery: effect of administration route and magnetic field topography.
abstract: Our previous studies demonstrated feasibility of magnetically-mediated retention of iron oxide nanoparticles in brain tumors after intravascular administration. The purpose of this study was to elucidate strategies for further improvement of this promising approach. In particular, we explored administration of the nanoparticles via a non-occluded carotid artery as a way to increase the passive exposure of tumor vasculature to nanoparticles for subsequent magnetic entrapment. However, aggregation of nanoparticles in the afferent vasculature interfered with tumor targeting. The magnetic setup employed in our experiments was found to generate a relatively uniform magnetic flux density over a broad range, exposing the region of the afferent vasculature to high magnetic force. To overcome this problem, the magnetic setup was modified with a 9-mm diameter cylindrical NdFeB magnet to exhibit steeper magnetic field topography. Six-fold reduction of the magnetic force at the injection site, achieved with this modification, alleviated the aggregation problem under the conditions of intact carotid blood flow. Using this setup, carotid administration was found to present 1.8-fold increase in nanoparticle accumulation in glioma compared to the intravenous route at 350mT. This increase was found to be in reasonable agreement with the theoretically estimated 1.9-fold advantage of carotid administration, R(d). The developed approach is expected to present an even greater advantage when applied to drug-loaded nanoparticles exhibiting higher values of R(d).
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Chertok
authors.forename: Allan E
authors.initials: AE
authors.lastname: David
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D000818:Animals; D001931:Brain Mapping; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D002339:Carotid Arteries; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004574:Electromagnetic Fields; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009368:Neoplasm Transplantation; D010316:Particle Size; D051381:Rats; D011916:Rats, Inbred F344; D013499:Surface Properties; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; C000499:ferric oxide