title: The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia.
abstract: We investigated the use of in situ implant formation that incorporates superparamagnetic iron oxide nanoparticles (SPIONs) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. We developed injectable formulations that form gels entrapping magnetic particles into a tumor. We used SPIONs embedded in silica microparticles to favor syringeability and incorporated the highest proportion possible to allow large heating capacities. Hydrogel, single-solvent organogel and cosolvent (low-toxicity hydrophilic solvent) organogel formulations were injected into human cancer tumors xenografted in mice. The thermoreversible hydrogels (poloxamer, chitosan), which accommodated 20% w/v of the magnetic microparticles, proved to be inadequate. Alginate hydrogels, however, incorporated 10% w/v of the magnetic microparticles, and the external gelation led to strong implants localizing to the tumor periphery, whereas internal gelation failed in situ. The organogel formulations, which consisted of precipitating polymers dissolved in single organic solvents, displayed various microstructures. A 8% poly(ethylene-vinyl alcohol) in DMSO containing 40% w/v of magnetic microparticles formed the most suitable implants in terms of tumor casting and heat delivery. Importantly, it is of great clinical interest to develop cosolvent formulations with up to 20% w/v of magnetic microparticles that show reduced toxicity and centered tumor implantation.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Pol-Edern
authors.initials: PE
authors.lastname: Le Renard
authors.forename: Olivier
authors.initials: O
authors.lastname: Jordan
authors.forename: Antonin
authors.initials: A
authors.lastname: Faes
authors.forename: Alke
authors.initials: A
authors.lastname: Petri-Fink
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hofmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Rüfenacht
authors.forename: Frederik
authors.initials: F
authors.lastname: Bosman
authors.forename: Franz
authors.initials: F
authors.lastname: Buchegger
authors.forename: Eric
authors.initials: E
authors.lastname: Doelker
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001943:Breast Neoplasms / Q000628:therapy; D048271:Chitosan / Q000737:chemistry; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D006979:Hyperthermia, Induced / Q000379:methods*; D008280:Magnetics; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D012997:Solvents; D020723:Glucuronic Acid; D048271:Chitosan