The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia.
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.
Le Renard
Pol-Edern
PE
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
Jordan
Olivier
O
Faes
Antonin
A
Petri-Fink
Alke
A
Hofmann
Heinrich
H
Rüfenacht
Daniel
D
Bosman
Frederik
F
Buchegger
Franz
F
Doelker
Eric
E
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
D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D012997:Solvents; D020723:Glucuronic Acid; D048271:Chitosan