The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia

In situ forming implants are attractive for minimally invasive localized therapies such as aneurysm embolization. As for the superparamagnetic iron oxide nanoparticles (SPIONs), their deposition/injection in a target tissue area allows magnetically induced hyperthermia for local cancer treatment. In this view, the present work has been dedicated to the development of injectable formulations that can form in situ physical gels retaining magnetic particles into a tumor. Here, silica microparticles embed the SPIONs, favoring safety and syringeability of formulations. Incorporating the highest proportion of magnetic microparticles in this implant formulation would allow large heating capacities. Selected formulations were tested in vivo by injecting them in solid tumors of human cancer cell lines, subcutaneously engrafted in mice. Firstly, we investigated hydrogel formulations. Among thermoreversible formulations, the poloxamer solution could accommodate 20 % w/V magnetic microparticles but the formed implant was not satisfyingly strong and leaked out the tumor. Alginate formulations could incorporate 10 % w/V magnetic microparticles. Whereas internal gelation failed in vivo, formulations based on external gelation, injected through a dual syringe device led to strong implants localized in the peripheral tumor tissues. Secondly, we investigated organogel formulations based on organic solutions of precipitating polymers. Injecting in vivo a 8 % solution of poly(ethylene-vinyl alcohol) in DMSO containing 40 % w/V magnetic microparticles had limited toxicity and formed elastic implants well distributed in the tumor. Co-solvent formulations (containing some proportion of low-toxicity hydrophilic solvent), with up to 20 % w/V magnetic microparticles, allowed suitable tumor core implantation. This might be interesting for upscaling to a clinical application.