Hydrophilic Particles Exit While Hydrophobic Particles Persist Following In Vivo Biodegradation of Nanoparticle-Laden Polymeric Devices

Abstract

Longitudinally monitoring biomedical devices postimplantation can improve patient outcomes by allowing targeted intervention during healing. Most polymeric devices are not visible via biomedical imaging technologies. Incorporation of nanoparticle contrast agents into polymer matrices creates imageable devices, but understanding and controlling nanoparticle clearance from the implant site after polymer degradation is needed for clinical translation. To achieve homogeneous distribution throughout biomedical devices, nanoparticle surface chemistry, particularly hydrophobicity, is often manipulated to generate stable suspensions during manufacture. As nanoparticle surface chemistry is a key parameter determining blood circulation, the effects of nanoparticle hydrophilicity on tissue clearance of nanoparticles from implant sites following polymeric device degradation are investigated. Hydrophilic and hydrophobic radiopaque tantalum oxide (TaO_x) nanoparticles are incorporated at 10 wt% tantalum into gelatin phantoms. In vitro, the diffusion coefficient of released hydrophilic nanoparticles after phantom degradation is significantly greater than hydrophobic nanoparticles, 1.29 ± 0.26 × 10⁻⁵ and 0.40 ± 0.16 × 10⁻⁵cm²s⁻¹, respectively. After subcutaneous implantation in mouse and subsequent phantom degradation, hydrophilic nanoparticles clear skin and muscle tissue within 24 h, whereas hydrophobic nanoparticles remained at the implant site >14 days without change in radiopacity. This clearly demonstrates that nanoparticle surface chemistry must be balanced for initial device manufacturing and final excretion.