Particle-size-dependent biological distribution of gold nanoparticles after interstitial injection

The physical properties of nanomaterials, such as particle size, affect their biological activity and distribution in the organs. Intervaginal space injection (ISI) is emerging as a promising alternative administration route that can result in organ-specific accumulation because drugs are transported through the interstitial fluid rather than the blood. However, the mechanism by which the physical properties of nanoparticles affect biological distribution is unclear. Therefore, in this study, we investigated the effect of particle size (48 and 88 nm) on organ-specific accumulation after ISI in the carpal tunnel space of mice. The distribution of nanoparticles with respect to their size, as well as their accumulation in the blood, heart, liver, spleen, lung, kidney, intestine, and brain, was monitored after different intervals over a period of three days using single particle inductively coupled plasma mass spectrometry. Using traditional tail vein injection (IV) administration as a control, we found that ISI results in considerable differences in the accumulation of nanoparticles in different organs, whereas IV administration did not. Furthermore, the smaller nanoparticles were more favorably accumulated in the organs than the larger nanoparticles, suggesting that the transport of large particles in the interstitial spaces was hindered. These results shed light on the mechanism of interstitial transport in vivo and will help to improve the utilization of nanoparticle-based therapies, as well as the ISI technique. There are significant differences in the biological distribution of AuNPs 48 and AuNPs 88 after interstitial injection, suggesting that we should consider the size effect of drugs when designing nanodrugs through interstitial injection.