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Hepatic uptake of polystyrene microspheres in rats: effect of particle size on intrahepatic distribution
Abstract:
The in vivo disposition of polystyrene microsphere (MS) with the particle size of 50 nm (MS-50) or 500 nm (MS-500) was characterized after intravenous administration to rats. A rapid elimination from systemic circulation was observed for both MSs. Tissue distribution of MS-50 and MS-500 at 1 h after intravenous injection indicated that both MSs were exclusively distributed to liver and that small but significant amounts of MS-50 and MS-500 were also distributed to lung and spleen, respectively. To investigate the intrahepatic distribution of MS, liver was separated into liver parenchymal cells (PC) and non-parenchymal cells (NPC) at 1 or 6 h after intravenous administration. The contribution of each cell fraction was dependent on both the size of MS and the time after administration. Furthermore, by separating the NPC into endothelial cells and Kupffer cells using a centrifugal elutriation method, their contribution was also evaluated. For both MSs, Kupffer cells were recognized to be mostly responsible for the hepatic uptake, although a significant amount of MS-50 (about 28% of total uptake) was taken up by PC. On the other hand, there was little contribution of PC (about 5%) to the hepatic uptake of MS-500. The endothelial cells were contributed larger to the uptake of MS-500 (about 24%) than that of MS-50 (13%).
Insights
Polystyrene microspheres (MS) of 50 nm and 500 nm were rapidly eliminated from rat circulation. Kupffer cells primarily mediated hepatic uptake, with parenchymal cells playing a larger role for smaller microspheres.
Area of Science:
- Pharmacokinetics and Drug Delivery
- Nanotoxicology
- Hepatobiliary System
Background:
- Understanding nanoparticle disposition is crucial for developing targeted drug delivery systems.
- Polystyrene microspheres (MS) are common models for nanoparticle research.
- In vivo behavior, including tissue distribution and cellular uptake, dictates nanoparticle efficacy and safety.
Purpose of the Study:
- To characterize the in vivo disposition of 50 nm (MS-50) and 500 nm (MS-500) polystyrene microspheres in rats.
- To investigate the intrahepatic distribution of MS within different liver cell populations.
- To determine the influence of MS size and time post-administration on cellular uptake.
Main Methods:
- Intravenous administration of MS-50 and MS-500 to rats.
- Tissue distribution analysis at 1 hour post-injection.
- Separation of liver into parenchymal cells (PC) and non-parenchymal cells (NPC).
- Further isolation of NPC into endothelial cells and Kupffer cells using centrifugal elutriation.
Main Results:
- Both MS sizes showed rapid systemic elimination and were primarily distributed to the liver.
- Kupffer cells were the main site of hepatic uptake for both MS sizes.
- MS-50 showed significant uptake by PC (approx. 28%), while MS-500 had minimal PC uptake (approx. 5%).
- Endothelial cells contributed more to MS-500 uptake (approx. 24%) than MS-50 uptake (13%).
Conclusions:
- Hepatic uptake of polystyrene microspheres is size-dependent and mediated by Kupffer cells, with a notable contribution from parenchymal cells for smaller nanoparticles.
- The findings provide insights into the cellular mechanisms governing nanoparticle-liver interactions.
- This study aids in the design of nanoparticles for liver-targeted therapies and risk assessment.