Time-dependent biodistribution profiles and reaction of polyethylene glycol-coated iron oxide nanoclusters in the spleen after intravenous injection in the mice. 2022

Aziz Awaad, and Elham Farghal Elkady, and Safaa Mohammed El-Mahdy
Department of Zoology, Faculty of Science, Sohag University, Sohag 82524, Egypt. Electronic address: awaad@science.sohag.edu.eg.

Polyethylene glycol (PEG) is widely used polymer in the field of pharmaceutics, particularly in which related to drug delivery systems (DDS). Surface coating of the nanoparticles (NPs) with PEG (i.e. pegylation) adds novel characteristics that make their use in vivo more effective with lower cytotoxicity. The biodistribution profiles, reaction, and fate of PEG-coated NPs in vivo still unclear and need more detailed studies. Here in this study, we prepared PEG-coated iron oxide nanoclusters (PEG-coated IONCs) to investigate their biodistribution profiles and reactions in spleen after intravenous injection time-dependently. Using Prussian blue staining method as specific histochemical reaction for iron detection in the tissues, the PEG-coated IONCs were observed in a higher ratio in spleen red pulp after 1 day of injection but decreased time-dependently after 10 days and 20 days. Interestingly, PEG-coated IONCs moved from red pulp into the white pulp specially after 20 days of injection. After long time exposure (20 days), higher amount of PEG-coated IONCs was observed in the center of spleen white pulp follicle. Using histological staining, the reaction of PEG-coated IONCs with splenocytes or immune cells induced cellular abnormalities such as, nucleic acid damages, induction of megakaryocytes number, and sever vacuolation in the white pulp area specially after 20 days of injection. Histochemically, the localization of PEG-coated IONCs in the splenic parenchyma induced the level of the collagen fibers particularly after 1 day and 10 days of injection. Interestingly, cellular abnormalities in the splenic red pulp as well as collagen levels decreased after 20 days of injection due to the clearance of PEG-coated IONCs from this area. This data indicated that cytotoxicity produced by the reaction of PEG-coated IONCs in the spleen are reversible specially after 20 days of in the intravenous injection. Understanding the detailed mechanism of the fate and reaction of the coated nanomaterials after intravenous injection is important to design effective and safe DDS based NPs.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D005290 Ferric Compounds Inorganic or organic compounds containing trivalent iron. Compounds, Ferric
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013154 Spleen An encapsulated lymphatic organ through which venous blood filters.
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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