Advertisement

Pharmaceutical Research

, 36:46 | Cite as

Pharmacokinetics, Tissue Distribution and Excretion of Ag2S Quantum Dots in Mice and Rats: the Effects of Injection Dose, Particle Size and Surface Charge

  • Jaber Javidi
  • Azadeh Haeri
  • Fatemeh Nowroozi
  • Simin DadashzadehEmail author
Research Paper
  • 34 Downloads

Abstract

Purpose

We systematically investigated the effects of injection dose, particle size and surface charge on the pharmacokinetics, tissue distribution and excretion of Ag2S quantum dots (Qds) in rats and mice.

Methods

Three different doses of Ag2S Qds with similar size and composition were administrated to rats and mice. The effect of size and surface charge was investigated with the injection of three sizes (5, 15 and 25 nm) of Ag2S Qds possessing similar surface charge, as well as 5 nm Qds with a positive surface charge.

Results

Results indicated that pharmacokinetics and biodistribution of Ag2S Qds were strongly dose, particle size and surface charge dependent. By increasing the dose from 0.5 to 4.0 mg/kg, mean residence time (MRT) and apparent volume of distribution at steady state (Vss) were increased while clearance (CL) was decreased. Qds with a negative surface charge had significantly larger MRT and Vss values than positively charged particles, but their CL was about 50% lower than that of positively charged ones. By increasing Qds size from 5 to 25 nm, CL was increased while MRT and AUC were decreased.

Conclusions

This study establishes comprehensive principles for the rational design and tailoring of Ag2S Qds for biomedical applications.

Graphical Abstract

The effects of injection dose, particle size and surface charge on pharmacokinetics and tissue distribution of Ag2S Qds after intravenous injection into rats and mice were investigated.

Keywords

Ag2excretion pharmacokinetics quantum dots tissue distribution 

Notes

Acknowledgments and Disclosures

This study was supported by a grant from Shahid Beheshti University of Medical Sciences. The authors report no conflicts of interest.

References

  1. 1.
    Carey GH, Abdelhady AL, Ning Z, Thon SM, Bakr OM, Sargent EH. Colloidal Quantum Dot Solar Cells. Chem Rev. 2015;115(23):12732–63.CrossRefGoogle Scholar
  2. 2.
    Frecker T, Bailey D, Arzeta-Ferrer X, McBride J, Rosenthal SJ. Review—quantum dots and their application in lighting, displays, and biology. ECS Journal of Solid State Science and Technology. 2016;5(1):R3019–31.CrossRefGoogle Scholar
  3. 3.
    Chen X, Liu Y, Ma Q. Recent advances in quantum dot-based electrochemiluminescence sensors. J Mater Chem C. 2018;6(5):942–59.CrossRefGoogle Scholar
  4. 4.
    Abbasi E, Kafshdooz T, Bakhtiary M, Nikzamir N, Nikzamir N, Nikzamir M, et al. Biomedical and biological applications of quantum dots. Artificial Cells, Nanomedicine and Biotechnology. 2016;44(3):885–91.Google Scholar
  5. 5.
    Tang H, Yang S-T, Ke D-M, Yang Y-F, Liu J-H, Chen X, et al. Biological behaviors and chemical fates of Ag2Se quantum dots in vivo: the effect of surface chemistry. Toxicology Research. 2017;6(5):693–704.CrossRefGoogle Scholar
  6. 6.
    Liang GX, Gu MM, Zhang JR, Zhu JJ. Preparation and bioapplication of high-quality, water-soluble, biocompatible, and near-infrared-emitting CdSeTe alloyed quantum dots. Nanotechnology. 2009;20(41):415103.CrossRefGoogle Scholar
  7. 7.
    Chen H, Cui S, Tu Z, Ji J, Zhang J, Gu Y. Characterization of CdHgTe/CdS QDs for near infrared fluorescence imaging of spinal column in a mouse model. Photochem Photobiol. 2011;87(1):72–81.CrossRefGoogle Scholar
  8. 8.
    Blackman B, Battaglia D, Peng X. Bright and water-soluble near IR-emitting CdSe/CdTe/ZnSe type-II/type-I nanocrystals, tuning the efficiency and stability by growth. Chem Mater. 2008;20(15):4847–53.CrossRefGoogle Scholar
  9. 9.
    Aswathy RG, Yoshida Y, Maekawa T, Kumar DS. Near-infrared quantum dots for deep tissue imaging. Anal Bioanal Chem. 2010;397(4):1417–35.CrossRefGoogle Scholar
  10. 10.
    Li C, Li F, Zhang Y, Zhang W, Zhang XE, Wang Q. Real-time monitoring surface chemistry-dependent in vivo behaviors of protein Nanocages via encapsulating an NIR-II Ag2S quantum dot. ACS Nano. 2015;9(12):12255–63.CrossRefGoogle Scholar
  11. 11.
    Zhu CN, Jiang P, Zhang ZL, Zhu DL, Tian ZQ, Pang DW. Ag(2) Se quantum dots with tunable emission in the second near-infrared window. ACS Appl Mater Interfaces. 2013;5(4):1186–9.CrossRefGoogle Scholar
  12. 12.
    Tan L, Wan A, Li H. Conjugating S-nitrosothiols with glutathione stabilized silver sulfide quantum dots for controlled nitric oxide release and near-infrared fluorescence imaging. ACS Appl Mater Interfaces. 2013;5(21):11163–71.CrossRefGoogle Scholar
  13. 13.
    Chen H, Li B, Zhang M, Sun K, Wang Y, Peng K, et al. Characterization of tumor-targeting Ag2S quantum dots for cancer imaging and therapy in vivo. Nanoscale. 2014;6(21):12580–90.CrossRefGoogle Scholar
  14. 14.
    Zhang Y, Zhang Y, Hong G, He W, Zhou K, Yang K, et al. Biodistribution, pharmacokinetics and toxicology of Ag2S near-infrared quantum dots in mice. Biomaterials. 2013;34(14):3639–46.CrossRefGoogle Scholar
  15. 15.
    Lin Z, Monteiro-Riviere NA, Riviere JE. Pharmacokinetics of metallic nanoparticles. Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology. 2015;7(2):189–217.CrossRefGoogle Scholar
  16. 16.
    Yoo JW, Chambers E, Mitragotri S. Factors that control the circulation time of nanoparticles in blood: challenges, solutions and future prospects. Curr Pharm Des. 2010;16(21):2298–307.CrossRefGoogle Scholar
  17. 17.
    Javidi J, Haeri A, Shirazi FH, Kobarfard F, Dadashzadeh S. Synthesis, characterization, in vivo imaging, hemolysis, and toxicity of hydrophilic Ag2S near-infrared quantum dots. J Clust Sci. 2016;28(1):165–78.CrossRefGoogle Scholar
  18. 18.
    Zhang Y, Huo M, Zhou J, Xie S. PKSolver: an add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft excel. Comput Methods Prog Biomed. 2010;99(3):306–14.CrossRefGoogle Scholar
  19. 19.
    FDA. Guidance for Industry: Bioanalytical Method Validation. 2011.Google Scholar
  20. 20.
    Bailer AJ. Testing for the equality of area under the curves when using destructive measurement techniques. J Pharmacokinet Biopharm. 1988;16(3):303–9.CrossRefGoogle Scholar
  21. 21.
    Li SD, Huang L. Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm. 2008;5(4):496–504.CrossRefGoogle Scholar
  22. 22.
    Yu M, Zheng J. Clearance pathways and tumor targeting of imaging nanoparticles. ACS Nano. 2015;9(7):6655–74.CrossRefGoogle Scholar
  23. 23.
    Mahmoudi M, Serpooshan V. Large protein absorptions from small changes on the surface of nanoparticles. J Phys Chem C. 2011;115(37):18275–83.CrossRefGoogle Scholar
  24. 24.
    Ishii M, Vroman B, LaRusso NF. Morphologic demonstration of receptor-mediated endocytosis of epidermal growth factor by isolated bile duct epithelial cells. Gastroenterology. 1990;98(5 PART 1):1284–91.CrossRefGoogle Scholar
  25. 25.
    Fawaz F, Bonini F, Guyot M, Lagueny AM, Fessi H, Devissaguet JP. Influence of Poly (DL-Lactide) Nanocapsules on the biliary clearance and enterohepatic circulation of indomethacin in the rabbit. Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists. 1993;10(5):750–6.CrossRefGoogle Scholar
  26. 26.
    Sukhanova A, Bozrova S, Sokolov P, Berestovoy M, Karaulov A, Nabiev I. Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Res Lett. 2018;13(1):44.CrossRefGoogle Scholar
  27. 27.
    Schweiger C, Hartmann R, Zhang F, Parak WJ, Kissel TH, Rivera Gil P. Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge. Journal of nanobiotechnology. 2012;10:28.CrossRefGoogle Scholar
  28. 28.
    Takakura Y, Mahato RI, Nishikawa M, Hashida M. Control of pharmacokinetic profiles of drug-macromolecule conjugates. Adv Drug Deliv Rev. 1996;19(3):377–99.CrossRefGoogle Scholar
  29. 29.
    Longmire M, Choyke PL, Kobayashi H. Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine. 2008;3(5):703–17.CrossRefGoogle Scholar
  30. 30.
    Tang Y, Han S, Liu H, Chen X, Huang L, Li X, et al. The role of surface chemistry in determining in vivo biodistribution and toxicity of CdSe/ZnS core-shell quantum dots. Biomaterials. 2013;34(34):8741–55.CrossRefGoogle Scholar
  31. 31.
    Balogh L, Nigavekar SS, Nair BM, Lesniak W, Zhang C, Sung LY, et al. Significant effect of size on the in vivo biodistribution of gold composite nanodevices in mouse tumor models. Nanomedicine. 2007;3(4):281–96.CrossRefGoogle Scholar
  32. 32.
    Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, et al. Renal clearance of quantum dots. Nat Biotechnol. 2007;25(10):1165–70.CrossRefGoogle Scholar
  33. 33.
    Roohi F, Lohrke J, Ide A, Schutz G, Dassler K. Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles. Int J Nanomedicine. 2012;7:4447–58.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Puisney C, Baeza-Squiban A, Boland S. Mechanisms of uptake and translocation of nanomaterials in the lung. In: Advances in experimental medicine and biology; 2018. p. 21–36.Google Scholar
  35. 35.
    Townsley MI. Structure and composition of pulmonary arteries, capillaries, and veins. Comprehensive Physiology. 2012;2(1):675–709.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Ernsting MJ, Murakami M, Roy A, Li SD. Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J Control Release. 2013;172(3):782–94.CrossRefGoogle Scholar
  37. 37.
    Hoshyar N, Gray S, Han H, Bao G. The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine. 2016;11(6):673–92.CrossRefGoogle Scholar
  38. 38.
    Hirn S, Semmler-Behnke M, Schleh C, Wenk A, Lipka J, Schaffler M, et al. Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration. European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik Ev. 2011;77(3):407–16.CrossRefGoogle Scholar
  39. 39.
    Su Y, Peng F, Jiang Z, Zhong Y, Lu Y, Jiang X, et al. In vivo distribution, pharmacokinetics, and toxicity of aqueous synthesized cadmium-containing quantum dots. Biomaterials. 2011;32(25):5855–62.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutics, School of PharmacyShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Pharmaceutical Sciences Research CenterShahid Beheshti University of Medical SciencesTehranIran

Personalised recommendations