DOI QR코드

DOI QR Code

Comparative in vivo biodistributions of nanoparticles and polymers of 177lutetium-labeled hyaluronic acids in mice during 28 days

  • Lin, Chunmei (College of Chinese Medicinal Materials, Jilin Agricultural University) ;
  • Jeong, Ju-Yeon (College of Veterinary Medicine and Veterinary Medical Center, Chungbuk National University) ;
  • Yon, Jung-Min (Division of Biosafety Evaluation and Control, Centers for Disease Control & Prevention) ;
  • Park, Seul Gi (College of Veterinary Medicine and Veterinary Medical Center, Chungbuk National University) ;
  • Gwon, Lee Wha (College of Veterinary Medicine and Veterinary Medical Center, Chungbuk National University) ;
  • Lee, Jong-Geol (College of Veterinary Medicine and Veterinary Medical Center, Chungbuk National University) ;
  • Baek, In-Jeoung (Asan Institute for Life Sciences, Asan Medical Center and University of Ulsan) ;
  • Nahm, Sang-Soep (College of Veterinary Medicine, Konkuk University) ;
  • Lee, Beom Jun (College of Veterinary Medicine and Veterinary Medical Center, Chungbuk National University) ;
  • Yun, Young Won (College of Veterinary Medicine and Veterinary Medical Center, Chungbuk National University) ;
  • Nam, Sang-Yoon (College of Veterinary Medicine and Veterinary Medical Center, Chungbuk National University)
  • Received : 2017.02.21
  • Accepted : 2017.05.23
  • Published : 2017.06.30

Abstract

Hyaluronic acid (HA) has been investigated for biomedical and pharmaceutical applications. This study was conducted to determine the distributions of HA nanoparticles (NPs; size 350-400 nm) and larger HA polymers in mice at intervals after application. $^{177}Lutetium$ (Lu)-labeled HA-NPs or HA polymers were intravenously injected (5 mg/kg) into male ICR mice, and radioactivity levels in blood and target organs were measured from 0.25 h to 28 days post-injection. In blood, the radioactivities of HA-NPs and HA polymer peaked at 0.5 h after injection but were remarkably decreased at 2 h; subsequently, they maintained a constant level until 6 days post-injection. HA-NPs and HA polymers were observed in the liver, spleen, lung, kidney, and heart (in ascending order) but were seldom observed in other organs. After 3 days, both the HA-NP and HA polymer levels showed similar steady decreases in lung, kidney, and heart. However, in liver and spleen, the HA-NP levels tended to decrease gradually after 1 day and both were very low after 14 days, whereas the HA polymer level accumulated for 28 days. The results indicate that HA-NPs, with their faster clearance pattern, may act as a better drug delivery system than HA polymers, especially in the liver and spleen.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF), Korea Food and Drug Administration

References

  1. Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24 ed. McGraw-Hill, Hong Kong, 2012.
  2. Bharadwaj AG, Kovar JL, Loughman E, Elowsky C, Oakley GG, Simpson MA. Spontaneous metastasis of prostate cancer is promoted by excess hyaluronan synthesis and processing. Am J Pathol 2009, 174, 1027-1036. https://doi.org/10.2353/ajpath.2009.080501
  3. Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases 2007, 2, MR17-71. https://doi.org/10.1116/1.2815690
  4. Chertok B, Moffat BA, David AE, Yu F, Bergemann C, Ross BD, Yang VC. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials 2008, 29, 487-496. https://doi.org/10.1016/j.biomaterials.2007.08.050
  5. Cho M, Cho WS, Choi M, Kim SJ, Han BS, Kim SH, Kim HO, Sheen YY, Jeong J. The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles. Toxicol Lett 2009, 189, 177-183. https://doi.org/10.1016/j.toxlet.2009.04.017
  6. Cho WS, Cho M, Jeong J, Choi M, Han BS, Shin HS, Hong J, Chung BH, Jeong J, Cho MH. Size-dependent tissue kinetics of PEG-coated gold nanoparticles. Toxicol Appl Pharmacol 2010, 245, 116-123. https://doi.org/10.1016/j.taap.2010.02.013
  7. Choi KY, Chung H, Min KH, Yoon HY, Kim K, Park JH, Kwon IC, Jeong SY. Self-assembled hyaluronic acid nanoparticles for active tumor targeting. Biomaterials 2010, 31, 106-114. https://doi.org/10.1016/j.biomaterials.2009.09.030
  8. Choi KY, Min KH, Na JH, Choi K, Kim K, Park JH, Kwon IC, Jeong SY. Self-assembled hyaluronic acid nanoparticles as a potential drug carrier for cancer therapy: synthesis, characterization, and in vivo biodistribution. J Mater Chem 2009, 19, 4102-4107. https://doi.org/10.1039/b900456d
  9. De Jong WH, Borm PJ. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine 2008, 3, 133-149.
  10. De Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJAM, Geertsma RE. Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 2008, 29, 1912-1919. https://doi.org/10.1016/j.biomaterials.2007.12.037
  11. Falcone SJ, Palmeri DM, Berg RA. Rheological and cohesive properties of hyaluronic acid. J Biomed Mater Res A 2006, 76, 721-728.
  12. Fraser JRE, Laurent TC, Laurent UBG. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med 1997, 242, 27-33. https://doi.org/10.1046/j.1365-2796.1997.00170.x
  13. Han SY, Han HS, Lee SC, Kang YM, Kim IS, Park JH. Mineralized hyaluronic acid nanoparticles as a robust drug carrier. J Mater Chem 2011, 21, 7996-8001. https://doi.org/10.1039/c1jm10466g
  14. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005, 57, 173-185. https://doi.org/10.1124/pr.57.2.4
  15. He Q, Zhang Z, Gao F, Li Y, Shi J. In vivo biodistribution and urinary excretion of mesoporous silica nanoparticles: effects of particle size and PEGylation. Small 2011, 7, 271-280. https://doi.org/10.1002/smll.201001459
  16. Koo H, Huh MS, Ryu JH, Lee DE, Sun IC, Choi K, Kim K, Kwon IC. Nanoprobes for biomedical imaging in living systems. Nano Today 2011, 6, 204-220. https://doi.org/10.1016/j.nantod.2011.02.007
  17. Laznicek M, Laznickova A, Cozikova D, Velebny V. Preclinical pharmacokinetics of radiolabelled hyaluronan. Pharmacol Rep 2012, 64, 428-437. https://doi.org/10.1016/S1734-1140(12)70784-3
  18. Lee MJ, Veiseh O, Bhattarai N, Sun C, Hansen SJ, Ditzler S, Knoblaugh S, Lee D, Ellenbogen R, Zhang M, Olson JM. Rapid pharmacokinetic and biodistribution studies using cholorotoxin-conjugated iron oxide nanoparticles: a novel non-radioactive method. PLoS One 2010, 5, e9536. https://doi.org/10.1371/journal.pone.0009536
  19. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2007, 2, 751-760. https://doi.org/10.1038/nnano.2007.387
  20. Rossin R, Pan D, Qi K, Turner JL, Sun X, Wooley KL, Welch MJ. $^{64}Cu$-labeled folate-conjugated shell cross-linked nanoparticles for tumor imaging and radiotherapy: synthesis, radiolabeling, and biologic evaluation. J Nucl Med 2005, 46, 1210-1218.
  21. Saini R, Saini S, Sharma S. Nanotechnology: the future medicine. J Cutan Aesthet Surg 2010, 3, 32-33. https://doi.org/10.4103/0974-2077.63301