Assessment of pulmonary mucociliary transport using magnetic nanoparticles: influence of their surface potential

Document Type : Research Paper

Authors

1 Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

2 Global Center for Medical Engineering and Informatics, Osaka University, Suita, Osaka, Japan

Abstract

Objective(s): Inhaled aerocontaminants are removed from the lungs by pulmonary mucociliary transport (MCT) as an important defense mechanism. This study was undertaken to investigate the influence of the surface potential of magnetic nanoparticles (MNPs) on the MCT in murine lungs by use of magnetic particle imaging (MPI).
Materials and Methods: Three kinds of MNPs (carboxymethyl dextran magnetite (CM), alkali-treated dextran magnetite (AM), and trimethylammonium dextran magnetite (TM)) with almost the same hydrodynamic diameters (50-55 nm) but different surface (zeta) potentials (−24 mV for CM, −15 mV for AM, and +2 mV for TM) were intratracheally injected to anesthetized ICR male mice at 10 weeks old using a nebulizing microsprayer containing 50 μL of MNPs. MPI images were acquired at 0.5, 6, 24, 72, and 168 hours after the injection of agents for each mouse. The retention value of the MNPs in the lungs was quantified from the average pixel value of the lungs in the MPI image.
Results: The retention value of TM in the lungs was significantly greater than that of AM at 6 and 168 hours after the injection of agents, and was significantly greater than that of CM at 72 and 168 hours after injection. The retention value of AM was significantly greater than that of CM at 168 hours after injection.
Conclusion: The surface potential of MNPs affects the clearance of MNPs from the lungs due to MCT, suggesting that the retention of MNPs in the lungs can be controlled by manipulating the surface potential of MNPs. MPI will be useful for the visual and quantitative assessment of MCT, because MPI allows for repeated and long-term studies with a single injection of MNPs and with no radiation exposure.

Keywords

References

1. Clarke SW, Pavia D. Lung mucus production and mucociliary clearance: methods of assessment. Br J Clin Pharmacol. 1980; 9: 537-546.
2. Antunesa MB, Cohen NA. Mucociliary clearance - a critical upper airway host defense mechanism and methods of assessment. Curr Opin Allergy Clin Immunol. 2007; 7: 5–10.
3. Mikhaylov G, Mikac U, Magaeva AA, Itin VI, Naiden EP, Psakhye I, Babes L, Reinheckel T, Peters C, Zeiser R, Bogyo M, Turk V, Psakhye SG, Turk B, Vasiljeva O. Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nature Nanotechnol. 2011; 6: 594-602.
4. Kuzmov A, Minko T. Nanotechnology approaches for inhalation treatment of lung diseases. J Control Release. 2015; 219: 500–518.
5. Banura, N, Murase, K. Magnetic particle imaging for aerosol-based magnetic targeting. Jpn J Appl Phys. 2017; 56.
6. Srinivas A, Rao PJ, Selvam G, Goparaju A, Murthy PB, Reddy PN. Oxidative stress and inflammatory responses of rat following acute inhalation exposure to iron oxide nanoparticles. Hum Exp Toxicol. 2012; 31: 1113-1131.
7. Sadeghi L, Yousefi BV, Espanani HR. Toxic effects of the Fe2O3 nanoparticles on the liver and lung tissue. Bratisl Lek Listy. 2015; 116: 373-378.
8. Lippmann M, Yeates DB, Albert RE. Deposition, retention, and clearance of inhaled particles. Br J Ind Med. 1980; 37: 337-362.
9. Karacavus S, Intepe YS. The role of Tc-99m DTPA aerosol scintigraphy in the differential diagnosis of COPD and asthma. Clin Respir J. 2015; 9: 189-195.
10. Fleming J, Conway J, Majoral C, Tossici-Bolt L, Katz I, Caillibotte G, Perchet D, Pichelin M, Muellinger B, Martonen T, Kroneberg P, Apiou-Sbirlea G. The use of combined single photon emission computed tomography and x-ray computed tomography to assess the fate of inhaled aerosol. J Aerosol Med Pulm Drug Deliv. 2011; 24: 49-60.
11. Gleich B, Weizenecker J. Tomographic imaging using the nonlinear response of magnetic particles. Nature. 2005; 435: 1214-1217.
12. Murase K, Aoki M, Banura N, Nishimoto K, Mimura A, Kuboyabu T, Yabata I. Usefulness of magnetic Particle Imaging for Predicting the Therapeutic Effect of Magnetic Hyperthermia. Open J Med Imaging. 2015; 5: 85-99.
13. Nishimoto K, Mimura A, Aoki M, Banura N, Murase K. Application of magnetic particle imaging to pulmonary imaging using nebulized magnetic nanoparticles. Open J Med Imaging. 2015; 5: 49-55.
14. Herrera AP, Barrera C, Rinaldi C. Synthesis and functionalization of magnetite nanoparticles with aminopropylsilane and carboxymethyldextran. J Mater Chem. 2008; 18: 3650-3654.
15. Oishi K, Miyamoto Y, Saito H, Murase K, Ono K, Sawada M, Watanabe M, Noguchi Y, Fujiwara T, Hayashi S, Noguchi H. In vivo imaging of transplanted islets labeled with a novel cationic nanoparticle. PLoS ONE. 2013; 8(2): e57046.
16. Murase K, Hiratsuka S, Song R, Takeuchi Y. Development of a system for magnetic particle imaging using neodymium magnets and gradiometer. Jpn J Appl Phys. 2014; 53: 067001.
17. Murase K, Banura N, Mimura A, Nishimoto K. Simple and practical method for correcting the inhomogeneous sensitivity of a receiving coil in magnetic particle imaging. Jpn J Appl Phys. 2015; 54: 038001.
18. Murase K, Song R, Hiratsuka K. Magnetic particle imaging of blood coagulation. Appl Phys Lett. 2014; 104: 2524409.
19. Chen EYT, Wang YC, Chen CS, Chin WC. Functionalized positive nanoparticles reduce mucin swelling and dispersion. PLoS ONE. 2010; 5: e15434.
20. Chen EY, Daley D, Wang YC, Garnica M, Chen CS, Chin WC. Functionalized carboxyl nanoparticles enhance mucus dispersion and hydration. Sci Rep. 2012; 2: 211.
21. El-Sherbiny IM, El-Baz NM, Yacoub MH. Inhaled nano- and microparticles for drug delivery. Glob Caridol Sci Pract. 2015; 2: 1-14.
22. Roa WH, Azarmi S, Al-Hallak MHDK, Finlay WH, Magliocco AM, Löbenberg R. Inhalable nanoparticles, a non-invasive approach to treat lung cancer in a mouse model. J Control Release. 2011, 150: 49-55.
23. Woods A, Ptel A, Spina D, Riffo-Vasquez Y, Babin-Morgan A, de Rosales RTM, Sunassee K, Clark S, Cllins H, Bruce K, Dailey LA, Forbes B. In vivo biocompatibility, clearance, and biodistribution of albumin vehicles for pulmonary drug delivery. J Control Release. 2015; 210: 1-9.
 
Nanomedicine Journal
Volume 6, Issue 3
July 2019
Pages 161-166

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