Pulmonary Delivery of Magnetically Targeted Nano-in-Microparticles

  • Amber A. McBride
  • Dominique N. Price
  • Pavan MuttilEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1530)


This chapter details the intratracheal delivery of dry powder microparticles termed nano-in-microparticles (NIMs) for the purpose of in vivo targeted pulmonary drug delivery. The dry powder NIMs technology improves on previous inhaled chemotherapy platforms designed as liquid formulations. Dry powder microparticles were created through the process of spray drying; a protocol detailing the formulation of NIMs dry powder is included as a separate chapter in this book. Dry powder NIMs containing fluorescent nanoparticles and magnetically-responsive superparamagnetic iron oxide nanoparticles are intratracheally delivered (insufflated) in the presence of a magnetic field and targeted to the left lung of mice. The targeting efficiency of dry powder NIMs is compared to the targeting efficiency of liquid NIMs to demonstrate the superiority of dry power targeting platforms. Targeting is assessed using fluorescence associated with NIMs detected in the mouse trachea, left lung, and right lung by an in vivo imaging system.

Key words

Dry powder Nano-in-microparticles Intratracheal delivery Insufflation Superparamagnetism Iron oxide nanoparticles Pulmonary delivery Targeted drug delivery 



This research was supported by the University of New Mexico Health Science Center Research and Allocations Committee (RAC) grant. AAM was supported by NSF-IGERT Integrating Nanotechnology with Cell Biology and Neuroscience Fellowship (DGE-0549500) and the NCI Alliance for Nanotechnology in Cancer New Mexico CNTC Training Center. DNP was supported by Bill and Melinda Gates Grand Challenge Exploration (No OPP1061393) and UNM IDIP T32 training grant (T32-A1007538, P.I.– M. Ozbun).


  1. 1.
    Labiris NR, Dolovich MB (2003) Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 56:588–599CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Wolff RK (1998) Safety of inhaled proteins for therapeutic use. J Aerosol Med 11:197–219. doi: 10.1089/jam.1998.11.197 CrossRefPubMedGoogle Scholar
  3. 3.
    Patton JS, Byron PR (2007) Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 6:67–74. doi: 10.1038/nrd2153 CrossRefPubMedGoogle Scholar
  4. 4.
    Agnew JE, Pavia D, Clarke SW (1981) Airways penetration of inhaled radioaerosol: an index to small airways function? Eur J Respir Dis 62:239–255PubMedGoogle Scholar
  5. 5.
    McBride AA, Price DN, Lamoureux LR et al (2013) Preparation and characterization of novel magnetic nano-in-microparticles for site-specific pulmonary drug delivery. Mol Pharm 10:3574–3581. doi: 10.1021/mp3007264 CrossRefPubMedGoogle Scholar
  6. 6.
    Sharma S, White D, Imondi AR et al (2001) Development of inhalational agents for oncologic use. J Clin Oncol 19:1839–1847PubMedGoogle Scholar
  7. 7.
    Azarmi S, Tao X, Chen H et al (2006) Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles. Int J Pharm 319:155–161. doi: 10.1016/j.ijpharm.2006.03.052 CrossRefPubMedGoogle Scholar
  8. 8.
    Tseng C-L, Su W-Y, Yen K-C et al (2009) The use of biotinylated-EGF-modified gelatin nanoparticle carrier to enhance cisplatin accumulation in cancerous lungs via inhalation. Biomaterials 30:3476–3485. doi: 10.1016/j.biomaterials.2009.03.010 CrossRefPubMedGoogle Scholar
  9. 9.
    Rao R, Markovic S, Anderson P (2003) Aerosol therapy for malignancy involving the lungs. Curr Cancer Drug Targets 3:239–250. doi: 10.2174/1568009033481895 CrossRefPubMedGoogle Scholar
  10. 10.
    Hershey AE, Kurzman ID, Forrest LJ et al (1999) Inhalation chemotherapy for macroscopic primary or metastatic lung tumors: proof of principle using dogs with spontaneously occurring tumors as a model. Clin Cancer Res 5:2653–2659PubMedGoogle Scholar
  11. 11.
    Dames P, Gleich B, Flemmer A et al (2007) Targeted delivery of magnetic aerosol droplets to the lung. Nat Nanotechnol 2:495–499. doi: 10.1038/nnano.2007.217 CrossRefPubMedGoogle Scholar
  12. 12.
    Hasenpusch G, Geiger J, Wagner K et al (2012) Magnetized aerosols comprising superparamagnetic iron oxide nanoparticles improve targeted drug and gene delivery to the lung. Pharm Res 29:1308–1318. doi: 10.1007/s11095-012-0682-z CrossRefPubMedGoogle Scholar
  13. 13.
    Gagnadoux F, Hureaux J, Vecellio L et al (2008) Aerosolized chemotherapy. J Aerosol Med Pulm Drug Deliv 21:61–70. doi: 10.1089/jamp.2007.0656 CrossRefPubMedGoogle Scholar
  14. 14.
    Rodriguez CO, Crabbs TA, Wilson DW et al (2010) Aerosol gemcitabine: preclinical safety and in vivo antitumor activity in osteosarcoma-bearing dogs. J Aerosol Med Pulm Drug Deliv 23:197–206. doi: 10.1089/jamp.2009.0773 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Yi D, Wiedmann TS (2010) Inhalation adjuvant therapy for lung cancer. J Aerosol Med Pulm Drug Deliv 23:181–187. doi: 10.1089/jamp.2009.0787 CrossRefPubMedGoogle Scholar
  16. 16.
    Otterson GA, Villalona-Calero MA, Sharma S et al (2007) Phase I study of inhaled Doxorubicin for patients with metastatic tumors to the lungs. Clin Cancer Res 13:1246–1252. doi: 10.1158/1078-0432.CCR-06-1096 CrossRefPubMedGoogle Scholar
  17. 17.
    Otterson GA, Villalona-Calero MA, Hicks W et al (2010) Phase I/II study of inhaled doxorubicin combined with platinum-based therapy for advanced non-small cell lung cancer. Clin Cancer Res 16:2466–2473. doi: 10.1158/1078-0432.CCR-09-3015 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tatsumura T, Koyama S, Tsujimoto M et al (1993) Further study of nebulisation chemotherapy, a new chemotherapeutic method in the treatment of lung carcinomas: fundamental and clinical. Br J Cancer 68:1146–1149CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Zarogoulidis P, Darwiche K, Krauss L et al (2013) Inhaled cisplatin deposition and distribution in lymph nodes in stage II lung cancer patients. Future Oncol 9:1307–1313. doi: 10.2217/fon.13.111 CrossRefPubMedGoogle Scholar
  20. 20.
    Lemarie E, Vecellio L, Hureaux J et al (2011) Aerosolized gemcitabine in patients with carcinoma of the lung: feasibility and safety study. J Aerosol Med Pulm Drug Deliv 24:261–270. doi: 10.1089/jamp.2010.0872 CrossRefPubMedGoogle Scholar
  21. 21.
    Tatsumura T, Yamamoto K, Murakami A et al (1983) New chemotherapeutic method for the treatment of tracheal and bronchial cancers—nebulization chemotherapy. Gan No Rinsho 29:765–770PubMedGoogle Scholar
  22. 22.
    Hitzman CJ, Elmquist WF, Wattenberg LW, Wiedmann TS (2006) Development of a respirable, sustained release microcarrier for 5-fluorouracil I: in vitro assessment of liposomes, microspheres, and lipid coated nanoparticles. J Pharm Sci 95:1114–1126. doi: 10.1002/jps.20591 CrossRefPubMedGoogle Scholar
  23. 23.
    Azarmi S, Lobenberg R, Roa WH et al (2008) Formulation and in vivo evaluation of effervescent inhalable carrier particles for pulmonary delivery of nanoparticles. Drug Dev Ind Pharm 34:943–947. doi: 10.1080/03639040802149079 CrossRefPubMedGoogle Scholar
  24. 24.
    Gerrity TR, Lee PS, Hass FJ et al (1979) Calculated deposition of inhaled particles in the airway generations of normal subjects. J Appl Physiol 47:867–873PubMedGoogle Scholar
  25. 25.
    Morello M, Krone CL, Dickerson S et al (2009) Dry-powder pulmonary insufflation in the mouse for application to vaccine or drug studies. Tuberculosis (Edinb) 89:371–377. doi: 10.1016/ CrossRefGoogle Scholar
  26. 26.
    Hoppentocht M, Hoste C, Hagedoorn P et al (2014) In vitro evaluation of the DP-4M PennCentury insufflator. Eur J Pharm Biopharm 88:153–159. doi: 10.1016/j.ejpb.2014.06.014 CrossRefPubMedGoogle Scholar
  27. 27.
    Duret C, Wauthoz N, Sebti T et al (2012) Solid dispersions of itraconazole for inhalation with enhanced dissolution, solubility and dispersion properties. Int J Pharm 428:103–113. doi: 10.1016/j.ijpharm.2012.03.002 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Amber A. McBride
    • 1
  • Dominique N. Price
    • 2
  • Pavan Muttil
    • 2
    Email author
  1. 1.Sandia National LaboratoriesAlbuquerqueUSA
  2. 2.Department of Pharmaceutical Sciences, College of PharmacyUniversity of New MexicoAlbuquerqueUSA

Personalised recommendations