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BioNanoScience

, Volume 9, Issue 1, pp 131–140 | Cite as

Lysozyme-Based Composite Drug Preparations for Inhalation Administration

  • Artur Boldyrev
  • Marat Ziganshin
  • Alexander Osipov
  • Timur Mukhametzyanov
  • Nikolay Lyadov
  • Alexander Klimovitskii
  • Alexander GerasimovEmail author
Article
  • 132 Downloads

Abstract

Inhalation delivery is a promising route for drug administration. The particles of drug aerosol must have a diameter between 1 and 3 μm. The use of microspherical particles based on protein matrix allows for enhanced bioavailability of poorly water-soluble drugs and improved biocompatibility. In the present work, spray drying method was employed for the preparation of the microspherical particles of lysozyme with a model drug compound phenacetin. The average aerodynamic radius of the prepared particle is 1 μm. We show that the spray drying regime produces microparticles with low residual solvent content. The release time of phenacetin from the microspherical particles is much lower than that of the pure drug. These results allow developing a strategy for the production of the protein matrix-based systems for the inhalation delivery of poorly water-soluble drugs.

Keywords

Inhalation administration Lysozyme Phenacetin Microparticles Spray drying Dissolution 

Notes

Funding

The reported study was funded by the Russian Foundation for Basic Research according to the research project no. 18-015-00267. N. Lyadov declares that SEM study was performed in the frame of budget plans.

References

  1. 1.
    Vraníková, B., & Gajdziok, J. (2015). Methods used in pharmaceutical technology to increase bioavailability of poorly soluble drugs after oral administration. Ceska A Slovenska Farmacie, 64, 159–172.Google Scholar
  2. 2.
    Savjani, K. T., Gajjar, A. K., & Savjani, J. K. (2012). Drug solubility: importance and enhancement techniques. ISRN Pharmaceutics, 2012, 1–10.  https://doi.org/10.5402/2012/195727.CrossRefGoogle Scholar
  3. 3.
    Krasnyuk Jr., I. I., Beliatskaya, V., Krasnyuk, I. I., Stepanova, O. I., Korol, L. A., Valeeva, A. M., Grikh, V. V., Ovsyannikova, L. V., & Kosheleva, T. M. (2017). Effect of solid dispersions on the dissolution of ampicillin. BioNanoScience, 7, 340–344.  https://doi.org/10.1007/s12668-016-0342-6.CrossRefGoogle Scholar
  4. 4.
    Donath, E., Sukhorukov, G. B., Caruso, F. S., Davis, A., & Möhwald, H. (1998). Novel hollow polymer shells by colloid-templated assembly of polyelectrolytes. Angewandte Chemie International Edition, 37, 2201–2205. https://doi.org/10.1002/(SICI)1521-3773(19980904)37:16<2201::AID-ANIE2201>3.0.CO;2-E.CrossRefGoogle Scholar
  5. 5.
    Gai, M., Kudryavtseva, V. L., Sukhorukov, G. B., & Frueh, J. (2018). Micro-patterned polystyrene sheets as templates for interlinked 3D polyelectrolyte multilayer microstructures. Bionanoscience, 8, 654–660.  https://doi.org/10.1007/s12668-017-0403-5.CrossRefGoogle Scholar
  6. 6.
    Hu, N., Frueh, J., Zheng, C., Zhang, B., & He, Q. (2015). Photo-crosslinked natural polyelectrolyte multilayer capsules for drug delivery. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 482, 315–323.  https://doi.org/10.1016/j.colsurfa.2015.06.014.CrossRefGoogle Scholar
  7. 7.
    Kiryukhin, M. V., Gorelik, S. R., Man, S. M., Sandhya, G., Antipina, M. N., Low, H. Y., & Sukhorukov, G. B. (2013). Individually addressable patterned multilayer microchambers for site-specific release-on-demand. Macromolecular Rapid Communications, 34, 87–93.  https://doi.org/10.1002/marc.201200564.CrossRefGoogle Scholar
  8. 8.
    Kumar, S., Dilbaghi, N., Saharan, R., & Bhanjana, G. (2012). BioNanoScience, 2, 227–250.  https://doi.org/10.1007/s12668-012-0060-7.CrossRefGoogle Scholar
  9. 9.
    Serajuddin, A. (2007). Salt formation to improve drug solubility. Advanced Drug Delivery Reviews, 59, 603–616.  https://doi.org/10.1016/j.addr.2007.05.010.CrossRefGoogle Scholar
  10. 10.
    Loh, Z., Samanya, A., & Heng, P. (2015). Overview of milling techniques for improving the solubility of poorly water-soluble drugs. Asian Journal of Pharmaceutical Sciences, 10, 255–274.  https://doi.org/10.1016/j.ajps.2014.12.006.CrossRefGoogle Scholar
  11. 11.
    Ma, X., & Zhao, Y. (2015). Biomedical applications of supramolecular systems based on host–guest interactions. Chemical Reviews, 115, 7794–7839.  https://doi.org/10.1021/cr500392w.CrossRefGoogle Scholar
  12. 12.
    Grohganz, H., Priemel, P. A., Löbmann, K., Nielsen, L. H., Laitinen, R., Mullertz, A., Van den Mooter, G., & Rades, T. (2014). Refining stability and dissolution rate of amorphous drug formulations. Expert Opinion on Drug Delivery, 11, 977–989.  https://doi.org/10.1517/17425247.2014.911728.CrossRefGoogle Scholar
  13. 13.
    Sung, J. C., Pulliam, B. L., & Edwards, D. A. (2007). Nanoparticles for drug delivery to the lungs. Trends in Biotechnology, 25, 563–570.  https://doi.org/10.1016/j.tibtech.2007.09.005.CrossRefGoogle Scholar
  14. 14.
    Lee, W. H., Loo, C. Y., Traini, D., & Young, P. M. (2015). Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges. Asian Journal of Pharmaceutical Sciences, 10, 481–489.  https://doi.org/10.1016/j.ajps.2015.08.009.CrossRefGoogle Scholar
  15. 15.
    Sharma, A., Kumar, R., Nishal, B., & Das, O. (2013). Nanocarriers as promising drug vehicles for the management of tuberculosis. BioNanoScience, 3, 102–111.  https://doi.org/10.1007/s12668-013-0084-7.CrossRefGoogle Scholar
  16. 16.
    Elzoghby, A. O., Samy, W. M., & Elgindy, N. A. (2012). Protein-based nanocarriers as promising drug and gene delivery systems. Journal of Controlled Release, 161, 38–49.  https://doi.org/10.1016/j.jconrel.2012.04.036.CrossRefGoogle Scholar
  17. 17.
    Sahoo, S. K., & Labhasetwar, V. (2008). Nanotech approaches to drug delivery and imaging. Drug Discovery Today, 8, 1112–1120.  https://doi.org/10.1016/S1359-6446(03)02903-9.CrossRefGoogle Scholar
  18. 18.
    Blanco, E., Shen, H., & Ferrari, M. (2015). Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33, 941–951.  https://doi.org/10.1038/nbt.3330.CrossRefGoogle Scholar
  19. 19.
    Roy, S., & Ghosh, A. (2016). Characterization of the binding of flavanone hesperetin with chicken egg lysozyme using spectroscopic techniques: Effect of pH on the binding. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 84, 21–34.  https://doi.org/10.1007/s10847-015-0578-8.CrossRefGoogle Scholar
  20. 20.
    Wang, J., Yang, X., Wang, J., Xu, C., Zhang, W., Liu, R., & Zong, W. (2016). Probing the binding interaction between cadmium(II) chloride and lysozyme. New Journal of Chemistry, 40, 3738–3746.  https://doi.org/10.1039/C5NJ02911B.CrossRefGoogle Scholar
  21. 21.
    Huang, S. L., Maiorov, V., Huang, P. L., Ng, A., Lee, H. C., Chang, Y. T., Kallenbach, N., Huang, P. L., & Chen, H. C. (2005). Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity. Biochemistry, 44, 4648–4655.  https://doi.org/10.1021/bi0477081.CrossRefGoogle Scholar
  22. 22.
    Mine, Y., Ma, F., & Lauriau, S. (2004). Antimicrobial peptides released by enzymatic hydrolysis of hen egg white lysozyme. Journal of Agricultural and Food Chemistry, 52, 1088–1094.  https://doi.org/10.1021/jf0345752.CrossRefGoogle Scholar
  23. 23.
    Parrot, J. L., & Nicot, G. (1963). Antihistaminic action of lysozyme. Nature, 197, 496.  https://doi.org/10.1038/197496a0.CrossRefGoogle Scholar
  24. 24.
    Gorbenko, G. P., Ioffe, V. M., & Kinnunen, P. K. (2007). Binding of lysozyme to phospholipid bilayers: Evidence for protein aggregation upon membrane association. Biophysical Journal, 93, 140–153.  https://doi.org/10.1529/biophysj.106.102749.CrossRefGoogle Scholar
  25. 25.
    Franssen, E. J. F., van Amsterdam, R. G. M., Visser, J., Moolenaar, F., de Zeeuw, D., & Meijer, D. K. (1991). Low molecular weight proteins as carriers for renal drug targeting: Naproxen–lysozyme. Pharmaceutical Research, 8, 1223–1230.  https://doi.org/10.1023/A:1015835325321.CrossRefGoogle Scholar
  26. 26.
    Hass, M., Kluppel, A. C., Wartna, E. S., Moolenaar, F., Meijer, D. K., de Jong, P. E., & de Zeeuw, D. (1997). Drug targeting to the kidney: Renal delivery and degradation of a naproxen–lysozyme conjugate in vivo. Kidney International, 52, 1693–1699.  https://doi.org/10.1038/ki.1997.504.CrossRefGoogle Scholar
  27. 27.
    Zhou, P., Sun, X., & Zhang, Z. (2014). Kidney–targeted drug delivery systems. Acta Pharmaceutica Sinica B, 4, 37–42.  https://doi.org/10.1016/j.apsb.2013.12.005.CrossRefGoogle Scholar
  28. 28.
    Karimi, M., Bahrami, S., Ravari, S. B., Zangabad, P. S., Mirshekari, H., Bozorgomid, M., Shahreza, S., Sori, M., & Hamblin, M. R. (2016). Albumin nanostructures as advanced drug delivery systems. Expert Opinion on Drug Delivery, 13, 1609–1623.  https://doi.org/10.1080/17425247.2016.1193149.CrossRefGoogle Scholar
  29. 29.
    Malekzad, H., Mirshekariet, H., Sahandi Zangabad, P., Moosavi Basri, S. M., Baniasadi, F., Sharifi Aghdam, M., Karimi, M., & Hamblin, M. R. (2017). Plant protein-based hydrophobic fine and ultrafine carrier particles in drug delivery systems. Critical Reviews in Biotechnology, 38, 47–67.  https://doi.org/10.1080/07388551.2017.1312267.CrossRefGoogle Scholar
  30. 30.
    Labib, G. (2018). Overview on zein protein: A promising pharmaceutical excipient in drug delivery systems and tissue engineering. Expert Opinion on Drug Delivery, 15, 65–75.  https://doi.org/10.1080/17425247.2017.1349752.CrossRefGoogle Scholar
  31. 31.
    Patton, J. S., Fishburn, C. S., & Weers, J. G. (2004). The lungs as a portal of entry for systemic drug delivery. Proceedings of the American Thoracic Society, 1, 338–344.  https://doi.org/10.1513/pats.200409-049TA.CrossRefGoogle Scholar
  32. 32.
    Williams III, R. O., Watts, A. B., & Miller, D. A. (2016). Formulating poorly water soluble drugs. New York: Springer-Verlag.CrossRefGoogle Scholar
  33. 33.
    Gharsallaoui, A., Roudaut, G., Chambin, O., Voilley, A., & Saurel, R. (2007). Applications of spray-drying in microencapsulation of food ingredients: An overview. Food Research International, 40, 1107–1121.  https://doi.org/10.1016/j.foodres.2007.07.004.CrossRefGoogle Scholar
  34. 34.
    Usmanova, L. S., Ziganshin, M. A., Rakipov, I. T., Lyadov, N. M., Klimovitskii, A. E., Mukhametzyanov, T. A., & Gerasimov, A. V. (2018). Microspherical particles of solid dispersion of Polyvinylpyrrolidone K29-32 for inhalation administration. BioMed Research International, 2018, 1–12.  https://doi.org/10.1155/2018/2412156.CrossRefGoogle Scholar
  35. 35.
    Lee, S. H., Heng, D., Ng, W. K., Chan, H. K., & Tan, R. B. (2011). Nano spray drying: A novel method for preparing protein nanoparticles for protein therapy. International Journal of Pharmaceutics, 403, 192–200.  https://doi.org/10.1016/j.ijpharm.2010.10.012.CrossRefGoogle Scholar
  36. 36.
    Galukhin, A., Khelkhal, M. A., Gerasimov, A., Biktagirov, T., Gafurov, M., Rodionov, A., & Orlinskii, S. (2016). Mn-catalyzed oxidation of heavy oil in porous media: Kinetics and some aspects of the mechanism. Energy & Fuels, 30, 7731–7737.  https://doi.org/10.1021/acs.energyfuels.6b01234.CrossRefGoogle Scholar
  37. 37.
    Gerasimov, A. V., Ziganshin, M. A., & Gorbatchuk, V. V. (2013). A calorimetric study of the formation of phenacetin solid dispersions with PEG-1400 and pluronic F127. World Applied Sciences Journal, 24, 920–927.  https://doi.org/10.5829/idosi.wasj.2013.24.07.13235.Google Scholar
  38. 38.
    Ziganshin, M. A., Bikmukhametova, A. A., Gerasimov, A. V., Gorbatchuk, V. V., Ziganshina, S. A., & Bukharaev, A. A. (2014). The effect of substrate and air humidity on morphology of films of L-leucyl-L-leucine dipeptide. Protection of Metals and Physical Chemistry of Surfaces, 50, 49–54.  https://doi.org/10.1134/S2070205114010171.CrossRefGoogle Scholar
  39. 39.
    Ziganshin, M. A., Gerasimov, A. V., Ziganshina, S. A., Gubina, N. S., Abdullina, G. R., Klimovitskii, A. E., Gorbatchuk, V. V., & Bukharaev, A. A. (2016). Thermally induced diphenylalanine cyclization in solid phase. Journal of Thermal Analysis and Calorimetry, 125, 905–912.  https://doi.org/10.1007/s10973-016-5458-y.CrossRefGoogle Scholar
  40. 40.
    Jarunglumlert, T., & Nakagawa, K. (2013). Spray drying of casein aggregates loaded with 훽-carotene: Influences of acidic conditions and storage time on surface structure and encapsulation efficiencies. Drying Technology, 31, 1459–1465.  https://doi.org/10.1080/07373937.2013.800548.CrossRefGoogle Scholar
  41. 41.
    Bhardwaj, U., & Burgess, D. J. (2010). A novel USP apparatus 4 based release testing method for dispersed systems. International Journal of Pharmaceutics, 388, 287–294.  https://doi.org/10.1016/j.ijpharm.2010.01.009.CrossRefGoogle Scholar
  42. 42.
    Goodsell, D. S., Morris, G. M., & Olson, A. J. (1996). Automated docking of flexible ligands: Application of AutoDock. Journal of Molecular Recognition, 9, 1–5. https://doi.org/10.1002/(SICI)1099-1352(199601)9:1<1::AID-JMR241>3.0.CO;2-6.CrossRefGoogle Scholar
  43. 43.
    Alam, P., Chaturvedi, S. K., Anwar, T., Siddiqi, M. K., Ajmal, M. R., Badr, G., Mahmoud, M. H., & Khan, R. H. (2015). Biophysical and molecular docking insight into the interaction of cytosine β-D arabinofuranoside with human serum albumin. Journal of Luminescence, 164, 123–130.  https://doi.org/10.1016/j.jlumin.2015.03.011.CrossRefGoogle Scholar
  44. 44.
    Gerasimov, A. V., Ziganshin, M. A., Gorbatchuk, V. V., & Usmanova, L. S. (2013). Formation of solid dispersion of PEG-1000 with phenacetin according to differential scanning calorimetry. Der Pharma Chemica, 5, 149–155.Google Scholar
  45. 45.
    Buzatu, D., Petrescu, E., Buzatu, F. D., & Albright, J. G. (2004). Measurements of multicomponent diffusion coefficients for lysozyme chloride in water and aqueous Na2SO4. Revista de Chimie, 55, 435–438.Google Scholar
  46. 46.
    Babu, N. J., & Nangia, A. (2011). Solubility advantage of amorphous drugs and pharmaceutical Cocrystals. Crystal Growth & Design, 11, 2662–2679.  https://doi.org/10.1021/cg200492w.CrossRefGoogle Scholar
  47. 47.
    Johari, G. P., Ram, S., Astl, G., & Mayer, E. (1990). Characterizing amorphous and microcrystalline solids by calorimetry. Journal of Non-Crystalline Solids, 116, 282–285.  https://doi.org/10.1016/0022-3093(90)90703-O.CrossRefGoogle Scholar
  48. 48.
    Hinds, W. C. (1999). Aerosol technology: Properties, behavior, and measurement of airborne particles. New-York: John Wiley & Sons.Google Scholar
  49. 49.
    Potts, D. E., Levin, D. C., & Sahn, S. A. (1976). Pleural fluid pH in parapneumonic effusions. Chest, 70, 328–331.  https://doi.org/10.1378/chest.70.3.328.CrossRefGoogle Scholar
  50. 50.
    Houston, M. C. (1987). Pleural fluid pH: diagnostic, therapeutic and prognostic value. The American Journal of Surgery, 154, 333–337.  https://doi.org/10.1016/0002-9610(89)90623-5.CrossRefGoogle Scholar

Copyright information

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Authors and Affiliations

  1. 1.Department of Physical Chemistry, A.M. Butlerov Institute of ChemistryKazan Federal UniversityKazanRussia
  2. 2.Zavoisky Physical-Technical Institute, FRC Kazan Scientific Center of RASKazanRussia

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