Advertisement

Targeted Delivery of Antibiotics Using Microparticles to Combat Multidrug-Resistant Tuberculosis

  • Tarun K. Upadhyay
  • Akanksha Sharma
  • Nida Fatima
  • Amit Singh
  • Pavan Muttil
  • Rolee SharmaEmail author
Chapter

Abstract

Tuberculosis (TB) continues to be a major global challenge, claiming about two million deaths each year. The emergence of drug resistance due to high incidence of poor patient compliance has further worsened the situation. Targeted delivery of drugs to macrophage, the site of Mycobacterium tuberculosis infection and replication, has been shown to have implications as a promising option in TB treatment. A variety of biocompatible and biodegradable polymer-based carrier-based delivery systems have emerged as potential drug delivery systems (DDS). Such targeted delivery systems have been shown to have significant merits over free drug, including improved drug bioavailability, limiting adverse drug effects and requiring less frequent administration regimes and lowering drug doses. The pulmonary administration of inhalable dry powders incorporating multiple drugs has particularly exhibited encouraging results against MDR-TB, and is expected to shorten the treatment duration, thereby improving patient compliance. Recently, the administration of pulmonary drug delivery as an adjunct to existing oral treatment regimens has been shown to achieve sufficient drug concentrations in certain systemic compartments and thus further enhance treatment effectiveness. The present chapter discusses the recent research updates on carriers used in preclinical or clinical studies against TB, the challenges associated, and future perspectives.

Keywords

Tuberculosis MDR-TB Microparticles Pulmonary delivery Dry powder 

References

  1. Ahmad, S. (2010). Pathogenesis, immunology, and diagnosis of latent Mycobacterium tuberculosis infection. Clinical & Developmental Immunology, 2011, 814943.Google Scholar
  2. Ahmad, Z., Sharma, S., & Khuller, G. K. (2007). Chemotherapeutic evaluation of alginate nanoparticle-encapsulated azole antifungal and antitubercular drugs against murine tuberculosis. Nanomedicine: Nanotechnology, Biology and Medicine, 3(3), 239–243.CrossRefGoogle Scholar
  3. Ahmad, Z., Pandey, R., Sharma, S., & Khuller, G. K. (2008). Novel chemotherapy for tuberculosis: Chemotherapeutic potential of econazole-and moxifloxacin-loaded PLG nanoparticles. International Journal of Antimicrobial Agents, 31, 142–146.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Ahmad, Z., Maqbool, M., & Raja, A. F. (2011). Nanomedicine for tuberculosis: Insights from animal models. International Journal of Nano Dimension, 2(1), 67–84.Google Scholar
  5. Ahmed, M. M., Velayati, A. A., & Mohammed, S. H. (2016). Epidemiology of multidrug-resistant, extensively drug resistant, and totally drug resistant tuberculosis in Middle East countries. International Journal of Mycobacteriology, 5(3), 249–256.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Chan, J. G. Y., Wong, J., Zhou, Q. T., Leung, S. S. Y., & Chan, H. K. (2014). Advances in device and formulation technologies for pulmonary drug delivery. AAPS PharmSciTech, 15(4), 882–897.PubMedPubMedCentralCrossRefGoogle Scholar
  7. D’Ambrosio, L., Centis, R., Tiberi, S., Tadolini, M., Dalcolmo, M., Rendon, A., et al. (2017). Delamanid and bedaquiline to treat multidrug-resistant and extensively drug-resistant tuberculosis in children: A systematic review. Journal of Thoracic Disease, 9(7), 2093–2101.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Deol, P., & Khuller, G. K. (1997). Lung specific stealth liposomes: Stability, biodistribution and toxicity of liposomal antitubercular drugs in mice. Biochimica et Biophysica Acta (BBA) – General Subjects, 1334(2–3), 161–172.CrossRefGoogle Scholar
  9. Deretic, V., Via, L. E., Fratti, R. A., & Deretic, D. (1997). Mycobacterial phagosome maturation, Rab proteins and intracellular trafficking. Electrophoresis, 18(14), 2542–2547.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Dharmadhikari, A. S., Kabadi, M., Gerety, B., Hickey, A. J., Fourie, P. B., & Nardell, E. (2013). Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin: A new approach to therapy of drug-resistant tuberculosis. Antimicrobial Agents and Chemotherapy, 57(6), 2613–2619.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Fernstrom, A., & Goldblatt, M. (2013). Aerobiology and its role in the transmission of infectious diseases. J Pathogens, 2013, 493960.Google Scholar
  12. Flannagan, R. S., Jaumouille, V., & Grinstein, S. (2012). The cell biology of phagocytosis. Annual Review of Pathology, 7, 61–98.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Garcia-Contreras, L., Padilla-Carlin, D. J., Sung, J., VerBerkmoes, J., Muttil, P., Elbert, K., & Hickey, A. (2017). Pharmacokinetics of ethionamide delivered in spray-dried microparticles to the lungs of Guinea pigs. Journal of Pharmaceutical Sciences, 106(1), 331–337.PubMedCrossRefPubMedCentralGoogle Scholar
  14. Grace, A. G., Mittal, A., Jain, S., Tripathy, J. P., Satyanarayana, S., Tharyan, P., & Kirubakaran, R. (2018). Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis. The Cochrane Library.Google Scholar
  15. Guirado, E., Schlesinger, L. S., & Kaplan, G. (2013, September). Macrophages in tuberculosis: Friend or foe. In: Seminars in immunopathology (Vol. 35, No. 5, pp. 563–583). Springer: Berlin/Heidelberg.Google Scholar
  16. Hanif, S. N. M., & Garcia-Contreras, L. (2012). Pharmaceutical aerosols for the treatment and prevention of tuberculosis. Frontiers in Cellular and Infection Microbiology, 2, 118.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Hickey, A. J., Durham, P. G., Dharmadhikari, A., & Nardell, E. A. (2016). Inhaled drug treatment for tuberculosis: Past progress and future prospects. Journal of Controlled Release, 240, 127–134.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Hirota, K., & Terada, H. (2014). Particle-manufacturing technology-based inhalation therapy for pulmonary diseases. In H. Ohshima & K. Makino (Eds.), Colloid and interface science in pharmaceutical research and development (Vol. 2014, Ist ed., pp. 103–119). Oxford: Elsevier.Google Scholar
  19. Hoffmann, H., Kohl, T. A., Hofmann-Thiel, S., Merker, M., Beckert, P., Jaton, K., Nedialkova, L., Sahalchyk, E., Rothe, T., Keller, P. M., & Niemann, S. (2016). Delamanid and bedaquiline resistance in Mycobacterium tuberculosis ancestral Beijing genotype causing extensively drug-resistant tuberculosis in a Tibetan refugee. American Journal of Respiratory and Critical Care Medicine, 193(3), 337–340.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Hou, S., Wu, J., Li, X., & Shu, H. (2015). Practical, regulatory and clinical considerations for development of inhalation drug products. Asian Journal of Pharmaceutical Sciences, 10(6), 490–500.CrossRefGoogle Scholar
  21. Kahnert, A., Seiler, P., Stein, M., Bandermann, S., Hahnke, K., Mollenkopf, H., & Kaufmann, S. H. (2006). Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis. European Journal of Immunology, 36(3), 631–647.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Kaur, J., Muttil, P., Verma, R. K., Kumar, K., Yadav, A. B., Sharma, R., & Misra, A. (2008). A hand-held apparatus for “nose-only” exposure of mice to inhalable microparticles as a dry powder inhalation targeting lung and airway macrophages. European Journal of Pharmaceutical Sciences, 34(1), 56–65.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Kendall, E. A., Azman, A. S., Cobelens, F. G., & Dowdy, D. W. (2017). MDR-TB treatment as prevention: The projected population-level impact of expanded treatment for multidrug-resistant tuberculosis. PLoS One, 12(3), e0172748.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Kerantzas, C. A., & Jacobs, W. R. (2017). Origins of combination therapy for tuberculosis: Lessons for future antimicrobial development and application. MBio, 8(2), e01586-16.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Kunda, N. K., Wafula, D., Tram, M., Wu, T. H., & Muttil, P. (2016). A stable live bacterial vaccine. European Journal of Pharmaceutics and Biopharmaceutics, 103, 109–117.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Kvasnovsky, C. L., Peter, C. J., & Van dW. M. L. (2016). Treatment outcomes for patients with extensively drug-resistant tuberculosis, KwaZulu-Natal and Eastern cape provinces, South Africa. Emerging Infectious Diseases, 22(9), 1529–1536.PubMedCentralCrossRefGoogle Scholar
  27. Lee, J. Y. (2015). Diagnosis and treatment of extrapulmonary tuberculosis. Tuberculosis Respiratory Disease, 78(2), 47–55.CrossRefGoogle Scholar
  28. Legentil, L., Paris, F., Ballet, C., Trouvelot, S., Daire, X., Vetvicka, V., & Ferrières, V. (2015). Molecular interactions of β-(1→ 3)-glucans with their receptors. Molecules, 20(6), 9745–9766.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Malcomson, R. J., & Embleton, J. K. (1998). Dry powder formulations for pulmonary delivery. Pharmaceutical Science & Technology Today, 1(9), 394–398.CrossRefGoogle Scholar
  30. Matteelli, A., Roggi, A., & Carvalho, A. C. (2014). Extensively drug-resistant tuberculosis: Epidemiology and management. Clinical Epidemiology, 6, 111–118.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Miller, J. B., Abramson, H. A., & Ratner, B. (1950). Aerosol streptomycin treatment of advanced pulmonary tuberculosis in children. American Journal of Diseases of Children, 80(2), 207–237.PubMedPubMedCentralGoogle Scholar
  32. Mitragotri, S. (2005). Immunization without needles. Nature Reviews. Immunology, 5(12), 905–916.PubMedCrossRefPubMedCentralGoogle Scholar
  33. Muttil, P., Kaur, J., Kumar, K., Yadav, A. B., Sharma, R., & Misra, A. (2007). Inhalable microparticles containing large payload of anti-tuberculosis drugs. European Journal of Pharmaceutical Sciences, 32(2), 140–150.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Muttil, P., Wang, C., & Hickey, A. J. (2009). Inhaled drug delivery for tuberculosis therapy. Pharmaceutical Research, 26(11), 2401–2416.PubMedCrossRefPubMedCentralGoogle Scholar
  35. Nasiruddin, M., Neyaz, M., & Das, S. (2017). Nanotechnology-based approach in tuberculosis treatment. Tuberculosis Research and Treatment, 2017. Article ID 4920209, 12 (Review).Google Scholar
  36. O’Garra, A., Redford, P. S., McNab, F. W., Bloom, C. I., Wilkinson, R. J., & Berry, M. P. (2013). The immune response in tuberculosis. Annual Review of Immunology, 31, 475–527.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Pai, M., Behr, M. A., Dowdy, D., Dheda, K., Divangahi, M., Boehme, C. C., Ginsberg, A., Swaminathan, S., Spigelman, M., Getahun, H., Menzies, D., & Raviglione, M. (2016). Tuberculosis. Nature Reviews. Disease Primers, 2, 16076. 1–23.PubMedCrossRefPubMedCentralGoogle Scholar
  38. Pandey, R., Sharma, S., & Khuller, G. K. (2005). Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis, 85(5–6), 415–420.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Parikh, R., Patel, L., & Dalwadi, S. (2014). Microparticles of rifampicin: Comparison of pulmonary route with oral route for drug uptake by alveolar macrophages, phagocytosis activity and toxicity study in albino rats. Drug Delivery, 21(6), 406–411.PubMedCrossRefPubMedCentralGoogle Scholar
  40. Parumasivam, T., Chang, R. Y. K., Abdelghany, S., Ye, T. T., Britton, W. J., & Chan, H. K. (2016). Dry powder inhalable formulations for anti-tubercular therapy. Advanced Drug Delivery Reviews, 102, 83–101.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Petersen, E., Maeurer, M., Marais, B., Migliori, G. B., Mwaba, P., Ntoumi, F., et al. (2017). World TB day 2017: Advances, challenges and opportunities in the “end-TB” era. International Journal of Infectious Diseases, 56, 1–5.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Pham, D. D., Fattal, E., & Tsapis, N. (2015). Pulmonary drug delivery systems for tuberculosis treatment. International Journal of Pharmaceutics, 478(2), 517–529.PubMedCrossRefPubMedCentralGoogle Scholar
  43. Pinheiro, M., Lúcio, M., Lima, J. L., & Reis, S. (2011). Liposomes as drug delivery systems for the treatment of TB. Nanomedicine, 6(8), 1413–1428.CrossRefGoogle Scholar
  44. Prasad, R., Singh, A., Balasubramanian, V., & Gupta, N. (2017). Extensively drug-resistant tuberculosis in India: Current evidence on diagnosis & management. The Indian Journal of Medical Research, 145(3), 271–293.PubMedPubMedCentralGoogle Scholar
  45. Price, D. N., Kunda, N. K., & Muttil, P. (2018). Challenges associated with the pulmonary delivery of therapeutic dry powders for preclinical testing. Kona Powder and Particle Journal, 36, 2019008.Google Scholar
  46. Qurrat-ul-Ain, Sharma, S., Khuller, G., & Garg, S. K. (2003). Alginate based oral drug delivery system for tuberculosis: Pharmacokinetics and therapeutic effects. The Journal of Antimicrobial Chemotherapy, 51(4), 931–938.Google Scholar
  47. Raviglione, M., & Sulis, G. (2016). Tuberculosis 2015: Burden, challenges and strategy for control and elimination. Infectious Disease Reports, 8(2), 6570.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Rom, W. N., & Garay, S. M. (2003). Tuberculosis (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.Google Scholar
  49. Sacks, L. V., Pendle, S., Orlovic, D., Andre, M., Popara, M., Moore, G., Thonell, L., & Hurwitz, S. (2001). Adjunctive salvage therapy with inhaled aminoglycosides for patients with persistent smear-positive pulmonary tuberculosis. Clinical Infectious Diseases, 32(1), 44–49.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Sen, H., Jayanthi, S., Sinha, R., Sharma, R., & Muttil, P.. (2003). Inhalable biodegradable microparticles for target-specific drug delivery in tuberculosis and a process thereof. PCT/IB03/04694.Google Scholar
  51. Sharma, R., Saxena, D., Dwivedi, A. K., & Misra, A. (2001). Inhalable microparticles containing drug combinations to target alveolar macrophages for treatment of pulmonary tuberculosis. Pharmaceutical Research, 18(10), 1405–1410.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Sharma, R., Yadav, A. B., Muttil, P., Kajal, H., & Misra, A. (2011). Inhalable microparticles modify cytokine secretion by lung macrophages of infected mice. Tuberculosis, 91(1), 107–110.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Shegokar, R., Al Shaal, L., & Mitri, K. (2011). Present status of nanoparticle research for treatment of tuberculosis. Journal of Pharmacy & Pharmaceutical Sciences, 14(1), 100–116.CrossRefGoogle Scholar
  54. Sotgiu, G., Centis, R., D’ambrosio, L., & Migliori, G. B. (2015). Tuberculosis treatment and drug regimens. Cold Spring Harbor Perspectives in Medicine, 5(5), a017822.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Soto, E., Kim, Y. S., Lee, J., Kornfeld, H., & Ostroff, G. (2010). Glucan particle encapsulated rifampicin for targeted delivery to macrophages. Polymers, 2(4), 681–689.CrossRefGoogle Scholar
  56. Thomas, S., & Bagyalakshmi, J. (2013). Design, development and characterization of pyrazinamide niosomal dosage form. American Journal of PharmTech Research, 3(6), 532–544.Google Scholar
  57. Tiberi, S., Scardigli, A., Centis, R., D’Ambrosio, L., Munoz-Torrico, M., Salazar-Lezama, M. A., Spanevello, A., Visca, D., Zumla, A., Migliori, G. B., & Luna, J. A. C. (2017). Classifying new anti-tuberculosis drugs: Rationale and future perspectives. International Journal of Infectious Diseases, 56, 181–184.PubMedCrossRefPubMedCentralGoogle Scholar
  58. Turner, M. T., Haskal, R., McGowan, K., Nardell, E., & Sabbag, R. (1998). Inhaled kanamycin in the treatment of multidrug-resistant tuberculosis: A study of five patients. Infectious Diseases in Clinical Practice, 7(1), 49–53.CrossRefGoogle Scholar
  59. Upadhyay, T. K., Fatima, N., Sharma, D., Saravanakumar, V., & Sharma, R. (2017). Preparation and characterization of beta-glucan particles containing a payload of nanoembedded rifabutin for enhanced targeted delivery to macrophages. EXCLI Journal, 16, 210–228.PubMedPubMedCentralGoogle Scholar
  60. Uplekar, M., Weil, D., Lonnroth, K., Jaramillo, E., Lienhardt, C., Dias, H. M., et al. (2015). WHO’s new end TB strategy. The Lancet, 385, 1799–1801.CrossRefGoogle Scholar
  61. Verma, R. K., Singh, A. K., Mohan, M., Agrawal, A. K., & Misra, A. (2011). Inhaled therapies for tuberculosis and the relevance of activation of lung macrophages by particulate drug-delivery systems. Therapeutic Delivery, 2(6), 753–768.PubMedCrossRefPubMedCentralGoogle Scholar
  62. Verma, R. K., Germishuizen, W. A., Motheo, M. P., Agrawal, A. K., Singh, A. K., Mohan, M., Gupta, P., Gupta, U. D., Cholo, M., Anderson, R., Fourie, P. B., & Fourie, P. B. (2013a). Inhaled microparticles containing clofazimine are efficacious in treatment of experimental tuberculosis in mice. Antimicrobial Agents and Chemotherapy, 57(2), 1050–1052.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Verma, R., Khanna, P., & Mehta, B. (2013b). Revised national tuberculosis control program in India: The need to strengthen. International Journal of Preventive Medicine, 4(1), 1–5.PubMedPubMedCentralGoogle Scholar
  64. WHO. (2017). Guidelines for treatment of drug-susceptible tuberculosis and patient care (2017 update). http://www.who.int/tb/publications/2017/dstb_guidance_2017/en/. Accessed 25 Mar 2018.
  65. World Health Organization. Global tuberculosis report 2017. WHO/HTM/TB/2017.23. Geneva: World Health Organization. 2017, 21–63.Google Scholar
  66. Zumla, A. I., Gillespie, S. H., Hoelscher, M., Philips, P. P., Cole, S. T., Abubakar, I., McHugh, T. D., Schito, M., Maeurer, M., & Nunn, A. J. (2014). New antituberculosis drugs, regimens, and adjunct therapies: Needs, advances, and future prospects. The Lancet Infectious Diseases, 14(4), 327–340.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Tarun K. Upadhyay
    • 1
    • 2
  • Akanksha Sharma
    • 1
  • Nida Fatima
    • 1
  • Amit Singh
    • 3
  • Pavan Muttil
    • 4
  • Rolee Sharma
    • 1
    Email author
  1. 1.Department of BiosciencesIntegral UniversityLucknowIndia
  2. 2.School of Applied Sciences and Agriculture ResearchSuresh Gyan Vihar UniversityJaipurIndia
  3. 3.National JALMA Institute for Leprosy and Other Mycobacterial DiseasesAgraIndia
  4. 4.Department of Pharmaceutical Sciences, College of PharmacyThe University of New Mexico, Health Sciences CenterAlbuquerqueUSA

Personalised recommendations