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Antibacterial Drug Discovery to Combat MDR pp 441–457Cite as

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

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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.

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References

  • Ahmad, S. (2010). Pathogenesis, immunology, and diagnosis of latent Mycobacterium tuberculosis infection. Clinical & Developmental Immunology, 2011, 814943.

    Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Ahmad, Z., Maqbool, M., & Raja, A. F. (2011). Nanomedicine for tuberculosis: Insights from animal models. International Journal of Nano Dimension, 2(1), 67–84.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Deretic, V., Via, L. E., Fratti, R. A., & Deretic, D. (1997). Mycobacterial phagosome maturation, Rab proteins and intracellular trafficking. Electrophoresis, 18(14), 2542–2547.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernstrom, A., & Goldblatt, M. (2013). Aerobiology and its role in the transmission of infectious diseases. J Pathogens, 2013, 493960.

    Google Scholar 

  • Flannagan, R. S., Jaumouille, V., & Grinstein, S. (2012). The cell biology of phagocytosis. Annual Review of Pathology, 7, 61–98.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed Central  Google Scholar 

  • Lee, J. Y. (2015). Diagnosis and treatment of extrapulmonary tuberculosis. Tuberculosis Respiratory Disease, 78(2), 47–55.

    Article  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malcomson, R. J., & Embleton, J. K. (1998). Dry powder formulations for pulmonary delivery. Pharmaceutical Science & Technology Today, 1(9), 394–398.

    Article  Google Scholar 

  • Matteelli, A., Roggi, A., & Carvalho, A. C. (2014). Extensively drug-resistant tuberculosis: Epidemiology and management. Clinical Epidemiology, 6, 111–118.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • Mitragotri, S. (2005). Immunization without needles. Nature Reviews. Immunology, 5(12), 905–916.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Muttil, P., Wang, C., & Hickey, A. J. (2009). Inhaled drug delivery for tuberculosis therapy. Pharmaceutical Research, 26(11), 2401–2416.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Pandey, R., Sharma, S., & Khuller, G. K. (2005). Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tuberculosis, 85(5–6), 415–420.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Pham, D. D., Fattal, E., & Tsapis, N. (2015). Pulmonary drug delivery systems for tuberculosis treatment. International Journal of Pharmaceutics, 478(2), 517–529.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    PubMed  PubMed Central  Google Scholar 

  • 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 

  • 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 

  • Raviglione, M., & Sulis, G. (2016). Tuberculosis 2015: Burden, challenges and strategy for control and elimination. Infectious Disease Reports, 8(2), 6570.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rom, W. N., & Garay, S. M. (2003). Tuberculosis (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.

    Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

  • World Health Organization. Global tuberculosis report 2017. WHO/HTM/TB/2017.23. Geneva: World Health Organization. 2017, 21–63.

    Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India

    Tarun K. Upadhyay, Akanksha Sharma, Nida Fatima & Rolee Sharma

  2. School of Applied Sciences and Agriculture Research, Suresh Gyan Vihar University, Jaipur, Rajasthan, India

    Tarun K. Upadhyay

  3. National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, Uttar Pradesh, India

    Amit Singh

  4. Department of Pharmaceutical Sciences, College of Pharmacy, The University of New Mexico, Health Sciences Center, Albuquerque, NM, USA

    Pavan Muttil

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  1. Tarun K. Upadhyay
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  2. Akanksha Sharma
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  3. Nida Fatima
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  4. Amit Singh
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  5. Pavan Muttil
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  6. Rolee Sharma
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Correspondence to Rolee Sharma .

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Editors and Affiliations

  1. Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

    Iqbal Ahmad

  2. Institute of Ophthalmology, JN Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

    Shamim Ahmad

  3. School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    Kendra P. Rumbaugh

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Upadhyay, T.K., Sharma, A., Fatima, N., Singh, A., Muttil, P., Sharma, R. (2019). Targeted Delivery of Antibiotics Using Microparticles to Combat Multidrug-Resistant Tuberculosis. In: Ahmad, I., Ahmad, S., Rumbaugh, K. (eds) Antibacterial Drug Discovery to Combat MDR. Springer, Singapore. https://doi.org/10.1007/978-981-13-9871-1_20

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