{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:41:02Z","timestamp":1791726062104,"version":"4.3.4"},"reference-count":133,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Tuberculosis (TB) remains a significant worldwide health challenge due to the limitations of conventional treatments and the rising incidence of drug-resistant Mycobacterium tuberculosis strains. This review consolidates the advancements in nanotechnology-based therapeutics, inhalable formulations, CRISPR\u2013Cas tools, host-directed therapies (HDTs), and nanoparticle-based vaccine development aimed at enhancing TB management. Novel nanocarriers such as liposomes, solid-lipid nanoparticles (SLNs), dendrimers, and polymeric nanoparticles (NPs) offer enhanced bioavailability of drugs, sustained release, as well as targeted delivery to infected macrophages, thereby reducing systemic toxicity and dosing frequency. Inhalable nanomedicines provide localized delivery to the pulmonary site, enhancing the concentration of the drug at the primary site of infection. CRISPR\u2013Cas technology is emerging as a transformative approach to disabling drug-resistant genes and enhancing diagnostic precision. HDTs, including agents like vitamin D and metformin, show potential in modulating host immune responses and enhancing pathogen clearance. Nanoparticle-based vaccines, including mRNA and antigen-conjugated platforms, aim to overcome the limitations of the BCG vaccine by enhancing antigen presentation and eliciting stronger, longer-lasting immunity. Collectively, these modalities mark a shift toward more personalized, effective, and less toxic TB therapies. However, challenges such as regulatory approval, safety, scalability, and accessibility remain. This review highlights the integrated potential of nanomedicine, gene editing, and immunomodulation to transform TB care and combat drug resistance, paving the way for more robust and durable treatment strategies.<\/jats:p>","DOI":"10.3390\/pharmaceutics17111459","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T07:58:32Z","timestamp":1762934312000},"page":"1459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Advanced Nanosystems and Emerging Therapies: Innovations in Tuberculosis Treatment and Drug Resistance"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5377-0961","authenticated-orcid":false,"given":"Akhil","family":"Sharma","sequence":"first","affiliation":[{"name":"School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar 144411, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-1056","authenticated-orcid":false,"given":"Vikas","family":"Sharma","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar 144411, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivika","family":"Sharma","sequence":"additional","affiliation":[{"name":"School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar 144411, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0064-7094","authenticated-orcid":false,"given":"Sonu","family":"Sharma","sequence":"additional","affiliation":[{"name":"Baba Nahar Biotech and Research, Bilaspur 174001, Himachal Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monu","family":"Sharma","sequence":"additional","affiliation":[{"name":"Baba Nahar Biotech and Research, Bilaspur 174001, Himachal Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7447-6392","authenticated-orcid":false,"given":"Iyyakkannu","family":"Sivanesan","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Science, Human and Eco Care Center, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/S1473-3099(23)00589-3","article-title":"The TB Vaccine Accelerator Council: Harnessing the power of vaccines to end the tuberculosis epidemic","volume":"23","author":"Ghebreyesus","year":"2023","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S161","DOI":"10.1016\/j.ijmyco.2016.09.066","article-title":"Overview of drug-resistant tuberculosis worldwide","volume":"5","author":"Velayati","year":"2016","journal-title":"Int. J. Mycobacteriology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103955","DOI":"10.1016\/j.drudis.2024.103955","article-title":"Tuberculosis treatment-shortening","volume":"29","author":"Singh","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kumar, M., Virmani, T., Kumar, G., Deshmukh, R., Sharma, A., Duarte, S., Brand\u00e3o, P., and Fonte, P. (2023). Nanocarriers in Tuberculosis Treatment: Challenges and Delivery Strategies. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101360"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mignani, S., Tripathi, R.P., Chen, L., Caminade, A.-M., Shi, X., and Majoral, J.-P. (2018). New Ways to Treat Tuberculosis Using Dendrimers as Nanocarriers. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030105"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez, A., Mej\u00eda, S.P., and Orozco, J. (2020). Recent advances in polymeric nanoparticle-encapsulated drugs against intracellular infections. Molecules, 25.","DOI":"10.3390\/molecules25163760"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1021\/acsinfecdis.9b00357","article-title":"Liposomes for antibiotic encapsulation and delivery","volume":"6","author":"Hosseinidoust","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.15171\/apb.2015.043","article-title":"Solid lipid nanoparticles and nanostructured lipid carriers: Structure, preparation and application","volume":"5","author":"Naseri","year":"2015","journal-title":"Adv. Pharm. Bull."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1039\/C7PY02000G","article-title":"A mannose-conjugated multi-layered polymeric nanocarrier system for controlled and targeted release on alveolar macrophages","volume":"9","author":"Praphakar","year":"2018","journal-title":"Polym. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ijpharm.2018.07.030","article-title":"Dendrimers: A versatile nanocarrier for drug delivery and targeting","volume":"548","author":"Sherje","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119435","DOI":"10.1016\/j.ijpharm.2020.119435","article-title":"Advances in nanogel formulations provide controlled drug release","volume":"584","author":"Ahmed","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1093\/infdis\/jiy712","article-title":"Remembering the Host in Tuberculosis Drug Development","volume":"219","author":"Frank","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ijtb.2023.05.011","article-title":"Metformin has immunomodulatory effects which support its potential use as adjunctive therapy in tuberculosis","volume":"71","author":"Sutter","year":"2024","journal-title":"Indian J. Tuberc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/jac\/dkab437","article-title":"Utilization of CRISPR interference to investigate the contribution of genes to pathogenesis in a macrophage model of Mycobacterium tuberculosis infection","volume":"77","author":"Cheung","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Allu\u00e9-Guardia, A., Saranathan, R., Chan, J., and Torrelles, J.B. (2021). Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020735"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117594","DOI":"10.1016\/j.lfs.2020.117594","article-title":"Tuberculosis vaccine: A journey from BCG to present","volume":"252","author":"Fatima","year":"2020","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1177\/2472630317738699","article-title":"Theranostic Nanoparticles for Tracking and Monitoring Disease State","volume":"23","author":"Zavaleta","year":"2018","journal-title":"JALA J. Assoc. Lab. Autom."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hua, S., de Matos, M.B.C., Metselaar, J.M., and Storm, G. (2018). Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00790"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.15406\/jbmoa.2022.10.00333","article-title":"A multidimensional approach to the elimination of tuberculosis","volume":"10","author":"Singh","year":"2022","journal-title":"J. Bacteriol. Mycol. Open Access"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sharma, D.K. (2025). Current advancements in nanoparticles for vaccines and drug delivery for the treatment of tuberculosis. J. Microbiol. Methods, 232\u2013234.","DOI":"10.1016\/j.mimet.2025.107138"},{"key":"ref_21","first-page":"4920209","article-title":"Nanotechnology-Based Approach in Tuberculosis Treatment","volume":"2017","author":"Nasiruddin","year":"2017","journal-title":"Tuberc. Res. Treat."},{"key":"ref_22","first-page":"14","article-title":"Nanotechnology-Based Drug Delivery System in Tuberculosis","volume":"3","author":"Sharma","year":"2017","journal-title":"Int. J. Nanobiotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Shi, L., Gu, R., Long, J., Duan, G., and Yang, H. (2024). Application of CRISPR\u2013cas-based technology for the identification of tuberculosis, drug discovery and vaccine development. Mol. Biol. Rep., 51.","DOI":"10.1007\/s11033-024-09424-6"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/mi.2012.19","article-title":"Mechanisms of delayed anti-tuberculosis protection in the lung of parenteral BCG-vaccinated hosts: A critical role of airway luminal T cells","volume":"5","author":"Horvath","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1080\/10837450.2023.2279691","article-title":"Review of inhalable nanoparticles for the pulmonary delivery of anti-tuberculosis drugs","volume":"28","author":"Ramachandran","year":"2023","journal-title":"Pharm. Dev. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.52711\/2231-5691.2023.00005","article-title":"Side Effects of TB Therapy and Recent Therapeutic Approaches for Tuberculosis Management","volume":"13","author":"Bandgar","year":"2023","journal-title":"Asian J. Pharm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1602308","DOI":"10.1183\/13993003.02308-2016","article-title":"World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update","volume":"49","author":"Falzon","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_28","first-page":"CD012918","article-title":"Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis","volume":"12","author":"Grace","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1002\/cpt.1393","article-title":"Contemporary Drug\u2013Drug Interactions in HIV Treatment","volume":"105","author":"Devanathan","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1801350","DOI":"10.1183\/13993003.01350-2018","article-title":"A new era for treatment of drug-resistant tuberculosis","volume":"52","author":"Gandhi","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nair, A., Greeny, A., Nandan, A., Sah, R.K., Jose, A., Dyawanapelly, S., Junnuthula, V., KV, A., and Sadanandan, P. (2023). Advanced drug delivery and therapeutic strategies for tuberculosis treatment. J. Nanobiotechnology, 21.","DOI":"10.1186\/s12951-023-02156-y"},{"key":"ref_32","unstructured":"World Health Organization (2022). WHO consolidated guidelines on tuberculosis. Module 4: Treatment-Drug-Resistant Tuberculosis Treatment, 2022 Update, World Health Organization."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"102208","DOI":"10.1016\/j.tube.2022.102208","article-title":"Nanotechnology and tuberculosis: An old disease with new treatment strategies","volume":"135","author":"Cavalcanti","year":"2022","journal-title":"Tuberculosis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2000113","DOI":"10.1002\/adtp.202000113","article-title":"Nanotechnology-Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis","volume":"4","author":"Baranyai","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e3702518","DOI":"10.1155\/2019\/3702518","article-title":"Smart Nanoparticles for Drug Delivery Application: Development of Versatile Nanocarrier Platforms in Biotechnology and Nanomedicine","volume":"2019","author":"Lombardo","year":"2019","journal-title":"J. Nanomater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2400177","DOI":"10.1002\/ppsc.202400177","article-title":"Encapsulation of Rifampicin in Solid Lipid Nanoparticles by Microwave-Assisted Microemulsion Method","volume":"42","author":"Nguyen","year":"2024","journal-title":"Part. Part. Syst. Charact."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/lam.13082","article-title":"Antimicrobial activity and toxicity of gold nanoparticles: Research progress, challenges and prospects","volume":"67","author":"Tao","year":"2018","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20230139","DOI":"10.1002\/EXP.20230139","article-title":"Unveiling the promise: Exosomes as game-changers in anti-infective therapy","volume":"4","author":"Chavda","year":"2024","journal-title":"Exploration"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22159\/ijpps.2016v8i10.11295","article-title":"Drug-resistant tuberculosis: Recent approach in polymer-based nanomedicine","volume":"8","author":"Shaji","year":"2016","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100095","DOI":"10.1016\/j.jciso.2023.100095","article-title":"Micro and nano-carriers-based pulmonary drug delivery system: Their current updates, challenges, and limitations\u2014A review","volume":"12","author":"Kumar","year":"2023","journal-title":"JCIS Open"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1039\/D1BM01664D","article-title":"Macrophage membrane coated nanoparticles: A biomimetic approach for enhanced and targeted delivery","volume":"10","author":"Khatoon","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_42","first-page":"e71697","article-title":"Revolutionizing Tuberculosis Management With Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas Technology: A Comprehensive Literature Review","volume":"16","author":"Shetty","year":"2024","journal-title":"Cureus"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Qi, Y., Li, K., Li, Y., Guo, D., Xu, J., Li, Y., and Gong, W. (2022). CRISPR-based diagnostics: A potential tool to address the diagnostic challenges of tuberculosis. Pathogens, 11.","DOI":"10.3390\/pathogens11101211"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1080\/10717544.2022.2120565","article-title":"Nanomaterials in tuberculosis DNA vaccine delivery: Historical perspective and current landscape","volume":"29","author":"Luo","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhao, Z., Wang, Q., Shi, J., Wong, D.W.-C., and Cheung, J.C.-W. (2024). Advancements in Nanoparticle-Based Adjuvants for Enhanced Tuberculosis Vaccination: A Review. Vaccines, 12.","DOI":"10.3390\/vaccines12121335"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6959","DOI":"10.1016\/j.vaccine.2011.07.039","article-title":"Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis","volume":"29","author":"Ballester","year":"2011","journal-title":"Vaccine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1900189","DOI":"10.1002\/adtp.201900189","article-title":"Next-generation Theranostics: Functionalized Nanomaterials Enable Efficient Diagnosis and Therapy of Tuberculosis","volume":"3","author":"Li","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_48","first-page":"1134","article-title":"Recent Advances in Nanocarrier Based Therapeutic and Diagnostic Approaches in Tuberculosis","volume":"6","author":"Ahmad","year":"2023","journal-title":"Precis. Nanomed."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lukeman, H., Al-Wassiti, H., Fabb, S.A., Lim, L., Wang, T., Britton, W.J., Steain, M., Pouton, C.W., Triccas, J.A., and Counoupas, C. (2024). A lipid nanoparticle-mRNA vaccine provides potent immunogenicity and protection against Mycobacterium tuberculosis. bioRxiv.","DOI":"10.1101\/2024.07.31.605765"},{"key":"ref_50","first-page":"181","article-title":"Principles of Therapy for Tuberculosis","volume":"23","author":"Ortona","year":"1998","journal-title":"Rays"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"547","DOI":"10.2174\/1568026621999201211200447","article-title":"Tuberculosis: An update on pathophysiology, molecular mechanisms of drug resistance, newer anti-TB drugs, treatment regimens, and host-directed therapies","volume":"21","author":"Borah","year":"2021","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_52","first-page":"163","article-title":"First-and second-line drugs and drug resistance","volume":"20","author":"Jnawali","year":"2013","journal-title":"Tuberc.-Curr. Issues Diagn. Manag."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1586\/14787210.5.5.857","article-title":"Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis: Epidemiology and control","volume":"5","author":"Matteelli","year":"2007","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Abreu, R., Giri, P., and Quinn, F. (2020). Host-pathogen interaction as a novel target for host-directed therapies in tuberculosis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01553"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/17460441.2023.2157811","article-title":"Advances in the design of combination therapies for the treatment of tuberculosis","volume":"18","author":"Aldridge","year":"2023","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"572","DOI":"10.5588\/ijtld.24.0121","article-title":"Examining effective monotherapy hypothesis for TB therapy failure and resistance emergence","volume":"28","author":"Srivastava","year":"2024","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dos Santos, J.L., and Chin, C.M. (2014). Pharmacology of Antitubercular Drugs: Challenges and Advances. Biochem. Pharmacol., 3.","DOI":"10.4172\/2167-0501.1000e164"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Cronan, M.R. (2022). In the Thick of It: Formation of the Tuberculous Granuloma and Its Effects on Host and Therapeutic Responses. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.820134"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gibson, S.E., Harrison, J., and Cox, J.A. (2018). Modelling a silent epidemic: A review of the in vitro models of latent tuberculosis. Pathogens, 7.","DOI":"10.20944\/preprints201810.0701.v1"},{"key":"ref_60","first-page":"197","article-title":"Future implications: Compliance and failure with antiretroviral treatment","volume":"52","author":"Patel","year":"2006","journal-title":"J. Postgrad. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.2174\/0115672018265571231011093546","article-title":"Recent Updates in Inhalable Drug Delivery System against Various Pulmonary Diseases: Challenges and Future Perspectives","volume":"21","author":"Chaudhary","year":"2024","journal-title":"Curr. Drug Deliv."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Rajput, A., Mandlik, S., and Pokharkar, V. (2021). Nanocarrier-based approaches for the efficient delivery of anti-tubercular drugs and vaccines for the management of tuberculosis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.749945"},{"key":"ref_63","first-page":"43","article-title":"Pulmonary drug delivery systems of antibiotics for the treatment of respiratory tract infections","volume":"89","author":"Karimi","year":"2019","journal-title":"Acta Pharm. Hung."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jconrel.2014.05.038","article-title":"Respirable nanocarriers as a promising strategy for antitubercular drug delivery","volume":"187","author":"Mehanna","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yin, J., Yuan, J., Hu, Y., and Wei, X. (2016). Association between Directly Observed Therapy and Treatment Outcomes in Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150511"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1515\/ntrev-2022-0004","article-title":"The contribution of microfluidics to the fight against tuberculosis","volume":"11","author":"Vaquero","year":"2021","journal-title":"Nanotechnol. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e2105909","DOI":"10.1002\/advs.202105909","article-title":"Human Mesenchymal Stem Cell-Derived Miniature Joint System for Disease Modeling and Drug Testing","volume":"9","author":"Li","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1038\/s41467-024-48269-2","article-title":"Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy","volume":"15","author":"Mistretta","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Berry, S.B., Gower, M.S., Su, X., Seshadri, C., and Theberge, A.B. (2020). A modular microscale granuloma model for immune-microenvironment signaling studies in vitro. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00931"},{"key":"ref_70","first-page":"58","article-title":"Tuberculosis and Its Treatment: An Overview","volume":"18","author":"Bansal","year":"2018","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Iacobino, A., Fattorini, L., and Giannoni, F. (2020). Drug-Resistant Tuberculosis 2020: Where We Stand. Appl. Sci., 10.","DOI":"10.3390\/app10062153"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Jeong, E.-K., Lee, H.-J., and Jung, Y.-J. (2022). Host-Directed Therapies for Tuberculosis. Pathogens, 11.","DOI":"10.3390\/pathogens11111291"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Adikesavalu, H., Gopalaswamy, R., Kumar, A., Ranganathan, U.D., and Shanmugam, S. (2021). Autophagy Induction as a Host-Directed Therapeutic Strategy against Mycobacterium tuberculosis Infection. Medicina, 57.","DOI":"10.3390\/medicina57060522"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.tips.2021.11.016","article-title":"Host-directed therapies for tuberculosis: Quantitative systems pharmacology approaches","volume":"43","author":"Mehta","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1042\/BCJ20200194","article-title":"The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host\u2019s immune system","volume":"477","author":"Batt","year":"2020","journal-title":"Biochem. J."},{"key":"ref_76","first-page":"729","article-title":"The diagnosis and treatment of tuberculosis","volume":"116","author":"Rademacher","year":"2019","journal-title":"Dtsch. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.meegid.2016.09.004","article-title":"Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis","volume":"45","author":"Unissa","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1128\/JB.181.7.2044-2049.1999","article-title":"Role of Acid pH and Deficient Efflux of Pyrazinoic Acid in Unique Susceptibility of Mycobacterium tuberculosis to Pyrazinamide","volume":"181","author":"Zhang","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1128\/AAC.33.9.1493","article-title":"Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis","volume":"33","author":"Takayama","year":"1989","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"a017863","DOI":"10.1101\/cshperspect.a017863","article-title":"Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis","volume":"5","author":"Seung","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"19192","DOI":"10.1039\/C9CP03631H","article-title":"Binding energies of the drugs capreomycin and streptomycin in complex with tuberculosis bacterial ribosome subunits","volume":"21","author":"Vianna","year":"2019","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1021\/acsinfecdis.4c00128","article-title":"Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance","volume":"10","author":"Collins","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/14740338.2020.1712357","article-title":"Protective effects of pharmacological agents against aminoglycoside-induced nephrotoxicity: A systematic review","volume":"19","author":"Yaghoubi","year":"2020","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1039\/D4MD00829D","article-title":"Breaking the energy chain: Importance of ATP synthase in Mycobacterium tuberculosis and its potential as a drug target","volume":"16","author":"Perveen","year":"2025","journal-title":"RSC Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"300","DOI":"10.4103\/0022-3859.138772","article-title":"Bedaquiline: A novel antitubercular drug for multidrug-resistant tuberculosis","volume":"60","author":"Nagabushan","year":"2014","journal-title":"J. Postgrad. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.2147\/DDDT.S164515","article-title":"Linezolid: A review of its properties, function, and use in critical care","volume":"12","author":"Hashemian","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10276","DOI":"10.1074\/jbc.M110.200501","article-title":"Reduction of clofazimine by mycobacterial type 2 NADH: Quinone oxidoreductase: A pathway for the generation of bactericidal levels of reactive oxygen species","volume":"286","author":"Yano","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1358\/dot.2020.56.10.3161237","article-title":"Pretomanid for the treatment of pulmonary tuberculosis","volume":"56","author":"Thakare","year":"2020","journal-title":"Drugs Today"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.trsl.2020.03.007","article-title":"New tuberculosis drug targets, their inhibitors, and potential therapeutic impact","volume":"220","author":"Shetye","year":"2020","journal-title":"Transl. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"103690","DOI":"10.1016\/j.jddst.2022.103690","article-title":"Recent developments, challenges and future prospects in advanced drug delivery systems in the management of tuberculosis","volume":"75","author":"Verma","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Mourenza, \u00c1., Gil, J.A., Mateos, L.M., and Letek, M. (2020). Novel treatments against Mycobacteriumtuberculosis based on drug repurposing. Antibiotics, 9.","DOI":"10.3390\/antibiotics9090550"},{"key":"ref_92","first-page":"2","article-title":"Trends and Correlations of Major Infectious Diseases in Indonesia Before and After the COVID-19 Pandemic: A Comprehensive Seven-Year Analysis (2017\u20132023)","volume":"57","author":"Sari","year":"2025","journal-title":"J. Commun. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.2147\/PPA.S219920","article-title":"Drug non-adherence and reasons among multidrug-resistant tuberculosis patients in Guizhou, China: A cross-sectional study","volume":"13","author":"Wang","year":"2019","journal-title":"Patient Prefer. Adherence"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Quncuo, C., Ye, W.D., Yang, J., and He, J.-Q. (Infection, 2025). Predictors of therapeutic exposure and pharmacokinetic variability of second-line anti-TB drugs in MDR-TB patients: A retrospective study, Infection, Online ahead of print.","DOI":"10.1007\/s15010-025-02620-x"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"102978","DOI":"10.1016\/j.jiph.2025.102978","article-title":"Mapping the immunological research landscape of tuberculosis: A bibliometric review of global trends and clinical themes (2016\u20132025)","volume":"18","author":"Mathkour","year":"2025","journal-title":"J. Infect. Public Health"},{"key":"ref_96","unstructured":"Fuseini, S. (2025). Living with Tuberculosis: A Qualitative Study of patients\u2019 Experiences with Disease and Treatment at the Tamale Teaching Hospital. [Doctoral Dissertation, University For Development Studies]."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"76","DOI":"10.18231\/j.ijrimcr.2024.054","article-title":"The key factors influencing tuberculosis treatment outcomes: A literature review","volume":"6","author":"Mohammed","year":"2024","journal-title":"Int. J. Recent Innov. Med. Clin. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.rppnen.2017.11.003","article-title":"Tuberculosis, social determinants and co-morbidities (including HIV)","volume":"24","author":"Duarte","year":"2018","journal-title":"Pulmonology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.5455\/ijmsph.2016.20062016529","article-title":"Determinants of sputum conversion at two months of treatment under National Tuberculosis Programme, South India","volume":"5","author":"Yellappa","year":"2016","journal-title":"Int. J. Med Sci. Public Health"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1046\/j.1365-3156.2003.01156.x","article-title":"Multidrug-resistant tuberculosis: Public health challenges","volume":"9","author":"Coker","year":"2004","journal-title":"Trop. Med. Int. Health"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"a017822","DOI":"10.1101\/cshperspect.a017822","article-title":"Tuberculosis treatment and drug regimens","volume":"5","author":"Sotgiu","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Nezenega, Z.S., Perimal-Lewis, L., and Maeder, A.J. (2020). Factors Influencing Patient Adherence to Tuberculosis Treatment in Ethiopia: A Literature Review. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17155626"},{"key":"ref_103","first-page":"182","article-title":"Systematic Literature Review: Analysis of Quality of the Pulmonary TB Program with the DOTS (Directly Observed Treatment Shortcourse) Strategy","volume":"2","author":"PH","year":"2023","journal-title":"Menara J. Health Sci."},{"key":"ref_104","first-page":"28","article-title":"Transmission dynamics of tuberculosis: An epidemiological and biological perspective","volume":"1","author":"Bekzod","year":"2025","journal-title":"Kazakh J. Ecosyst. Restor. Biodivers."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Navasardyan, I., Miwalian, R., Petrosyan, A., Yeganyan, S., and Venketaraman, V. (2024). HIV\u2013TB Coinfection: Current Therapeutic Approaches and Drug Interactions. Viruses, 16.","DOI":"10.3390\/v16030321"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"100444","DOI":"10.1016\/j.jctube.2024.100444","article-title":"Role of therapeutic drug monitoring in the treatment of multi-drug resistant tuberculosis","volume":"36","author":"Maranchick","year":"2024","journal-title":"J. Clin. Tuberc. Other Mycobact. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1080\/17512433.2024.2363847","article-title":"Therapeutic drug monitoring of antiretroviral therapy: Current progresses and future directions","volume":"17","author":"Cattaneo","year":"2024","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Dlatu, N., Faye, L.M., and Apalata, T. (2025). Outcomes of Treating Tuberculosis Patients with Drug-Resistant Tuberculosis, Human Immunodeficiency Virus, and Nutritional Status: The Combined Impact of Triple Challenges in Rural Eastern Cape. Int. J. Environ. Res. Public Health, 22.","DOI":"10.3390\/ijerph22030319"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ijtb.2025.03.011","article-title":"Navigating the dual burden of diabetes mellitus and tuberculosis: A comprehensive review of clinical and public health strategies","volume":"72","author":"Gupta","year":"2025","journal-title":"Indian J. Tuberc."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/17425255.2021.1836158","article-title":"Therapeutic drug monitoring in patients with tuberculosis and concurrent medical problems","volume":"17","author":"Burch","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Bisht, S., Jaiswal, V., and Singh, M.F. (2025). Nanotherapeutics in tuberculosis: Pulmonary and extrapulmonary applications. Applications of Nanotherapeutics and Nanotheranostics in Managing Infectious Diseases, Academic Press.","DOI":"10.1016\/B978-0-443-28836-4.00011-1"},{"key":"ref_112","unstructured":"McIvor, A. (2018). Characterization of Differentially Culturable Bacteria in Ex-Situ Culture and from Tuberculosis Patients. [Doctoral Dissertation, University of the Witwatersrand]."},{"key":"ref_113","first-page":"1","article-title":"Risk Factors of Tuberculosis and Strategies for Prevention and Control","volume":"12","author":"Etim","year":"2024","journal-title":"Int. J. Innov. Healthc. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2471\/BLT.06.038737","article-title":"Tuberculosis control in vulnerable groups","volume":"86","year":"2008","journal-title":"Bull. World Health Organ."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1080\/17476348.2021.1832469","article-title":"Social determinants of tuberculosis: Context, framework, and the way forward to ending TB in India","volume":"15","author":"Bhargava","year":"2021","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s40258-022-00785-2","article-title":"Analysing the Efficiency of Health Systems: A Systematic Review of the Literature","volume":"21","author":"Mbau","year":"2023","journal-title":"Appl. Health Econ. Health Policy"},{"key":"ref_117","first-page":"578","article-title":"Assessment of medicine stock-outs challenges in public health services","volume":"10","author":"Zuma","year":"2022","journal-title":"Afr. Public Serv. Deliv. Perform. Rev."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e002281","DOI":"10.1136\/bmjresp-2023-002281","article-title":"Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: A systematic review and meta-analysis","volume":"11","author":"Vega","year":"2024","journal-title":"BMJ Open Respir. Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Obeno, O.E., Amaral, E.E.A.D., Soares, A., Eflin, M.F., and Amaral, S.J.G.D.S. (2025). Analysis of The Adverse Effects of Anti-Tuberculosis Drugs (ATDs) on Patients with Tuberculosis, 2024. KESANS: Int. J. Health Sci., 4.","DOI":"10.54543\/kesans.v4i4.343"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Satish, S., Joshi, N., Alavala, R.R., and Khan, A.A. (2025). Drug Discovery and Computational Strategies in Multi-Drug-Resistant Tuberculosis. Applications of Computational Tools in Drug Design and Development, Springer.","DOI":"10.1007\/978-981-96-4154-3_26"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Munro, S.A., Lewin, S.A., Smith, H.J., Engel, M.E., Fretheim, A., and Volmink, J. (2007). Patient Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040238"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e419","DOI":"10.1002\/mco2.419","article-title":"Mycobacterium tuberculosis: Immune response, biomarkers, and therapeutic intervention","volume":"5","author":"Zhuang","year":"2024","journal-title":"Medcomm"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S2213-2600(25)00124-9","article-title":"Sepsis in patients who are immunocompromised: Diagnostic challenges and future therapies","volume":"13","author":"Chousterman","year":"2025","journal-title":"Lancet Respir. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/imr.12951","article-title":"Host-directed therapy to combat mycobacterial infections","volume":"301","author":"Saris","year":"2021","journal-title":"Immunol. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s41479-024-00133-z","article-title":"Early detection of tuberculosis: A systematic review","volume":"16","author":"Yayan","year":"2024","journal-title":"Pneumonia"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Gilmour, B., and Alene, K.A. (2024). Ending tuberculosis: Challenges and opportunities. Front. Tuberc., 2.","DOI":"10.3389\/ftubr.2024.1487518"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"853","DOI":"10.4239\/wjd.v15.i5.853","article-title":"Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges","volume":"15","author":"Peake","year":"2024","journal-title":"World J. Diabetes"},{"key":"ref_128","first-page":"5","article-title":"Tuberculosis in India\u2013Evolution of National Programmes and Treatment Regimens","volume":"78","author":"Deepak","year":"2025","journal-title":"Indian Pract."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3343\/alm.2017.37.2.97","article-title":"Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations","volume":"37","author":"Choi","year":"2017","journal-title":"Ann. Lab. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"82","DOI":"10.4046\/trd.2022.0148","article-title":"Improving Tuberculosis Medication Adherence: The Potential of Integrating Digital Technology and Health Belief Model","volume":"86","author":"Sazali","year":"2023","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_131","unstructured":"Herchline, T.E., and Bronze, M.S. (2025, July 16). Tuberculosis (TB). Medscape 2019. Available online: https:\/\/sim.uphillhealth.com\/resources\/3\/pdf\/TB1_eMedicine.pdf."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s12939-023-01991-7","article-title":"Factors affecting ability of TB patients to follow treatment guidelines\u2014Applying a capability approach","volume":"22","author":"Chandru","year":"2023","journal-title":"Int. J. Equity Health"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Pradipta, I.S., Idrus, L.R., Probandari, A., Lestari, B.W., Diantini, A., Alffenaar, J.-W.C., and Hak, E. (2021). Barriers and strategies to successful tuberculosis treatment in a high-burden tuberculosis setting: A qualitative study from the patient\u2019s perspective. 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