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Volume 20, Issue 2
  • ISSN: 2772-4344
  • E-ISSN: 2772-4352

Abstract

Multidrug-resistant tuberculosis (MDR-TB) poses a persistent challenge to global health, necessitating continuous efforts to enhance treatment efficacy. Bedaquiline, a cornerstone in MDR-TB management, presents biopharmaceutical challenges that impact its therapeutic potential. This review provides a comprehensive analysis of recent innovations in drug delivery strategies designed to optimize Bedaquiline's efficacy and improve MDR-TB treatment outcomes. Through a systematic examination of various delivery systems, including nanotechnology and formulation advancements, we explore their potential in addressing drug solubility and bioavailability challenges. Emphasizing the integration of Quality by Design (QbD) principles, this review aims to present a cohesive overview of evolving Bedaquiline delivery innovations, providing valuable insights for researchers and healthcare practitioners working towards advancing MDR-TB treatment strategies.

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2024-10-25
2025-04-22

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References

  1. MiglioriG.B. TiberiS. WHO drug-resistant TB guidelines 2022: What is new?Int. J. Tuberc. Lung Dis.202226759059110.5588/ijtld.22.0263 35768917
     [Google Scholar]
  2. GroenwegheE. SwenssonL. WinansK.D. Outbreak of multidrug-resistant tuberculosis — Kansas.MMWR Morb. Mortal. Wkly. Rep.2023723595796010.15585/mmwr.mm7235a4 37651293
     [Google Scholar]
  3. XiY. ZhangW. QiaoR.J. TangJ. Risk factors for multidrug-resistant tuberculosis: A worldwide systematic review and meta-analysis.PLoS One2022176e027000310.1371/journal.pone.0270003 35709161
     [Google Scholar]
  4. AkaluT.Y. ClementsA.C.A. WoldeH.F. AleneK.A. Economic burden of multidrug-resistant tuberculosis on patients and households: A global systematic review and meta-analysis.Sci. Rep.20231312236110.1038/s41598‑023‑47094‑9 38102144
     [Google Scholar]
  5. SongZ. LiuC. HeW. Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant Mycobacterium tuberculosis in China.Microbiol. Spectr.2023115e01324e2310.1128/spectrum.01324‑23 37732780
     [Google Scholar]
  6. MollaK.A. RetaM.A. AyeneY.Y. Prevalence of multidrug-resistant tuberculosis in East Africa: A systematic review and meta-analysis.PLoS One2022176e027027210.1371/journal.pone.0270272 35771884
     [Google Scholar]
  7. MohamedM.A. AliO.A. OsmanA.M. Assessment of drug-susceptible and multidrug-resistant tuberculosis (MDR-TB) in the Central Region of Somalia: A 3-year retrospective study.PLOS Glob. Public Health202339e000231910.1371/journal.pgph.0002319 37676848
     [Google Scholar]
  8. PaiH. NdjekaN. MbuagbawL. Bedaquiline safety, efficacy, utilization and emergence of resistance following treatment of multidrug-resistant tuberculosis patients in South Africa: A retrospective cohort analysis.BMC Infect. Dis.202222187010.1186/s12879‑022‑07861‑x 36414938
     [Google Scholar]
  9. JahanR.N. KhanZ. AkhtarM.S. Development of Bedaquiline-Loaded SNEDDS Using quality by design (QbD) approach to improve biopharmaceutical attributes for the management of multidrug-resistant Tuberculosis (MDR-TB).Antibiotics20231210151010.3390/antibiotics12101510 37887211
     [Google Scholar]
  10. DiaconA.H. DawsonR. von Groote-BidlingmaierF. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial.Lancet2012380984698699310.1016/S0140‑6736(12)61080‑0 22828481
     [Google Scholar]
  11. DiaconA.H. PymA. GrobuschM.P. Multidrug-resistant tuberculosis and culture conversion with bedaquiline.N. Engl. J. Med.2014371872373210.1056/NEJMoa1313865 25140958
     [Google Scholar]
  12. NdjekaN. ConradieF. SchnippelK. Treatment of drug-resistant Tuberculosis with bedaquiline in a high HIV prevalence setting: An interim cohort analysis.Int. J. Tuberc. Lung Dis.201519979985
     [Google Scholar]
  13. OlayanjuO. LimberisJ. EsmailA. Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa.Eur. Respir. J.2018515180054410.1183/13993003.00544‑2018 29700106
     [Google Scholar]
  14. EsmailA. OelofseS. LombardC. An all-oral 6-month regimen for multidrug-resistant tuberculosis: A multicenter, randomized controlled clinical trial (the next study).Am. J. Respir. Crit. Care Med.2022205101214122710.1164/rccm.202107‑1779OC 35175905
     [Google Scholar]
  15. TweedC.D. DawsonR. BurgerD.A. Bedaquiline, moxifloxacin, pretomanid, and pyrazinamide during the first 8 weeks of treatment of patients with drug-susceptible or drug-resistant pulmonary tuberculosis: A multicentre, open-label, partially randomised, phase 2b trial.Lancet Respir. Med.20197121048105810.1016/S2213‑2600(19)30366‑2 31732485
     [Google Scholar]
  16. TauneM UsteroP HiashiriS Successful implementation of bedaquiline for multidrug-resistant TB treatment in remote Papua New Guinea public health action20199S7379
     [Google Scholar]
  17. KempkerR.R. MikiashviliL. ZhaoY. Clinical outcomes among patients with drug-resistant tuberculosis receiving bedaquiline or delamanid containing regimens.Clin. Infect. Dis.2019ciz110710.1093/cid/ciz1107 31712809
     [Google Scholar]
  18. PadayatchiN. BionghiN. OsmanF. Treatment outcomes in patients with drug-resistant TB-HIV co-infection treated with bedaquiline and linezolid.Int. J. Tuberc. Lung Dis.20202410241031
     [Google Scholar]
  19. SchnippelK. NdjekaN. MaartensG. Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: A retrospective cohort study.Lancet Respir. Med.20186969970610.1016/S2213‑2600(18)30235‑2 30001994
     [Google Scholar]
  20. WuS.H. ChanH.H. HsiaoH.C. JouR. Primary bedaquiline resistance among cases of drug-resistant tuberculosis in Taiwan.Front. Microbiol.20211275424910.3389/fmicb.2021.754249 34745058
     [Google Scholar]
  21. XiaH ZhengY ZhaoB Van Den HofS CobelensF ZhaoY. Assessment of a 96-well plate assay of quantitative drug susceptibility testing for Mycobacterium Tuberculosis complex in China PLoS ONE201712e0169413
     [Google Scholar]
  22. KanigaK. HasanR. JouR. Bedaquiline drug resistance emergence assessment in multidrug-resistant tuberculosis (MDR-TB): a 5-year prospective in vitro surveillance study of bedaquiline and other second-line drug susceptibility testing in MDR-TB isolates.J. Clin. Microbiol.2022601e02919e0292010.1128/JCM.02919‑20 34705538
     [Google Scholar]
  23. PardhiV.P. PathakA. JainK. Solid dispersions of bedaquiline fumarate to improve its pharmaceutical attributes: A comparative study between PEG and PVP.J. Drug Deliv. Sci. Technol.20249410546110.1016/j.jddst.2024.105461
     [Google Scholar]
  24. PardhiV.P. SutharT. SharmaA. JainK. Bedaquiline fumarate microemulsion: Formulation optimization, rheological characterization and in vitro studies.Nanomedicine (Lond.)202217211529154610.2217/nnm‑2022‑0132 36416115
     [Google Scholar]
  25. VermaN. AroraV. AwasthiR. Recent developments, challenges and future prospects in advanced drug delivery systems in the management of tuberculosis.J. Drug Deliv. Sci. Technol.20227510369010.1016/j.jddst.2022.103690
     [Google Scholar]
  26. ShangY. ChenS. ShiW. Bedaquiline resistance pattern in clofazimine-resistant clinical isolates of tuberculosis patients.J. Glob. Antimicrob. Resist.20233329430010.1016/j.jgar.2023.04.003 37142094
     [Google Scholar]
  27. DousaK.M. KurzS.G. BarkC.M. BonomoR.A. FurinJ.J. Drug-resistant tuberculosis.Infect. Dis. Clin. North Am.202034486388610.1016/j.idc.2020.06.001 33011048
     [Google Scholar]
  28. DesaiG. PurohitG. BoranaH. DeokarK. YogiS. Comparison of efficacy of bedaquiline and moxifloxacin in drug resistant pulmonary tuberculosis. A prospective observational study.Monaldi Arch. Chest Dis.20229319310.4081/monaldi.2022.2231 35535455
     [Google Scholar]
  29. HoqueM. HossainM.S. AkramT. DasS.R. Advancing healthcare: Exploring recent innovations in drug delivery systems.Multidiscip Res J202345505510.54660/.IJMRGE.2023.4.5.50‑55
     [Google Scholar]
  30. WalP. WalA. SaxenaB. Insights into the innovative approaches in fiber technology for drug delivery and pharmaceuticals.J. Drug Deliv. Sci. Technol.20238710487710.1016/j.jddst.2023.104877
     [Google Scholar]
  31. YangY. LockwoodA. Topical ocular drug delivery systems: Innovations for an unmet need.Exp. Eye Res.202221810900610.1016/j.exer.2022.109006 35248559
     [Google Scholar]
  32. De MatteisL. JaryD. LucíaA. New active formulations against M. tuberculosis: Bedaquiline encapsulation in lipid nanoparticles and chitosan nanocapsules.Chem. Eng. J.201834018119110.1016/j.cej.2017.12.110
     [Google Scholar]
  33. Azger DustachkeerV.N. NirmalC.R. RajadasS.E. SaadhaliS.A. KannayanS. PadmanabanV.P. Nanotheranostic management of drug-resistant tuberculosis.A Mechanistic Approach to Medicines for Tuberculosis Nanotherapy.Academic Press202114917310.1016/B978‑0‑12‑819985‑5.00004‑8
     [Google Scholar]
  34. PardhiV.P. JainK. Impact of binary/ternary solid dispersion utilizing poloxamer 188 and TPGS to improve pharmaceutical attributes of bedaquiline fumarate.J. Drug Deliv. Sci. Technol.20216210234910.1016/j.jddst.2021.102349
     [Google Scholar]
  35. GoelD. Bedaquiline: A novel drug to combat multiple drug-resistant tuberculosis.J. Pharmacol. Pharmacother.201451767810.4103/0976‑500X.124435 24554919
     [Google Scholar]
  36. DahanayakeM.H. JayasunderaA.C.A. Nano-based drug delivery optimization for tuberculosis treatment: A review.J. Microbiol. Methods202118110612710.1016/j.mimet.2020.106127 33359155
     [Google Scholar]
  37. SuriS.S. FenniriH. SinghB. Nanotechnology-based drug delivery systems.J. Occup. Med. Toxicol.2007211610.1186/1745‑6673‑2‑16 18053152
     [Google Scholar]
  38. GoldK. SlayB. KnackstedtM. GaharwarA.K. Antimicrobial activity of metal and metal‐oxide based nanoparticles.Adv. Ther. (Weinh.)201813170003310.1002/adtp.201700033
     [Google Scholar]
  39. SinghM. MallickA.K. BanerjeeM. KumarR. Loss of outer membrane integrity in Gram-negative bacteria by silver nanoparticles loaded with Camellia sinensis leaf phytochemicals: Plausible mechanism of bacterial cell disintegration.Bull. Mater. Sci.20163971871187810.1007/s12034‑016‑1317‑5
     [Google Scholar]
  40. WypijM. CzarneckaJ. ŚwiecimskaM. DahmH. RaiM. GolinskaP. Synthesis, characterization and evaluation of antimicrobial and cytotoxic activities of biogenic silver nanoparticles synthesized from Streptomyces xinghaiensis OF1 strain.World J. Microbiol. Biotechnol.20183422310.1007/s11274‑017‑2406‑3 29305718
     [Google Scholar]
  41. Sánchez-LópezE. GomesD. EsteruelasG. Metal-based nanoparticles as antimicrobial agents: An overview.Nanomaterials202010229210.3390/nano10020292 32050443
     [Google Scholar]
  42. GeitaniR. AyoubM.C. TouquiL. Karam SarkisD. Cationic antimicrobial peptides: Alternatives and/or adjuvants to antibiotics active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa.BMC Microbiol.20191915410.1186/s12866‑019‑1416‑8 30849936
     [Google Scholar]
  43. MengJ. HeG. WangH. Reversion of antibiotic resistance by inhibiting mecA in clinical methicillin-resistant Staphylococci by antisense phosphorothioate oligonucleotide.J. Antibiot. (Tokyo)201568315816410.1038/ja.2014.132 25269464
     [Google Scholar]
  44. BecskeiA. Tuning up transcription factors for therapy.Molecules2020258190210.3390/molecules25081902 32326099
     [Google Scholar]
  45. HibbittsA. O’LearyC. Emerging nanomedicine therapies to counter the rise of methicillin-resistant Staphylococcus aureus.Materials201811232110.3390/ma11020321 29473883
     [Google Scholar]
  46. Ur RehmanO. FatimaE. AliA. AkramU. NashwanA. YunusF. Efficacy and safety of bedaquiline containing regimens in patients of drug-resistant tuberculosis: An updated systematic review and meta-analysis.J. Clin. Tuberc. Other Mycobact. Dis.20243410040510.1016/j.jctube.2023.100405 38152568
     [Google Scholar]
  47. FerreiraA.P. TobynM. Multivariate analysis in the pharmaceutical industry: Enabling process understanding and improvement in the PAT and QbD era.Pharm. Dev. Technol.201520551352710.3109/10837450.2014.898656 24641280
     [Google Scholar]
  48. MehtaK. GuoT. Van Der GraafP.H. Van HasseltJ.G.C. Model‐based dose optimization framework for bedaquiline, pretomanid and linezolid for the treatment of drug‐resistant tuberculosis.Br. J. Clin. Pharmacol.202490246347410.1111/bcp.15925 37817504
     [Google Scholar]
  49. PadmapriyadarsiniC. DevaleenalB. PonnurajaC. Randomised trial to evaluate the effectiveness and safety of varying doses of linezolid with bedaquiline and pretomanid in adults with pre-extensively drug-resistant or treatment intolerant/non-responsive multidrug-resistant pulmonary tuberculosis: Study protocol.BMJ Open2022128e05860610.1136/bmjopen‑2021‑058606 36038181
     [Google Scholar]
  50. PadmapriyadarsiniC. VohraV. BhatnagarA. Bedaquiline, delamanid, linezolid, and clofazimine for treatment of pre-extensively drug-resistant tuberculosis.Clin. Infect. Dis.2023763e938e94610.1093/cid/ciac528 35767251
     [Google Scholar]
  51. SalingerD.H. NedelmanJ.R. MendelC. SpigelmanM. HermannD.J. Daily dosing for bedaquiline in patients with tuberculosis.Antimicrob. Agents Chemother.20196311e00463e1910.1128/AAC.00463‑19 31451504
     [Google Scholar]
  52. ShaoG. BaoZ. Davies ForsmanL. Population pharmacokinetics and model-based dosing evaluation of bedaquiline in multidrug-resistant tuberculosis patients.Front. Pharmacol.202314102209010.3389/fphar.2023.1022090 37050904
     [Google Scholar]
  53. SinghB. SinghC. Bedaquiline in drug-resistant tuberculosis: A mini-review.Curr. Mol. Pharmacol.202316324325310.2174/1874467215666220421130707 36919348
     [Google Scholar]
  54. DeshkarA.T. ShirureP.A. DeshkarA. ShirureP. Bedaquiline: A novel diarylquinoline for multidrug-resistant pulmonary tuberculosis.Cureus2022148e2851910.7759/cureus.28519 36185922
     [Google Scholar]
  55. MehtaK. GuoT. Van Der GraafP.H. Van HasseltJ.G.C. Predictions of bedaquiline and pretomanid target attainment in lung lesions of tuberculosis patients using translational minimal physiologically based pharmacokinetic modeling.Clin. Pharmacokinet.202362351953210.1007/s40262‑023‑01217‑7 36802057
     [Google Scholar]
  56. TongE. WuQ. ChenY. The efficacy and safety of bedaquiline in the treatment of pulmonary tuberculosis patients: A systematic review and meta-analysis.Antibiotics2023129138910.3390/antibiotics12091389 37760686
     [Google Scholar]
  57. SotgiuG. CentisR. D’ambrosioL. MiglioriG.B. Tuberculosis treatment and drug regimens.Cold Spring Harb. Perspect. Med.201555a017822a210.1101/cshperspect.a017822 25573773
     [Google Scholar]
  58. BezawadaV. MogiliP. Rao PolaganiS. DoddaS. Bioanalysis of bedaquiline in human plasma by liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study.J. Mass Spectrom. Adv. Clin. Lab202431273210.1016/j.jmsacl.2024.01.001 38375487
     [Google Scholar]
  59. SarathyJ.P. GruberG. DickT. Re-understanding the mechanisms of action of the Anti-Mycobacterial drug bedaquiline.Antibiotics20198426110.3390/antibiotics8040261 31835707
     [Google Scholar]
  60. NguyenT.V.A. CaoT.B.T. AkkermanO.W. TiberiS. VuD.H. AlffenaarJ.W.C. Bedaquiline as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis.Expert Rev. Clin. Pharmacol.2016981025103710.1080/17512433.2016.1200462 27322153
     [Google Scholar]
  61. KhoshnoodS. GoudarziM. TakiE. Bedaquiline: Current status and future perspectives.J. Glob. Antimicrob. Resist.202125485910.1016/j.jgar.2021.02.017 33684606
     [Google Scholar]
  62. VaninoE. GranozziB. AkkermanO.W. Update of drug-resistant tuberculosis treatment guidelines: A turning point.Int. J. Infect. Dis.2023130Suppl. 1S12S1510.1016/j.ijid.2023.03.013 36918080
     [Google Scholar]
  63. KimJ. ChoiJ. KangH. Safety, tolerability, pharmacokinetics, and metabolism of telacebec (Q203) for the treatment of tuberculosis: A randomized, placebo-controlled, multiple ascending dose phase 1B trial.Antimicrob. Agents Chemother.2023671e01123e2210.1128/aac.01123‑22 36507677
     [Google Scholar]
  64. MirnejadR. AsadiA. KhoshnoodS. Clofazimine: A useful antibiotic for drug-resistant tuberculosis.Biomed. Pharmacother.20181051353135910.1016/j.biopha.2018.06.023 30021373
     [Google Scholar]
  65. GuglielmettiL. ChiesiS. EimerJ. Bedaquiline and delamanid for drug-resistant tuberculosis: A clinician’s perspective.Future Microbiol.202015977979910.2217/fmb‑2019‑0309 32700565
     [Google Scholar]
  66. GuglielmettiL. JaspardM. Le DûD. Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis.Eur. Respir. J.2017493160179910.1183/13993003.01799‑2016 28182570
     [Google Scholar]
  67. ChahineE.B. KaraouiL.R. MansourH. Bedaquiline.Ann. Pharmacother.201448110711510.1177/1060028013504087 24259600
     [Google Scholar]
  68. ChesovE. ChesovD. MaurerF.P. Emergence of bedaquiline resistance in a high tuberculosis burden country.Eur. Respir. J.2022593210062110.1183/13993003.00621‑2021 34503982
     [Google Scholar]
  69. PerrinC. AthersuchK. ElderG. MartinM. AlsalhaniA. Recently developed drugs for the treatment of drug-resistant tuberculosis: A research and development case study.BMJ Glob. Health202274e00749010.1136/bmjgh‑2021‑007490 35440441
     [Google Scholar]
  70. GuptaR WellsCD HittelN HafkinJ GeiterLJ Delamanid in the treatment of multidrug-resistant tuberculosis.int j tuberc lung dis201620337
     [Google Scholar]
  71. DooleyK.E. ParkJ.G. SwindellsS. Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS clinical trials group study A5267.J. Acquir. Immune Defic. Syndr.201259545546210.1097/QAI.0b013e3182410503 22126739
     [Google Scholar]
  72. SvenssonE.M. MurrayS. KarlssonM.O. DooleyK.E. Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug.J. Antimicrob. Chemother.20157041106111410.1093/jac/dku504 25535219
     [Google Scholar]
  73. HealanA.M. GriffissJ.M. ProskinH.M. Impact of Rifabutin or Rifampin on bedaquiline safety, tolerability, and pharmacokinetics assessed in a randomized clinical trial with healthy adult volunteers.Antimicrob. Agents Chemother.2017621e00855e17 29061739
     [Google Scholar]
  74. ConradieF. DiaconA.H. NgubaneN. Treatment of highly drug-resistant pulmonary tuberculosis.N. Engl. J. Med.20203821089390210.1056/NEJMoa1901814 32130813
     [Google Scholar]
  75. DooleyK.E. RosenkranzS.L. ConradieF. QT effects of bedaquiline, delamanid, or both in patients with rifampicin-resistant tuberculosis: a phase 2, open-label, randomised, controlled trial.Lancet Infect. Dis.202121797598310.1016/S1473‑3099(20)30770‑2 33587897
     [Google Scholar]
  76. ConradieF. BagdasaryanT.R. BorisovS. Bedaquiline–pretomanid–linezolid regimens for drug-resistant tuberculosis.N. Engl. J. Med.2022387981082310.1056/NEJMoa2119430 36053506
     [Google Scholar]
  77. CrisafulliS. KhanZ. KaratasY. TuccoriM. TrifiròG. An overview of methodological flaws of real-world studies investigating drug safety in the post-marketing setting.Expert Opin. Drug Saf.202322537338010.1080/14740338.2023.2219892 37243676
     [Google Scholar]
  78. ColomboS. Beck-BroichsitterM. BøtkerJ.P. MalmstenM. RantanenJ. BohrA. Transforming nanomedicine manufacturing toward quality by design and microfluidics.Adv. Drug Deliv. Rev.201812811513110.1016/j.addr.2018.04.004 29626549
     [Google Scholar]
  79. GinsbergA. The TB Alliance: Overcoming challenges to chart the future course of TB drug development.Future Med. Chem.20113101247125210.4155/fmc.11.82 21859299
     [Google Scholar]
  80. ZumlaA. PetersenE. NyirendaT. ChakayaJ. Tackling the tuberculosis epidemic in sub-Saharan Africa – unique opportunities arising from the second European Developing Countries Clinical Trials Partnership (EDCTP) programme 2015-2024.Int. J. Infect. Dis.201532464910.1016/j.ijid.2014.12.039 25809755
     [Google Scholar]
  81. GothamD. McKennaL. FrickM. LessemE. Public investments in the clinical development of bedaquiline.PLoS ONE202015e023911810.1371/journal.pone.0239118
     [Google Scholar]
/content/journals/raaidd/10.2174/0127724344318310241018113206
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Bedaquiline Delivery Innovations: A Review on Advancing MDR-TB Treatment Strategies
Recent Adv Antiinfect Drug Discov 20, 92 (2025); https://doi.org/10.2174/0127724344318310241018113206
/content/journals/raaidd/10.2174/0127724344318310241018113206
/content/journals/raaidd/10.2174/0127724344318310241018113206
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  • Article Type:     Review Article
Keyword(s): Bedaquiline; bioavailability drug delivery; MDR-TB Treatment; multidrug resistance; systematic; tuberculosis

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