Skip to content
2000
Volume 22, Issue 5
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Ribavirin has been used as an antiviral agent to treat a variety of viral infections since the 1970s. Over the past few decades, studies have been conducted on the pharmacology of ribavirin, and the possibility of its use in new indications has been explored. According to the results of a number of studies, ribavirin efficacy in the therapy of malignant neoplasms of various genesis has been proven. Furthermore, due to the complexity of brain tumor therapy using surgical methods, targeted delivery of ribavirin to the brain becomes a promising alternative to existing treatment methods. Targeting of active pharmaceutical ingredient (API) to the brain tumor is achieved by intranasal drug delivery a Nose-to-Brain mechanism. In addition, using this delivery mechanism, it is possible to reach the brain while bypassing the blood-brain barrier (BBB), thus avoiding the effects of the first passage through the liver. Despite the significant advantages of the method, there are limiting factors to its application - mucociliary clearance, which aims to remove foreign bodies from the surface of the nasal mucosa. systems are able to reduce the intensity of interfering factors on API and allow the achievement of maximum bioavailability during intranasal administration.

Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018305548240614113451
2025-06-01
2025-10-25
Loading full text...

Full text loading...

References

  1. GolivetsT.P. KovalenkoB.S. Analysis of world and russian trends in cancer incidence in the twenty-first century.research result.Med. Pharm. Ser.2015110.18413/2313‑8955‑2015‑1‑4‑79‑86
    [Google Scholar]
  2. SidwellR.W. HuffmanJ.H. KhareG.P. AllenL.B. WitkowskiJ.T. RobinsR.K. Broad-spectrum antiviral activity of Virazole: 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide.Science1972177405070570610.1126/science.177.4050.7054340949
    [Google Scholar]
  3. WitkowskiJ.T. RobinsR.K. SidwellR.W. SimonL.N. Design, synthesis, and broad spectrum antiviral activity of 1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides.J. Med. Chem.197215111150115410.1021/jm00281a0144347550
    [Google Scholar]
  4. HuffmanJ.H. SidwellR.W. KhareG.P. WitkowskiJ.T. AllenL.B. RobinsR.K. In vitro effect of 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses.Antimicrob. Agents Chemother.19733223524110.1128/AAC.3.2.2354208281
    [Google Scholar]
  5. LinC.C. PhilipsL. XuC. YehL.T. Pharmacokinetics and safety of viramidine, a prodrug of ribavirin, in healthy volunteers.J. Clin. Pharmacol.200444326527510.1177/009127000426297414973309
    [Google Scholar]
  6. McJunkinJ.E. NahataM.C. De Los ReyesE.C. HuntW.G. CaceresM. KhanR.R. ChebibM.G. TaravathS. MinnichL.L. CarrR. WelchC.A. WhitleyR.J. Safety and pharmacokinetics of ribavirin for the treatment of la crosse encephalitis.Pediatr. Infect. Dis. J.2011301086086510.1097/INF.0b013e31821c922c21544005
    [Google Scholar]
  7. PischkeS. HardtkeS. BodeU. BirknerS. ChatzikyrkouC. KauffmannW. BaraC.L. GottliebJ. WenzelJ. MannsM.P. WedemeyerH. Ribavirin treatment of acute and chronic hepatitis E: A single‐centre experience.Liver Int.201333572272610.1111/liv.1211423489973
    [Google Scholar]
  8. HopkinsA.L. Network pharmacology:The next paradigm in drug discovery.Nat. Chem. Biol.200841168269010.1038/nchembio.11818936753
    [Google Scholar]
  9. LevyG. Kinetics of drug action: An overview.J. Allergy Clin. Immunol.198678475476110.1016/0091‑6749(86)90057‑63534056
    [Google Scholar]
  10. PorfiryevaN.N. SeminaI.I. MoustafineR.I. KhutoryanskiyV. V. Intranasal administration as a route to deliver drugs to the brain (Review).Drug develop. regist.20211011712710.33380/2305‑2066‑2021‑10‑4‑117‑127
    [Google Scholar]
  11. ChenJ. XuX. ChenJ. Clinically relevant concentration of anti-viral drug ribavirin selectively targets pediatric osteosarcoma and increases chemosensitivity.Biochem. Biophys. Res. Commun.2018506360461010.1016/j.bbrc.2018.10.12430454696
    [Google Scholar]
  12. WambeckeA. Laurent-IssartelC. Leroy-DudalJ. GiffardF. CossonF. Lubin-GermainN. UzielJ. KelloucheS. CarreirasF. Evaluation of the potential of a new ribavirin analog impairing the dissemination of ovarian cancer cells.PLoS One20191412e022586010.1371/journal.pone.022586031825993
    [Google Scholar]
  13. XiC. WangL. YuJ. YeH. CaoL. GongZ. Inhibition of eukaryotic translation initiation factor 4E is effective against chemo-resistance in colon and cervical cancer.Biochem. Biophys. Res. Commun.201850342286229210.1016/j.bbrc.2018.06.15029959920
    [Google Scholar]
  14. MeštrovićT. Ribavirin Chemistry.Available from: https://www.news-medical.net/health/Ribavirin-Chemistry.aspx (accessed on 29-5-2024).
  15. CasaosJ. HuqS. LottT. FelderR. ChoiJ. GorelickN. PetersM. XiaY. MaxwellR. ZhaoT. JiC. SimonT. SesenJ. ScotlandS.J. KastR.E. RubensJ. RaabeE. EberhartC.G. JacksonE.M. BremH. TylerB. SkuliN. Ribavirin as a potential therapeutic for atypical teratoid/rhabdoid tumors.Oncotarget2018988054806710.18632/oncotarget.2388329487714
    [Google Scholar]
  16. De La Cruz-HernandezE. Medina-FrancoJ.L. TrujilloJ. Chavez-BlancoA. Dominguez-GomezG. Perez-CardenasE. Gonzalez-FierroA. Taja-ChayebL. Dueñas-GonzalezA. Ribavirin as a tri-targeted antitumor repositioned drug.Oncol. Rep.20153352384239210.3892/or.2015.3816
    [Google Scholar]
  17. ShenX. ZhuY. XiaoZ. DaiX. LiuD. LiL. XiaoB. Antiviral drug ribavirin targets thyroid cancer cells by inhibiting the eIF4E-β-catenin axis.Am. J. Med. Sci.2017354218218910.1016/j.amjms.2017.03.02528864377
    [Google Scholar]
  18. UrtishakK.A. WangL.S. Culjkovic-KraljacicB. DavenportJ.W. PorazziP. VincentT.L. TeacheyD.T. TasianS.K. MooreJ.S. SeifA.E. JinS. BarrettJ.S. RobinsonB.W. ChenI.M.L. HarveyR.C. CarrollM.P. CarrollA.J. HeeremaN.A. DevidasM. DreyerZ.E. HildenJ.M. HungerS.P. WillmanC.L. BordenK.L.B. FelixC.A. Targeting EIF4E signaling with ribavirin in infant acute lymphoblastic leukemia.Oncogene201938132241226210.1038/s41388‑018‑0567‑730478448
    [Google Scholar]
  19. IsakovicA.M. DulovicM. MarkovicI. Kravic-StevovicT. BumbasirevicV. TrajkovicV. IsakovicA. Autophagy suppression sensitizes glioma cells to IMP dehydrogenase inhibition-induced apoptotic death.Exp. Cell Res.20173501324010.1016/j.yexcr.2016.11.00127818246
    [Google Scholar]
  20. OchiaiY. SanoE. OkamotoY. YoshimuraS. MakitaK. YamamuroS. OhtaT. OginoA. TadakumaH. UedaT. NakayamaT. HaraH. YoshinoA. KatayamaY. Efficacy of ribavirin against malignant glioma cell lines: Follow-up study.Oncol. Rep.2017201753754410.3892/or.2017.614929251333
    [Google Scholar]
  21. OginoA. SanoE. OchiaiY. YamamuroS. TashiroS. YachiK. OhtaT. FukushimaT. OkamotoY. TsumotoK. UedaT. YoshinoA. KatayamaY. Efficacy of ribavirin against malignant glioma cell lines.Oncol. Lett.2014862469247410.3892/ol.2014.256925364409
    [Google Scholar]
  22. LiangT. WangF. ElhassanR.M. ChengY. TangX. ChenW. FangH. HouX. Targeting histone deacetylases for cancer therapy: Trends and challenges.Acta Pharm. Sin. B20231362425246310.1016/j.apsb.2023.02.00737425042
    [Google Scholar]
  23. HuqS. KannapadiN.V. CasaosJ. LottT. FelderR. SerraR. GorelickN.L. Ruiz-CardozoM.A. DingA.S. CeciaA. MedikondaR. EhresmanJ. BremH. SkuliN. TylerB.M. Preclinical efficacy of ribavirin in SHH and group 3 medulloblastoma.J. Neurosurg. Pediatr.202127448248810.3171/2020.8.PEDS2056133545678
    [Google Scholar]
  24. CasaosJ. GorelickN.L. HuqS. ChoiJ. XiaY. SerraR. FelderR. LottT. KastR.E. SukI. BremH. TylerB. SkuliN. The use of ribavirin as an anticancer therapeutic: Will it go viral?Mol. Cancer Ther.20191871185119410.1158/1535‑7163.MCT‑18‑066631263027
    [Google Scholar]
  25. JinJ. XiangW. WuS. WangM. XiaoM. DengA. Targeting eIF4E signaling with ribavirin as a sensitizing strategy for ovarian cancer.Biochem. Biophys. Res. Commun.2019510458058610.1016/j.bbrc.2019.01.11730739792
    [Google Scholar]
  26. VolpinF. CasaosJ. SesenJ. MangravitiA. ChoiJ. GorelickN. FrikecheJ. LottT. FelderR. ScotlandS.J. Eisinger-MathasonT.S.K. BremH. TylerB. SkuliN. Use of an anti-viral drug, Ribavirin, as an anti-glioblastoma therapeutic.Oncogene201736213037304710.1038/onc.2016.45727941882
    [Google Scholar]
  27. KastR.E. HillQ.A. WionD. MellstedtH. FocosiD. Karpel-MasslerG. HeilandT. HalatschM.E. Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin.Tumour Biol.2017395101042831769979710.1177/101042831769979728459367
    [Google Scholar]
  28. CroweT.P. GreenleeM.H.W. KanthasamyA.G. HsuW.H. Mechanism of intranasal drug delivery directly to the brain.Life Sci.2018195445210.1016/j.lfs.2017.12.02529277310
    [Google Scholar]
  29. WangZ. XiongG. TsangW.C. SchätzleinA.G. UchegbuI.F. Nose-to-Brain Delivery.J. Pharmacol. Exp. Ther.2019370359360110.1124/jpet.119.25815231126978
    [Google Scholar]
  30. DanemanR. PratA. The blood-brain barrier.Cold Spring Harb. Perspect. Biol.201571a02041210.1101/cshperspect.a02041225561720
    [Google Scholar]
  31. QuY. LiA. MaL. IqbalS. SunX. MaW. LiC. ZhengD. XuZ. ZhaoZ. MaD. Nose-to-brain delivery of disulfiram nanoemulsion in situ gel formulation for glioblastoma targeting therapy.Int. J. Pharm.202159712025010.1016/j.ijpharm.2021.12025033486040
    [Google Scholar]
  32. Núñez‐CookS. Vidal‐MugicaF. SalinasP. Anatomy and computed tomography of the nasal cavity, nasal conchae, and paranasal sinuses of the endangered patagonian huemul deer (Hippocamelus Bisulcus).Anat. Rec.2023202314115410.1002/ar.2523037084232
    [Google Scholar]
  33. OgleO.E. WeinstockR.J. FriedmanE. Surgical anatomy of the nasal cavity and paranasal sinuses.Oral Maxillofac. Surg. Clin. North Am.201224215516610.1016/j.coms.2012.01.01122386856
    [Google Scholar]
  34. CaoY. ZhangR. The application of nanotechnology in treatment of Alzheimer’s disease.Front. Bioeng. Biotechnol.202210104298610.3389/fbioe.2022.104298636466349
    [Google Scholar]
  35. KanazawaT. TakiH. OkadaH. Nose-to-brain drug delivery system with ligand/cell-penetrating peptide-modified polymeric nano-micelles for intracerebral gliomas.Eur. J. Pharm. Biopharm.2020152859410.1016/j.ejpb.2020.05.00132387702
    [Google Scholar]
  36. SabirF. IsmailR. CsokaI. Nose-to-brain delivery of antiglioblastoma drugs embedded into lipid nanocarrier systems: status quo and outlook.Drug Discov. Today202025118519410.1016/j.drudis.2019.10.00531629966
    [Google Scholar]
  37. MaJ. WangC. SunY. PangL. ZhuS. LiuY. ZhuL. ZhangS. WangL. DuL. Comparative study of oral and intranasal puerarin for prevention of brain injury induced by acute high-altitude hypoxia.Int. J. Pharm.202059112000210.1016/j.ijpharm.2020.12000233141084
    [Google Scholar]
  38. LiuJ. LiY. LiuS. ZhangY. LuoY. YangY. ZhuangX. WangX. ZhaoB. XuT. XuL. Alkoxy cyanoacrylate-based nanoparticles with stealth and brain-targeting properties.J. Drug Target.202230221923110.1080/1061186X.2021.196179034319831
    [Google Scholar]
  39. AlabsiW. EedaraB.B. Encinas-BasurtoD. PoltR. MansourH.M. Nose-to-brain delivery of therapeutic peptides as nasal aerosols.Pharmaceutics2022149187010.3390/pharmaceutics1409187036145618
    [Google Scholar]
  40. ShipleyM.T. Transport of molecules from nose to brain: Transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium.Brain Res. Bull.198515212914210.1016/0361‑9230(85)90129‑73840049
    [Google Scholar]
  41. SmithA.L. BartholdS.W. BeckD.S. Intranasally administered alpha/beta interferon prevents extension of mouse hepatitis virus, strain JHM, into the brains of BALB/cByJ mice.Antiviral Res.198785-623924510.1016/S0166‑3542(87)80002‑52837142
    [Google Scholar]
  42. ThorneR.G. EmoryC.R. AlaT.A. FreyW.H.II Quantitative analysis of the olfactory pathway for drug delivery to the brain.Brain Res.19956921-227828210.1016/0006‑8993(95)00637‑68548316
    [Google Scholar]
  43. SakaneT. YamashitaS. YataN. SezakiH. Transnasal delivery of 5-fluorouracil to the brain in the rat.J. Drug Target.19997323324010.3109/1061186990908550610680979
    [Google Scholar]
  44. KuranoT. KanazawaT. OobaA. MasuyamaY. MaruhanaN. YamadaM. IiokaS. IbarakiH. KosugeY. KondoH. SuzukiT. Nose-to-brain/spinal cord delivery kinetics of liposomes with different surface properties.J. Control. Release202234422523410.1016/j.jconrel.2022.03.01735296406
    [Google Scholar]
  45. MontegioveN. CalzoniE. EmilianiC. CesarettiA. Biopolymer nanoparticles for nose-to-brain drug delivery: A new promising approach for the treatment of neurological diseases.J. Funct. Biomater.202213312510.3390/jfb1303012536135560
    [Google Scholar]
  46. ColomboG. LorenziniL. ZironiE. GalligioniV. SonvicoF. BalducciA.G. PagliucaG. GiulianiA. CalzàL. ScagliariniA. Brain distribution of ribavirin after intranasal administration.Antiviral Res.201192340841410.1016/j.antiviral.2011.09.01222001322
    [Google Scholar]
  47. GiulianiA. BalducciA.G. ZironiE. ColomboG. BortolottiF. LorenziniL. GalligioniV. PagliucaG. ScagliariniA. CalzàL. SonvicoF. In vivo nose-to-brain delivery of the hydrophilic antiviral ribavirin by microparticle agglomerates.Drug Deliv.201825137638710.1080/10717544.2018.142824229382237
    [Google Scholar]
  48. VasaD.M. BakriZ. DonovanM.D. O’DonnellL.A. WildfongP.L.D. Evaluation of ribavirin–poloxamer microparticles for improved intranasal absorption.Pharmaceutics2021138112610.3390/pharmaceutics1308112634452087
    [Google Scholar]
  49. CraftS. BakerL.D. MontineT.J. MinoshimaS. WatsonG.S. ClaxtonA. ArbuckleM. CallaghanM. TsaiE. PlymateS.R. GreenP.S. LeverenzJ. CrossD. GertonB. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: A pilot clinical trial.Arch. Neurol.2012691293810.1001/archneurol.2011.23321911655
    [Google Scholar]
  50. GodfreyL. IannitelliA. GarrettN.L. MogerJ. ImbertI. KingT. PorrecaF. SoundararajanR. LalatsaA. SchätzleinA.G. UchegbuI.F. Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia.J. Control. Release201827013514410.1016/j.jconrel.2017.11.04129191784
    [Google Scholar]
  51. ThorneR.G. HansonL.R. RossT.M. TungD. FreyW.H.II Delivery of interferon-β to the monkey nervous system following intranasal administration.Neuroscience2008152378579710.1016/j.neuroscience.2008.01.01318304744
    [Google Scholar]
  52. BakhrushinaE.O. DeminaN.B. ShumkovaM.M. RodyukP.S. ShulikinaD.S. KrasnyukI.I. In Situ intranasal delivery systems: application prospects and main pharmaceutical aspects of development (Review).Drug develop. regist.202110546310.33380/2305‑2066‑2021‑10‑4‑54‑63
    [Google Scholar]
  53. BakhrushinaE.O. MikhelI.B. PyzhovV.S. DeminaN.B. KrasnyukI.I.Jr KrasnyukI.I. Development of in situ intranasal system based on chitosan formate.Bull. Exp. Biol. Med.2023174333734010.1007/s10517‑023‑05704‑636723743
    [Google Scholar]
  54. BakhrushinaE.O. MikhelI.B. PyzhovV.S. DeminaN.B. KrasnyukI.I.Jr KrasnyukI.I. Main aspects of pharmaceutical development of in situ immunobiological drugs for intranasal administration.Curr. Pharm. Biotechnol.20232510.2174/0113892010260017231002075152
    [Google Scholar]
  55. PangL. ZhuS. MaJ. ZhuL. LiuY. OuG. LiR. WangY. LiangY. JinX. DuL. JinY. Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder.Acta Pharm. Sin. B20211172031204710.1016/j.apsb.2021.01.01434386336
    [Google Scholar]
  56. ZhangL. PangL. ZhuS. MaJ. LiR. LiuY. ZhuL. ZhuangX. ZhiW. YuX. DuL. ZuoH. JinY. Intranasal tetrandrine temperature-sensitive in situ hydrogels for the treatment of microwave-induced brain injury.Int. J. Pharm.202058311938410.1016/j.ijpharm.2020.11938432371003
    [Google Scholar]
  57. GadhaveD. QuadrosM. UgaleA.R. GoyalM. GuptaV. A Nanoemulgel for Nose-to-Brain delivery of Quetiapine – QbD-Enabled formulation development in-vitro characterization.Int. J. Pharm.202364812356610.1016/j.ijpharm.2023.12356637918496
    [Google Scholar]
  58. BadranM.M. AlanaziA.E. IbrahimM.A. AlshoraD.H. TahaE. H AlomraniA. Optimization of bromocriptine-mesylate-loaded polycaprolactone nanoparticles coated with chitosan for nose-to-brain delivery: In Vitro and In Vivo studies.Polymers20231519389010.3390/polym1519389037835942
    [Google Scholar]
  59. AssoulineS. Culjkovic-KraljacicB. BergeronJ. CaplanS. CocolakisE. LambertC. LauC.J. ZahreddineH.A. MillerW.H.Jr BordenK.L.B. A phase I trial of ribavirin and low-dose cytarabine for the treatment of relapsed and refractory acute myeloid leukemia with elevated eIF4E.Haematologica20151001e7e910.3324/haematol.2014.11124525425688
    [Google Scholar]
  60. AssoulineS. CuljkovicB. CocolakisE. RousseauC. BesluN. AmriA. CaplanS. LeberB. RoyD.C. MillerW.H.Jr BordenK.L.B. Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): A proof-of-principle clinical trial with ribavirin.Blood2009114225726010.1182/blood‑2009‑02‑20515319433856
    [Google Scholar]
  61. DunnL.A. FuryM.G. ShermanE.J. HoA.A. KatabiN. HaqueS.S. PfisterD.G. PhaseI. Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus‐associated oropharyngeal squamous cell cancer.Head Neck201840223324110.1002/hed.2493828963790
    [Google Scholar]
  62. HassanyM. ElsharkawyA. MagedA. MehrezM. AsemN. GomaaA. MostafaZ. AbbasB. SolimanM. EsmatG. HepatitisC. Hepatitis C virus treatment by direct-acting antivirals in successfully treated hepatocellular carcinoma and possible mutual impact.Eur. J. Gastroenterol. Hepatol.201830887688110.1097/MEG.000000000000115229727383
    [Google Scholar]
  63. HuangJ.F. YehM.L. YuM.L. DaiC.Y. HuangC.F. HuangC.I. TsaiP.C. LinP.C. ChenY.L. ChangW.T. HouN.J. LinZ.Y. ChenS.C. ChuangW.L. The tertiary prevention of hepatocellular carcinoma in chronic hepatitis C patients.J. Gastroenterol. Hepatol.201530121768177410.1111/jgh.1301226094738
    [Google Scholar]
  64. DavisS.S. Delivery of peptide and non-peptide drugs through the respiratory tract.Pharm. Sci. Technol. Today199921145045610.1016/S1461‑5347(99)00199‑610542391
    [Google Scholar]
  65. DjupeslandP.G. MessinaJ.C. MahmoudR.A. The nasal approach to delivering treatment for brain diseases: An anatomic, physiologic, and delivery technology overview.Ther. Deliv.20145670973310.4155/tde.14.4125090283
    [Google Scholar]
  66. TepperS.J. JohnstoneM.R. Breath-powered sumatriptan dry nasal powder: An intranasal medication delivery system for acute treatment of migraine.Med. Devices20181114715610.2147/MDER.S13090029760572
    [Google Scholar]
  67. AroraP. SharmaS. GargS. Permeability issues in nasal drug delivery.Drug Discov. Today200271896797510.1016/S1359‑6446(02)02452‑212546871
    [Google Scholar]
  68. BruinsmannF.A. Richter VazG. de Cristo Soares AlvesA. AguirreT. Raffin PohlmannA. Stanisçuaski GuterresS. SonvicoF. Nasal drug delivery of anticancer drugs for the treatment of glioblastoma: Preclinical and clinical trials.Molecules20192423431210.3390/molecules2423431231779126
    [Google Scholar]
/content/journals/cdd/10.2174/0115672018305548240614113451
Loading
/content/journals/cdd/10.2174/0115672018305548240614113451
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test