Skip to content
2000
Volume 22, Issue 7
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Background

Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs.

Objective

The main objectives of the present research were to develop and evaluate fluconazole-loaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis.

Methods

A 23 factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w).

Results

The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, – 33.10 mV zeta potential, and 65.38 ± 1.77% DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against than . HET-CAM study results demonstrated that both the hydrogels were non-irritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation.

Conclusion

The current research demonstrated a new way to enhance the ocular penetration of fluconazole transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018342369241018050810
2024-10-18
2025-11-05

  • From This Site

    /content/journals/cdd/10.2174/0115672018342369241018050810
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Díaz-ToméV. Bendicho-LavillaC. García-OteroX. Varela-FernándezR. Martín-PastorM. Llovo-TaboadaJ. Alonso-AlonsoP. AguiarP. González-BarciaM. Fernández-FerreiroA. Otero-EspinarF.J. Antifungal combination eye drops for fungal keratitis treatment.Pharmaceutics20221513510.3390/pharmaceutics15010035 36678663
     [Google Scholar]
  2. Harbiyeliİ.İ. ErdemE. GörkemliN. İbayevA. KandemirH. AçıkalınA. İlkitM. YağmurM. Clinical and mycological features of fungal keratitis: A retrospective single-center study (2012-2018).Turk. J. Ophthalmol.2022522758510.4274/tjo.galenos.2021.09515 35481727
     [Google Scholar]
  3. ManikandanP. Abdel-hadiA. Randhir Babu SinghY. RevathiR. AnitaR. BanawasS. Bin DukhyilA.A. AlshehriB. ShobanaC.S. Panneer SelvamK. NarendranV. Fungal keratitis: Epidemiology, rapid detection, and antifungal susceptibilities of Fusarium and Aspergillus isolates from corneal scrapings.BioMed Res. Int.201920191910.1155/2019/6395840 30800674
     [Google Scholar]
  4. LeckA.K. ThomasP.A. HaganM. KaliamurthyJ. AckuakuE. JohnM. NewmanM.J. CodjoeF.S. OpintanJ.A. KalavathyC.M. EssumanV. JesudasanC A N. JohnsonG.J. Aetiology of suppurative corneal ulcers in Ghana and south India, and epidemiology of fungal keratitis.Br. J. Ophthalmol.200286111211121510.1136/bjo.86.11.1211 12386069
     [Google Scholar]
  5. AnsariZ. MillerD. GalorA. Current thoughts in fungal keratitis: Diagnosis and treatment.Curr. Fungal Infect. Rep.20137320921810.1007/s12281‑013‑0150‑1 24040467
     [Google Scholar]
  6. HoffmanJ.J. BurtonM.J. LeckA. Mycotic keratitis-A global threat from the filamentous fungi.J. Fungi (Basel)20217427310.3390/jof7040273 33916767
     [Google Scholar]
  7. SharmaN. BaggaB. SinghalD. NagpalR. KateA. SalujaG. MaharanaP.K. Fungal keratitis: A review of clinical presentations, treatment strategies and outcomes.Ocul. Surf.202224223010.1016/j.jtos.2021.12.001 34915188
     [Google Scholar]
  8. RayA. AayilliathK.A. BanerjeeS. ChakrabartiA. DenningD.W. Burden of serious fungal infections in India.Open Forum Infect. Dis.2022912ofac60310.1093/ofid/ofac603 36589484
     [Google Scholar]
  9. RajN. VanathiM. AhmedN.H. GuptaN. LomiN. TandonR. Recent perspectives in the management of fungal keratitis.J. Fungi (Basel)202171190710.3390/jof7110907 34829196
     [Google Scholar]
  10. AwadR. GhaithA. AwadK. Mamdouh SaadM. ElmassryA. Fungal Keratitis: Diagnosis, management, and recent advances.Clin. Ophthalmol.2024188510610.2147/OPTH.S447138 38223815
     [Google Scholar]
  11. ThomasP.A. KaliamurthyJ. Mycotic keratitis: Epidemiology, diagnosis and management.Clin. Microbiol. Infect.201319321022010.1111/1469‑0691.12126 23398543
     [Google Scholar]
  12. Varela-FernándezR. Díaz-ToméV. Luaces-RodríguezA. Conde-PenedoA. García-OteroX. Luzardo-ÁlvarezA. Fernández-FerreiroA. Otero-EspinarF. Drug delivery to the posterior segment of the eye: Biopharmaceutic and pharmacokinetic considerations.Pharmaceutics202012326910.3390/pharmaceutics12030269 32188045
     [Google Scholar]
  13. GoteV. SikderS. SicotteJ. PalD. Ocular drug delivery: Present innovations and future challenges.J. Pharmacol. Exp. Ther.2019370360262410.1124/jpet.119.256933 31072813
     [Google Scholar]
  14. DasB. NayakA.K. MallickS. Lipid-based nanocarriers for ocular drug delivery: An updated review.J. Drug Deliv. Sci. Technol.20227610378010.1016/j.jddst.2022.103780
     [Google Scholar]
  15. LiS. ChenL. FuY. Nanotechnology-based ocular drug delivery systems: Recent advances and future prospects.J. Nanobiotechnology202321123210.1186/s12951‑023‑01992‑2 37480102
     [Google Scholar]
  16. GorantlaS. RapalliV.K. WaghuleT. SinghP.P. DubeyS.K. SahaR.N. SinghviG. Nanocarriers for ocular drug delivery: Current status and translational opportunity.RSC Advances20201046278352785510.1039/D0RA04971A 35516960
     [Google Scholar]
  17. DeyS. HasnainM.S. JhaS.K. SahooN. NayakA.K. Transferosomes: A novel nanotechnological approach for transdermal drug delivery.Advanced and Modern Approaches for Drug Delivery. NayakA.K. HasnainM.S. LahaB. MaitiS. United StatesAcademic Press, Elsevier Inc.202319922110.1016/B978‑0‑323‑91668‑4.00017‑4
     [Google Scholar]
  18. DasB. NayakA.K. MallickS. Transferosomes: A novel nanovesicular approach for drug delivery.Systems of Nanovesicular Drug Delivery. NayakA.K. HasnainM.S. AminabhaviT.M. TorchilinV.P. United StatesAcademic Press, Elsevier Inc.202210311410.1016/B978‑0‑323‑91864‑0.00022‑X
     [Google Scholar]
  19. DasB. NayakA.K. MallickS. Thyme oil-containing fluconazole-loaded transferosomal bigel for transdermal delivery.AAPS PharmSciTech202324824010.1208/s12249‑023‑02698‑2 37989918
     [Google Scholar]
  20. DasB. SenS.O. MajiR. NayakA.K. SenK.K. Transferosomal gel for transdermal delivery of risperidone: Formulation optimization and ex vivo permeation.J. Drug Deliv. Sci. Technol.201738597110.1016/j.jddst.2017.01.006
     [Google Scholar]
  21. MalakarJ. SenS.O. NayakA.K. SenK.K. Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery.Saudi Pharm. J.201220435536310.1016/j.jsps.2012.02.001 23960810
     [Google Scholar]
  22. DasB. NayakA.K. MallickS. Nanovesicles for delivery of antifungal drugs.Systems of Nanovesicular Drug Delivery; Nayak, A.K.; Hasnain, M.S.; Aminabhavi, T.M. TorchilinV.P. United StatesAcademic Press, Elsevier Inc.2022383397
     [Google Scholar]
  23. LynchC.R. KondiahP.P.D. ChoonaraY.E. du ToitL.C. AllyN. PillayV. Hydrogel biomaterials for application in ocular drug delivery.Front. Bioeng. Biotechnol.2020822810.3389/fbioe.2020.00228 32266248
     [Google Scholar]
  24. JiangH. XuZ. Hyaluronic acid-based nanoparticles to deliver drugs to the ocular posterior segment.Drug Deliv.2023301220420610.1080/10717544.2023.2204206 37194147
     [Google Scholar]
  25. Casey-PowerS. RyanR. BehlG. McLoughlinP. ByrneM.E. FitzhenryL. Hyaluronic acid: Its versatile use in ocular drug delivery with a specific focus on hyaluronic acid-based polyelectrolyte complexes.Pharmaceutics2022147147910.3390/pharmaceutics14071479 35890371
     [Google Scholar]
  26. GuterM. BreunigM. Hyaluronan as a promising excipient for ocular drug delivery.Eur. J. Pharm. Biopharm.2017113344910.1016/j.ejpb.2016.11.035 27914235
     [Google Scholar]
  27. YuanM. NiuJ. XiaoQ. YaH. ZhangY. FanY. LiL. LiX. Hyaluronan-modified transfersomes based hydrogel for enhanced transdermal delivery of indomethacin.Drug Deliv.20222911232124210.1080/10717544.2022.2053761 35403516
     [Google Scholar]
  28. EbnerF. HellerA. RippkeF. TauschI. Topical use of dexpanthenol in skin disorders.Am. J. Clin. Dermatol.20023642743310.2165/00128071‑200203060‑00005 12113650
     [Google Scholar]
  29. GorskiJ. ProkschE. BaronJ.M. SchmidD. ZhangL. Dexpanthenol in wound healing after medical and cosmetic interventions (postprocedure wound healing).Pharmaceuticals (Basel)202013713810.3390/ph13070138 32610604
     [Google Scholar]
  30. CamargoF.B.Jr GasparL.R. Maia CamposP.M. Skin moisturizing effects of panthenol-based formulations.J. Cosmet. Sci.2011624361370 21982351
     [Google Scholar]
  31. ScottL.N. FiumeM. BergfeldW.F. BelsitoD.V. HillR.A. KlaassenC.D. LieblerD.C. MarksJ.G.Jr ShankR.C. SlagaT.J. SnyderP.W. HeldrethB. Safety assessment of panthenol, pantothenic acid, and derivatives as used in cosmetics.Int. J. Toxicol.2022413_suppl)(Suppl.7712810.1177/10915818221124809 36177798
     [Google Scholar]
  32. FatimaI. RasulA. ShahS. SaadullahM. IslamN. KhamesA. SalawiA. AhmedM.M. AlmoshariY. AbbasG. AbourehabM.A.S. Mehmood KhanS. ChauhdaryZ. AlshamraniM. NamaziN.I. NaguibD.M. Novasomes as nano-vesicular carriers to enhance topical delivery of fluconazole: A new approach to treat fungal infections.Molecules2022279293610.3390/molecules27092936 35566287
     [Google Scholar]
  33. ChengZ. KandekarU. MaX. BhabadV. PanditA. LiuL. LuoJ. MunotN. ChorageT. PatilA. PatilS. TaoL. Optimizing fluconazole-embedded transfersomal gel for enhanced antifungal activity and compatibility studies.Front. Pharmacol.202415135379110.3389/fphar.2024.1353791 38606182
     [Google Scholar]
  34. GargA. SharmaG.S. GoyalA.K. GhoshG. SiS.C. RathG. Recent advances in topical carriers of anti-fungal agents.Heliyon202068e0466310.1016/j.heliyon.2020.e04663 32904164
     [Google Scholar]
  35. QushawyM. NasrA. Abd-AlhaseebM. SwidanS. Design, Optimization and characterization of a transfersomal gel using miconazole nitrate for the treatment of candida skin infections.Pharmaceutics20181012610.3390/pharmaceutics10010026 29473897
     [Google Scholar]
  36. AhadA. Al-SalehA.A. Al-MohizeaA.M. Al-JenoobiF.I. RaishM. YassinA.E.B. AlamM.A. Formulation and characterization of novel soft nanovesicles for enhanced transdermal delivery of eprosartan mesylate.Saudi Pharm. J.20172571040104610.1016/j.jsps.2017.01.006 29158713
     [Google Scholar]
  37. RazaK. SinghB. MahajanA. NegiP. BhatiaA. KatareO.P. Design and evaluation of flexible membrane vesicles (FMVs) for enhanced topical delivery of capsaicin.J. Drug Target.201119429330210.3109/1061186X.2010.499464 20615093
     [Google Scholar]
  38. BandyopadhyayP.K. NayakA.K. Thiolation of fenugreek seed polysaccharide; utilization as a novel biomucoadhesive agent in drug delivery.Int. J. Appl. Pharm.202315114715510.22159/ijap.2023v15i1.46647
     [Google Scholar]
  39. EldesoukyL.M. El-MoslemanyR.M. RamadanA.A. MorsiM.H. KhalafallahN.M. Cyclosporine lipid nanocapsules as thermoresponsive gel for dry eye management: Promising corneal mucoadhesion, biodistribution and preclinical efficacy in rabbits.Pharmaceutics202113336010.3390/pharmaceutics13030360 33803242
     [Google Scholar]
  40. HasnainM.S. RishishwarP. AliS. NayakA.K. Preparation and evaluation of aceclofenac dental pastes using dillenia fruit gum for periodontitis treatment.SN Applied Sciences20202342510.1007/s42452‑020‑2240‑3
     [Google Scholar]
  41. UbaidM. IlyasS. MirS. KhanA.K. RashidR. KhanM.Z.U. KanwalZ.G. NawazA. ShahA. MurtazaG. Formulation and in vitro evaluation of carbopol 934-based modified clotrimazole gel for topical application.An. Acad. Bras. Cienc.20168842303231710.1590/0001‑3765201620160162 27925034
     [Google Scholar]
  42. SamimiM.S. MahboobianM.M. MohammadiM. Ocular toxicity assessment of nanoemulsion in-situ gel formulation of fluconazole.Hum. Exp. Toxicol.202140122039204710.1177/09603271211017314 34036827
     [Google Scholar]
  43. OmarM.M. HasanO.A. El SisiA.M. Preparation and optimization of lidocaine transferosomal gel containing permeation enhancers: A promising approach for enhancement of skin permeation.Int. J. Nanomedicine2019141551156210.2147/IJN.S201356 30880964
     [Google Scholar]
  44. SatapathyB.S. SahooP.K. PattnaikS. NayakA.K. MaharanaL. SahooR.N. Conveyance of sofosbuvir through vesicular lipid nanocarriers as an effective strategy for management of viral meningitis.RSC Advances20231347335003351310.1039/D3RA06540E 38025868
     [Google Scholar]
  45. BhattacharjeeA. DasP.J. DeyS. NayakA.K. RoyP.K. ChakrabartiS. MarbaniangD. DasS.K. RayS. ChattopadhyayP. MazumderB. Development and optimization of besifloxacin hydrochloride loaded liposomal gel prepared by thin film hydration method using 32 full factorial design.Colloids Surf. A Physicochem. Eng. Asp.202058512407110.1016/j.colsurfa.2019.124071
     [Google Scholar]
  46. DasB. DuttaS. NayakA.K. NandaU. Zinc alginate-carboxymethyl cashew gum microbeads for prolonged drug release: Development and optimization.Int. J. Biol. Macromol.20147050651510.1016/j.ijbiomac.2014.07.030 25062990
     [Google Scholar]
  47. JanaS. AliS.A. NayakA.K. SenK.K. BasuS.K. Development of topical gel containing aceclofenac-crospovidone solid dispersion by “Quality by Design (QbD)” approach.Chem. Eng. Res. Des.201492112095210510.1016/j.cherd.2014.01.025
     [Google Scholar]
  48. AghaO.A. GirgisG.N.S. El-SokkaryM.M.A. SolimanO.A.E.A. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study.Int. J. Pharm. X2023610020110.1016/j.ijpx.2023.100201 37560488
     [Google Scholar]
  49. JanoriaK.G. GundaS. BodduS.H.S. MitraA.K. Novel approaches to retinal drug delivery.Expert Opin. Drug Deliv.20074437138810.1517/17425247.4.4.371 17683251
     [Google Scholar]
  50. OnugwuA.L. NwagwuC.S. OnugwuO.S. EchezonaA.C. AgboC.P. IhimS.A. EmehP. NnamaniP.O. AttamaA.A. KhutoryanskiyV.V. Nanotechnology based drug delivery systems for the treatment of anterior segment eye diseases.J. Control. Release202335446548810.1016/j.jconrel.2023.01.018 36642250
     [Google Scholar]
  51. AlmeidaH. AmaralM. LobaoP. FrigerioC. Sousa LoboJ. Nanoparticles in ocular drug delivery systems for topical administration: Promises and challenges.Curr. Pharm. Des.201521365212522410.2174/1381612821666150923095155 26412360
     [Google Scholar]
  52. VermaD. VermaS. BlumeG. FahrA. Particle size of liposomes influences dermal delivery of substances into skin.Int. J. Pharm.20032581-214115110.1016/S0378‑5173(03)00183‑2 12753761
     [Google Scholar]
  53. NémethZ. CsókaI. Semnani JazaniR. SiposB. HaspelH. KozmaG. KónyaZ. DobóD.G. Quality by design-driven zeta potential optimisation study of liposomes with charge imparting membrane additives.Pharmaceutics2022149179810.3390/pharmaceutics14091798 36145546
     [Google Scholar]
  54. MajiR. OmoloC.A. JaglalY. SinghS. DevnarainN. MocktarC. GovenderT. A transferosome-loaded bigel for enhanced transdermal delivery and antibacterial activity of vancomycin hydrochloride.Int. J. Pharm.202160712099010.1016/j.ijpharm.2021.120990 34389419
     [Google Scholar]
  55. RompicherlaN.C. JoshiP. ShettyA. SudhakarK. AminH.I.M. MishraY. MishraV. AlbuttiA. AlhumeedN. Design, formulation, and evaluation of aloe vera gel-based capsaicin transemulgel for osteoarthritis.Pharmaceutics2022149181210.3390/pharmaceutics14091812 36145560
     [Google Scholar]
  56. AbelsonM.B. UdellI.J. WestonJ.H. Normal human tear pH by direct measurement.Arch. Ophthalmol.198199230110.1001/archopht.1981.03930010303017 7469869
     [Google Scholar]
  57. HamanoT. HorimotoK. LeeM. KomemushiS. Sodium hyaluronate eyedrops enhance tear film stability.Jpn. J. Ophthalmol.19964016265 8739501
     [Google Scholar]
  58. AbdelmonemR. ElhabalS.F. AbdelmalakN.S. El-NabarawiM.A. TeaimaM.H. Formulation and characterization of acetazolamide/carvedilol niosomal gel for glaucoma treatment: In vitro, and in vivo study.Pharmaceutics202113222110.3390/pharmaceutics13020221 33562785
     [Google Scholar]
  59. DantasM.G.B. ReisS.A.G.B. DamascenoC.M.D. RolimL.A. Rolim-NetoP.J. CarvalhoF.O. Quintans-JuniorL.J. AlmeidaJ.R.G.S. Development and evaluation of stability of a gel formulation containing the monoterpene borneol.ScientificWorldJournal201620161410.1155/2016/7394685 27247965
     [Google Scholar]
  60. PawarP. KashyapH. MalhotraS. SindhuR. Hp-β-CD-voriconazole in situ gelling system for ocular drug delivery: In vitro, stability, and antifungal activities assessment.BioMed Res. Int.201320131910.1155/2013/341218 23762839
     [Google Scholar]
  61. WuY. LiuY. LiX. KebebeD. ZhangB. RenJ. LuJ. LiJ. DuS. LiuZ. Research progress of in-situ gelling ophthalmic drug delivery system.Asian Journal of Pharmaceutical Sciences201914111510.1016/j.ajps.2018.04.008 32104434
     [Google Scholar]
  62. El-NesrO.H. YahiyaS.A. El-GazayerlyO.N. Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes.Saudi Pharm. J.201018421722410.1016/j.jsps.2010.07.003 23960730
     [Google Scholar]
  63. Abdel-RashidR.S. HelalD.A. OmarM.M. El SisiA.M. Nanogel loaded with surfactant based nanovesicles for enhanced ocular delivery of acetazolamide.Int. J. Nanomedicine2019142973298310.2147/IJN.S201891 31118616
     [Google Scholar]
/content/journals/cdd/10.2174/0115672018342369241018050810
Loading
Fluconazole-loaded Hyaluronic Acid-modified Transfersomal Hydrogels Containing D-panthenol for Ocular Delivery in Fungal Keratitis Management
Curr. Drug Deliv. 22, 998 (2025); https://doi.org/10.2174/0115672018342369241018050810
/content/journals/cdd/10.2174/0115672018342369241018050810
/content/journals/cdd/10.2174/0115672018342369241018050810
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): antifungal; Drug delivery; eyes; fluconazole; hydrogels; ophthalmology; thyme oil

Most Cited Most Cited RSS feed

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