Skip to content
2000
image of Design and Evaluation of Econazole-Loaded Nanostructured Lipid Carriers for Ocular Treatment of Fungal Keratitis: In vitro and Ex vivo Studies

Abstract

Background

Fungal keratitis (FK) is a major cause of eye morbidity and monocular blindness, particularly in humid climates. Ocular drug delivery is challenging due to anatomical barriers, tear flow, and nasal drainage, which reduce corneal penetration and decrease bioavailability. Conventional antifungal treatments often lack efficacy for deep keratitis. In order to address these limitations, this study explores encapsulating econazole into nanostructured lipid carriers (NLCs).

Objective

To optimize, develop, and characterize econazole-loaded NLCs for ocular drug delivery.

Methods

NLCs were prepared using a modified pre-emulsification and probe sonication technique with stearic acid as the solid lipid and oleic acid as the liquid lipid. The resulting nano-emulsion was homogenized, cooled, and incorporated into a Carbopol 940-based gel. Optimization was performed using JMP software.

Results and Discussion

Optimised NLCs exhibited a particle size of 192.3 nm, PDI of 0.207, and zeta potential of -44.8, indicating stability. Drug content was 85.18% in NLCs and 83.8% in the gel, with entrapment efficiency of 66.9%. studies showed 84.51% drug permeation from the gel over 17 hours compared to 89.37% in 12 hours from conventional formulations. Permeation data obtained from the study revealed steady-state flux . (Jss) to be 88.53µg/cm2/hr, permeability co-efficient 0.0216 cm/hr, diffusion co-efficient 0.00325cm/hr. Drug release followed zero-order kinetics with anomalous transport. Stability testing confirmed gel’s stability for three months. Thus, developed ocular gel prolonged therapeutic action, thereby reducing dosing frequency which not only enhances patient compliance but minimizes side effects highlighting the formulation’s potential for improved ocular drug delivery.

Conclusion

The econazole-loaded NLC gel enhanced ocular retention, bioavailability, and sustained release, offering a promising treatment for FK.

Loading

Article metrics loading...

/content/journals/pnt/10.2174/0122117385385940250917075923
2025-10-08
2026-01-28
Loading full text...

Full text loading...

References

  1. Bremond-Gignac D. Chiambaretta F. Milazzo S. A european perspective on topical ophthalmic antibiotics: Current and evolving options. Ophthalmol. Eye Dis. 2011 3 29 43 10.4137/OED.S4866 23861622
    [Google Scholar]
  2. Wu H. Ong Z.Y. Liu S. Synthetic β-sheet forming peptide amphiphiles for treatment of fungal keratitis. Biomaterials 2015 43 44 49 10.1016/j.biomaterials.2014.11.052 25591960
    [Google Scholar]
  3. Xie L. Zhong W. Shi W. Sun S. Spectrum of fungal keratitis in north China. Ophthalmology 2006 113 11 1943 1948 10.1016/j.ophtha.2006.05.035 16935335
    [Google Scholar]
  4. Collier S.A. Gronostaj M.P. MacGurn A.K. Estimated burden of keratitis--United States, 2010. MMWR Morb. Mortal. Wkly. Rep. 2014 63 45 1027 1030 Centers for Disease Control and Prevention (CDC). 25393221
    [Google Scholar]
  5. Saha R. Das S. Mycological profile of infectious keratitis from delhi. Indian J. Med. Res. 2006 123 2 159 164 16575115
    [Google Scholar]
  6. Addo R.T. Ocular drug delivery: Advances, challenges and applications. Springer 2016 10.1007/978‑3‑319‑47691‑9
    [Google Scholar]
  7. El Hoffy N.M. Abdel Azim E.A. Hathout R.M. Fouly M.A. Elkheshen S.A. Glaucoma: Management and future perspectives for nanotechnology-based treatment modalities. Eur. J. Pharm. Sci. 2021 158 105648 10.1016/j.ejps.2020.105648 33227347
    [Google Scholar]
  8. Achouri D. Alhanout K. Piccerelle P. Andrieu V. Recent advances in ocular drug delivery. Drug Dev. Ind. Pharm. 2013 39 11 1599 1617 10.3109/03639045.2012.736515 23153114
    [Google Scholar]
  9. Zhang W. Yang H. Jiang L. Han L. Wang L. Use of potassium hydroxide, giemsa and calcofluor white staining techniques in the microscopic evaluation of corneal scrapings for diagnosis of fungal keratitis. J. Int. Med. Res. 2010 38 6 1961 1967 10.1177/147323001003800609 21226999
    [Google Scholar]
  10. Chaiwut C. Tadtong S. Akachaipaibul P. Thermosensitive in situ ophthalmic gel for effective local delivery and antifungal activity of ketoconazole nanoparticles. Gels 2024 11 1 13 10.3390/gels11010013 39851983
    [Google Scholar]
  11. Gower E.W. Keay L.J. Oechsler R.A. Trends in fungal keratitis in the United States, 2001 to 2007. Ophthalmology 2010 117 12 2263 2267 10.1016/j.ophtha.2010.03.048 20591493
    [Google Scholar]
  12. Paterson G.R. British pharmacopoeia 1980. Can. Med. Assoc. J. 1982 126 5 514
    [Google Scholar]
  13. Sakellari G.I. Zafeiri I. Batchelor H. Spyropoulos F. Formulation design, production and characterisation of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the encapsulation of a model hydrophobic active. Food Hydrocoll. Health 2021 1 100024 10.1016/j.fhfh.2021.100024 35028634
    [Google Scholar]
  14. Musielak E. Feliczak-Guzik A. Nowak I. Synthesis and potential applications of lipid nanoparticles in medicine. Materials 2022 15 2 682 10.3390/ma15020682 35057398
    [Google Scholar]
  15. Araújo J. Gonzalez E. Egea M.A. Garcia M.L. Souto E.B. Nanomedicines for ocular NSAIDs: Safety on drug delivery. Nanomedicine 2009 5 4 394 401 10.1016/j.nano.2009.02.003 19341814
    [Google Scholar]
  16. Schäferkorting M. Mehnert W. Korting H. Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv. Drug Deliv. Rev. 2007 59 6 427 443 10.1016/j.addr.2007.04.006 17544165
    [Google Scholar]
  17. Khosa A. Reddi S. Saha R.N. Nanostructured lipid carriers for site-specific drug delivery. Biomed. Pharmacother. 2018 103 598 613 10.1016/j.biopha.2018.04.055 29677547
    [Google Scholar]
  18. Fan Y. Liu J.H. Lu H.T. Zhang Q. Electrochemical behavior and voltammetric determination of paracetamol on Nafion/TiO2–graphene modified glassy carbon electrode. Colloids Surf. B Biointerfaces 2011 85 2 289 292 10.1016/j.colsurfb.2011.02.041 21435844
    [Google Scholar]
  19. Reddy S. Katyayani T. Navathe A. Ramya G. Review on self-micro emulsifying drug delivery systems. Int J Res Pharm Sci 2011 2 3 382 392
    [Google Scholar]
  20. Chaurasia G. A review on pharmaceutical preformulation studies in formulation and development of new drug molecules. Int. J. Pharm. Sci. Res. 2016 7 6 2313 2320 10.13040/IJPSR.0975‑8232.7(6).2313‑20
    [Google Scholar]
  21. Puri V. Savla R. Chen K. Robinson K. Virani A. Michniak-Kohn B. Antifungal nail lacquer for enhanced transungual delivery of econazole nitrate. Pharmaceutics 2022 14 10 2204 10.3390/pharmaceutics14102204 36297639
    [Google Scholar]
  22. Shah N.V. Seth A.K. Balaraman R. Aundhia C.J. Maheshwari R.A. Parmar G.R. Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study. J. Adv. Res. 2016 7 3 423 434 10.1016/j.jare.2016.03.002 27222747
    [Google Scholar]
  23. Suksaeree J. Thuengernthong A. Pongpichayasiri K. Maneewattanapinyo P. Settharaksa S. Pichayakorn W. Formulation and evaluation of matrix type transdermal patch containing silver nanoparticles. J. Polym. Environ. 2018 26 12 4369 4375 10.1007/s10924‑018‑1305‑5
    [Google Scholar]
  24. Ajiboye A.L. Nandi U. Galli M. Trivedi V. Olanzapine loaded nanostructured lipid carriers via high shear homogenization and ultrasonication. Sci. Pharm. 2021 89 2 25 10.3390/scipharm89020025
    [Google Scholar]
  25. Srivastava S. Verma U. Kumar R. Bhatt N. Preparation and evaluation of econazole nitrate containing film-forming gel. Eur. J. Mol. Clin. Med. 2021 8 3 2881 2895
    [Google Scholar]
  26. Gajra B. Pandya S.S. Singh S. Rabari H.A. Mucoadhesive hydrogel films of econazole nitrate: Formulation and optimization using factorial design. J. Drug Deliv. 2014 2014 1 14 10.1155/2014/305863 25006462
    [Google Scholar]
  27. Himesh S. Preformulation studies of tramadol HCl: Vital part of formulation design. EJBPS 2020 7 1 369 373
    [Google Scholar]
  28. Gupta P.C. Kapoor A. Pandey P. Designing and characterization of econazole nitrate nanostructured lipid carriers’ gel for topical delivery. Eur. J. Pharm. Med. Res. 2018 5 6 559 567
    [Google Scholar]
  29. Jaiswal S. Yadav K. Shukla S. Mitra R. Formulation, optimization, and evaluation of solid-lipid formulation for bioavailability enhancement utilizing diltiazem hydrochloride. Curr Appl Mater 2025 3 e26667312325351 10.2174/0126667312325351241009063848
    [Google Scholar]
  30. Castro S.R. Ribeiro L.N.M. Breitkreitz M.C. A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers. Sci. Rep. 2021 11 1 21463 10.1038/s41598‑021‑99743‑6 34728779
    [Google Scholar]
  31. Bhowmick M. Sengodan T. Mechanisms, kinetics and mathematical modelling of transdermal permeation-an updated review. Pharm. Glob. 2013 4 6 1
    [Google Scholar]
  32. Shinde U. Pokharkar S. Modani S. Design and evaluation of microemulsion gel system of nadifloxacin. Indian J. Pharm. Sci. 2012 74 3 237 247 10.4103/0250‑474X.106066 23439454
    [Google Scholar]
  33. Bin-Jumah M. Gilani S.J. Jahangir M.A. Clarithromycin-loaded ocular chitosan nanoparticle: Formulation, optimization, characterization, ocular irritation, and antimicrobial activity. Int. J. Nanomedicine 2020 15 7861 7875 10.2147/IJN.S269004 33116505
    [Google Scholar]
  34. Ghurghure S.M. Jadhav T. Kale S. Phatak A.A. Formulation and evaluation of posaconazole loaded nanostructured lipid carriers for topical drug delivery system. Curr Trends Pharm Pharm Chem 2022 4 3 126 134 10.18231/j.ctppc.2022.022
    [Google Scholar]
  35. Bhaskar K. Anbu J. Ravichandiran V. Venkateswarlu V. Rao Y. Lipid nanoparticles for transdermal delivery of flurbiprofen: Formulation, in vitro, ex vivo and in vivo studies. Lipids Health Dis. 2009 8 1 6 10.1186/1476‑511X‑8‑6 19243632
    [Google Scholar]
  36. Jaiswal S. Gupta G.D. Optimization, formulation, and ex vivo evaluation of solid lipid nanoparticles for transdermal delivery of diltiazem hydrochloride. Pharm. Nanotechnol. 2024 13 10.2174/0122117385330951240925064813 39400025
    [Google Scholar]
  37. Kandav G. Lochab A.K. Sharma T. Design and characterization of timolol loaded gellan gum nanoparticles for improved ocular drug delivery. Indian J Pharm Educ Res 2024 58 3 751 759 10.5530/ijper.58.3.83
    [Google Scholar]
  38. Abdallah M.H. Transfersomes as a transdermal drug delivery system for enhancement the antifungal activity of nystatin. Int. J. Pharm. Pharm. Sci. 2013 5 4 560 567
    [Google Scholar]
/content/journals/pnt/10.2174/0122117385385940250917075923
Loading
/content/journals/pnt/10.2174/0122117385385940250917075923
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