Skip to main content

Advertisement

SpringerLink
Log in

Advances in Liposomes-Based-Therapeutics as Cutting-Edge for Ocular Fungal Infections: An Updated Review

  • Review
  • Published:
BioNanoScience Aims and scope Submit manuscript

Abstract

The drug delivery through the eye has been challenging due to the complex physiology of the eye. The ocular region is commonly considered the most advantageous site for the topical application of medicines for management of eye disorders. The effectiveness of this approach is commonly impeded by the strong protective mechanisms of eye, leading to restricted access of the drugs. Ocular fungal infections are commonly reported as one of the predominant eye illnesses caused by various fungal species like Fusarium species, Candida glabrata, Aspergillus flavus, and Aspergillus fumigatus. Liposomes are biocompatible lipid nanocarriers which have emerged as innovative therapeutic technologies in ophthalmology to overcome ocular obstacles, provide targeted drug delivery along with enhancement of drug’s safety margin. This review elucidates about causes of ocular fungal infection, fungal evasion by host immune system, pharmacological profile of drug used for treatment of ocular fungal infections, and challenges of existing formulations in management of ocular infections. This article focused upon the current advancements in domain of topical applications of liposomes of ophthalmic medicines in management of ocular fungal infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

No datasets were generated or analyzed during the current study.

Abbreviations

AMB:

Amphotericin B

AMCase:

Acidic mammalian chitinase

DAmB:

Amphotericin B deoxycholate

FLZ:

Fluconazole

IL-1β:

Interleukin-1β

L-AMB:

Liposomal amphotericin B

MOP:

Microneedle ocular patch

PAMPs:

Pathogen-associated molecular patterns

PC:

Phosphatidylcholine

PRR:

Pattern recognition receptors

References

  1. Mishra, G. P., Bagui, M., Tamboli, V., & Mitra, A. K. (2011). Recent applications of liposomes in ophthalmic drug delivery. Journal of Drug Delivery, 2011.

  2. Lai, S., Wei, Y., Wu, Q., Zhou, K., Liu, T., Zhang, Y., … Liu, Q. (2019). Liposomes for effective drug delivery to the ocular posterior chamber. Journal of Nanobiotechnology, 17, 1–12.

  3. Garg, P. (2012). Fungal, mycobacterial, and Nocardia infections and the eye: An update. Eye (London, England), 26(2), 245–251.

    Article  Google Scholar 

  4. Gower, E. W., Keay, L. J., Oechsler, R. A., Iovieno, A., Alfonso, E. C., Jones, D. B., … Lee, S. M. (2010). Trends in fungal keratitis in the United States, 2001 to 2007. Ophthalmology, 117(12), 2263–2267.

  5. Srinivasan, M. (2004). Fungal keratitis. Current Opinion in Ophthalmology, 15(4), 321–327.

    Article  Google Scholar 

  6. Mills, B., Radhakrishnan, N., Rajapandian, S. G. K., Rameshkumar, G., Lalitha, P., & Prajna, N. V. (2021). The role of fungi in fungal keratitis. Experimental Eye Research, 202, 108372.

    Article  Google Scholar 

  7. Hariprasad, S. M., Mieler, W. F., Lin, T. K., Sponsel, W. E., & Graybill, J. R. (2008). Voriconazole in the treatment of fungal eye infections: A review of current literature. British Journal of Ophthalmology, 92(7), 871.

    Article  Google Scholar 

  8. Sanap, S. N., Kedar, A., Bisen, A. C., Agrawal, S., & Bhatta, R. S. (2022). A recent update on therapeutic potential of vesicular system against fungal keratitis. Journal of Drug Delivery Science and Technology, 75, 103721.

  9. Raj, N., Vanathi, M., Ahmed, N. H., Gupta, N., Lomi, N., & Tandon, R. (2021). Recent perspectives in the management of fungal keratitis. Journal of Fungi, 7(11), 907.

    Article  Google Scholar 

  10. López-Cano, J. J., González-Cela-Casamayor, M. A., Andrés-Guerrero, V., Herrero-Vanrell, R., & Molina-Martínez, I. T. (2021). Liposomes as vehicles for topical ophthalmic drug delivery and ocular surface protection. Expert Opinion on drug Delivery, 18(7), 819–847.

    Article  Google Scholar 

  11. Chang, E. H., Harford, J. B., Eaton, M. A. W., Boisseau, P. M., Dube, A., Hayeshi, R., … Lee, D. S. (2015). Nanomedicine: past, present and future–a global perspective. Biochemical and Biophysical Research Communications, 468(3), 511–517.

  12. Wicki, A., Witzigmann, D., Balasubramanian, V., & Huwyler, J. (2015). Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications. Journal of Controlled Release, 200, 138–157.

    Article  Google Scholar 

  13. Kumar, L., Verma, S., Bhardwaj, A., Vaidya, S., & Vaidya, B. (2014). Eradication of superficial fungal infections by conventional and novel approaches: A comprehensive review. Artificial Cells Nanomedicine and Biotechnology, 42(1), 32–46.

    Article  Google Scholar 

  14. Soliman, G. M. (2017). Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges. International Journal of Pharmaceutics, 523(1), 15–32.

    Article  Google Scholar 

  15. Mueller, J. B., & McStay, C. M. (2008). Ocular infection and inflammation. Emergency Medicine Clinics of North America, 26(1), 57–72.

  16. Klotz, S. A., Penn, C. C., Negvesky, G. J., & Butrus, S. I. (2000). Fungal and parasitic infections of the eye. Clinical Microbiology Reviews, 13(4), 662–685.

    Article  Google Scholar 

  17. Atta, S., Perera, C., Kowalski, R. P., & Jhanji, V. (2022). Fungal keratitis: Clinical features, risk factors, treatment, and outcomes. Journal of Fungi, 8(9), 962.

    Article  Google Scholar 

  18. Tabbara, K. F. (2014). Infections of the Lacrimal System. Ocular infections (pp. 45–49). Springer.

    Chapter  Google Scholar 

  19. Sodhi, G., Liu, E., Renz, J., Heher, K., & Kapadia, M. (2016). Infections of the eyelids, orbit, and ocular adnexa. In N. Laver, & C. Specht (Eds.), The Infected Eye, 163–175.

  20. Reginatto, P., Agostinetto, G. J., Fuentefria, R. N., Marinho, D. R., Pizzol, M. D., & Fuentefria, A. M. (2023). Eye fungal infections: A mini review. Archives of Microbiology, 205(6), 236.

    Article  Google Scholar 

  21. Nayak, N. (2008). Fungal infections of the eye: Laboratory diagnosis and treatment. Nepal Medical College Journal : Nmcj, 10(1), 48–63.

    Google Scholar 

  22. Thomas, P. A., & Kaliamurthy, J. (2013). Mycotic keratitis: Epidemiology, diagnosis and management. Clinical Microbiology and Infection, 19(3), 210–220.

    Article  Google Scholar 

  23. Maharana, P. K., Sharma, N., Nagpal, R., Jhanji, V., Das, S., & Vajpayee, R. B. (2016). Recent advances in diagnosis and management of mycotic keratitis. Indian Journal of Ophthalmology, 64(5), 346.

    Article  Google Scholar 

  24. Qiao, G. L., Ling, J., Wong, T., Yeung, S. N., & Iovieno, A. (2020). Candida keratitis: Epidemiology, management, and clinical outcomes. Cornea, 39(7), 801–805.

    Article  Google Scholar 

  25. Leck, A. K., Thomas, P. A., Hagan, M., Kaliamurthy, J., Ackuaku, E., John, M., … Kalavathy, C. M. (2002). Aetiology of suppurative corneal ulcers in Ghana and south India, and epidemiology of fungal keratitis. The British journal of ophthalmology, 86(11), 1211

  26. Rai, M., Ingle, A. P., Ingle, P., Gupta, I., Mobin, M., Bonifaz, A., & Alves, M. (2021). Recent advances on mycotic keratitis caused by dematiaceous hyphomycetes. Journal of Applied Microbiology, 131(4), 1652–1667.

    Article  Google Scholar 

  27. Durand, M. L. (2017). Bacterial and fungal endophthalmitis. Clinical Microbiology Reviews, 30(3), 597–613.

    Article  Google Scholar 

  28. Sheu, S. J. (2017). Endophthalmitis. Korean Journal of Ophthalmology, 31(4), 283–289.

    Article  Google Scholar 

  29. Mikosz, C. A., Smith, R. M., Kim, M., Tyson, C., Lee, E. H., Adams, E., … Grant-Greene, Y. (2014). Fungal endophthalmitis associated with compounded products. Emerging Infectious Diseases, 20(2), 248.

  30. Park, H. J., Kim, S. H., Ju, H. W., Lee, H., Lee, Y., Park, S., … Yang, J. (2018). Microplasma jet arrays as a therapeutic choice for fungal keratitis. Scientific Reports, 8(1), 2422.

  31. Farooq, A. V., Patel, R. M., Lin, A. Y., Setabutr, P., Sartori, J., & Aakalu, V. K. (2015). Fungal orbital cellulitis: Presenting features, management and outcomes at a referral center. Orbit, 34(3), 152–159.

    Article  Google Scholar 

  32. Aimanianda, V., Bayry, J., Bozza, S., Kniemeyer, O., Perruccio, K., Elluru, S. R., … Kaveri, S. V. (2009). Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature, 460(7259), 1117–1121.

  33. Carrion, S. J., Leal, S. M., Ghannoum, M. A., Aimanianda, V., Latgé, J. P., & Pearlman, E. (2013). The rodA hydrophobin on aspergillus fumigatus spores masks dectin-1–and dectin-2–dependent responses and enhances fungal survival in vivo. The Journal of Immunology, 191(5), 2581–2588.

    Article  Google Scholar 

  34. Fuchs, U., Czymmek, K. J., & Sweigard, J. A. (2004). Five hydrophobin genes in Fusarium verticillioides include two required for microconidial chain formation. Fungal Genetics and Biology, 41(9), 852–864.

    Article  Google Scholar 

  35. Niu, L., Liu, X., Ma, Z., Yin, Y., Sun, L., Yang, L., & Zheng, Y. (2020). Fungal keratitis: Pathogenesis, diagnosis and prevention. Microbial Pathogenesis, 138, 103802.

    Article  Google Scholar 

  36. Abbondante, S., Leal, S. M., Clark, H. L., Ratitong, B., Sun, Y., Ma, L. J., & Pearlman, E. (2023). Immunity to pathogenic fungi in the eye. Seminars in Immunology (Vol. 67, p. 101753). Elsevier.

    Google Scholar 

  37. Blango, M. G., Kniemeyer, O., & Brakhage, A. A. (2019). Conidial surface proteins at the interface of fungal infections. PLoS Pathogens, 15(9), e1007939.

    Article  Google Scholar 

  38. Netea, M. G., Brown, G. D., Kullberg, B. J., & Gow, N. A. R. (2008). An integrated model of the recognition of Candida albicans by the innate immune system. Nature Reviews Microbiology, 6(1), 67–78.

    Article  Google Scholar 

  39. Redfern, R. L., & McDermott, A. M. (2010). Toll-like receptors in ocular surface disease. Experimental eye Research, 90(6), 679–687.

    Article  Google Scholar 

  40. Hardison, S. E., & Brown, G. D. (2012). C-type lectin receptors orchestrate antifungal immunity. Nature Immunology, 13(9), 817–822.

    Article  Google Scholar 

  41. Yang, R.-B., Wu, L.-P., Lu, X.-X., Zhang, C., Liu, H., Huang, Y., … Zhao, S.-Z. (2021). Immunologic mechanism of fungal keratitis. International Journal of Ophthalmology, 14(7), 1100.

  42. Brown, G. D. (2011). Innate antifungal immunity: The key role of phagocytes. Annual Review of Immunology, 29, 1–21.

    Article  Google Scholar 

  43. Maneu, V., Yanez, A., Murciano, C., Molina, A., Gil, M. L., & Gozalbo, D. (2011). Dectin-1 mediates in vitro phagocytosis of Candida albicans yeast cells by retinal microglia. FEMS Immunology & Medical Microbiology, 63(1), 148–150.

    Article  Google Scholar 

  44. Rubin-Bejerano, I., Abeijon, C., Magnelli, P., Grisafi, P., & Fink, G. R. (2007). Phagocytosis by human neutrophils is stimulated by a unique fungal cell wall component. Cell host & Microbe, 2(1), 55–67.

    Article  Google Scholar 

  45. Sun, Y., Abbondante, S., Karmakar, M., de Jesus Carrion, S., Che, C., Hise, A. G., & Pearlman, E. (2018). Neutrophil caspase-11 is required for cleavage of caspase-1 and secretion of IL-1β in aspergillus fumigatus infection. The Journal of Immunology, 201(9), 2767–2775.

    Article  Google Scholar 

  46. Bourgeois, C., Majer, O., Frohner, I. E., Lesiak-Markowicz, I., Hildering, K.-S., Glaser, W., … Müller, M. (2011). Conventional dendritic cells mount a type I IFN response against Candida spp. requiring novel phagosomal TLR7-mediated IFN-β signaling. The Journal of Immunology, 186(5), 3104–3112.

  47. Karmakar, M., Katsnelson, M., Malak, H. A., Greene, N. G., Howell, S. J., Hise, A. G., … Pearlman, E. (2015). Neutrophil IL-1β processing induced by pneumolysin is mediated by the NLRP3/ASC inflammasome and caspase-1 activation and is dependent on K+ efflux. The Journal of Immunology, 194(4), 1763–1775.

  48. Brissette-Storkus, C. S., Reynolds, S. M., Lepisto, A. J., & Hendricks, R. L. (2002). Identification of a novel macrophage population in the normal mouse corneal stroma. Investigative Ophthalmology & Visual Science, 43(7), 2264–2271.

    Google Scholar 

  49. Hamrah, P., & Dana, M. R. (2007). Corneal antigen-presenting cells. Immune Response and the Eye, 92, 58–70.

    Article  Google Scholar 

  50. Mobeen, R., Stapleton, F., Chao, C., Madigan, M. C., Briggs, N., & Golebiowski, B. (2019). Corneal epithelial dendritic cell density in the healthy human cornea: A meta-analysis of in-vivo confocal microscopy data. The Ocular Surface, 17(4), 753–762.

    Article  Google Scholar 

  51. Palomar, A. P., del, Montolío, A., Cegoñino, J., Dhanda, S. K., Lio, C. T., & Bose, T. (2019). The innate immune cell profile of the cornea predicts the onset of ocular surface inflammatory disorders. Journal of Clinical Medicine, 8(12), 2110.

    Article  Google Scholar 

  52. Karmakar, M., Katsnelson, M., Malak, H. A., Greene, N. G., Howell, S. J., Hise, A. G., … Pearlman, E. (2015). Neutrophil IL-1β processing induced by pneumolysin is mediated by the NLRP3/ASC inflammasome and caspase-1 activation and is dependent on K+ efflux. The Journal of Immunology, 194(4), 1763–1775.

  53. Leal Jr, S. M., Cowden, S., Hsia, Y. C., Ghannoum, M. A., Momany, M., & Pearlman, E. (2010). Distinct roles for Dectin-1 and TLR4 in the pathogenesis of aspergillus fumigatus keratitis. PLoS Pathogens, 6(7), e1000976.

  54. Zhang, J., Zhao, G., Lin, J., Che, C., Li, C., Jiang, N., … Wang, Q. (2018). Role of PTX3 in corneal epithelial innate immunity against Aspergillus fumigatus infection. Experimental Eye Research, 167, 152–162.

  55. de Jesus Carrion, S., Abbondante, S., Clark, H. L., Marshall, M. E., Mouyna, I., Beauvais, A., … Armstrong, B. (2019). Aspergillus fumigatus corneal infection is regulated by chitin synthases and by neutrophil–derived acidic mammalian chitinase. European journal of immunology, 49(6), 918–927.

  56. Jin, X., Zhao, Y., Zhang, F., Wan, T., Fan, F., Xie, X., & Lin, Z. (2016). Neutrophil extracellular traps involvement in corneal fungal infection. Molecular Vision, 22, 944–952.

  57. Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., … Zychlinsky, A. (2004). Neutrophil extracellular traps kill bacteria. Science, 303(5663), 1532–1535.

  58. Desai, J. V., & Lionakis, M. S. (2018). The role of neutrophils in host defense against invasive fungal infections. Current Clinical Microbiology Reports, 5, 181–189.

    Article  Google Scholar 

  59. Lakhani, P., Patil, A., & Majumdar, S. (2019). Challenges in the polyene-and azole-based pharmacotherapy of ocular fungal infections. Journal of Ocular Pharmacology and Therapeutics, 35(1), 6–22.

    Article  Google Scholar 

  60. Lewis, R. E. (2011). Current concepts in antifungal pharmacology. Mayo Clinic Proceedings (Vol. 86, pp. 805–817). Elsevier.

    Google Scholar 

  61. Gote, V., Sikder, S., Sicotte, J., & Pal, D. (2019). Ocular drug delivery: Present innovations and future challenges. Journal of Pharmacology and Experimental Therapeutics, 370(3), 602–624.

    Article  Google Scholar 

  62. Mascarenhas, M., Chaudhari, P., & Lewis, S. A. (2023). Natamycin ocular delivery: Challenges and advancements in ocular therapeutics. Advances in Therapy, 40(8), 3332–3359.

    Article  Google Scholar 

  63. Kaur, I. P., Rana, C., & Singh, H. (2008). Development of effective ocular preparations of antifungal agents. Journal of Ocular Pharmacology and Therapeutics, 24(5), 481–494.

    Article  Google Scholar 

  64. Mehrandish, S., & Mirzaeei, S. (2021). A review on ocular novel drug delivery systems of antifungal drugs: Functional evaluation and comparison of conventional and novel dosage forms. Advanced Pharmaceutical Bulletin, 11(1), 28.

    Article  Google Scholar 

  65. Mushtaq, A., Baseer, A., Zaidi, S. S., Khan, M. W., Batool, S., Elahi, E., … ud Din, F. (2022). Fluconazole-loaded thermosensitive system: In vitro release, pharmacokinetics and safety study. Journal of Drug Delivery Science and Technology, 67, 102972.

  66. Farooq, M., Usman, F., Zaib, S., Shah, H. S., Jamil, Q. A., Akbar Sheikh, F., … El-Saber Batiha, G. (2022). Fabrication and evaluation of voriconazole loaded transethosomal gel for enhanced antifungal and antileishmanial activity. Molecules, 27(10), 3347.

  67. Swaminathan, S., Sangwai, M., Wawdhane, S., & Vavia, P. (2013). Soluble itraconazole in tablet form using disordered drug delivery approach: Critical scale-up considerations and bio-equivalence studies. An Official Journal of the American Association of Pharmaceutical Scientists, 14, 360–374.

    Google Scholar 

  68. Nimtrakul, P., Williams, D. B., Tiyaboonchai, W., & Prestidge, C. A. (2020). Copolymeric micelles overcome the oral delivery challenges of amphotericin B. Pharmaceuticals, 13(6), 121.

    Article  Google Scholar 

  69. Nikam, A. N., Jacob, A., Raychaudhuri, R., Fernandes, G., Pandey, A., Rao, V., … Mutalik, S. (2023). Topical Micro-Emulsion of 5-Fluorouracil by a Twin Screw Processor-Based Novel Continuous Manufacturing Process for the Treatment of Skin Cancer: Preparation and In Vitro and In Vivo Evaluations. Pharmaceutics, 15(9), 2175.

  70. Bhandari, L., Patil, A. S., Bolmal, U., Masareddy, R., & Dandagi, P. (2022). Formulation and evaluation of natamycin solid dispersion incorporated ophthalmic films. Indian Journal of Pharmaceutical Education and Research, 56(1), 103–111.

  71. Patil, A. ., Lakhani, P., Taskar, P., Avula, B., & Majumdar, S. (2020). Carboxyvinyl polymer and guar-borate gelling system containing natamycin loaded pegylated nanolipid carriers exhibit improved ocular pharmacokinetic parameters. Journal of Ocular Pharmacology and Therapeutics, 36(6), 410–420.

    Article  Google Scholar 

  72. Chhonker, Y. S., Kumar, D., Shrivastava, P., Kumar, D., Singh, R., Chandasana, H., & Bhatta, R. S. (2013). LC–MS/MS assay for the determination of natamycin in rabbit and human plasma: Application to a pharmacokinetics and protein binding study. Journal of Pharmaceutical Analysis, 3(2), 144–148.

    Article  Google Scholar 

  73. Meena, M., Prajapati, P., Ravichandran, C., & Sehrawat, R. (2021). Natamycin: a natural preservative for food applications—A review. Food Science and Biotechnology, 30, 1481–1496.

  74. Hosoya, K., Lee, V. H. L., & Kim, K. J. (2005). Roles of the conjunctiva in ocular drug delivery: A review of conjunctival transport mechanisms and their regulation. European Journal of Pharmaceutics and Biopharmaceutics, 60(2), 227–240.

    Article  Google Scholar 

  75. Patel, P., Shastri, D., Shelat, P., & Shukla, A. (2010). Ophthalmic drug delivery system: Challenges and approaches. Systematic Reviews in Pharmacy, 1(2), 113.

    Article  Google Scholar 

  76. Chen, Y., Ye, Z., Chen, H., & Li, Z. (2024). Breaking barriers: Nanomedicine-based drug delivery for cataract treatment. International Journal of Nanomedicine 19, 4021–4040.

  77. Akhter, M. H., Ahmad, I., Alshahrani, M. Y., Al-Harbi, A. I., Khalilullah, H., Afzal, O., … Karim, S. (2022). Drug delivery challenges and current progress in nanocarrier-based ocular therapeutic system. Gels, 8(2), 82.

  78. Sahoo, S. K., Dilnawaz, F., & Krishnakumar, S. (2008). Nanotechnology in ocular drug delivery. Drug Discovery Today, 13(3–4), 144–151.

    Article  Google Scholar 

  79. Wadhwa, S., Paliwal, R., Paliwal, S. R., & Vyas, S. P. (2009). Nanocarriers in ocular drug delivery: An update review. Current Pharmaceutical Design, 15(23), 2724–2750.

    Article  Google Scholar 

  80. Din, F. U., Aman, W., Ullah, I., Qureshi, O. S., Mustapha, O., Shafique, S., & Zeb, A. (2017). Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. International Journal of Nanomedicine, 12, 7291–7309.

  81. Bangham, A. D., Standish, M. M., & Watkins, J. C. (1965). Diffusion of univalent ions across the lamellae of swollen phospholipids. Journal of Molecular Biology, 13(1), 238-IN27.

    Article  Google Scholar 

  82. Mainardes, R. M., Urban, M. C., Cinto, P. O., Khalil, N. M., Chaud, M. V., Evangelista, R. C., & Daflon Gremiao, M. P. (2005). Colloidal carriers for ophthalmic drug delivery. Current Drug Targets, 6(3), 363–371.

    Article  Google Scholar 

  83. Jin, Q., Li, H., Jin, Z., Huang, L., Wang, F., Zhou, Y., … Wu, J. (2018). TPGS modified nanoliposomes as an effective ocular delivery system to treat glaucoma. International Journal of Pharmaceutics, 553(1–2), 21–28.

  84. de Lima, P. H. C., Butera, A. P., Cabeça, L. F., & Ribeiro-Viana, R. M. (2021). Liposome surface modification by phospholipid chemical reactions. Chemistry and Physics of Lipids, 237, 105084.

    Article  Google Scholar 

  85. Kaur, I. P., Garg, A., Singla, A. K., & Aggarwal, D. (2004). Vesicular systems in ocular drug delivery: An overview. International Journal of Pharmaceutics, 269(1), 1–14.

    Article  Google Scholar 

  86. Habib, F. S., Fouad, E. A., Abdel-Rhaman, M. S., & Fathalla, D. (2010). Liposomes as an ocular delivery system of fluconazole: In-vitro studies. Acta Ophthalmologica, 88(8), 901–904.

    Article  Google Scholar 

  87. Tan, G., Yu, S., Pan, H., Li, J., Liu, D., Yuan, K., … Pan, W. (2017). Bioadhesive chitosan-loaded liposomes: A more efficient and higher permeable ocular delivery platform for timolol maleate. International journal of biological macromolecules, 94, 355–363.

  88. Agarwal, R., Iezhitsa, I., Agarwal, P., Abdul Nasir, N. A., Razali, N., Alyautdin, R., & Ismail, N. M. (2016). Liposomes in topical ophthalmic drug delivery: An update. Drug Delivery, 23(4), 1075–1091.

    Article  Google Scholar 

  89. Mishra, A., Bano, M., Bisen, A. C., Verma, S., Sanap, S. N., Kishor, R., … Bhatta, R. S. (2020). Topical corneal targeted sustained release amphotericin B liposomal formulation for the treatment of fungal keratitis and its PK-PD evaluation. Journal of Drug Delivery Science and Technology, 60, 101944.

  90. Jain, A. K., Chalasani, K. B., Khar, R. K., Ahmed, F. J., & Diwan, P. V. (2007). Muco-adhesive multivesicular liposomes as an effective carrier for transmucosal insulin delivery. Journal of drug Targeting, 15(6), 417–427.

    Article  Google Scholar 

  91. Ebrahim, S., Peyman, G. A., & Lee, P. J. (2005). Applications of liposomes in ophthalmology. Survey of Ophthalmology, 50(2), 167–182.

    Article  Google Scholar 

  92. Jensen, G. M. (2017). The care and feeding of a commercial liposomal product: Liposomal amphotericin B (AmBisome®). Journal of Liposome Research, 27(3), 173–179.

    Article  Google Scholar 

  93. Sakai, D., Imai, H., & Nakamura, M. (2021). Multiple intravitreal liposomal amphotericin B for a case of Candida Glabrata Endophthalmitis. Case Reports in Ophthalmology, 12(2), 485–491.

    Article  Google Scholar 

  94. Imago, M., Imai, H., Nakanishi, Y., & Azumi, A. (2009). Optical coherence tomography for monitoring the process of Candida Endophthalmitis. Acta Ophthalmologica, 87(6), 680–682.

    Article  Google Scholar 

  95. Pappas, P. G., Kauffman, C. A., Andes, D. R., Clancy, C. J., Marr, K. A., Ostrosky-Zeichner, L., … Walsh, T. J. (2016). Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 62(4), e1–e50.

  96. Axelrod, A. J., Peyman, G. A., & Apple, D. J. (1973). Toxicity of intravitreal injection of amphotericin B. American Journal of Ophthalmology, 76(4), 578–583.

    Article  Google Scholar 

  97. Celenza, G., Iorio, R., Cracchiolo, S., Petricca, S., Costagliola, C., Cinque, B., … Bellio, P. (2020). Antimycotic Activity of Ozonized Oil in Liposome Eye Drops against Candida spp. Translational Vision Science & Technology, 9(8), 4.

  98. Ando, T., Kawakami, H., Mochizuki, K., Murata, K., Manabe, Y., Takagi, D., … Ogura, S. (2021). Intraocular penetration of liposomal amphotericin B after intravenous injection in inflamed human eyes. Journal of Infection and Chemotherapy, 27(9), 1319–1322.

  99. Ghosh, A. K., Rudramurthy, S. M., Gupta, A., Choudhary, H., Singh, S., Thakur, A., & Jatana, M. (2019). Evaluation of liposomal and conventional amphotericin B in experimental fungal keratitis rabbit model. Translational Vision Science & Technology, 8(3), 35.

    Article  Google Scholar 

  100. Sanap, S. N., Bisen, A. C., Mishra, A., Biswas, A., Agrawal, S., Yadav, K. S., … Bhatta, R. S. (2022). QbD based antifungal drug-loaded ophthalmic liposomal formulation for the management of fungal keratitis: in vitro, ex vivo and in vivo pharmacokinetic studies. Journal of Drug Delivery Science and Technology, 74, 103517.

  101. Salem, H. F., Ahmed, S. M., & Omar, M. M. (2016). Liposomal flucytosine capped with gold nanoparticle formulations for improved ocular delivery. Drug Design, Development and Therapy, 10, 277–295.

  102. de Sá, F. A. P., Taveira, S. F., Gelfuso, G. M., Lima, E. M., & Gratieri, T. (2015). Liposomal voriconazole (VOR) formulation for improved ocular delivery. Colloids and Surfaces B: Biointerfaces, 133, 331–338.

    Article  Google Scholar 

  103. Gelfuso, G. M., Ferreira-Nunes, R., Dalmolin, L. F., Re, A. C. dos S., Dos Santos, G. A., de Sá, F. A. P., … Anjos, J. L. V. (2020). Iontophoresis enhances voriconazole antifungal potency and corneal penetration. International Journal of Pharmaceutics, 576, 118991.

  104. Leal, A. F. G., Leite, M. C., Medeiros, C. S. Q., Cavalcanti, I. M. F., Wanderley, A. G., Magalhães, S., N. S., & Neves, R. P. (2015). Antifungal activity of a liposomal itraconazole formulation in experimental aspergillus flavus keratitis with endophthalmitis. Mycopathologia, 179, 225–229.

    Article  Google Scholar 

  105. Moustafa, M. A., Elnaggar, Y. S. R., El-Refaie, W. M., & Abdallah, O. Y. (2017). Hyalugel-integrated liposomes as a novel ocular nanosized delivery system of fluconazole with promising prolonged effect. International Journal of Pharmaceutics, 534(1–2), 14–24.

    Article  Google Scholar 

  106. Moustafa, M. A., El-Refaie, W. M., Elnaggar, Y. S. R., & Abdallah, O. Y. (2018). Gel in core carbosomes as novel ophthalmic vehicles with enhanced corneal permeation and residence. International Journal of Pharmaceutics, 546(1–2), 166–175.

    Article  Google Scholar 

  107. Roy, G., Galigama, R. D., Thorat, V. S., Mallela, L. S., Roy, S., Garg, P., & Venuganti, V. V. K. (2019). Amphotericin B containing microneedle ocular patch for effective treatment of fungal keratitis. International Journal of Pharmaceutics, 572, 118808.

    Article  Google Scholar 

  108. Zhang, Z. H., Teng, F., Sun, Q. X., Wang, S. Z., Liu, C., & Zhao, G. Q. (2019). Rapamycin liposome gutta inhibiting fungal keratitis of rats. International Journal of Ophthalmology, 12(4), 536.

    Google Scholar 

  109. https://clinicaltrials.gov/. (https://clinicaltrials.gov/).

  110. Jinzhong, Z., & Masaaki, K. (2018). Fungal keratitis prophylactic or therapeutic agent. CN108025000.

  111. Mazumder, R., Swarupanjali Padhi, S., & Gupta, P. (2019). Glycerosomes of Natamycin for Treatment of Ophthalmic Fungal Keratitis. IN201911040868.

  112. Chengye, C. H. E., & Leyu, L. Y. U. (2020). Application of secretoglobins in preparation of medicine for treating fungal keratitis. CN112057604.

  113. Jin, Y., Xiaoxia, Z., Xuan, Z., Jing, Z., & Xin, Z. U. O. (2021). Medical material for treating fungal keratitis and preparation method thereof. CN112773778.

  114. Weifen, Z., Xiuwen, G., Jinlong, M. A., Jingjing, Z., & Xiaoming, C. U. I. (2021). Contact lenses loaded with natamycin nanoparticles and preparation method thereof. CN112904590.

  115. Guiqiu, Z., Cui, L. I., Daohao, L. I., Xudong, P., Kuiwen, S., & Qian, W. (2021). Voriconazole-coated carrageenan corneal contact lens and preparation method thereof. CN112999354.

  116. Shengli, M. I., & Anyang, W. (2021). Ocular surface in-situ drug and preparation method thereof. CN113041215.

  117. Guiqiu, Z., Cui, L. I., Daohao, L. I., Xudong, P., Jing, L. I. N., Min, Y. I. N., … Guibo, L. I. U. (2021). Natamycin-grafted oxidized alginic acid fiber membrane and preparation method thereof. CN113069556.

  118. Cui, L. I., Guiqiu, Z., Daohao, L. I., Min, Y. I. N., Xudong, P., Chengye, C. H. E., & Zhaodong, D. U. (2021). Oxidized sodium alginate modified natamycin eye drops and preparation method thereof. CN113081956.

  119. Jing, L. I. N., Guiqiu, Z., Xudong, P., Cui, L. I., Xing, L. I. U., & QIAN, W. (2021). Specific lectin-1 nano antibody as well as preparation method and application thereof. CN113354735.

  120. Chengye, C. H. E., Qian, Z., & Leyu, L. Y. U. (2021). Application of C-type lectin-like receptor-1 as therapeutic marker of fungal keratitis. CN113156140.

  121. Cui, L. I., Guiqiu, Z., Lingwen, G. U., Daohao, L. I., Nan, J., & Qiang, X. U. (2021). Nanometer mesoporous carbon eye drops loaded with natamycin and silver as well as preparation method and application thereof. CN113520997.

  122. Ruibo, Y., Zhongwei, N. I. U., Xiaoyan, J. U., Shaozhen, Z., Ye, T., Liping, W. U., & Ning, G. A. O. (2021). Application of polysaccharide polypeptide conjugate in treatment of infectious keratitis. CN113577302.

  123. Xiangrong, D. A. I., Lingzhen, D., Gang, L. I., & Xiaoyi, L. I. (2021). Voriconazole-containing ophthalmic gel as well as preparation method and application thereof. CN113662914.

  124. Wal, P., Pandey, P., Singh, A., Pant, A., Gautam, A., Kr, D., Kushawah, D. K., Garg, D., Nivatya, H. K., Singh, H., Kumar, N., Kumar, P., & Rashmi, Sharma, V. (2022). A novel herbal microemulsion for ocular drug delivery. IN202211009279.

  125. Cheng, L. I., Yi, H. A. N., Chenfang, X. U., & Yunlong, W. U. (2022). Amphotericin B nano-micelle as well as preparation method and application thereof. CN114788810.

  126. Han, G. A. O. (2022). Preparation of glabridin eye-fixing medicine and application of glabridin eye-fixing medicine in treatment of fungal keratitis. CN114831936.

  127. Olegovich, P. V., Nikolaevich, K. V., Leonidovich, T. V., & Andreevich, T. K. (2023). Drug for the treatment of resistant fungal keratitis and its method of use. RU0002790703.

  128. Bhatta, R. S., Mishra, A., Sanap, S. N., Bisen, A., Verma, S., Kumar, M., Sharma, G., Shukla, S. K., Mugale, M. M., & Shukla, P. K. (2023). Polymeric liposomal formulation for keratitis. IN202111015517.

  129. Sharma, U. K., Vishvakarma, P., Kumar, P., Dang, M., Dhurandhar, Y., Kumari, R., Antal, S., Mohapatra, L., Bhargava, J., Maurya, P., Tiwari, P., Srivastava, R., & Mandal, S. Non-irritating ocular nano emulsion with micafungin. IN202311024937.

  130. Valeria, M., Vincenzo, P., Sudano, R. A., Donato, S., & Ilenia, A. (2023). Formulation based on polyhexamethylene biguanide for use in the treatment of acanthamoeba keratitis and/or fungal infections. EP4216966.

  131. Boswell, G. W., Buell, D., & Bekersky, I. (1998). AmBisome (liposomal amphotericin B): a comparative review. The Journal of Clinical Pharmacology 38(7), 583–592.

  132. Jadhav, M. P., Bamba, A., Shinde, V. M., Gogtay, N., Kshirsagar, N. A., Bichile, L. S., … Digumarathi, R. (2010). Liposomal amphotericin B (FungisomeTM) for the treatment of cryptococcal meningitis in HIV/AIDS patients in India: a multicentric, randomized controlled trial. Journal of postgraduate medicine, 56(2), 71–75.

  133. Stone, N. R. H., Bicanic, T., Salim, R., & Hope, W. (2016). Liposomal amphotericin B (AmBisome®): A review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs, 76, 485–500.

    Article  Google Scholar 

  134. Adler-Moore, J., & Proffitt, R. T. (2002). AmBisome: Liposomal formulation, structure, mechanism of action and pre-clinical experience. Journal of Antimicrobial Chemotherapy, 49(suppl_1), 21–30.

    Article  Google Scholar 

  135. Sanath, S., Gogtay, N. J., & Kshirsagar, N. A. (2005). Post-marketing study to assess the safety, tolerability and effectiveness of FungisomeTM: An Indian liposomal amphotericin B Preparation. Journal of Postgraduate Medicine, 51(Suppl 1), S58–S63.

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana, India, 133207, for providing facilities for the completion of this review.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana, 133207, India

    Himanshu Mehendiratta, Sukhbir Singh & Neelam Sharma

  2. Maharaja Agrasen School of Pharmacy, Maharaja Agrasen University, Baddi, Solan, Himachal Pradesh, 174103, India

    Ladli Kishore

  3. Hygia Institute of Pharmaceutical Education & Research, Lucknow, Uttar Pradesh, 226020, India

    Madhaw Dwivedi

  4. Janta College of Pharmacy, Butana, Sonipat, Haryana, 131302, India

    Anita Rani

Authors
  1. Himanshu Mehendiratta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sukhbir Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neelam Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ladli Kishore
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Madhaw Dwivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anita Rani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.M., S.S., and N.S. conceived this study and wrote the final manuscript. L.K., M.D., and A.R. revised and edited this manuscript. H.M. and N.S. prepared figures.

Corresponding authors

Correspondence to Sukhbir Singh or Neelam Sharma.

Ethics declarations

Ethical Approval 

Not applicable. 

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mehendiratta, H., Singh, S., Sharma, N. et al. Advances in Liposomes-Based-Therapeutics as Cutting-Edge for Ocular Fungal Infections: An Updated Review. BioNanoSci. (2024). https://doi.org/10.1007/s12668-024-01447-4

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12668-024-01447-4

Keywords

Search

Navigation