2,275
Views
2
CrossRef citations to date
0
Altmetric
Invited Review

Review of Preclinical Outcomes of a Topical Cationic Emulsion of Cyclosporine A for the Treatment of Ocular Surface Diseases

, PhD, , MD, PhD, , MD, PhD, , PhD, , MD, PhD & , PharmD, MScORCID Icon
Pages 1945-1955 | Received 06 May 2021, Accepted 12 Jul 2021, Published online: 04 Aug 2021

References

  • Gipson IK. The ocular surface: the challenge to enable and protect vision. Invest Ophthalmol Vis Sci. 2007;48(10):4390–4398. doi:10.1167/iovs.07-0770.
  • Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf. 2017;15(3):334–365. doi:10.1016/j.jtos.2017.05.003.
  • Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol. 2011;151(5):792–798.e1. doi:10.1016/j.ajo.2010.10.032.
  • Baudouin C, Messmer EM, Aragona P, et al. Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction. Br J Ophthalmol. 2016;100(3):300–306. doi:10.1136/bjophthalmol-2015-307415.
  • Cohen DJ, Loertscher R, Rubin MF, Tilney NL, Carpenter CB, Strom TB. Cyclosporine: a new immunosuppressive agent for organ transplantation. Ann Intern Med. 1984;101(5):667–682. doi:10.7326/0003-4819-101-5-667.
  • Ellis CN, Gorsulowsky DC, Hamilton TA, et al. Cyclosporine improves psoriasis in a double-blind study. JAMA. 1986;256(22):3110–3116. doi:10.1001/jama.1986.03380220076026.
  • Brynskov J, Freund L, Rasmussen SN, et al. A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic crohn’s disease. N Engl J Med. 1989;321(13):845–850. doi:10.1056/NEJM198909283211301.
  • Faulds D, Goa KL, Benfield P. Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs. 1993;45(6):953–1040. doi:10.2165/00003495-199345060-00007.
  • Hunter PA, Wilhelmus KR, Rice NS, Jones BR. Cyclosporin A applied topically to the recipient eye inhibits corneal graft rejection. Clin Exp Immunol. 1981;45:173–177.
  • Akpek EK, Amescua G, Farid M, et al. Dry eye syndrome preferred practice pattern®. Ophthalmology. 2019;126(1):P286–P334. doi:10.1016/j.ophtha.2018.10.023.
  • Wan KH-N, Chen LJ, Rong SS, Pang CP, Young AL. Topical cyclosporine in the treatment of allergic conjunctivitis: a meta-analysis. Ophthalmology. 2013;120(11):2197–2203. doi:10.1016/j.ophtha.2013.03.044.
  • Fauquert J-L. Diagnosing and managing allergic conjunctivitis in childhood: the allergist’s perspective. Pediatr Allergy Immunol. 2019;30(4):405–414. doi:10.1111/pai.13035.
  • Vichyanond P, Pacharn P, Pleyer U, Leonardi A. Vernal keratoconjunctivitis: a severe allergic eye disease with remodeling changes. Pediatr Allergy Immunol. 2014;25(4):314–322. doi:10.1111/pai.12197.
  • PubChem. Cyclosporin A. https://pubchem.ncbi.nlm.nih.gov/compound/5284373. Accessed January 26, 2021.
  • Jumelle C, Gholizadeh S, Annabi N, Dana R. Advances and limitations of drug delivery systems formulated as eye drops. J Control Release. 2020;321:1–22. doi:10.1016/j.jconrel.2020.01.057.
  • Lallemand F, Felt-Baeyens O, Besseghir K, Behar-Cohen F, Gurny R. Cyclosporine A delivery to the eye: a pharmaceutical challenge. Eur J Pharm Biopharm. 2003;56(3):307–318. doi:10.1016/S0939-6411(03)00138-3.
  • Lallemand F, Schmitt M, Bourges J-L, Gurny R, Benita S, Garrigue J-S. Cyclosporine A delivery to the eye: a comprehensive review of academic and industrial efforts. Eur J Pharm Biopharm. 2017;117:14–28. doi:10.1016/j.ejpb.2017.03.006.
  • Weiss SL, Kramer WG. Ocular distribution of cyclosporine following topical administration of OTX-101 in New Zealand white rabbits. J Ocul Pharmacol Ther. 2019;35(7):395–402. doi:10.1089/jop.2018.0106.
  • Jester JV, Li HF, Petroll WM, et al. Area and depth of surfactant-induced corneal injury correlates with cell death. Invest Ophthalmol Vis Sci. 1998;39(6):922–936.
  • Maurer JK, Li HF, Petroll WM, Parker RD, Cavanagh HD, Jester JV. Confocal microscopic characterization of initial corneal changes of surfactant-induced eye irritation in the rabbit. Toxicol Appl Pharmacol. 1997;143(2):291–300. doi:10.1006/taap.1996.8097.
  • Khanal S, Tomlinson A, Pearce EI, Simmons PA. Effect of an oil-in-water emulsion on the tear physiology of patients with mild to moderate dry eye. Cornea. 2007;26(2):175–181. doi:10.1097/ICO.0b013e31802b492d.
  • McCulley JP, Arciniega JC. Effects of an oil-in-water emulsion eye drop on tear film evaporation in patients with dry eye disease. Invest Ophthalmol Vis Sci. 2011;52:3822–3822.
  • Quinteros DA, Ferreira LM, Schaffazick SR, Palma SD, Allemandi DA, Cruz L. Novel polymeric nanoparticles intended for ophthalmic administration of acetazolamide. J Pharm Sci. 2016;105(10):3183–3190. doi:10.1016/j.xphs.2016.06.023.
  • Imperiale JC, Acosta GB, Sosnik A. Polymer-based carriers for ophthalmic drug delivery. J Control Release. 2018;285:106–141. doi:10.1016/j.jconrel.2018.06.031.
  • Jordan D. An overview of the common technical document (CTD) regulatory dossier. MEW. 2014;23:101–105.
  • Gershanik T, Benita S. Positively charged self-emulsifying oil formulation for improving oral bioavailability of progesterone. Pharm Dev Technol. 1996;1(2):147–157. doi:10.3109/10837459609029889.
  • Klang S, Abdulrazik M, Benita S. Influence of emulsion droplet surface charge on indomethacin ocular tissue distribution. Pharm Dev Technol. 2000;5(4):521–532. doi:10.1081/pdt-100102035.
  • Borel JF, Feurer C, Gubler HU, Stähelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. 1976;6(4):468–475. doi:10.1007/BF01973261.
  • Matsuda S, Koyasu S. Mechanisms of action of cyclosporine. Immunopharmacology. 2000;47(2):119–125. doi:10.1016/S0162-3109(00)00192-2.
  • Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol. 1997;15:707–747. doi:10.1146/annurev.immunol.15.1.707.
  • Liddicoat AM, Lavelle EC. Modulation of innate immunity by cyclosporine A. Biochem Pharmacol. 2019;163:472–480. doi:10.1016/j.bcp.2019.03.022.
  • Warcoin E, Baudouin C, Gard C, Brignole-Baudouin F. In Vitro Inhibition of NFAT5-mediated induction of CCL2 in hyperosmotic conditions by cyclosporine and dexamethasone on human HeLa-modified conjunctiva-derived cells. PLoS One. 2016;11(8):e0159983. doi:10.1371/journal.pone.0159983.
  • Power WJ, Mullaney P, Farrell M, Collum LM. Effect of topical cyclosporin A on conjunctival T cells in patients with secondary Sjögren’s syndrome. Cornea. 1993;12(6):507–511. doi:10.1097/00003226-199311000-00008.
  • El-asrar AM, Tabbara KF, Geboes K, Missotten L, Desmet V. An immunohistochemical study of topical cyclosporine in vernal keratoconjunctivitis. Am J Ophthalmol. 1996;121(2):156–161. doi:10.1016/s0002-9394(14)70579-3.
  • Kunert KS, Tisdale AS, Gipson IK. Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine. Arch Ophthalmol. 2002;120(3):330–337. doi:10.1001/archopht.120.3.330.
  • Tamilvanan S, Benita S. The potential of lipid emulsion for ocular delivery of lipophilic drugs. Eur J Pharm Biopharm. 2004;58(2):357–368. doi:10.1016/j.ejpb.2004.03.033.
  • Thomassen MJ, Antal JM, Divis LT, Wiedemann HP. Regulation of human alveolar macrophage inflammatory cytokines by tyloxapol: a component of the synthetic surfactant Exosurf. Clin Immunol Immunopathol. 1995;77(2):201–205. doi:10.1006/clin.1995.1144.
  • Thomassen MJ, Antal JM, Barna BP, Divis LT, Meeker DP, Wiedemann HP. Surfactant downregulates synthesis of DNA and inflammatory mediators in normal human lung fibroblasts. Am J Physiol. 1996;270(1 Pt 1):L159–163. doi:10.1152/ajplung.1996.270.1.L159.
  • Soliman KA, Ullah K, Shah A, Jones DS, Singh TRR. Poloxamer-based in situ gelling thermoresponsive systems for ocular drug delivery applications. Drug Discov Today. 2019;24(8):1575–1586. doi:10.1016/j.drudis.2019.05.036.
  • Corrales RM, Luo L, Chang EY, Pflugfelder SC. Effects of osmoprotectants on hyperosmolar stress in cultured human corneal epithelial cells. Cornea. 2008;27(5):574–579. doi:10.1097/ICO.0b013e318165b19e.
  • Sindt CW, Foulks GN. Efficacy of an artificial tear emulsion in patients with dry eye associated with meibomian gland dysfunction. Clin Ophthalmol. 2013;7:1713–1722. doi:10.2147/OPTH.S35833.
  • Royle L, Matthews E, Corfield A, et al. Glycan structures of ocular surface mucins in man, rabbit and dog display species differences. Glycoconj J. 2008;25(8):763–773. doi:10.1007/s10719-008-9136-6.
  • Benita S. Prevention of topical and ocular oxidative stress by positively charged submicron emulsion. Biomed Pharmacother. 1999;53(4):193–206. doi:10.1016/S0753-3322(99)80088-2.
  • Yang SC, Benita S. Enhanced absorption and drug targeting by positively charged submicron emulsions. Drug Dev Res. 2000;50(3–4):476–486. doi:10.1002/1098-2299(200007/08)50:3/4<476::AID-DDR31>3.0.CO;2-6.
  • Kuppens EV, de Jong CA, Stolwijk TR, de Keizer RJ, Van Best JA. Effect of timolol with and without preservative on the basal tear turnover in glaucoma. Br J Ophthalmol. 1995;79(4):339–342. doi:10.1136/bjo.79.4.339.
  • Burstein NL. Preservative cytotoxic threshold for benzalkonium chloride and chlorhexidine digluconate in cat and rabbit corneas. Invest Ophthalmol Vis Sci. 1980;19:308–313.
  • Baudouin C, Labbé A, Liang H, Pauly A, Brignole-Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010;29(4):312–334. doi:10.1016/j.preteyeres.2010.03.001.
  • Daull P, Lallemand F, Garrigue J-S. Benefits of cetalkonium chloride cationic oil-in-water nanoemulsions for topical ophthalmic drug delivery. J Pharm Pharmacol. 2014;66(4):531–541. doi:10.1111/jphp.12075.
  • Georgiev GA, Yokoi N, Nencheva Y, Peev N, Daull P. Surface chemistry interactions of cationorm with films by human meibum and tear film compounds. Int J Mol Sci. 2017;18(7). doi:10.3390/ijms18071558.
  • Butovich IA. Tear film lipids. Exp Eye Res. 2013;117:4–27. doi:10.1016/j.exer.2013.05.010.
  • Lam SM, Tong L, Duan X, Petznick A, Wenk MR, Shui G. Extensive characterization of human tear fluid collected using different techniques unravels the presence of novel lipid amphiphiles1. J Lipid Res. 2014;55(2):289–298. doi:10.1194/jlr.M044826.
  • Brown SHJ, Kunnen CME, Duchoslav E, et al. A comparison of patient matched meibum and tear lipidomes. Invest Ophthalmol Vis Sci. 2013;54(12):7417–7424. doi:10.1167/iovs.13-12916.
  • Garrigue J-S, Amrane M, Faure M-O, Holopainen JM, Tong L. Relevance of lipid-based products in the management of dry eye disease. J Ocul Pharmacol Ther. 2017;33(9):647–661. doi:10.1089/jop.2017.0052.
  • Hwang S-B, Park JH, Kang -S-S, et al. Protective effects of cyclosporine A emulsion versus cyclosporine A cationic emulsion against desiccation stress in human corneal epithelial cells. Cornea. 2020;39(4):508–513. doi:10.1097/ICO.0000000000002244.
  • Daull P, Guenin S. Hamon de Almeida V, Garrigue J-S. Anti-inflammatory activity of CKC-containing cationic emulsion eye drop vehicles. Mol Vis. 2018;24:459–470.
  • Liang H, Baudouin C, Daull P, Garrigue J-S, Brignole-Baudouin F. Ocular safety of cationic emulsion of cyclosporine in an in vitro corneal wound-healing model and an acute in vivo rabbit model. Mol Vis. 2012;18:2195–2204.
  • Liang H, Baudouin C, Daull P, Riancho L, Garrigue J-S, Brignole-Baudouin F. Ocular safety evaluation of newly developed cyclosporine in cationic emulsion in an in vitro corneal wound healing model and in an acute in vivo rabbit model. Invest Ophthalmol Vis Sci. 2011;52:2026–2026.
  • Burade V, Zalawadia R, Patel A, Ogundele A. Preclinical efficacy comparison of cyclosporine ophthalmic solution 0.09% vs cyclosporine ophthalmic emulsion 0.05% vs ciclosporin ophthalmic emulsion 0.1% in a NOD mouse model of dry eye disease. Clin Ophthalmol. 2020;14:2747–2755. doi:10.2147/OPTH.S259331.
  • Daull P, Nagano T, Okada S, Gros E, Feraille L, Garrigue J-S. Efficacy of preservative-free cyclosporine emulsion eye drops in a mouse model of dry eye. Invest Ophthalmol Vis Sci. 2019;60:292–292.
  • Daull P, Barabino S, Feraille L, et al. Modulation of inflammation-related genes in the cornea of a mouse model of dry eye upon treatment with cyclosporine eye drops. Curr Eye Res. 2019;44(5):476–485. doi:10.1080/02713683.2018.1563197.
  • Garrigue J-S, Nicolas C, Kessal K, et al. Comparative efficacy of preservative-free anti-inflammatory eye drops in a mouse model of dry eye. Invest Ophthalmol Vis Sci. 2017;58(8):800–800.
  • Daull P, Feraille L, Barabino S, et al. Efficacy of a new topical cationic emulsion of cyclosporine A on dry eye clinical signs in an experimental mouse model of dry eye. Exp Eye Res. 2016;153:159–164. doi:10.1016/j.exer.2016.10.016.
  • Daull P, Feraille L, Barabino S, Garrigue J-S. Efficacy evaluation of a cationic emulsion of cyclosporine in a mouse model of dry eye. Invest Ophthalmol Vis Sci. 2015;56:4468–4468.
  • Garrigue J-S, Daull P, Feraille L, Barabino S. Comparative efficacy of cyclosporine eye drop formulations in a mouse model of dry eye. Invest Ophthalmol Vis Sci. 2016;57:421–421.
  • Daull P, Feraille L, Amrane M, Elena PP, Garrigue J-S. Cationic Emulsion of Cyclosporine for the Management of Ocular Surface Inflammation: A Preclinical Evaluation. 2015.
  • Filion MC, Phillips NC. Anti-inflammatory activity of cationic lipids. Br J Pharmacol. 1997;122(3):551–557. doi:10.1038/sj.bjp.0701396.
  • Barabino S, Shen L, Chen L, Rashid S, Rolando M, Dana MR. The controlled-environment chamber: a new mouse model of dry eye. Invest Ophthalmol Vis Sci. 2005;46(8):2766–2771. doi:10.1167/iovs.04-1326.
  • Barba KR, Samy A, Lai C, Perlman JI, Bouchard CS. Effect of topical anti-inflammatory drugs on corneal and limbal wound healing. J Cataract Refract Surg. 2000;26(6):893–897. doi:10.1016/s0886-3350(00)00364-3.
  • Petroutsos G, Guimaraes R, Giraud JP, Pouliquen Y. Corticosteroids and corneal epithelial wound healing. Br J Ophthalmol. 1982;66(11):705–708. doi:10.1136/bjo.66.11.705.
  • Robert P-Y, Cochener B, Amrane M, et al. Efficacy and safety of a cationic emulsion in the treatment of moderate to severe dry eye disease: a randomized controlled study. Eur J Ophthalmol. 2016;26(6):546–555. doi:10.5301/ejo.5000830.
  • Baudouin C, Figueiredo FC, Messmer EM, et al. A randomized study of the efficacy and safety of 0.1% cyclosporine A cationic emulsion in treatment of moderate to severe dry eye. Eur J Ophthalmol. 2017;27(5):520–530. doi:10.5301/EJO.5000952.
  • Agarwal P, Scherer D, Günther B, Rupenthal ID. Semifluorinated alkane based systems for enhanced corneal penetration of poorly soluble drugs. Int J Pharm. 2018;538(1–2):119–129. doi:10.1016/j.ijpharm.2018.01.019.
  • Grimaudo MA, Pescina S, Padula C, et al. Poloxamer 407/TPGS mixed micelles as promising carriers for cyclosporine ocular delivery. Mol Pharm. 2018;15(2):571–584. doi:10.1021/acs.molpharmaceut.7b00939.
  • Daull P, Lallemand F, Philips B, Lambert G, Buggage R, Garrigue J-S. Distribution of cyclosporine A in ocular tissues after topical administration of cyclosporine A cationic emulsions to pigmented rabbits. Cornea. 2013;32(3):345–354. doi:10.1097/ICO.0b013e31825e83f4.
  • Liang H, Brignole-Baudouin F, Rabinovich-Guilatt L, et al. Reduction of quaternary ammonium-induced ocular surface toxicity by emulsions: an in vivo study in rabbits. Mol Vis. 2008;14:204–216.
  • Leonardi A, Van Setten G, Amrane M, et al. Efficacy and safety of 0.1% cyclosporine A cationic emulsion in the treatment of severe dry eye disease: a multicenter randomized trial. Eur J Ophthalmol. 2016;26(4):287–296. doi:10.5301/ejo.5000779.
  • Leonardi A, Doan S, Amrane M, et al. A randomized, controlled trial of cyclosporine a cationic emulsion in pediatric vernal keratoconjunctivitis: the VEKTIS study. Ophthalmology. 2019;126(5):671–681. doi:10.1016/j.ophtha.2018.12.027.
  • Kessal K, Liang H, Rabut G, et al. Conjunctival inflammatory gene expression profiling in dry eye disease: correlations with HLA-DRA and HLA-DRB1. Front Immunol. 2018;9. doi:10.3389/fimmu.2018.02271.