Evaluating of Two Type of Cyclosporine-A Containing Nanosuspension for Ophthalmic Administration

Yıl 2021, Cilt: 5 Sayı: 3, 107 - 116, 20.09.2021

Tuğhan Duran Osman Karakuş , İsmail Tuncer Değim , Burcu Eser Sermet Sezigen , Zafer Güney Canan Uluoğlu

https://doi.org/10.30621/jbachs.926640

Cited By: 1

Öz

Dry eye is both a common symptom and a disease. It is known that the ophthalmic emulsion of the immunomodulator cyclosporine-A (Cyc-A) has a positive effect on this condition but its’ absorption to intraocular tissues is limited. Nanosuspension is a drug formulation that aims to increase the bioavailability. The aim of this study was to develop a Cyc-A nanosuspension formulation for a better intraocular absorption via ocular delivery and to investigate the effectiveness of the formulation by comparing it with two marketed ophthalmic emulsions (Restasis® and Depores®). Two type of Cyc-A loaded Eudragit S100 nanosuspension (A and B) were prepared. Drug formulations were applied to both eyes of 20 male Albino New Zealand rabbits with an interval of 12 hours for 14 days. In vitro drug release was tested using a dialysis sac and quantitative analysis was performed by HPLC for evaluating Cyc-A amounts in all formulations. Although all four formulations had similar particle size and polydispersity indexes, nanosuspension B which had a positive zeta potential value, had released more Cyc-A than other formulations. It was showed that Cyc-A loaded nanosuspension formulations which had good ocular tolerability could be a better alternative to commercial formulations for the treatment of dry eye. The nanosuspensions have ideal mean particle size range with a positive surface charge for ophthalmic applications of Cyc-A.

Anahtar Kelimeler

Cyclosporine-A, Dry Eye, nanosuspension

Kaynakça

• Pflugfelder SC, Solomon A, Stern ME. The Diagnosis and Management of Dry Eye. Cornea 2000;19: 644–649
• Pflugfelder SC, Paiva CS, Villarreal AL, Stern ME. Effects of Sequential Artificial Tear and Cyclosporine Emulsion Therapy on Conjunctival Goblet Cell Density and Transforming Growth Factor-b2 Production. Cornea 2008;27: 64–69
• Perry HD, Donnenfeld ED.Dry eye diagnosis and management in 2004. Current Opinion in Ophthalmology 2004;15: 299–304
• Small DS, Acheampong A, Reıs B, Stern K, Stewart W, Berdy G et al. Blood Concentrations of Cyclosporin A During Long-Term Treatment With Cyclosporin A Ophthalmic Emulsions in Patients With Moderate to Severe Dry Eye Disease. Journal of Ocular Pharmacology and Therapeutics 2002;18: 411–418
• Wilson SE, Stulting RD. Agreement of Physician Treatment Practices With the International Task Force Guidelines for Diagnosis and Treatment of Dry Eye Disease. Cornea 2007;26: 284–289
• Stevenson D, Tauber J, Reis B. Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate to severe dry eye desease. Ophthalmology 2000;107: 967–974
• Moon WJ, Lee HJ, Shin KC, Wee WR, Lee JH, Kim MK. Short term effects of topical cyclosporine and viscoelastic on the ocular surface in patients with dry eye. Korean Journal of Ophthalmology 2007;21: 189–194
• Wilson SE, Perry HD. Long term resolution of chronic dry eye symptoms and signs after topical cyclosporine treatment. Ophthalmology 2007;114: 76–79
• Stern ME, Gao J, Schwalb TA, Ngo M, Tieu DD, Chan CC et al Conjunctival T-Cell Subpopulations in Sjogren’s and Non-Sjogren’s Patients with Dry Eye. IOVS 2002;43: 2609–2614
• Foulks GN. Pharmacological Management of Dry Eye in the Elderly Patient. Drugs Aging 2008;25: 105–118
• Pflugfelder SC. Antiinflammatory Therapy for Dry Eye. American Journal of Ophthalmology 2004;137: 337–342
• Perry HD, Donnenfeld ED. Topical 0.05% cyclosporin in the treatment of dry eye. Expert Opinion 2004: 2099–2107
• Sall KN, Cohen SM, Christensen MT, Stein JM. An Evaluation of the Efficacy of a Cyclosporine-Based Dry Eye Therapy When Used With Marketed Artificial Tears as Supportive Therapy in Dry Eye. Eye & Contact Lens 2006;32: 21–26
• 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: 330–337
• Foulks GN. Topical Cyclosporine for Treatment of Ocular Surface Disease: 105–122
• Turner K, Pflugfelder SC, Ji Z,Feuer WF, Stern M, Reis BL. Interleukin- 6 Levels in the Conjunctival Epithelium of Patients with Dry Eye Disease Treated with Cyclosporine Ophthalmic Emulsion. Cornea 2000;19: 492–496
• Acheampong AA, Shackleton M, Tang-Liu DD, et al. Distribution of cyclosporin A in ocular tissues after topical administration to albino rabbits and beagle dogs. Curr Eye Res. 1999;18:91–103.
• R. H. Muller, C. Jacobs, and O. Kayser. Nanosuspensions as particulate drug formulations in therapy. P - 557 the future. Adv Drug Deliv Rev. 47(1):3–19 (2001).
• K. Kreuter. Peroral administration of nanoparticles. Advanced Drug Delivery Reviews. 7:71–86 (1991).
• Liversidge GG, Cundy KC.Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: Absolute oralbioavailability of nanocrystalline danazol in beagle dogs.Int J Pharm. 1995; 125(1): 91–97.doi:10.1016/0378-5173(95)00122-Y
• Kawashima, Y., Niwa, T., Handa, T., Takeuchi, H., Iwamoto, T., Itoh, K., 1989. Preparation of controlled-release microspheres of ibuprofen with acrylic polymers by a novel quasi-emulsion solvent diffusion method. J. Pharm. Sci. 78, 68–72.
• Pignatello, R.,Vandelli, M.A., Giunchedi, P., Puglisi, G., 1997. Properties of tolmetin-loaded Eudragit RL100 and RS100 microparticles prepared antiinflamby different techniques. S.T.P. Pharma Sci. 7, 148–157.
• Pernille TN, Troels KB, Niels J, Ulf S, Jens L. BCPT policy for experimental and clinical studies. Basic and Clinical Pharmacology and Toxicology doi/10.1111/bcpt.13492
• Swamy N.G.N., Zaheer Abbas2 and Santosh Kumar I.H., Eudragit RS 100 nanosuspensions for the controlled ophthalmic delivery of diclofenac sodium, Thai J. Pharm. Sci. 37 (2013) 157-170 157
• Nanocomposıx's Guıde To Dynamıc Lıght Scatterıng Measurement And Analysıs. February 2015, V 1.4
• A. Amrite, H. Edelhauser, S. Singh, and U. Kompella. Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration, Mol. Vis. 14: 150-160 (2008).
• S. Das, and P.K. Suresh. Nanosuspension: a new vehicle for the improvement of the delivery of drugs to ocular surface. Application to amphotericin B, Nanomedicine 7: 242-247 (2011).
• Mahendra Nakaranı, Priyal Patel, Jayvadan Patel, Pankaj Patel, Rayasa S. R. Murthy, Subhash S. Vaghanı. Cyclosporine A-Nanosuspension: Formulation, Characterization and In Vivo Comparison with a Marketed Formulatio. Sci Pharm. 2010; 78: 345–361 doi:10.3797/scipharm.0908-1
• Rowe RC, Sheskey PJ, Owen SC. Handbook of Pharmaceutical Excipients. 5th ed. London: PhP. 2006: 449-453, 535–538