Mehmet Doğan AŞIK, Nagihan UĞURLU, Fatma YÜLEK, Sema TUNCER, Mustafa TÜRK, Emir Baki DENKBAŞ

Göz Hastalıkları İçin Nanoterapötik Sistem Olarak Ketorolak Trometamin Yüklü Kitosan Nanopartiküller

B u çalışmanın temel amacı, psedofakik kistoid maküler ödem, allerjik konjuktivit, diabetik maküler ödem gibi çeşitli göz hastalıklarının tedavisi için ketorolak trometamin yüklü kitosan nanopartiküllerin geliştirilmesi ve karakterizasyonunun yapılmasıdır. Bu amaçla, önce iyonik çöktürme yöntemiyle boş kitosan partiküller hazırlanmıştır. Sonrasında ketorolak yüklenmiş kitosan nanopartiküller üç temel kısımda karakterize edilmiştir. İlk kısımda Atomik Kuvvet Mikroskobu AKM ve zeta sizer kullanılarak morfolojik değerlendirmeler yapılırken, ikinci kısımda Fourier Transform Infrared Spektroskopi FTIR kullanılarak fizikokimyasal incelemeler yapılmış, üçüncü kısımda ise farklı formülasyonlardan elde edilen salım profilleri incelenmiştir. Çalışmaların sonucunda boyutları ortalama 180-200 nm aralığında değişen ketorolak yüklü kitosan nanopartiküller sentezlenmiş ve oldukça yüksek bir oranda ilaç yükleme verimi % 50 düzeylerinde elde edilmiştir. Ayrıca, başlangıçtaki ketorolak konsantrasyonuna bağlı olarak farklı salım profilleri elde edilmiştir

Anahtar Kelimeler:

Ketorolak Trometamin, Kitosan Nanopartikül, İlaç Taşınımı, Nanoterapötik

Ketorolac Tromethamine Loaded Chitosan Nanoparticles as a Nanotherapeutic System for Ocular Diseases

This study mainly focused on the preparation and characterization of Ketorolac tromethamine ketorolac loaded chitosan nanoparticles to improve novel drug carrier for the treatment of different ocular diseases such as pseudophakic cystoid macular edema, allergic conjunctivitis and diabetic macular edema. For this purpose; first bare chitosan nanoparticles were prepared ionic co-precipitation technique. Prepared ketorolac loaded chitosan nanoparticles were characterized in three main part of the studies. First morphological evaluations were performed by using Atomic Force Microscope AFM and zeta sizer, in second part physicochemical characterization were performed with Fourier Transform Infrared Spectroscopy FTIR and finally drug loading-release studies were performed to get different formulations. At the end of the studies, 180-200 nm average size in diameter of the ketorolac loaded chitosan nanoparticles could be produced and proved the ketorolac loading with rather high loading efficiency around 50 % . Additionally different release profiles could be obtained by using different amount of initial ketorolac concentration during the formulation.

Keywords:

Ketorolac Tromethamine, Chitosan Nanoparticles, Drug delivery, Nanotherapeutic,

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M. Raizman, Corticosteroid therapy of eye disease: Şfty years later. Arch Ophthalmol, 114 (1996) 1000.
J.B. Jonas, R.F. Degenring, I. Kreissig, I. Akkoyun, B.A. Kamppeter, Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology, 112 (2005) 593.
M.C. Carnahan, D.A., Goldstein Ocular complications of topical, peri-ocular, and systemic corticosteroids. Curr Opin Ophthalmol, 11 (2000) 478.
M.C. Gillies, M. Kuzniarz, J. Craig, M. Ball, W. Luo, J.M. Simpson, Intravitreal triamcinolone-induced elevated intraocular pressure is associated with the development of posterior subcapsular cataract. Ophthalmology, 112 (2005) 139.
D.M. Moshfeghi, P.K. Kaiser, S.J. Bakri et al., Presumed sterile endophthalmitis following intravitreal triam- cinolone acetonide injection. Ophthalmic Surg Lasers Imaging, 36 (2005) 24.
J.S. Heier, T.M. Topping, W. Baumann, M.S. Dirks, S. Chern, Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology, 107 (2000) 2034. 7. W.Y. Shen, I.J. Constable, E. Chelva, P.E. Rakoczy, Inhibition of diclofenac formulated in hyaluronan on angiogenesis in vitro and its intraocular tolerance in the rabbit eye, Graefes. Arch. Clin. Exp. Ophthalmol., 238 (2000) 273.
P.K. Rabiah, R.G. Fiscella, H.H. Tessler, Intraocular penetration of periocular ketorolac and efficacy in experimental uveitis, Invest Ophthalmol. Vis. Sci., 37 (1996) 613.
F.T. Fraunfelder, C. Hanna, Ophthalmic drug delivery systems, Surv Ophthalmol., 18 (1974) 292.
A.J. Flach, L.M. Jampol, D. Weinberg et al., Improvement in visual acuity in chronic aphakic and pseudophakic cystoid macular edema after treatment with topical 0.5% ketorolac tromethamine, Am. J. Ophthalmol., 112 (1991) 514.
W.H. Rooks, Pharmacologic activity of ketorolac tromethamine, Pharmacotherapy, 10 (1990) 308.
D.G. Tinkelman, G. Rupp, H. Kaufman, J Pugely, N. Schultz, Double-masked, paired-comparison clinical study of ketorolac tromethamine 0.5% ophthalmic solution compared with placebo eyedrops in the treatment of seasonal allergic conjunctivitis, Surv Ophthalmol., 38 (1993) 133.
A.J. Flach, C.J. Lavelle, K.W. Olander, J.A. Retzlaff, L.W. Sorenson, The effect of ketorolac tromethamine solution 0.5% in reducing postoperative inflammation after cataract extraction and intraocular lens implantation, Ophthalmol., 195 (1988) 1279.
S.J. Kim, N.A. Adams, H.S. Toma et al., Safety of intravitreal ketorolac and diclofenac: an electroretinographic and histopathologic study, Retina, 28 (2008) 595.
D. Kavaz, S. Odabaş, E. Güven, M. Demirbilek, E.B. Denkbas, Bleomycin loaded magnetic chitosan nanoparticles as multifunctional nanocarriers, J Bioactive Compatible Polym., 25 (2010) 305.
S.K. Basu, K. Kavitha, M. Rupeshkumar, Evaluation of ketorolac tromethamine microsphere by chitosan/ gelatin B complex coacervation, Sci. Pharm., 78 (2010) 79.
M.Y. Begum, M.R. Shaik, K. Abbulu, M. Sudhakar, Ketorolac Tromethamine Loaded Liposomes of Long Alkyl Chain Lipids: Development, Characterization and In Vitro Performance, Int. J. Pharm. Tech Res., 4 (2012) 218.
E. Vega, M.A. Egea, O. Valls, M. Espina, M.L. Garcia, Flurbiprofen loaded biodegradable nanoparticles for ophtalmic administration, J. Pharm. Sci., 95 (2006) 2393.
F. Li, B. Hurley, Y. Liu, B. Leonard, M. Griffith, Controlled release of bevacizumab through nano- spheres for extended treatment of age-related macular degeneration, Open Ophtalmol. J., 6 (2012) 54.