Celecoxib/Cyclodextrin Eye Drop Microsuspensions: Evaluation of In Vitro Cytotoxicity and Anti-VEGF Efficacy for Retinal Diseases

• Published in: Pharmaceutics Vol. 15; no. 12; p. 2689
• Main Authors: Jansook, Phatsawee, Soe, Hay Man Saung Hnin, Asasutjarit, Rathapon, Tun, Theingi, Hnin, Hay Marn, Maw, Phyo Darli, Watchararot, Tanapong, Loftsson, Thorsteinn
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.11.2023; MDPI
• Subjects: anti-VEGF; celecoxib; Contact angle; cyclodextrin; Cyclodextrins; Cytotoxicity; Diabetes; Diabetic retinopathy; Drug therapy; Ethylenediaminetetraacetic acid; eye drop; Hyaluronic acid; Instrument industry; Macular degeneration; microsuspensions; Ophthalmic drugs; Phosphates; Retina; RNA; Vascular endothelial growth factor; Viscosity; Visual impairment; United Kingdom; California; Thailand; United States; Germany; United States > US; Japan; anti-VEGF; eye drop; celecoxib; cytotoxicity; cyclodextrin; microsuspensions
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics15122689

Celecoxib (CCB), a cyclooxygenase-2 inhibitor, is capable of reducing oxidative stress and vascular endothelial growth factor (VEGF) expression in retinal cells and has been shown to be effective in the treatment of diabetic retinopathy and age-related macular degeneration. However, the ocular bioavailability of CCB is hampered due to its very low aqueous solubility. In a previous study, we developed 0.5% ( / ) aqueous CCB eye drop microsuspensions (MS) containing randomly methylated β-cyclodextrin (RMβCD) or γ-cyclodextrin (γCD) and hyaluronic acid (HA) as ternary CCB/CD/HA nanoaggregates. Both formulations exhibited good physicochemical properties. Therefore, we further investigated their cytotoxicity and efficacy in a human retina cell line in this study. At a CCB concentration of 1000 μg/mL, both CCB/RMβCD and CCB/γCD eye drop MS showed low hemolysis activity (11.1 ± 0.3% or 4.9 ± 0.2%, respectively). They revealed no signs of causing irritation and were nontoxic to retinal pigment epithelial cells. Moreover, the CCB eye drop MS exhibited significant anti-VEGF activity by reducing VEGF mRNA and protein levels compared to CCB suspended in phosphate buffer saline. The ex vivo transscleral diffusion demonstrated that a high quantity of CCB (112.47 ± 37.27 μg/mL) from CCB/γCD eye drop MS was deposited in the porcine sclera. Our new findings suggest that CCB/CD eye drop MS could be safely delivered to the ocular tissues and demonstrate promising eye drop formulations for retinal disease treatment.