Safety and Tolerability of Topical Ophthalmic Triamcinolone Acetonide-Loaded Liposomes Formulation and Evaluation of Its Biologic Activity in Patients with Diabetic Macular Edema.

Jose Navarro-Partida,Carlos Rodrigo Castro-Castaneda,Juan Armendariz-Borunda,Juan Carlos Altamirano-Vallejo,Alejandro Gonzalez-De La Rosa,Arturo Santos

doi:10.3390/pharmaceutics13030322

Jose Navarro-Partida, Carlos Rodrigo Castro-Castaneda + Show 4 more

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https://doi.org/10.3390/pharmaceutics13030322

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Abstract

Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA-loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled on the ocular surface. To evaluate the safety, tolerability, and biological activity of TALF, an animal study and a phase I clinical assay were performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biological activity of the formulation. No inflammation, lens opacity, swelling, or increase in intraocular pressure were recorded after the instillation of TALF in any of the animal or clinical studies. Mainly, mild and transient adverse events such as dry eye and burning were reported. TALF significantly improves visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biological activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroid IVTs and their associated hazards.

Highlights

Intravitreal injections of corticosteroids are commonly used for the treatment of many vitreous and retinal disorders such as retinal vein occlusions [1], uveitis [2], and diabetic macular edema (DME) [3]
Examination of the ocular surface, as well as the inner parts of the eye of rabbits was performed in order to characterize the potential side effects that may result from a high number of daily instillations of TA-loaded liposomes formulation (TALF)
We showed that TALF, a novel system used to deliver triamcinolone acetonide (TA) to the posterior segment of the eye, reaches significant concentrations in the posterior segment of the intraocular tissues and is non-toxic for human keratocyte cultures [18], but the in vivo safety and tolerability of this formulation was still a concern, and the biological and therapeutic effects on a chronic retinal disorder such as diabetic macular edema had not been explored previously

Summary

Introduction

Intravitreal injections of corticosteroids are commonly used for the treatment of many vitreous and retinal disorders such as retinal vein occlusions [1], uveitis [2], and diabetic macular edema (DME) [3]. Among the different synthetic corticosteroids, triamcinolone acetonide (TA) is extensively used in intravitreal injections (IVTs). Oral or topical corticosteroid routes of administration could be safer than. To diminish the ocular risks associated with intravitreal injections, different topical approaches have been developed to deliver TA into the vitreous cavity [15,16,17,18]. LPs constitute the only topical system to deliver TA into the vitreous area with clinical evidence of its Pharmaceutics 2021, 13, 322.

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