Drug-Loaded Hydrogels for Intraocular Lenses with Prophylactic Action against Pseudophakic Cystoid Macular Edema.

Nadia Toffoletto,Ana Paula Serro,Madalena Salema-Oom,Benilde Saramago,Soledad Anguiano Igea,Carmen Alvarez-Lorenzo

doi:10.3390/pharmaceutics13070976

Abstract

Pseudophakic cystoid macular edema (PCME), caused by chronic inflammation, is the most common cause of visual impairment in the medium-term after cataract surgery. Therefore, the prophylactic topical administration of combined steroidal and non-steroidal anti-inflammatory drugs is commonly done. Drug-eluting intraocular lenses (IOLs) gained interest as an efficient way to overcome the compliance issues related to the use of ocular drops without the need for additional surgical steps. The incorporation of functional monomers and molecular imprinting were herein applied to design hydrogels suitable as IOLs and able to co-deliver steroidal (dexamethasone sodium phosphate) and non-steroidal (bromfenac sodium) drugs. The incorporation of N-(2-aminopropyl) methacrylamide (APMA) increased the drug uptake and improved the in vitro release kinetics. Imprinting with bromfenac resulted in a decreased drug release due to permanent drug bonding, while imprinting with dexamethasone increased the amount of dexamethasone released after dual-drug loading. The application of a mathematical model to predict the in vivo drug release behavior suggests the feasibility of achieving therapeutic drug concentrations of bromfenac and dexamethasone in the aqueous humor for about 2 and 8 weeks, respectively, which is compatible with the current topical prophylaxis after cataract surgery.

Highlights

Cataracts are the leading cause of vision loss in the elderly population worldwide [1,2].The pathology consists in the opacification of the natural crystalline lens and is commonly treated by surgical replacement of the damaged crystalline with an artificial intraocular lens (IOL)
Hydrogels with a HEMA-BEM backbone were designed as IOL materials able to be simultaneously loaded with bromfenac sodium and dexamethasone sodium
Bromfenac sodium and dexamethasone sodium were simultaneously loaded into the hydrogels

Summary

Introduction

Cataracts are the leading cause of vision loss in the elderly population worldwide [1,2]. The pathology consists in the opacification of the natural crystalline lens and is commonly treated by surgical replacement of the damaged crystalline with an artificial intraocular lens (IOL). Cataract surgery is currently one of the most cost-effective procedures in healthcare [3], some post-surgical complications may occur. The most common cause of visual impairment in the medium-term after IOL implant is pseudophakic cystoid macular edema (PCME), called Irvine-Gass syndrome [4,5]. Its incidence increases with the concomitance of preexisting risk factors, such as contralateral PCME, diabetes mellitus, uveitis, history of retinal vein occlusion and retinal degeneration, macular degeneration, retinopathy, epiretinal

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