Suchergebnisse

The permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release system ; This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 813440 (ORBITAL—Ocular Research by Integrated Training And Learning) and is also supported by the Fundação para a Ciência e Tecnologia (FCT) [UID/QUI/00100/2019, UIDB/00100/2020 and UID/BIM/04585/2020] ; SI

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 ; This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 813440 (OR-BITAL—Ocular Research by Integrated Training and Learning) and is also supported by Fundação para a Ciência e Tecnologia (FCT) [UID/QUI/00100/2019, UIDB/00100/2020, and UID/BIM/04585/2020]. ; SI

Statins are receiving increasing attention in the ophthalmic field. Their activity as 3-hydroxy-3-methylglutaryl–CoA (HMG–CoA) reductase inhibitors is clinically used to regulate cholesterol levels and leads to pleiotropic effects, which may help in the management of diabetes-related ocular pathologies. This work aims to design bioinspired contact lenses (CLs) with an affinity for atorvastatin by mimicking the active site of HMG–CoA reductase. Sets of imprinted and nonimprinted 2-hydroxyethyl methacrylate (HEMA) hydrogels were synthesized, varying the contents in functional monomers that bear chemical groups that resemble those present in HMG–CoA reductase, namely, ethylene glycol phenyl ether methacrylate (EGPEM), 2-aminoethyl methacrylate hydrochloride (AEMA), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). The hydrogels were characterized in terms of suitability as CLs (solvent uptake, light transmission, mechanical properties, and biocompatibility) and capability to load and release atorvastatin. Three sterilization protocols (steam heat, gamma radiation, and high hydrostatic pressure) were implemented and their effects on hydrogel properties were evaluated. Copolymerization of AEMA and, particularly, APMA endowed the hydrogels with a high affinity for atorvastatin (up to 11 mg/g; KN/W > 200). Only high hydrostatic pressure sterilization preserved atorvastatin stability and hydrogel performance. Permeability studies through the porcine cornea and sclera tissues revealed that the amount of atorvastatin accumulated in the cornea and sclera could be effective to treat ocular surface diseases ; This project is funded by the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions grant agreement N° 813440 (ORBITAL–Ocular Research by Integrated Training and Learning). The work was also partially supported by MINECO [SAF2017-83118-R], Agencia Estatal de Investigación (AEI) Spain, Xunta de Galicia [ED431C 2020/17], FEDER and by Fundação para a Ciência e a ...

Endophthalmitis, an inflammation of the eye due to perioperative infection, may occur after cataract surgery. Intraocular lenses (IOLs) loaded with an antibiotic have been proposed as an alternative to the conventional postoperative endophthalmitis prophylaxis, since the antibiotic is delivered directly to the target site. In this work, an IOL-based antibiotic releasing system was prepared from a copolymer used in the production of IOLs and a fluoroquinolone used in endophthalmitis prophylaxis (moxifloxacin, MFX). Argon plasma-assisted grafting with 2- hydroxyethyl methacrylate (HEMA) in the presence of MFX was the approach selected for surface modification, with MFX loaded both by entrapment in the grafted polyHEMA coating and by soaking. Surface and bulk properties were evaluated before and after surface modification and the MFX release profiles were obtained both in batch mode (sink conditions) and under hydrodynamic conditions, employing a purpose-built microfluidic cell, which simulated the hydrodynamic conditions around the eye lens. The effect of storage on the release profile of the best system was also assessed. The best system released MFX for ca. 15 days above the minimum inhibitory concentration for Staphylococcus aureus and Staphylococcus epidermidis. The released MFX showed antimicrobial activity against these bacteria and was non-cytotoxic against corneal endothelial cells. ; Work developed under the M-era.Net research project titled SurfLenses − Surface modifications to control drug release from therapeutic ophthalmic lenses, funded by Fundação para a Ciência e a Tecnologia (FCT; grants M-ERA.NET/0005/2012, M-ERA.NET/0006/2012 and PTDC/CTMBIO/ 3640/2014), and co-funded by the European Union through the QREN, POFC-COMPETE and FEDER programmes. Additional funding from grant PEstOE/QUI/UI0100/2013 (FCT) is also acknowledged. I. J. Correia and T. R. Correia acknowledge support by FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation (grant POCI-01-0145-FEDER-007491) and National Funds by FCT (grant UID/Multi/00709/2013). A. Pimenta, P. Alves and P. Coimbra thank FCT for personal grants SFRH/BD/52334/2013, SFRH/BPD/69410/2010 and SFRH/BPD/73367/2010, respectively.