Common in myopia and aging, vitreous opacities arise from clumped collagen fibers within the vitreous body that cast shadows on the retina, appearing as ‘floaters’ to the patient. Vitreous opacities...
Reaching
the corneal endothelium through the topical administration
of therapeutic drugs remains a challenge in ophthalmology. Besides,
endothelial cells are not able to regenerate, and diseases at this
site can lead to corneal blindness. Targeting the corneal endothelium
implies efficient penetration through the three corneal layers, which
still remains difficult for small molecules. Carbon quantum dots (CQDs)
have demonstrated great potential for ocular nanomedicine. This study
focuses on the corneal penetration abilities of differently charged
CQDs and their use as permeation enhancers for drugs. Excised whole
bovine eyes were used as an ex vivo model to investigate
corneal penetration of CQDs derived from glucosamine using β-alanine,
ethylenediamine, or spermidine as a passivation agent. It was found
that negatively charged CQDs have limited corneal penetration ability,
while positively charged CQDs derived from glucosamine hydrochloride
and spermidine (CQD-S) penetrate the entire corneal epithelium all
the way down to the endothelium. CQD-S were shown to enhance the penetration
of FITC-dextran 150 kDa, suggesting that they could be used as efficient
penetration enhancers for therapeutic delivery to the corneal endothelium.
Drug permeation across the cornea remains a major challenge due to its unique and complex anatomy and physiology. Static barriers such as the different layers of the cornea, as well as dynamic aspects such as the constant renewal of the tear film and the presence of the mucin layer together with efflux pumps, all present unique challenges for effective ophthalmic drug delivery. To overcome some of the current ophthalmic drug limitations, the identification and testing of novel drug formulations such as liposomes, nanoemulsions, and nanoparticles began to be considered and widely explored. In the early stages of corneal drug development reliable in vitro and ex vivo alternatives, are required, to be in line with the principles of the 3Rs (Replacement, Reduction, and Refinement), with such methods being in addition faster and more ethical alternatives to in vivo studies. The ocular field remains limited to a handful of predictive models for ophthalmic drug permeation. In vitro cell culture models are increasingly used when it comes to transcorneal permeation studies. Ex vivo models using excised animal tissue such as porcine eyes are the model of choice to study corneal permeation and promising advancements have been reported over the years. Interspecies characteristics must be considered in detail when using such models. This review updates the current knowledge about in vitro and ex vivo corneal permeability models and evaluates their advantages and limitations.
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