The promise of nanoparticles

Molecular-scale particles could advance ocular drug delivery.

The promise of nanoparticles
Howard Larkin
Howard Larkin
Published: Wednesday, July 29, 2020
David Smadja MD
The multiple lipid, aqueous, mucin and lysozyme-rich layers of the tear film and cornea are highly effective at keeping irritants and pathogens out of the eye. The trouble is, they are nearly as effective at keeping out topical drugs – only 5-to-10% administered typically reach the anterior chamber, David Smadja MD told the 37th Congress of the ESCRS in Paris, France. Similarly, the sclera blocks topical drugs from the retina and vitreous while the blood-retinal and retinal pigment epithelium barriers restrict systemic drugs. That leaves invasive injections and intravitreal depots as the most effective administration routes for back-of-the-eye treatments, and these are subject to rapid chemical breakdown, added Dr Smadja, who directs and conducts research at Shaare Zedek Medical Centre, Jerusalem, and Bar-Ilan University, Ramat Gan, Israel. Nanotechnology could change that, Dr Smadja believes. Nanosystems measuring 300nm or less – about three times the diameter of the HIV virus – may overcome problems that reduce drug efficiency by combining and layering even smaller nanoparticles – of 1-to-100nm – with varying chemical, electrical, biologic and physical characteristics. Together, these may be designed to address major challenges in anterior and posterior drug delivery, including drug washout, lack of penetration and enzymatic destruction. Trojan horse Adding positively charged mucoadhesive particles, such as chitosan, to the surface of a nanocapsule could greatly increase residence time in the precorneal space by sticking to the posterior layer of tear film, Dr Smadja said. This allows more time for smaller drug particles in the capsule to penetrate the corneal epithelium, reducing washout. Residence time could be further enhanced by placing nanocapsules in a hydrogel matrix or contact lens placed on the ocular surface. On the corneal surface, nanocapsules could slowly release even smaller capsules coated with lipophilic material designed to move hydrophilic drugs through the lipid-rich epithelium and endothelium. Materials such as hyaluronic acid-chitosan nanoparticles have successfully penetrated cell barriers. “It’s the old trick we all know, the Trojan horse, where you encapsulate the drug in something that looks friendly,” Dr Smadja said. Sustainability of release is a major challenge for posterior segment drugs. Particles smaller than 200nm, anionic particles, and PEGylated particles are more likely to diffuse to the retina, Dr Smadja said. Nanoparticles also can be engineered to resist enzymatic attack and slow release by surrounding drugs with compounds that resist lysozymes. “The future of ocular drug delivery systems is bright,” he concluded.
Tags: nanoparticles
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