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As esteemed cryptographer and computer scientist, Ralph Merkle, once remarked, “Nanotechnology is an idea that most people simply do not believe.” But if one remains faithful that such invisible technology actually exists, nanotechnology’s potential was clear to the Chair of the Department of Ophthalmology and Visual Science at Rutgers New Jersey Medical School, Marco Zarbin, back in 2010 (1), providing therapeutic value through “full-scale monitoring, regulation, development, restoration, defense, and improvement of human natural systems at the cellular level.”

Drug delivery applications of nanotechnology could well be the most attractive, lowest hanging fruit in ophthalmology – especially as there are several pressing “anatomical and physiological challenges which serve as obstacles to effective drug delivery, including the tear film, cornea, conjunctiva, sclera, vitreous, inner limiting membrane, blood-aqueous barrier (BAB), and blood-retinal barrier (BRB).” So say the authors of a recent paper in Advanced Drug Delivery Reviews highlighting the potential of cell-targeted, dendrimer-based therapies in a “new era” ocular drug delivery (2).

Dendrimers – compounds previously described as “the newest class of macromolecular nano-scale delivery devices” (3) – are highly defined artificial macromolecules that offer a range of beneficial characteristics for drug delivery, including chemical stability, solubility, and low cytotoxicity, as well as having the ability to “efficiently encapsulate drugs and allow tunable release rates” (4).

Explaining how dendrimers could be used for sustained posterior segment drug delivery, Rangaramanujam M. Kannan, co-director of the Center for Nanomedicine at the Wilmer Eye Institute and first author on the aforementioned paper, notes, “The dendrimer nanoparticles are administered systemically, but target the disease-associated cells in the choroid/retina. Once they are there, they can stay there for at least 30 days and provide sustained therapy. Therefore, the pharmacodynamic effect may last even longer.”


Such therapies are arguably safer as well, according to Kannan: “It benefits patients because intravitreal delivery is avoided or reduced, minimizing inconveniences associated with them. It also helps free-up ophthalmologist's time, opening more treatments that can provide for many unmet needs,” adds Kannan. “Systemic treatments enable ophthalmologists to provide treatments for a broad array of ocular disorders, improving their practice.”

Also, Kannan notes, this type of treatment allows for earlier stage treatments of certain diseases, meaning that it could have a transformative impact on AMD and DME patients: “[Dendrimers] target key cells associated with pathology, enabling disease cell-targeted delivery! This is a holy grail in many ways. Because the dendrimer-drug conjugates are cleared intact through the urine from off-target organs, systemic side effects are minimized, enabling an improved therapeutic index for the drugs.”

Evoking Ralph Merkle’s remark about nanotechnology being not quite believable, Kannan admits there was significant “initial resistance” to this innovative technique: “When a new approach comes it takes time for it to gain acceptance, so we needed to provide substantial preclinical and clinical proof of concept data.” The systemic dendrimer-drug therapies (D-4517.2) devised by Kannan and his team are now undergoing phase II trials for wet AMD and DME and, if successful, would be followed by larger phase IIb/phase III trials and, once validated, potentially lead to the treatments being used for early AMD and other ocular disorders.

While no breakthrough nanotechnology treatments have yet emerged within the clinical ophthalmic space, and challenges still exist for scientists – e.g., understanding the biomechanical properties of the ocular tissues being injected into, how these tissues change with age and disease, and being able to accurately gauge dosage accuracy – the technology, especially as it relates to sustained ocular drug delivery, demonstrates great possibilities for – one day in the near future – providing safer, more effective and comfortable methods to a range of patients suffering from ocular disorders.

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  1. M Zarbin et al., “Nanotechnology in ophthalmology,” Canadian Journal of Ophthalmology, 45, 457 (2010). PMID: 20871642.
  2. R Kannan et al., “A new era in posterior segment ocular drug delivery: Translation of systemic, cell-targeted, dendrimer-based therapies,” Advanced Drug Delivery Reviews, [Online ahead of print] (2023). PMID: 37419213.
  3. JB Wolinsky, MW Grinstaff, “Therapeutic and diagnostic applications of dendrimers for cancer treatment,” Advanced Drug Delivery Reviews, 9, 1037 (2008). PMID: 18448187.
  4. K Wu et al., “A New Era in Ocular Therapeutics: Advanced Drug Delivery Systems for Uveitis and Neuro-Ophthalmologic Conditions,” Pharmaceutics, 15, 1952 (2023). PMID: 37514137.
About the Author
Alun Evans

Coming from a creative writing background, I have a great interest in fusing original, narrative-driven concepts with informative, educational content. Working at The Ophthalmologist allows me to connect with the great minds working in the field of contemporary eye care, and explore the human element involved in their scientific breakthroughs.

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