Non-Invasive Ocular Drug Delivery Science and Technology

Dear Colleagues,

Topical ophthalmic drug delivery still remains a mainstream method for local and noninvasive dosing to the eye. However, the eye is a paradox, in being very accessible as an organ and least permissive towards drugs entering ocular tissues following topical eye drop instillation. With the average fraction of doses absorbed being less than 5% (seen only in animal models), this poses a significant challenge.

Any topical ocular drug delivery technology that increases the fractions of doses absorbed by even two-fold can have a significant impact on the pharmacotherapy of my anterior segment diseases. Nanotechnology has garnered a lot of research and development attention with several commercialized examples, e.g., Inveltys^®. Furthermore, reaching the posterior segment tissues following topical ophthalmic dosing remains an enigma. Compared to anterior segment exposure, even lower fractions of a dose reach the back of the eye, e.g., layers of the retina. Furthermore, a mechanistic understanding of topical noninvasive delivery access to posterior segment tissues remains controversial. Contribution from direct ocular penetration from formulation technologies vs. local systemic absorption and recirculation into posterior segment tissues are competing processes that are difficult to clearly delineate.

Systemic ophthalmic drug delivery also offers a noninvasive alternative. For example, drugs delivered to the eye using pills or subcutaneous injections with an autoinjector have been researched, developed, and a few have been commercialized. Where there are inevitably cases with validation, disease biology plays a key role here. The systemic exposure versus the required pharmacological exposure at target tissues of the eye with sufficient capacity for the drug to engage remains a hallmark for further research. Noninfectious uveitis and thyroid eye disease, more recently, are two examples of disease biology with successfully commercialized drugs that are dosed systemically for ocular indications.

Computational methods for ophthalmic drug design and candidate selection (in repositioning or repurposing) have the potential to efficiently deliver many optimized drug candidates for clinical testing. Optimal ocular absorption, distribution, metabolism, and elimination (ADME) for noninvasive delivery is more feasible to factor in by design using modeling and simulation methods that combine molecular drug multiparameter optimization and computational models of ocular compartmental absorption and transit (OCAT^®). Furthermore, it is possible to employ large datasets of molecules with well-defined physicochemical, pharmacological, and pharmacokinetic properties in machine learning to predict noninvasive delivery and efficacy potential. Artificial intelligence (A.I.) algorithms designed for drug discovery, lead election, or drug repurposing may be powerful tools for defining and perhaps expanding the boundaries of drugs and delivery technologies for both local and systemic noninvasive ocular drug delivery.

Dr. Hovhannes J. Gukasyan
Guest Editor

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• topical ophthalmic formulation
• eye drops
• nanotechnology and modeling of it
• subcutaneous injection for ocular disease, disease biology
• oral drug delivery to eye, disease biology
• computational methods
• drug design, selection, and discovery
• ocular pharmacokinetics, ADME
• modeling and simulation of drugs
• modeling and simulation of delivery technology, formulations
• machine learning and artificial intelligence for optimizing noninvasive delivery