Visual impairment and blindness are major global health issues that affect 253 million people worldwide. The prevalence of ocular diseases is increasing as a result of population ageing. The anterior segment of the eye is commonly treated with the instillation of eye drops, which are usually self-administered by the patients. Although topical administration is often seen as the most desirable, less invasive and patient-friendly delivery route, many patients have difficulties instilling eye drops. In addition, the duration of drug action after instillation is relatively short, and thus frequent drug administration of up to eight times per day is required. These issues can lead to low patient compliance; for example, only ∼50% of glaucoma patients use their medication properly. Clearly, there is a need to develop more patient-friendly and long-acting topical delivery systems to treat diseases of the anterior segment.
Drug delivery to the posterior segment of the eye is also of great importance, because retinal disorders are leading causes of blindness worldwide. Unfortunately, eye drops cannot be used, because topical administration has so far failed to achieve adequate drug concentrations in the posterior segment. For this reason, retinal disorders must be treated with monthly intraocular injections or implants administered by ophthalmologists or specialised nurses. The burden of these injections to the patients and the healthcare system is enormous; for example, nearly 20 million anti-vascular endothelial growth factor (VEGF) injections are given intravitreally per year to treat wet age-related macular degeneration. New, less invasive and longer-acting delivery approaches are clearly needed.
The Ocular Drug Delivery group develops improved drug delivery methods for targeted and prolonged drug delivery to both the anterior and posterior segments of the eye. We are currently pursuing studies in two main research areas: ocular drug delivery systems and ocular pharmacokinetics.
Ocular drug delivery systems
We develop new drug delivery systems based on polymer conjugates, hydrogels, light-activated liposomes, and cleavable peptide linkers which allow us to control and fine-tune drug release. In addition, we employ targeting moieties such as peptides selected by phage display and aptamers selected by SELEX (systematic evolution of ligands by exponential enrichment) to target the drug delivery systems to the desired tissue inside the eye. We investigate these technologies in physico-chemical studies, cell assays and preclinical in vivo experiments. Our aim is to develop drug delivery systems that are suitable for various kinds of compounds ranging from small drug molecules to biologicals and gene medicines.
Although the fundamental concepts of pharmacokinetics (absorption, distribution, metabolism, and elimination of a drug) remain the same, ocular pharmacokinetics is a unique and challenging field due to the special features of the eye. These features include for example the ocular tissue/fluid barriers, the fluid flow inside the eye, and drug binding to ocular tissues and melanin. The understanding of ocular pharmacokinetics is of crucial importance to deliver the correct drug dose at the target site using the desired administration route (i.e. by systemic administration or via local routes such as topical, subconjunctival, intravitreal, or suprachoroidal).
One approach we use to elucidate ocular pharmacokinetics is to study drug permeation, which may be driven by passive diffusion or active transport, across ocular barriers. Another approach is the study of ocular drug-metabolizing enzymes, whose unique profile may contribute to e.g. prodrug activation, elimination and toxicity of the ocular medications. In addition, we also elucidate the effect of binding to ocular tissues on drug disposition.
Furthermore, we build computational models that can predict the most relevant pharmacokinetic properties in relation to a drug’s structure, and can estimate the drug release profiles from a delivery system. We have also used modeling approaches to explore animal-to-man translation of ocular pharmacokinetics. These methods include chemoinformatic models, physiologically-based pharmacokinetic/pharmacodynamic models and finite element (3D) models. We believe that computational models are becoming increasingly useful tools for ocular drug discovery and development.