The doctoral dissertation in the field of Drug Research will be examined at the Faculty of Health Sciences. The public examination will be held in Helsinki and streamed online.
What is the topic of your doctoral research? Why is it important to study the topic?
Research on this topic is important because vision-threatening and even blinding diseases, like glaucoma, age-related macular degeneration, and diabetic retinopathy, are becoming increasingly common, particularly with aging and the rising prevalence of diabetes. These conditions affect the growing elderly populations, but also working population, leading to higher healthcare costs and productivity loss. These conditions may require lifelong treatment, but current drug delivery methods, such as frequent eye drops and ocular injections, come with serious limitations. Adherence to eye drop treatment regimens is often suboptimal, and injections are invasive, uncomfortable, and involve risks.
Through my research, I aim to develop long-acting drug delivery using melanin binding to pigmented eye tissues. This approach would offer non-invasive, effective treatment options that improve patient compliance and reduce the burden of frequent dosing. By addressing the limitations of existing therapies, my work has the potential to provide more efficient treatments, reduce the reliance on invasive procedures, and ease the strain on healthcare systems dealing with these widespread eye conditions.
What are the key findings or observations of your doctoral research?
This research systematically explored the potential of melanin binding as a strategy for generation of long-acting ocular drugs. To support this, a label-free microscale thermophoresis method was developed using water-soluble melanin nanoparticles. This innovative screening tool enables identification and classification of melanin-binding compounds early in the drug discovery process, thereby aiding in the design of better drug candidates.
In addition, cell culture models were established to study drug retention in pigmented cells. A dynamic flow system was implemented to enable drug release studies for up to two weeks, providing critical insights into prolonged drug retention and release from pigment depots. Furthermore, a pharmacokinetic model was validated using drug release data from melanin, intact melanosomes, and pigmented cells. Such models are useful in translational drug development, since they can be used as predictive tools bridging cell studies with animal experiments and clinical situation.
An in vivo rabbit study demonstrated that levofloxacin, a high melanin-binding drug, exhibited significantly prolonged retention in pigmented ocular tissues, such as the retinal pigment epithelium and choroid. This confirms that melanin binding can be harnessed to enhance drug retention and reduce the need for frequent dosing.
How can the results of your doctoral research be utilised in practice?
The research introduces new methodologies for studying melanin binding, which can be applied in developing more effective treatments for eye diseases.
The results of this research can be applied to further develop new drugs that are more convenient and effective. By leveraging melanin binding, long-acting drug products can be generated, thereby reducing the need for frequent dosing or invasive ocular injections. This approach has the potential to improve patient adherence, lessen the burden on healthcare systems, and enhance the quality of life for individuals with chronic eye diseases. In the proof-of-concept study, findings demonstrated that topical eyedrops of melanin binding drugs may be feasible for home therapy of retinal diseases that are now treated with ocular injections in the hospitals. This opens the door for innovative therapies that could replace or complement current invasive treatment options.
What are the key research methods and materials used in your doctoral research?
A combination of laboratory techniques was used to investigate melanin binding as a strategy for drug retention in the eye. Microscale thermophoresis was employed to screen drug binding to melanin, while a dynamic flow system was developed to better understand prolonged drug release from pigmented cells as well as measuring the rate of dissociation from melanin and melanosomes. Additionally, intracellular pharmacokinetics were examined by measuring free and bound drug levels in pigmented and non-pigmented retinal cells, providing insights into how melanin binding influences drug distribution at the cellular level. Rabbit studies were conducted to further understand drug behaviour in the eye. Different drug delivery methods, including eye drops, intravitreal injections, and intravenous injections, were tested to assess how melanin-binding drugs are distributed and retained in various ocular tissues. By incorporating both a top-down approach from in vivo studies and a bottom-up pharmacokinetic approach from in vitro assays, a more comprehensive understanding of drugs with strong melanin binding properties was achieved, supporting the advancement of long-acting ocular therapies.
The doctoral dissertation of Sina Bahrpeyma, Pharm.D., entitled Binding of ocular drugs to melanin and melanosomes: new in vitro methodology and pharmacokinetic impact will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Sara Nicoli of the University of Parma, and the Custos will be Professor Arto Urtti of the University of Eastern Finland. The public examination will be held in English.
