NPF-Funded Research

Project Summary:

Psoriasis is a chronic inflammatory skin disease that affects millions of people and can have a major impact on quality of life. Although injectable biologic medicines that target key inflammatory proteins such as IL-17A can be highly effective, they circulate throughout the body and are generally reserved for people with more severe disease. For people with mild-to-moderate psoriasis, existing topical treatments do not always provide adequate control and may cause problems with long-term use. There is therefore a need for effective treatments that can act directly in the skin while minimizing exposure throughout the body. Our project is developing a new approach to deliver biologic medicines directly to psoriatic skin. We are using protamine, a well-characterized peptide that has been used clinically for many years, to temporarily increase the ability of the skin to allow large therapeutic molecules to enter. Our preliminary studies show that protamine can enhance penetration of antibody medicines through the skin and into deeper skin layers. In a mouse model of psoriasis, a topical formulation containing protamine and an anti-IL-17A antibody produced strong improvements in disease compared with the antibody delivered by injection.

In this project, we will investigate how much of the antibody reaches the skin compared with the bloodstream, test whether the treatment can penetrate and reduce inflammation in human skin samples, and evaluate the stability of the topical formulation during storage. These studies will provide important evidence needed to determine whether this approach can be further developed toward a patient-friendly topical biologic treatment.

Our long-term goal is to develop effective, convenient, and safer topical biologic therapies for people with mild-to-moderate psoriasis. If successful, this technology could provide a new way to deliver highly effective biologic medicines directly to areas of affected skin while reducing unnecessary systemic exposure. The same delivery platform may also have potential applications for other inflammatory skin diseases and other biologic medicines.

How will your project help improve the lives of the 125 million affected by psoriatic disease?

Psoriatic disease affects approximately 125 million people worldwide, many of whom live with chronic skin symptoms that can significantly affect daily life and quality of life. Our project addresses an important unmet need for people with mild-to-moderate plaque psoriasis, who often rely on topical treatments but may not achieve adequate disease control.

We are developing a topical formulation that could deliver highly effective anti-IL-17A biologic therapy directly into psoriatic skin while minimizing exposure throughout the body. Our preliminary studies show that protamine can temporarily enhance skin penetration of therapeutic antibodies and that topical anti-IL-17A with protamine can strongly reduce psoriasis-like inflammation in mice.

If successful, this research could establish a new treatment strategy that combines the effectiveness of biologic therapy with the convenience of a topical treatment. By concentrating treatment at affected skin sites and potentially reducing systemic exposure, this approach could offer an attractive alternative for patients who do not need or do not want systemic biologic therapy. A self-administered topical biologic could also reduce the burden associated with injections and facilitate earlier treatment of localized disease.

The proposed studies will provide critical evidence on skin delivery, therapeutic activity in human skin, and formulation stability needed to advance this technology toward clinical development. In the longer term, the same delivery platform could potentially be adapted for other biologic medicines and inflammatory skin diseases, broadening its potential impact on people living with psoriatic disease.

Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?

Psoriatic disease research is important to me because my career has been focused on overcoming biological barriers that prevent effective medicines from reaching the tissues where they are needed. Psoriasis presents a particularly compelling challenge: highly effective biologic therapies are available, yet delivering these medicines specifically to affected skin remains difficult. I believe that improving drug delivery can help make powerful therapies more accessible, convenient, and safer for people living with chronic disease.

The NPF award will be an important catalyst for advancing this research from an encouraging laboratory discovery toward a clinically relevant therapeutic strategy. It will allow my team to define the pharmacokinetic advantages of topical anti-IL-17A delivery, validate the approach in human psoriatic skin, and establish the formulation information needed for further development. The award will also provide an opportunity to strengthen collaborations between pharmaceutical scientists and dermatologists and to train the next generation of researchers in translational drug delivery.

More broadly, this project represents an important direction for my research program: developing patient-friendly delivery technologies that can expand the potential of biologic medicines beyond systemic administration. Support from the NPF will help generate the critical proof-of-concept data needed to pursue larger-scale funding, industry partnerships, and ultimately clinical translation. I am particularly motivated by the possibility that this work could contribute to a new treatment option for people with psoriasis who need better control of their disease but may not require systemic biologic therapy

Researcher Profile:

Dr. Shyh-Dar Li, BSc(Pharm), PhD, is the Tong Louie Chair Professor in Pharmaceutical Sciences at the University of British Columbia (UBC). He received his Bachelor of Science in Pharmacy from National Taiwan University and his PhD in Pharmaceutical Sciences from the University of North Carolina at Chapel Hill, followed by postdoctoral training at the University of California, San Diego. He joined UBC in 2014, where he leads a research program focused on developing innovative drug delivery technologies to improve the delivery and therapeutic effectiveness of biological medicines.

Dr. Li’s research spans targeted drug delivery, lipid and polymer-based nanoparticles, and delivery technologies for proteins, peptides, and nucleic acids. His research has been supported by the Canadian Institutes of Health Research (CIHR), the National Institutes of Health (NIH), and other national funding agencies. His team has successfully licensed three drug delivery technologies to industry, including a technology that has advanced to Phase II clinical trials. He has also trained numerous undergraduate and graduate students and postdoctoral fellows and serves on research funding review panels for organizations including CIHR and the NIH.

Dr. Li’s laboratory at UBC is developing new approaches to overcome biological barriers to the delivery of biologic medicines. This expertise provides the foundation for the current NPF-supported project, which aims to develop a topical delivery technology that enables anti-IL-17A biologics to reach psoriatic skin while minimizing systemic exposure.