Awarded a one-year, $99,206 grant from Pachyonychia Congenita Project.
All potential therapies for PC (Pachyonychia Congenita), from traditional drug molecules to advanced gene-editing approaches, must eventually confront a common challenge: delivery of the therapeutic agents into the upper layer (also known as epidermis) of skin covering the bottom of the foot (also known as plantar skin), which is the target treatment area for the most problematic symptom of PC – the development of excessive and often debilitatingly painful calluses. Ideally PC therapies would be delivered directly to these skin areas, to minimize side effects and other problems that often occur when drugs are circulated through the entire body. However the skin’s ability to protect us from the outside world also becomes a significant impediment against delivering drugs into the skin. There are existing technologies to overcome this barrier and enable drug delivery into the skin, but they have predominantly been developed for nonplantar skin, and are often incompatible with the physical properties of plantar skin, which is highly specialized due to its unique weight-bearing function. The lack of a practical drug delivery method for plantar skin has long been a critical roadblock that has derailed previous attempts to develop PC therapies. We propose to adapt two laser technologies that are effective in greatly enhancing drug uptake in the skin, namely full-field ablation (FFA) and ablative fractional lasers (AFL), optimize their application settings to the unique structure of plantar skin, and validate the ability to enhance drug delivery into the plantar epidermis. If successful, these methods could be broadly applicable for PC therapies.
Project Title: Laser-Assisted Drug Delivery to the Plantar Epidermis
Principal Investigator (PI) Name: Joshua Tam, PhD
PI Affiliations: Massachusetts General Hospital
Abstract
Virtually all potential therapies for PC (Pachyonychia Congenita), from traditional drug molecules to advanced gene editing approaches, must eventually confront a common challenge: delivery of the therapeutic agents into the plantar epidermis. The lack of a practical drug delivery method has long been a critical roadblock that has derailed previous attempts to develop PC therapies. Existing topical drug delivery technologies have predominantly been developed for non-plantar skin, and are often incompatible with the specialized physical properties of plantar skin in larger species.
We propose to leverage our group’s expertise in the specialized physiology of plantar skin and in developing laser assisted topical drug delivery, to develop a solution for this problem. Specifically, we will adapt two laser technologies that have demonstrated effectiveness in greatly enhancing skin uptake of topically applied drugs, namely full-field ablation (FFA) and ablative fractional lasers (AFL), optimize their application settings to the specialized structure of the plantar epidermis, and validate the ability to enhance delivery of topically applied agents representing three major drug categories that are relevant for PC yet challenging to deliver: hydrophilic molecules, siRNA, and gene therapy vectors. From these studies we expect to establish the feasibility and effective application characteristics for laser-assisted drug delivery into the plantar epidermis, which should be broadly applicable for PC therapies.
