GHES U.S. Fellow 2018-2019
FELLOWSHIP SITE: Centro Internacional de Entrenamiento e
Investigaciones Medicas (CIDEIM), Cali, Colombia
U.S. INSTITUTION: Yale UNIVERSITY
Project Title: A rational approach to the design of a topical delivery platform for treatment of cutaneous leishmaniasis
There is a high burden of cutaneous leishmaniasis (CL) in Colombia and throughout the region. This parasitic disease is notable due its disfiguring dermal lesions and high chronicity. Current treatments have significant issues with toxicity and efficacy and no front-line therapeutic for CL offers local drug delivery even though the wound repair response dictates disease severity and clinical outcome. The development and evaluation of CL therapeutics that exploit pharmacological knowledge of the altered skin physiology and local inflammatory responses due to infection remains a pertinent, yet underrepresented, research area. There is an urgent need for improved CL treatments that are less toxic, more potent, enhance lesion healing, and avoid the parenteral administration route. This work aims to establish a basis for such a multifunctional therapeutic platform by initially characterizing critical biophysical and biomechanical properties of ulcerative CL lesions and evaluating the treatment experience and preferences of CL patients to subsequently guide the design of a topical therapeutic platform (e.g. patch) that targets the infection site and leverages both anti-parasitic and wound healing activity. Multiple drug delivery platforms will be explored including electrospun scaffolds with electrosprayed nanoparticles and microneedles. CL lesion characterization will also spatially identify regions of high pathology for enhanced therapeutic targeting and regions with enhanced absorption/retention to optimize patch placement. Ultimately, using an engineering and human-centered design approach will allow for the development of more effective, less toxic therapeutics for CL with accelerated treatment time irrespective of local medical infrastructure and with greater CL patient acceptability. This has direct implications for reducing the excess burden of CL in Colombia and in other endemic LMICs.