METAloproteinases-responsive NANOparticles for drug delivery into perianal fistulas in Crohn´s disease
admin-cespu
Principal Investigator:
Rute Nunes
Leader Institution:
UNIPRO, U.CESPU
Research Team:
Andreia Sofia Sousa Barros, Cláudia de Freitas Martins, Diogo Rafael Dias Coelho, Catarina da Silva Leal, Mariana Ferreira da Silva
Funding entity:
CESPU
Budget:
3606,56 €
Period covered:
01/09/2026-2027
Abstract:
Perianal fistulas (PF) are one of the most debilitating complications, occurring in up to 30–40% of patients with Crohn´s Disease (CD) and are associated with significant morbidity, impaired quality of life, and increased risk of sepsis and surgery. Current treatments for PFCD are often insufficient to achieve durable fistula closure, underscoring the need for innovative approaches. Leveraging one of the most important features of the fistula environment - the overexpression of metalloproteinases (MPPs) - we propose developing nanocarriers able to selective deliver drugs in response to these enzymes after local administration. In addition, given the role of MPPs in the pathogenesis of the disease, the antibiotic doxycycline (DOX), the only MPPs inhibitor approved by the FDA, will be encapsulated as model drug. The aim of this work is to develop a selective drug delivery system based on nanoparticles that respond to the aggressive environment of fistulizing CD. Delivering the drug DOX from NPs triggered by local MPPs will assure target delivery and a dualaction therapeutic profile: DOX will inhibit MPPs and modulate extracellular matrix breakdown, while also halting infections.
Perianal fistulas (PF) are one of the most debilitating complications, occurring in up to 30–40% of patients with Crohn´s Disease (CD) and are associated with significant morbidity, impaired quality of life, and increased risk of sepsis and surgery. Current treatments for PFCD are often insufficient to achieve durable fistula closure, underscoring the need for innovative approaches. Leveraging one of the most important features of the fistula environment - the overexpression of metalloproteinases (MPPs) - we propose developing nanocarriers able to selective deliver drugs in response to these enzymes after local administration. In addition, given the role of MPPs in the pathogenesis of the disease, the antibiotic doxycycline (DOX), the only MPPs inhibitor approved by the FDA, will be encapsulated as model drug. The aim of this work is to develop a selective drug delivery system based on nanoparticles that respond to the aggressive environment of fistulizing CD. Delivering the drug DOX from NPs triggered by local MPPs will assure target delivery and a dualaction therapeutic profile: DOX will inhibit MPPs and modulate extracellular matrix breakdown, while also halting infections.