UVA-Degradable Collagenase Nanocapsules as a Potential Treatment for Fibrotic Diseases
Víctor M. Moreno,
Carolina Meroño,
Alejandro Baeza,
Alicia Usategui,
Pablo L. Ortiz-Romero,
José L. Pablos,
María Vallet-Regí
Affiliations
Víctor M. Moreno
Departamento de Química en Ciencias Farmacéuticas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
Carolina Meroño
Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense de Madrid, Avenida Córdoba s/n, 28041 Madrid, Spain
Alejandro Baeza
Departamento de Materiales y Producción Aeroespacial, ETSI Aeronáutica y del Espacio, Universidad Politécnica de Madrid, 28040 Madrid, Spain
Alicia Usategui
Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense de Madrid, Avenida Córdoba s/n, 28041 Madrid, Spain
Pablo L. Ortiz-Romero
Servicio de Dermatología, Hospital 12 de Octubre, Instituto (i+12 Medical School), Universidad Complutense de Madrid, Avenida Córdoba s/n, 28041 Madrid, Spain
José L. Pablos
Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense de Madrid, Avenida Córdoba s/n, 28041 Madrid, Spain
María Vallet-Regí
Departamento de Química en Ciencias Farmacéuticas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
Peyronie and Dupuytren are pathologies characterized by the appearance of localized fibrotic lesions in an organ. These disorders originate from an excessive production of collagen in the tissue provoking dysfunction and functional limitations to the patients. Local administration of collagenase is the most used treatment for these fibrotic-type diseases, but a high lability of the enzyme limits its therapeutic efficacy. Herein, we present a novel methodology for the preparation of collagenase nanocapsules without affecting its enzymatic activity and capable of releasing the enzyme in response to an ultraviolet A (UVA) light stimulus. Polymeric coating around collagenase was formed by free-radical polymerization of acrylamide-type monomers. Their degradation capacity under UVA irradiation was provided by incorporating a novel photocleavable acrylamide-type crosslinker within the polymeric framework. This property allowed collagenase release to be triggered in a controlled manner by employing an easily focused stimulus. Additionally, UVA irradiation presents considerable benefits by itself due to its capacity to induce collagenase production in situ. An expected synergistic effect of collagenase nanocapsules in conjunction with UVA effect may present a promising treatment for these fibrotic diseases.