Intraplaque injection of collagenase Clostridium histolyticum (CCH) is a therapeutic approach for treating Peyronie's disease (PD) that may represent an alternative to surgery in some patients. However, the efficacy of collagenase injection is rather variable among patients. Nanocapsules (NC) provide therapeutic advantages by allowing sustained protein release and preserving enzymatic activity. The aim was to evaluate the in vitro efficacy of preparation of polymeric NC containing collagenase in reducing human PD plaque.
Polymeric nanocapsules containing collagenase type I (ColNC) or blank NC were synthesized. Enzymatic activity of ColNC and free-collagenase (Col) was determined. The impact of NC, ColNC, and Col on cell viability of commercially available fibroblasts and myofibroblasts was determined. The effects of treatments on differentiation of fibroblasts obtained from plaques of PD patients into myofibroblast and differential cell viabilities were evaluated. Plaque tissues from PD patients (n = 13) were injected with phosphate-buffered saline solution, Col (0.1%), ColNC (0.1%), or equivalent amount of NC. Seven days after, the reduction in plaque tissue weight, type 1 collagen content, and the release of protein to the medium were determined.
Nanocapsules exerted protective effect for collagenase by preserving its activity for 10 days versus 48 h for Col. Although fibroblasts from PD patients were unaffected, ColNC decreased the viability of myofibroblasts by 80% compared to 20% reduction obtained by Col. Single injection of ColNC into PD plaque reduced weight by 30%, compared to 10% by Col. This was related to significant reduction in collagen content in the plaque and increased protein content in the medium.
Extending CCH activity and efficacy by nanoencapsulation may reduce injection repeats and improve therapeutic response to CCH injection, potentially representing a therapeutic strategy. Superiority of ColNC was demonstrated with biochemical assays, cell culture procedures, and in vitro functional evidence in plaque tissue from PD patients. Main limitation was the relatively low number of human samples due to limited human tissue availability. Encapsulation of collagenase into polymeric NC extends enzymatic activity and efficiency to degrade fibrous PD plaque. These results suggest that treatment with ColNC may represent a potential therapeutic strategy to reduce injection repeats in the management of PD but requires validation in in vivo and clinical studies.
The journal of sexual medicine. 2026 Jul 03 [Epub]
Carla Jiménez-Jiménez, Esaú Fernández-Pascual, Javier Angulo, Félix Campos-Juanatey, Rodrigo García-Baquero, Consuelo Conde-Redondo, Borja García-Gómez, Giuseppe Maiolino, Luiz Pedro Palma-Hendges, Enrique Lledó-García, Daniel Arcos, Juan Ignacio Martínez-Salamanca
Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Universidad Complutense de Madrid, 28040-Madrid, Spain., Urology Department, University Hospital La Paz, 28029-Madrid, Spain., Servicio de Investigación Histológica, Unidad de Investigación Traslacional en Cardiología-IRYCIS, Hospital Universitario Ramón y Cajal, 28034-Madrid, Spain., Andrology and Reconstructive Urology Unit, School of Medicine, Marqués de Valdecilla University Hospital, Cantabria University, IDIVAL, 38008-Santander, Spain., Urology Department, University Hospital Puerta del Mar, 11009-Cádiz, Spain., Urology Department, University Hospital Río Hortega, 47012-Valladolid, Spain., Urology Department, University Hospital Doce de Octubre, 28041-Madrid, Spain., Lyx Institute of Urology, Universidad Francisco de Vitoria, 28006-Madrid, Spain.