Collagenase nanocapsules: An approach to fibrosis treatment

Fibrosis is a common lesion in different pathologic diseases and defined by the excessive accumulation of collagen. Different approaches have been used to treat different conditions characterized by fibrosis. The FDA and EMA approved the use of collagenase to treat palmar fibromatosis (Dupuytren's contracture). The EMA approved additionally its use in severe Peyronie's disease, but it has been used off label in other conditions [1,2]. The approved treatment includes up to three (in palmar fibromatosis) or up to eight (in penile fibromatosis) injections followed by finger extension or penile modeling procedures, typically causing severe pain. Frequent single injections are adequate to treat palmar fibromatosis [3]. The need to repeatedly inject doses of this enzyme can be due to the labile nature of collagenase, which exhibits a complete activity loss after a short period of time. This study presents a novel strategy to manage this enzyme based on the synthesis of polymeric nanocapsules that contain collagenase encapsulated within their matrix. These nanocapsules have been engineered for achieving a gradual release of the encapsulated enzyme for a longer time, which can be up to ten days. The efficacy of these nanocapsules has been tested in a murine model of local dermal fibrosis, and the results demonstrate a reduction in fibrosis greater than that with the injection of free enzyme; this type of treatment showed a significant improvement compared to conventional therapy of free collagenase.

The use of proteins as therapeutic molecules has recently attracted great interest. Collagenase injection is the current treatment for fibrotic diseases. Unfortunately, proteins have a low stability and presume several repetition cycles to obtain an effective treatment. This article describes a novel treatment for these types of diseases using collagenase nanocapsules designed to exhibit a sustainable release of the encapsulated enzyme, which maintains the enzymatic activity for a long period of time. The therapeutic effect of nanocapsules was tested in a murine mouse model of local dermal fibrosis, and the results showed an important improved effect compared to the effect of the administration of free enzyme. These results indicate a high potential for this novel system to improve the current treatment for fibrotic diseases.