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.
STATEMENT OF SIGNIFICANCE: 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.