Collagenase nanocapsules: An approach to fibrosis treatment

Abstract

Fibrosis is a common lesion in different pathologic diseases and defined by the excessive accumulation ofcollagen. Different approaches have been used to treat different conditions characterized by fibrosis. TheFDA 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 otherconditions [1,2]. The approved treatment includes up to three (in palmar fibromatosis) or up to eight (inpenile fibromatosis) injections followed by finger extension or penile modeling procedures, typicallycausing severe pain. Frequent single injections are adequate to treat palmar fibromatosis [3]. The needto repeatedly inject doses of this enzyme can be due to the labile nature of collagenase, which exhibitsa complete activity loss after a short period of time. This study presents a novel strategy to manage thisenzyme based on the synthesis of polymeric nanocapsules that contain collagenase encapsulated withintheir matrix. These nanocapsules have been engineered for achieving a gradual release of the encapsu-lated enzyme for a longer time, which can be up to ten days. The efficacy of these nanocapsules has beentested in a murine model of local dermal fibrosis, and the results demonstrate a reduction in fibrosisgreater than that with the injection of free enzyme; this type of treatment showed a significant improve-ment compared to conventional therapy of free collagenase.