Nanoparticles designed to carry collagenase in addition to other drugs.
Collagenase is useful to treat any disease characterized by excess collagen, such as Dupuytrem's disease; Lapeyronie's disease or keloids.
Fibrosis is caused by the excess growth of fibrous tissue. As a result, a chronic inflammatory process occurs that triggers an increase in the production and accumulation of extracellular matrix in the tissue. The main component of this extracellular matrix is collagen.
Current treatments are surgery or the administration of collagenase. The former are very invasive, can cause side effects and require long recovery times.
Another option in the treatment of these diseases is the local administration of collagenase, an enzyme that degrades collagen, in the affected area. This enzyme causes a significant reduction of the collagen fibers present in the fibrotic plaques, thus alleviating the symptoms of these pathologies. The main factor limiting the use of this enzyme is its high sensitivity since it loses its activity in less than 24 hours. This problem can be solved by periodically injecting multiple doses of collagenase, but it causes significant local pain and side effects resulting from overdose, which in turn cause tissue damage.
The research group of Professor María Vallet-Regí, in collaboration with doctors José Luis Pablos and Pablo Ortiz, from Hospital 12 de Octubre, has developed a novel methodology for the controlled release of Collagenase. By coating the enzyme with a polymer sensitive to UV light, they have managed to produce nanocapsules that protect collagenase without affecting its enzymatic activity, thus increasing its useful life in blood, to be released in a controlled way at the fibrotic tissue, in response to an external stimulus such as UV radiation.
In this way, these nanocapsules allow the administration of collagenase in specific regions in a sustained, prolonged and less damaging way to the tissue, using a stimulus that is easy to focus. In addition, UVA phototherapy can reduce the thickness and stiffness of the skin and also has a benefit in the treatment of these fibrotic lesions due to its potential anti-inflammatory effect and its ability to stimulate collagenase production in the tissue. Hence, UV radiation yields a dual beneficial effect: it triggers the controlled release of collagenase in the tissue, while playing a therapeutic role per se.
Pros: it keeps collagenase active more than 10 days when encapsulated and bound to its vehicle, the silica mesoporous particle.
Non-encapsulated collagenase remains active only for a few hours.
The great advantage is that keeping collagenase active for days instead of hours destroys collagen much more efficiently.
These new UV activated nanocapsules allow doing it on demand and releasing collagenase exclusively at the desired areas.
Furthermore, these nanocapsules can be adapted to carry other species of interest in medicine, aesthetic procedures or cosmetics.
The transportation and rapid release features are also applicable to different therapeutic agents of interest, allowing a sustained release, which is a great advantage over current therapies in use.
Professor Vallet's group has also developed another novel methodology to produce polymeric nanocapsules capable of encapsulating collagenase without affecting its enzymatic activity and releasing it in a controlled way, once they reach the diseased tissue, in response to an internal stimulus such as pH. This property has been used for the release of collagenase in tumor tissues that present an acidic environment, in order to degrade the extracellular matrix and increase the penetration of nanotherapeutic agents.
This work has been funded by ERC-2015-AdG Nº 694160 (VERDI) and ERC-2018-PoC Nº 825435 (DECOMPACT). A dissemination video has been produced.
https://www.youtube.com/watch?v=0_YX1qVsG4Y&feature=youtu.be(opens in new window)
