Preparation of novel polymeric nanocarriers for immobilization and controlled delivery of the proteolytic enzyme serratiopeptidase

Project КП-06-М69/3

Coordinator:

Assis. Prof. Katya Kamenova-Stoyanova

Base organization:

Institute of Polymers, Bulgarian Academy of Sciences

Start:

December 08, 2022

Duration:

24 months

Summary:

Acute and chronic inflammatory diseases are one of the most common health problems in the world. One of the challenges in controlling inflammation is the correct diagnosis and selection of appropriate therapy. Most of the anti-inflammatory drugs are related to symptomatic relief rather than treatment and have severe side effects and cause adverse reactions in the body. In the last decade, the use of enzymes as therapeutics has become an integral part of modern medicine mainly due to their selectivity and efficacy. Serratiopeptidase is a proteolytic enzyme defined as a “super enzyme” with proven powerful anti-inflammatory activity. Clinical use of the enzyme has been reported for many diseases such as arthritis, sinusitis, inflammatory bowel disease, fibrocystic breast disease, chronic bronchitis, post-operative swelling and pain, atherosclerosis, etc. The proven effect of serathiopeptidase is due to: 1) inhibition of the release of inflammatory mediators; 2) accelerating the liquefaction of secretions and sputum, and 3) enhancing the effect of antibiotics.
The critical problem in enzyme therapy arises from the large size of the protein molecule, susceptibility to denaturation and degradation, short half-life, and poor bioavailability. The design of delivery systems for these bioactive substances still remains a challenge and is the subject of great research interest. One of the promising strategies to solve these problems is the use of polymeric nanocarriers. Core-shell polymeric micelles, formed from amphiphilic block copolymers, have exceptional potential for the development of highly efficient systems for the controlled delivery of active substances in the treatment of many diseases. The multifunctionality of these systems and their unique structure enables them to be loaded with a wide variety of therapeutic agents, including not only a number of water-insoluble medicinal components, but also therapeutic proteins, peptides, DNA, SiRNA, etc. Polymeric micelles have emerged as particularly promising carriers due to their ability to incorporate both hydrophilic and hydrophobic medicinal substances into their structure, to control the release process and to provide targeted action. Compared with conventional delivery systems (e.g. tablets, capsules, microparticles), these systems possess a number of advantages, such as better therapeutic effect, biocompatibility, targeting to a cell or tissue, protecting the drug from degradation, controlling the concentration in the body, and etc.