Polylactide-Based Stent Coatings: Biodegradable Polymeric Coatings Capable of Maintaining Sustained Release of the Thrombolytic Enzyme Prourokinase

摘要

The novelty of the study is the development, creation, and investigation of biodegradable polymeric membranes based on polylactide, that are capable of directed release of large molecular weight biomolecules, particularly, prourokinase protein (MW = 46 kDa). Prourokinase is a medication with significant thrombolytic activity. The created membranes possess the required mechanical properties (relative extension value from 2% to 10%, tensile strength from 40 to 85 MPa). The membranes are biodegradable, but in the absence of living cells in a water solution they decompose by less than 10% in half a year. The created membranes are capable of controlled prourokinase release into intercellular space, and the total enzymatic activity of prourokinase does not decrease by more than 12%. The daily release of prourokinase from one square centimeter of the membrane ranges from 1 to 40 μg per day depending on the technique of membrane preparation. The membranes have no acute toxic effect on cells accreting these surfaces de novo. The number of viable cells is at least 96%−97% of the overall cell count. The mitotic index of the cells growing on the surface of the polymeric films comprised around 1.5%. Histological examination did not reveal any disorders in tissues of the animals after the implantation of polymer membranes based on polylactide, both alone and as components of stent cover. Implantation of stents covered with prourokinase-containing polymers led to the formation of a mature connective tissue capsule that is thicker than in the case of uncovered stents. Thus, various polylactide-based biodegradable polymeric membranes possessing the required mechanical properties and capable of prolonged and directed release of prourokinase macromolecules are developed and investigated in the study.