Biodegradable stent coatings on the basis of PLGA polymers of different molecular mass, sustaining a steady release of the thrombolityc enzyme streptokinase

The work describes synthesis of novel biodegradable polymer membranes based on poly(lactic-co-glycolic acid) (PLGA), as well as testing of their physicochemical properties. The membranes synthesized have been shown to possess the necessary mechanical properties and to be capable of sustained and directed release of large biomacromolecules, in particular, the molecules of streptokinase (m.w. 47 kDa). Streptokinase is a pharmaceutical drug with a high thrombolytic activity. The technology developed allows one to synthesize membranes with a relative elongation of 25 to 165% and a tensile strength of 20 to 55 MPa. The membranes are biodegradable; the rate of the polymer degradation in an isotonic solution is 0.5-1.0% per day. The streptokinase-infused membranes were demonstrated to release the protein in a controlled manner, with similar to 90% of the enzyme molecules retaining their activity. The rate of streptokinase release from the membranes was in the range of 0.01-0.07 mg/cm(2) per day. The polymer films did not exert any short-term toxic effects on the cells cultivated de novo on the film surface. The mitotic index of cells growing on the surface of polymer films was similar to 1.5%. The implantation of the synthesized polymers in animals - in the form of film samples and as a component of the coating of nitinol stents - had no complications during the postoperative period. The histological examination of the implant-surrounding tissues did not reveal any abnormalities. When the polymers were implanted as separate film samples, only traces of PGLA were detected in the tissues two months after the surgery. The implantation of stents coated with the streptokinase-infused polymers resulted in the formation of a mature and thick connective-tissue capsule. Thus, novel biodegradable PLGA-based polymer membranes have been synthesized and tested in this work - membranes which possess the necessary mechanical properties and are capable of a sustained and directional release of high-molecular biological compounds.