Development of a Biocompatible PLGA Polymers Capable to Release Thrombolytic Enzyme Prourokinase.

ABSTRACT

The novelty of the work lies in the creation and study of the physical and biological properties of biodegradable polymer coatings for stents based on poly(lactic-co-glycolic acid) (PLGA). Polymer coatings are capable of prolonged and directed release of molecules with a high molecular weight, in particular, protein molecules of prourokinase (m.w. 54 kDa). A technology has been developed to create coatings having a relative elongation of 40% to 165% and a tensile strength of 25-65 MPa. Coatings are biodegradable; the rate of degradation of the polymer in an isotonic solution varies in the range of 0.05%-1.0% per day. The created coatings are capable of controlled release of the protein of prourokinase, while about 90% of the molecules of prourokinase retain their enzymatic activity. The rate of release of prourokinase can vary from 0.01 to 0.08 mg/day/cm2. Coatings do not have a short-term toxic effect on mammalian cells. The mitotic index of cells growing on coatings is approximately 1.5%. When implanting the developed polymers in animals in the postoperative period, there are no complications. Histological examination did not reveal pathological processes. When implanting individual polymers 60 days after surgery, only traces of PLGA are detected. Thus, a biodegradable composite mechanically resistant polymer capable of prolonged release of the high molecular weight prourokinase enzyme has been developed.