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

Abstract

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.

Polylactide-based stent coatings: biodegradable polymeric coatings capable of maintaining sustained release of the thrombolytic enzyme streptokinase

“…2, 3, and 4. It should be noted that the polylactide films we synthesized have much higher yield strength as compared to other polylactide polymers [28,29]. It shown that with increasing streptokinase concentration in the polymer, the ultimate tensile strength decreases.…”

Addressing the Needs of the Rapidly Aging Society through the Development of Multifunctional Bioactive Coatings for Orthopedic Applications

“…Every bare metal implant possesses limited bioactivity. In order to further initiate interaction with the biological tissue and enable better bonding between the bone and the implant, medications and therapeutic agents can be incorporated directly into the implant surface or applied via (biodegradable) polymeric matrixes [ 87 , 88 ]. If properly selected, such polymers can enhance the biocompatibility of the metal implant, mitigate corrosion, and enable the controlled and tunable release of active ingredients [ 18 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 ].…”

A Novel Biodegradable Composite Polymer Material Based on PLGA and Silver Oxide Nanoparticles with Unique Physicochemical Properties and Biocompatibility with Mammalian Cells

“…Nano-and micromaterials contained of poly (lactic-co-glycolic acid) (PLGA) are promising candidates for many biomedical applications, in particular, oncology therapy, targeted drug delivery, and vaccine efficacy improvement [25][26][27]. PLGA is often used to make biodegradable stent coatings, as well as parts of the stents themselves and other materials used for implantation [28][29][30][31][32][33][34][35][36].…”