sirolimus and genipin

Recombinant elastin-like protein polymers are increasingly being investigated as component materials of a variety of implantable medical devices. This is chiefly a result of their favorable biological properties and the ability to tailor their physical and mechanical properties. In this report, we explore the potential of modulating the water content, mechanical properties, and drug release profiles of protein films through the selection of different crosslinking schemes and processing strategies. We find that the selection of crosslinking scheme and processing strategy has a significant influence on all aspects of protein polymer films. Significantly, utilization of a confined, fixed volume, as well as vapor-phase crosslinking strategies, decreased protein polymer equilibrium water content. Specifically, as compared to uncrosslinked protein gels, water content was reduced for genipin (15.5%), glutaraldehyde (GTA, 24.5%), GTA vapor crosslinking (31.6%), disulfide (SS, 18.2%) and SS vapor crosslinking (25.5%) (P<0.05). Distinct crosslinking strategies modulated protein polymer stiffness, strain at failure and ultimate tensile strength (UTS). In all cases, vapor-phase crosslinking produced the stiffest films with the highest UTS. Moreover, both confined, fixed volume and vapor-phase approaches influenced drug delivery rates, resulting in decreased initial drug burst and release rates as compared to solution phase crosslinking. Tailored crosslinking strategies provide an important option for modulating the physical, mechanical and drug delivery properties of protein polymers.

Topics: Cross-Linking Reagents; Disulfides; Drug Delivery Systems; Elastin; Fibronectins; Glutaral; Human Umbilical Vein Endothelial Cells; Humans; Iridoids; Mechanical Phenomena; Sirolimus; Water

A limitation with the use of polymers as stent matrices is their inherent mechanical weakness. In this study, a polymeric stent, made from chitosan-based films fixed by genipin which has a cyclic molecular structure, was developed (the genipin stent). The mechanical properties of the genipin stent were investigated; its counterpart fixed by a linear epoxy compound (the epoxy stent) and a commercially available metallic stent were used as controls. The results indicated that the cyclic crosslinking structures formed within the genipin stent matrix were beneficiary to the improvement of its mechanical property. Additionally, the tolerable compression load of the genipin stent was superior to that of the control metallic stent. The cytotoxicity of the genipin stent was significantly lower than the epoxy stent. The deployment of the genipin stent in rabbit infrarenal abdominal aortas was performed using a French sheath. At 3 months postoperatively, the retrieved arteries remained patent; no thrombosis was observed. A nearly intact layer of endothelial cells was seen on the stent-implanted vessel wall. To evaluate its possibility as a drug delivery vehicle, sirolimus (an anti-proliferative drug) was loaded in the genipin stent. It was found that the genipin stent with heparin coating exhibited a linear sustained-release profile and the released sirolimus still possessed its original activity in inhibiting smooth muscle cell proliferation. These findings suggest that the genipin stent with enhanced mechanical strength can be used as an attractive stent platform for local drug delivery.

Topics: Animals; Chitosan; Compressive Strength; Cross-Linking Reagents; Drug-Eluting Stents; Elastic Modulus; Equipment Design; Equipment Failure Analysis; Immunosuppressive Agents; Iridoid Glycosides; Iridoids; Polymers; Rabbits; Sirolimus

In the study, a novel drug-eluting stent for treating the coronary arterial stenosis was developed. Using a spray-coating method, aqueous bovine type I collagen and sirolimus were coated layer-by-layer alternatively onto the surface of a metallic stent and a topcoat of collagen was used as a barrier to control drug release. To prevent dissolution of the collagen matrices, the spray-coated collagen was further crosslinked by genipin, a naturally occurring crosslinking agent. The results obtained in the atomic force microscopy (AFM) examination suggested that the spray-coated collagen was tightly adhered to the surface of the stent. Additionally, the collagen coating was demonstrated by the scanning electron microscopy (SEM) to be sufficiently flexible to allow balloon expansion of the stent without cracking or peeling from the wire. The resistance against enzymatic degradation and the hemocompatibility of the collagen matrices increased significantly as their degree of crosslinking increased. All the studied sirolimus-loaded stents exhibited a nearly linear sustained-release profile (except at the end stage of release) with no significant burst releases. It was found that a topcoat of collagen on the collagen/sirolimus coated stent did slow down the release of sirolimus to some extent. Additionally, the number of layers of collagen/sirolimus coated significantly affected the duration of sirolimus released. Furthermore, the sustained-release duration of sirolimus was proportional to the actual amount of drug loaded on the stent. The aforementioned results indicated that the drug-eluting stent developed had a tightly adhered collagen coating and can be used as a drug reservoir to sustain release of sirolimus.

Topics: Animals; Coated Materials, Biocompatible; Collagen; Cross-Linking Reagents; Delayed-Action Preparations; Iridoid Glycosides; Iridoids; Materials Testing; Molecular Structure; Platelet Adhesiveness; Pyrans; Sirolimus; Solubility; Stents; Surface Properties