Protective Layer Development for Enhancing Stability and Drug-Delivery Capabilities of DES Surface-Crystallized Coatings.

Carrier-free drug-eluting stents (DES)-based crystalline coatings are gaining prominence because of their function, skipping many limitations and clinical complications of the currently marketed DES. However, their usage has been humbled by inflexibility of the crystalline coating and limited mechanical and physical properties. This study reports for the first time the development of a protective top coating for enhancing the merits and delivery capabilities of the crystalline coating. Flexible and water-soluble polysaccharide top coating was developed and applied onto rapamycin (RM) crystalline carpet. The top coating prevented crystalline coating delamination during stent crimping and expansion without affecting its release profile. Crystalline coating strata and its interfaces with the metallic substrate and top coating were fully studied and characterized. The crystalline top-coated stents showed significant physical, mechanical, and chemical stability enhancement with ∼2% RM degradation after 1 year under different storage conditions. Biocompatibility study of the top-coated stents implanted subcutaneously for 1 month into SD rats did not provoke any safety concerns. Incorporating RM into the top coating to develop a bioactive protective coating for multilayer release purposes was also investigated. The developed protective coating had wide applicability and may be further implemented for various drugs and implantable medical devices.

Crystalline paclitaxel coated DES with bioactive protective layer development.

Drug eluting stents (DES) based on polymeric-carriers currently lead the market, however, reports on clinical complications encourage the development of safer and more effective DES. We recently reported on carrier-free DES based on rapamycin crystalline coating as a potential therapeutic solution. Here, we report for the first time surface crystallization of paclitaxel (PT) onto metallic stents. The physicochemical principles of crystallization and key process parameters were extensively studied for fabrication of controllable and homogeneous crystalline coatings on stent scaffolds. Stents loaded with nearly 100µg PT were chosen as a potential therapeutic device with a multilayer coating of 4-7µm thickness. In vitro PT release from these coated stents shows constant release for at least 28days with 10% cumulatively released. The effect of fast dissolving top coating on the physical stability of the coated stent was determined. The top coating enhances the mechanical stability of the crystalline coating during deployment and expansion simulations. Also, incorporating PT in the protective top coating for developing bioactive top coating for multilayer controlled release purpose was intensively studied. This process has wide applications that can be further implemented for other drugs for effective local drug delivery from implantable medical devices.