Introduction: Being minimally invasive biomaterial in vascular space, drug eluting stents face several complications such as stent thrombosis, late stent restenosis and incomplete endothelization due to presence of an anti-proliferative agent [1]. For such complications, a single therapeutic drug is insufficient; therefore approaches to use multiple drug combinations have been made [2]. The current study reports a combination of dual drug loaded poly(L-lactide-co-caprolactone) system for its hemocompatibility and anti-proliferative nature.
Materials/Methods:
Whole blood assay and platelet adhesion assay: To determine hemocompatibility of dual drug loaded polymer films whole blood assay and platelet adhesion assay were performed. The films were incubated in freshly collected rat blood and isolated platelet rich plasma (PRP). After 2 h, films were washed and fixed with 2.5% glutaraldehyde followed by serial dilution with ethanol. Films were then imaged using scanning electon microscopy (SEM).
Cell migration assay: To evaluate an anti-proliferative nature of dual drug loaded polymer films a cell migration assay was conducted using smooth muscle cells (SMC). Films were inbcuated with cells until it formed a monolayer, after which it was scratched to create a wound. Migration of cells was checked for 48 h using phase contrast microscope.
Results and Discussion: Dual drug loaded films showed significant reduction in red blood cell adhesion and clot formation as compared to polymer film and controls. In case of platelet adhesion and aggregation, dual drug loaded films display a concentration dependent decrease in platelet aggregation (Figure 1). Cell migration assay shows delay in wound closure on combination films as compare to a tissue culture plate.
Conclusion: Dual drug loaded polymer films reported in this study possess anti-thrombogenic and anti-proliferative nature. This system may be explored further for stent applications.
Department of Science & Technology under the FIST programme (SR/FST/LSI-453/2010); SASTRA University (TA fund)
References:
[1] Guko Nakazawa, “Stent thrombosis of drug eluting stent: Pathological perspective” Journal of cardiology (2011),58,84-91.
[2] C.W. Lee, D.W. Park, K.B Seung, et al. “Comparison of Dual Drug-Eluting Cilotax Stent and Paclitaxel- Eluting Taxus Liberte Stent in Native Coronary Artery Lesions” Am J Cardiol (2011), 107, 990-994.