In-stent restenosis and late-stage thrombosis, the two major polymer-associated problems occurred in existing drug eluting stents (DESs) derive a need for a new generation DES made or coated by biodegradable materials for those 14 million Americans who suffered from coronary arterial disease. However, all current biogedarable materials used in making DESs are not successful due primarily to their sever inflammatory response to stented arterial walls. VasoTech Inc. has preliminarily developed an inflammatory-free, highly biocompatible and biodegradable material--BioDe(r) material by blending Amorphous Calcium Phosphate (ACP) with Poly (Lactide-co-Glycolide) (PLGA). The major purposes of this SBIR Fast Track application are to further characterize BioDe(r) polymer's biocompatibility and degradation kinetics (Phase I), and further utilize it as drug carrier to develop a powerful new generation of DES-PowerStent by coating BioDe(r) polymer and Combo(r) drug formulation--a potent anti- restenosis formulation consisting of equal amount of Sirolimus and Paclitaxel onto VasoTech(r) metal stent. In this Fast-Track application, Phase I studies will be 1) to optimize BioDe(r) polymer formulation and its coating process (SpecificAim1), and 2) characterize the biodegradation kinetics of optimized biodegradable polymer from Specific Aim 1 study through a well established rat carotid arterial stenting model (Specific Aim 2). In Phase II, PowerStent will be created by coating developed BioDe(r) biodegradable polymer with Combo(r) anti-restenosis drug formulation onto VasoTech(r) metal stent surface. Therefore, the Specific Aims in Phase II studies will be to characterize PowerStent's drug eluting profile in rabbit iliac arterial stenting model (Specific Aim 3), and performance testing of its anti-restenosis and thrombosis functions in a pig coronary stenting model for one month (Specific Aim 4). The proposal is also our response to NIH Program Announcement (PA-06-009) entitled: Bioengineering Nanotechnology Initiative, in which """"""""the in-vivo therapeutics: a development of nanoparticles that enable controlled release of therapeutic agents, antibodies, genes and vaccines into targeted cells"""""""" as described in the program announcement are perfect match to the objective of this SBIR application. Narrative: In-stent restenosis and late-stage thrombosis, the two major polymer-associated problems occurred in existing drug eluting stents (DESs) derive a need for a new generation DES made or coated by biodegradable materials for those 14 million Americans who suffered from coronary arterial disease. PowerStent--the combination of an inflammatory-free biodegradable polymer developed during Phase I studies, a potent anti-restenosis drug formulation and a featuring designed drug delivery platform as described in this SBIR Fast-Track application is such kind a stent.
