Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating

The long held assumption that sustained drug elution from stent coatings over weeks to months is imperative for clinical efficacy has limited the choice for stent coating materials. We developed and evaluated an omega-3 fatty acid (O3FA) based stent coating that is 85% absorbed and elutes 97% of its Sirolimus analog (Corolimus) load within 8d of implantation. O3FA coated stents sustained drug levels in porcine coronary arteries similarly to those achieved by slow-eluting durable coated Cypher Select Plus Stents and with significantly lower levels of granuloma formation and luminal stenosis. Computational modeling confirmed that diffusion and binding constants of Corolimus and Sirolimus are identical and explained that the sustained retention of Corolimus was facilitated by binding to high affinity intracellular receptors (FKBP12). First in man outcomes were positive—unlike Cypher stents where late lumen loss drops over 6 month, there was a stable effect without diminution in the presence of O3FA. These results speak to a new paradigm whereby the safety of drug eluting stents can be optimized through the use of resorbable biocompatible coating materials with resorption kinetics that coincide with the dissociation and tissue elimination of receptor-bound drug.National Institutes of Health (U.S.) (R01 GM-49039

Tracking of Drug Release and Material Fate for Naturally Derived Omega-3 Fatty Acid Biomaterials

In vitro and in vivo studies were conducted on omega-3 fatty acid-derived biomaterials to determine their utility as an implantable material for adhesion prevention following soft tissue hernia repair and as a means to allow for the local delivery of antimicrobial or antibiofilm agents. Naturally derived biomaterials offer several advantages over synthetic materials in the field of medical device development. These advantages include enhanced biocompatibility, elimination of risks posed by the presence of toxic catalysts and chemical crosslinking agents, and derivation from renewable resources. Omega-3 fatty acids are readily available from fish and plant sources and can be used to create implantable biomaterials either as a stand-alone device or as a device coating that can be utilized in local drug delivery applications. In-depth characterization of material erosion degradation over time using non-destructive imaging and chemical characterization techniques provided mechanistic insight into material structure: function relationship. This in turn guided rational tailoring of the material based on varying fatty acid composition to control material residence time and hence drug release. These studies demonstrate the utility of omega-3 fatty acid derived biomaterials as an absorbable material for soft tissue hernia repair and drug delivery applications.National Institutes of Health (U.S.) (R01 GM 49039