The use of a surgical implant often requires the administration of one or more drugs to increase the success of the surgery. The modification of implants to deliver the drug directly to the site of the surgery offers the promise of minimizing the drug dose needed, while maximizing the therapeutic benefit. Our long-term goal is to develop an advanced strategy for drug release from implants. The central hypothesis is that drugs may be attached to the surface through the use of a highly ordered molecular coating called a self-assembled monolayer (SAM) and subsequently released at a controlled rate. The rationale for this research is that drug-modified SAMs (DSAMs) will have therapeutic benefit which can enhance the value of any surgical implant. The initial target for implant modification is the coronary arterial stent, which has a strong need for a DSAM due to the prevalence of restenosis (arterial re-narrowing) as a post-surgical problem and complications resulting from polymer-based coatings. Specifically, the research objective proposed herein will focus on developing and optimizing DSAMs for coronary stents which deliver anti-restenotic drugs such as paclitaxel, sirolimus (rapamycin) or dexamethasone. This application is of acute urgency as complications from polymer-based coatings have been implicated in deaths.
The specific aims for this project are: (1) to develop methods to maximize the amount of drug loaded onto a metal surface through the use of DSAMs; (2) to optimize release rates of drugs present at surfaces; and (3) to adapt techniques to nanoporous surfaces.
These specific aims will be accomplished by a multifaceted program including chemical synthesis, surface studies, and drug release studies. ? ? This research offers the potential to modify any currently designed medical implant to deliver a drug directly to the site of the implantation surgery. This will result in implants that have additional therapeutic benefit and fewer side effects from surgery. ? ? ?
| Monda, Keri L; Chen, Gary K; Taylor, Kira C et al. (2013) A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat Genet 45:690-6 |
