Mathematical and Numerical Modeling of Controlled Drug Release

Minisini, Sara
Mathematical and Numerical Modeling of Controlled Drug Release
Monday 11th January 2010
Formaggia, L.
Advisor II:
Zunino, P.
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Over the last years, the rapid growth in the area of drug discovery, facilitated by novel technologies in chemistry and in high-throughput screening, has led to new drugs which are generally more effective than traditional ones. The development and use of these complex drugs has resulted in an increasing interest in novel techniques to deliver them effectively and efficiently. In this context the simulation of controlled drug delivery systems whose aim is to release the drug in a specific target tissue is becoming a crucial issue. In the field of arterial cardiovascular disease intravascular drug eluting stents (DES) are now an established medical therapy. Stents, initially used to restore the original vessel diameter and healthy fluidodynamic conditions in an artherosclerotic artery are now currently used as a method of local and sustained drug delivery to prevent the reappearing of the pathology. Clinical trials show a reduction in re-narrowing when a DES is employed but in the mean time underline that the efficacy of the therapy strongly depends on the release rate of the drug from the delivery system and on its distribution inside the arterial wall in the days following the implantation of the stent. Mathematical modeling and numerical simulations of drug transport inside the human vessels and inside the arterial wall can help to better understand the efficacy of the treatment and guide the design of a better stent. However, modeling the local drug release from a medical device remains a difficult and challenging task because of the complexity and heterogeneity of the physical phenomena involved, both in the arterial wall and in the delivery system. In particular, realistic numerical simulations cannot be performed without taking into consideration phenomena that take place on different scales and are characterized by different kinetics. The guideline of this work has been the mathematical modeling of the main transport mechanisms that take place inside the arterial wall after the stent implantation. We address different topics, focusing on the complete problem and on specific issues like the characterization of the tissue and the delivery system.