In vitro experimentation and modeling of drug release from polymeric carriers for the development of drug eluting stents

Overview & Synopsis

The cardiovascular system is prone to severe diseases such as atherosclerosis, most important cause of death in the recent decades. Therapeutic techniques continue to improve today: balloon angioplasty, bare stent, drug-eluting stent, bioresorbable stent. Stent thrombosis is one of the severe complications of the angioplasty. Maintaining an adequate dose of anticoagulants and antiplatelet agents during the therapy can minimize the risk of thrombosis. Optimizing the following parameters can improve the kinetics of the drug release during this therapy: initial concentration, solubility and particle size of drug, properties of the polymer matrix and coating methods. In this thesis, we have developed a bio-relevant apparatus in which we can consider the impact of the design choices, and that of the properties of the two mimicked media on the release of the drug. These two media are the systolic-diastolic blood circulation and the arterial wall. Furthermore, we have analyzed and quantified the effect of the flow pattern, polymer coating and type of drug on the in-vitro release tests. Two kinds of polymers, degradable (PLGA) and non-degradable (PU), and two kinds of drugs, hydrophile (DE) and hydrophobe (DS), were used. We have also developed some robust modeling allowing the characterization of the kinetic behavior for the drug carriers. We have implemented three types of modeling: the first model is related to a mathematical model based on the release kinetics. The second model proposes a mechanistic model based on the physical mechanisms involved in the release from the drug delivery carriers. Finally, the third approach is devoted to a implementation of a numerical simulation procedure. These models were validated on case studies taking into account the effects of the initial drug load and the type of flow. These developments thus make it possible to set design choices for new drug delivery systems in response to a desired release profile.