Abstract
Objective There is increasing interest in simultaneous endovascular delivery of more than one drug from a drug-loaded
stent into a diseased artery. There may be an opportunity to obtain a therapeutically desirable uptake profile of the two drugs
over time by appropriate design of the initial drug distribution in the stent. Due to the non-linear, coupled nature of diffusion
and reversible specific/non-specific binding of both drugs as well as competition between the drugs for a fixed binding site
density, a comprehensive numerical investigation of this problem is critically needed.
Methods This paper presents numerical computation of dual drug delivery in a stent-artery system, accounting for diffusion
as well as specific and non-specific reversible binding. The governing differential equations are discretized in space, followed
by integration over time using a stiff numerical solver. Three different cases of initial dual drug distribution are considered.
Results For the particular case of sirolimus and paclitaxel, results show that competition for a limited non-specific binding
site density and the significant difference in the forward/backward reaction coefficients play a key role in determining the
nature of drug uptake. The nature of initial distribution of the two drugs in the stent is also found to influence the binding
process, which can potentially be used to engineer a desirable dual drug uptake profile.
Conclusions These results help improve the fundamental understanding of endovascular dual drug delivery. In addition, the
numerical technique and results presented here may be helpful for designing and optimizing other drug delivery problems
as well.
Anno
2023
Autori IAC
Tipo pubblicazione
Altri Autori
S. Salvi, A. Jain, G. Pontrelli, S. McGinty
Editore
Thieme,
Rivista
Pharmaceutical research