Paclitaxel/sirolimus combination coated drug-eluting stent: In vitro and in vivo drug release studies

Abstract

Paclitaxel and sirolimus are the two major drugs for the treatment of coronary arterial disease in current drug eluting stents. The two drugs can effectively inhibit the in-stent restenosis through their independent pathways and show synergistic effect in preventing tumor tissue growth. We hypothesize that the combination of the two drugs in a drug eluting stent (DES) can also effectively suppress the neointima growth in the stented artery. The present work was focused on the investigation of paclitaxel/sirolimus combination release profiles from a novel biodegradable polymer (poly (D, L-lactide -co-glycolide) / amorphous calcium phosphate, PLGA/ACP) coated stent both in vitro and in vivo. For the in vitro, the drug releasing profiles were characterized by measuring the drug concentration in a drug release medium (Dulbecco’s phosphate buffered saline, DPBS, pH 7.4) at predetermined time points. For the in vivo, a rat aorta stenting model was employed. The results showed that both paclitaxel and sirolimus had a two-phase release profile both in vitro and in vivo, which is similar to the drug release profile of their individual coated DESs, and there is no evident of interference between two drugs. The data suggest that paclitaxel and sirolimus can be combined pharmacokinetically in a DES for the treatment of coronary arterial diseases.

Analytical modeling of drug dynamics induced by eluting stents in the coronary multi-layered curved domain

“…Therefore, proposed results clearly highlight that the variation of β and of the coating thickness produce some counteracting effects on the DES therapeutic effectiveness: when the therapeutic window (i.e., the duration of the therapeutic action) increases then the reacting drug fraction (i.e., the antiproliferative effectiveness) reduces, and viceversa. Accordingly, fully in agreement with clinical evidence (e.g., [6][7][8][9]12,31,32,55]) and other modeling approaches (e.g., [18][19][20][21][22][23][24][25][26][27][28][29][30][34][35][36]), applicative examples herein discussed suggest that a suitable therapeutic effectiveness can be obtained by choosing coating material and drug type such that drug diffusivity D 1 and topcoat permeability P 1 are small enough, as well as by prescribing values for coating thickness and drug reaction rate within certain optimal ranges.…”

“…In order to contribute to a better understanding and characterization of dominant effects related to the previously-mentioned factors, many in-vivo and in-vitro experimental studies, as well as (pre-)clinical trials and follow-up analyses have been recently carried out (e.g., [7][8][9][10][11][12][13][14][15][16][17]). Furthermore, in the last few years many theoretical and computational models have been also developed, aiming to provide insights into the drug-release mechanisms, as well as to establish analysis tools and parametric indications for conception and design of effective DESs and therapeutic strategies.…”

“…Other model parameters are set as inTable 1.by considering different sets of values for model parameters within typical physiological and clinical ranges-reveal the model capable to properly describe well-established evidence from in-vivo and invitro experimental analyses, as well as from (pre-)clinical trials and follow-up studies (e.g.,[7][8][9][10][11][12][13][14][15][16][17]31,32,55]). Further quantitative comparisons among present results and available experimental data have not been performed, due to the wide patient-dependent variability of many model parameters.…”

Use of growth factor-loaded acetylated polysaccharide as a coating material to improve endothelialization of vascular stents

“…[1][2][3] Understanding the composition and surface characteristics of stents is vital for the inhibition of acute thrombus and in-stent restenosis. [4][5][6] Although metal stents can easily provide mechanical stability, they have several drawbacks including inflammation, thrombosis, fibromuscular proliferation, and formation of restenosis. 7,8 Drug-eluting stents (DES) have dramatically reduced restenosis in comparison to bare-metal stents.…”

Effect of stents coated with a combination of sirolimus and alpha-lipoic acid in a porcine coronary restenosis model

“…To determine the total amount of sirolimus and ALA on the BMS, the coated stent was sonicated in 5 mL of acetonitrile (ACN) for 1 h to dissolve the coating layer with the drug and then analyzed with an ultraviolet-visible spectrophotometer (UV; UV-1800, Shimadz, Japan) at 278 and 330 nm, respectively. The in vitro drug release was measured using a simple shaking method with UV [16].…”