Dataset Information

Influence of Polymer Composition on the Controlled Release of Docetaxel: A Comparison of Non-Degradable Polymer Films for Oesophageal Drug-Eluting Stents.

ABSTRACT: Following the huge clinical success of drug-eluting vascular stents, there is a significant interest in the development of drug-eluting stents for other applications, such as the treatment of gastrointestinal (GI) cancers. Central to this process is understanding how particular drugs are released from stent coatings, which to a large extent is controlled by drug-polymer interactions. Therefore, in this study we investigated the release of docetaxel (DTX) from a selection of non-degradable polymer films. DTX-polymer films were prepared at various loadings (1, 5 and 10% w/w) using three commercially available polymers including poly(dimethylsiloxane) (PSi), poly (ethylene-co-vinyl acetate) (PEVA) and Chronosil polyurethane (PU). The formulations were characterised using different techniques such as photoacoustic Fourier-transform infrared (PA-FTIR) spectrophotometry, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The effect of DTX on the mechanical properties of the films, in-vitro release, and degradation tests were also assessed. For all polymers and DTX loadings, the drug was found to disperse homogenously without crystallisation within the polymer matrix. While no specific interactions were observed between DTX and PSi or PEVA, hydrogen-bonding appeared to be present between DTX and PU, which resulted in a concentration-dependent decrease in the Young's moduli of the films due to disruption of inter-polymeric molecular interactions. In addition, the DTX-PU interactions were found to modulate drug release, providing near-linear release over 30 days, which was accompanied by a significant reduction in degradation products. The results indicate that DTX-loaded PU films are excellent candidates for drug-eluting stents for the treatment of oesophageal cancer.

SUBMITTER: Fouladian P

PROVIDER: S-EPMC7284596 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Influence of Polymer Composition on the Controlled Release of Docetaxel: A Comparison of Non-Degradable Polymer Films for Oesophageal Drug-Eluting Stents.

Fouladian Paris P Afinjuomo Franklin F Arafat Mohammad M Bergamin Amanda A Song Yunmei Y Blencowe Anton A Garg Sanjay S

Pharmaceutics 20200511 5

Following the huge clinical success of drug-eluting vascular stents, there is a significant interest in the development of drug-eluting stents for other applications, such as the treatment of gastrointestinal (GI) cancers. Central to this process is understanding how particular drugs are released from stent coatings, which to a large extent is controlled by drug-polymer interactions. Therefore, in this study we investigated the release of docetaxel (DTX) from a selection of non-degradable polyme ...[more]

PMID: 32403329

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Project description:ObjectiveTo compare the efficacy and safety of biodegradable polymer drug eluting stents with those of bare metal stents and durable polymer drug eluting stents.DesignMixed treatment comparison meta-analysis of 258,544 patient years of follow-up from randomized trials.Data sources and study selectionPubMed, Embase, and Central were searched for randomized trials comparing any of the Food and Drug Administration approved durable polymer drug eluting stents (sirolimus eluting, paclitaxel eluting, cobalt chromium everolimus eluting, platinum chromium everolimus eluting, zotarolimus eluting-Endeavor, and zotarolimus eluting-Resolute) or biodegradable polymer drug eluting stents, with each other or against bare metal stents.OutcomesLong term efficacy (target vessel revascularization, target lesion revascularization) and safety (death, myocardial infarction, stent thrombosis). Landmark analysis at more than one year was evaluated to assess the potential late benefit of biodegradable polymer drug eluting stents.ResultsFrom 126 randomized trials and 258,544 patient years of follow-up, for long term efficacy (target vessel revascularization), biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.66, 95% credibility interval 0.57 to 0.78) and zotarolimus eluting stent-Endeavor (0.69, 0.56 to 0.84) but not to newer generation durable polymer drug eluting stents (for example: 1.03, 0.89 to 1.21 versus cobalt chromium everolimus eluting stents). Similarly, biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.61, 0.37 to 0.89) but inferior to cobalt chromium everolimus eluting stents (2.04, 1.27 to 3.35) for long term safety (definite stent thrombosis). In the landmark analysis after one year, biodegradable polymer drug eluting stents were superior to sirolimus eluting stents for definite stent thrombosis (rate ratio 0.29, 0.10 to 0.82) but were associated with increased mortality compared with cobalt chromium everolimus eluting stents (1.52, 1.02 to 2.22). Overall, among all stent types, the newer generation durable polymer drug eluting stents (zotarolimus eluting stent-Resolute, cobalt chromium everolimus eluting stents, and platinum chromium everolimus eluting stents) were the most efficacious (lowest target vessel revascularization rate) stents, and cobalt chromium everolimus eluting stents were the safest with significant reductions in definite stent thrombosis (rate ratio 0.35, 0.21 to 0.53), myocardial infarction (0.65, 0.55 to 0.75), and death (0.72, 0.58 to 0.90) compared with bare metal stents.ConclusionsBiodegradable polymer drug eluting stents are superior to first generation durable polymer drug eluting stents but not to newer generation durable polymer stents in reducing target vessel revascularization. Newer generation durable polymer stents, and especially cobalt chromium everolimus eluting stents, have the best combination of efficacy and safety. The utility of biodegradable polymer stents in the context of excellent clinical outcomes with newer generation durable polymer stents needs to be proven.

Project description:Background The choice of optimal drug-eluting stent therapy for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remains uncertain. We aimed to assess the long-term clinical outcomes after percutaneous coronary intervention with biodegradable polymer sirolimus-eluting stents (BP-SES) versus durable polymer everolimus-eluting stents (DP-EES) in patients with DM. Methods and Results In a prespecified subgroup analysis of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization) trial (NCT01443104), patients randomly assigned to ultrathin-strut BP-SES or thin-strut DP-EES were stratified according to diabetic status. The primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization, at 5 years. Among 2119 patients, 486 (22.9%) presented with DM. Compared with individuals without DM, patients with DM were older and had a greater baseline cardiac risk profile. In patients with DM, target lesion failure at 5 years occurred in 74 patients (cumulative incidence, 31.0%) treated with BP-SES and 57 patients (25.8%) treated with DP-EES (risk ratio, 1.23; 95% CI, 0.87-1.73 [P=0.24]). In individuals without DM, target lesion failure at 5 years occurred in 124 patients (16.8%) treated with BP-SES and 132 patients (16.8%) treated with DP-EES (risk ratio, 0.98; 95% CI, 0.77-1.26 [P=0.90; P for interaction=0.31]). Cumulative 5-year incidence rates of cardiac death, target vessel myocardial infarction, clinically indicated target lesion revascularization, and definite stent thrombosis were similar among patients with DM treated with BP-SES or DP-EES. There was no interaction between diabetic status and treatment effect of BP-SES versus DP-EES. Conclusions In a prespecified subgroup analysis of the BIOSCIENCE trial, we found no difference in clinical outcomes throughout 5 years between patients with DM treated with ultrathin-strut BP-SES or thin-strut DP-EES. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01443104.

Project description:BackgroundWhile thinner struts are associated with improved clinical outcomes in bare-metal stents (BMS), reducing strut thickness may affect drug delivery from drug-eluting stents (DES) and there are limited data comparing otherwise similar thin and thick strut DES. We assessed 2-year outcomes of patients treated with a thin strut (84-88um) cobalt-chromium, biodegradable polymer, Biolimus A9-eluting stent (CoCr-BP-BES) and compared these to patients treated with a stainless steel, biodegradable polymer, Biolimus A9-eluting stent (SS-BP-BES).MethodsIn total, 1257 patients were studied: 400 patients from 12 centres receiving ≥1 CoCr-BP-BES in the prospective Biomatrix Alpha registry underwent prespecified comparison with 857 patients who received ≥1 Biomatrix Flex SS-BP-BES in the LEADERS study (historical control). The primary outcome was major adverse cardiac events (MACE)-cardiac death, myocardial infarction (MI), or clinically driven target vessel revascularization (cd-TVR). Propensity analysis was used to adjust for differences in baseline variables and a landmark analysis at day-3 to account for differences in periprocedural MI definitions.ResultsMACE at 2 years occurred in 6.65% CoCr-BP-BES versus 13.23% SS-BP-BES groups (unadjusted HR 0.48 [0.31-0.73]; P=0.0005). Following propensity analysis, 2-year adjusted MACE rates were 7.4% versus 13.3% (HR 0.53 [0.35-0.79]; P=0.004). Definite or probable stent thrombosis, adjudicated using identical criteria in both studies, occurred less frequently with CoCr-BP-BES (1.12% vs. 3.22%; adjusted HR 0.32 [0.11-0.9]; P=0.034). In day-3 landmark analysis, the difference in 2-year MACE was no longer significant but there was a lower patient-orientated composite endpoint (11.7% vs. 18.4%; HR 0.6 [0.43-0.83]; P=0.006) and a trend to lower target vessel failure (5.8% vs. 9.1%; HR 0.63 [0.4-1.00]; P=0.078).ConclusionAt 2-year follow-up, propensity-adjusted analysis showed the thin strut (84-88um) Biomatrix Alpha CoCr-BP-BES was associated with improved clinical outcomes compared with the thicker strut (114-120um) Biomatrix Flex SS-BP-BES.

Dataset Information

Influence of Polymer Composition on the Controlled Release of Docetaxel: A Comparison of Non-Degradable Polymer Films for Oesophageal Drug-Eluting Stents.

Publications

Influence of Polymer Composition on the Controlled Release of Docetaxel: A Comparison of Non-Degradable Polymer Films for Oesophageal Drug-Eluting Stents.

Similar Datasets

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