“…As shown in Figure 1 , paclitaxel significantly reduced the migration of FBS-stimulated ( Figures 1 A and 1B) and PDGF-stimulated ( Figures 1 C and 1D) SMCs at doses ≥100 nM. In addition, consistent with our previous report, 17 RNA aptamer Apt 14 significantly inhibited PDGF-mediated SMC migration, similar to the effectiveness of 100 nM paclitaxel ( Figures 1 C and 1E) (wound confluence at 22 h: Apt 14-PDGF, 12.68% ± 1.18%; PDGF-paclitaxel, 15.30% ± 0.79%). Figure 1 Effects of paclitaxel (PTX) and RNA aptamer Apt 14 on porcine aortic smooth muscle cell (SMC) migration Cells were cultured to confluence followed by two days of serum starvation, subjected to scratch wound injury, and treated with fetal bovine serum (FBS; 5%) (A) or platelet-derived growth factor-BB (PDGF; 5 ng/mL) (C) following PTX (1–1,000 nM) or with Apt 14 (200 nM) following PDGF (5 ng/mL) (E).…”
Section: Resultssupporting
confidence: 90%
“…We previously showed that the perfusion catheter can effectively deliver Apt 14 to the vessel wall 18 and that Apt 14 attenuates neointimal formation in swine femoral arteries. 17 The DCB- and Apt 14-treated arteries were harvested at 14 and 28 days after treatment, with no evidence of thrombosis or dissection at the target site. En face scanning electron microscopy at 14 days demonstrated a confluent endothelium with an elongated EC morphology in the control saline- and Apt 14-treated arteries.…”
Section: Resultsmentioning
confidence: 99%
“… 16 Furthermore, we showed that Apt 14 delivered intraluminally inhibited neointimal growth in a clinically relevant swine iliofemoral injury model. 17 In this study, we extended these findings to test the ability of Apt 14 to facilitate vascular healing in a clinically relevant swine model of PAD.…”
Section: Introductionmentioning
confidence: 83%
“… 18 In addition, we demonstrated that Apt 14 inhibited vascular remodeling and neointimal growth in a swine iliofemoral injury model. 17 …”
“…As shown in Figure 1 , paclitaxel significantly reduced the migration of FBS-stimulated ( Figures 1 A and 1B) and PDGF-stimulated ( Figures 1 C and 1D) SMCs at doses ≥100 nM. In addition, consistent with our previous report, 17 RNA aptamer Apt 14 significantly inhibited PDGF-mediated SMC migration, similar to the effectiveness of 100 nM paclitaxel ( Figures 1 C and 1E) (wound confluence at 22 h: Apt 14-PDGF, 12.68% ± 1.18%; PDGF-paclitaxel, 15.30% ± 0.79%). Figure 1 Effects of paclitaxel (PTX) and RNA aptamer Apt 14 on porcine aortic smooth muscle cell (SMC) migration Cells were cultured to confluence followed by two days of serum starvation, subjected to scratch wound injury, and treated with fetal bovine serum (FBS; 5%) (A) or platelet-derived growth factor-BB (PDGF; 5 ng/mL) (C) following PTX (1–1,000 nM) or with Apt 14 (200 nM) following PDGF (5 ng/mL) (E).…”
Section: Resultssupporting
confidence: 90%
“…We previously showed that the perfusion catheter can effectively deliver Apt 14 to the vessel wall 18 and that Apt 14 attenuates neointimal formation in swine femoral arteries. 17 The DCB- and Apt 14-treated arteries were harvested at 14 and 28 days after treatment, with no evidence of thrombosis or dissection at the target site. En face scanning electron microscopy at 14 days demonstrated a confluent endothelium with an elongated EC morphology in the control saline- and Apt 14-treated arteries.…”
Section: Resultsmentioning
confidence: 99%
“… 16 Furthermore, we showed that Apt 14 delivered intraluminally inhibited neointimal growth in a clinically relevant swine iliofemoral injury model. 17 In this study, we extended these findings to test the ability of Apt 14 to facilitate vascular healing in a clinically relevant swine model of PAD.…”
Section: Introductionmentioning
confidence: 83%
“… 18 In addition, we demonstrated that Apt 14 inhibited vascular remodeling and neointimal growth in a swine iliofemoral injury model. 17 …”
“…Lastly, LDD devices can be used to test alternative therapeutic agents. The OPC has been used in preclinical trials to investigate the treatment efficacy of a vascular smooth muscle cell-targeting molecule, revealing successful reduction of neointimal growth in benchtop and porcine models ( 22 , 23 ). However, there are disadvantage of LDD.…”
IntroductionSirolimus is currently being explored as an alternative drug to paclitaxel for the treatment of peripheral artery disease (PAD). To date, sirolimus has only been used as drug coatings for stents and balloons and no studies have yet demonstrated the delivery of sirolimus in liquid form. The purpose of this pilot study was to investigate the feasibility of the delivery of liquid sirolimus into arterial segments in a benchtop peripheral artery bioreactor.MethodsThe feasibility to deliver liquid therapy was first tested on four drug delivery devices using a fluorescently tagged liquid drug and an ex vivo porcine artery benchtop model. The four devices included the Bullfrog micro-infusion device, ClearWay RX catheter, Occlusion perfusion catheter (OPC), and the targeted adjustable pharmaceutical administration system (TAPAS). Penetration of the fluorescently tagged drug was measured via microscopic imaging and quantification of the depth of drug penetration into all device-treated tissue. Based on the penetration outcome, we then selected a single device to deliver liquid sirolimus into the ex vivo porcine artery model undergoing physiological flow and pressure conditions. The liquid sirolimus-treated arteries were collected from the ex vivo bioreactor at 1- and 24-hour post-delivery and arterial drug retention analyzed by liquid chromatography-tandem mass spectrometry.ResultsFluorescent microscopy demonstrated that drug delivery with the OPC had greater drug penetration into the medial wall as compared to other devices (OPC: 234 ± 161 µm; TAPAS: 127 ± 68 µm; ClearWay: 118 ± 77 µm; Bullfrog: 2.12 ± 3.78 µm; p = 0.098). The results of the ex vivo flow-circuit bench top model showed that the OPC device successfully delivered the liquid sirolimus at 1-hour (5.17 ± 4.48 ng/mg) and 24-hour (0.78 ± 0.55 ng/mg).ConclusionsThese results demonstrate for the first time the ability to deliver liquid sirolimus directly to the medial layer of an artery via a liquid delivery catheter.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
