Ultrasound controlled paclitaxel releasing system—A novel method for improving the availability of coronary artery drug coated balloon

Abstract

Objectives: The aim of this study is to improve local-drug delivery efficiency and tissue absorption using the ultrasound (US)-responsible drug coating based on a newly developed US-controlled paclitaxel release balloon. Background: Low availability of the drug coating remains a major concern of the current drug coated balloon (DCB). The goal of this study is to develop a method to use an US-responsible paclitaxel-loaded microcapsules (PM) as the main content of balloon drug coating to enhance bioavailability of DCB. Methods: An US-controlled paclitaxel release balloon is designed and fabricated based on the US-responsible paclitaxel-loaded poly (lactic-co-glycolic acid) (PLGA) microcapsules. Rapid exchange percutaneous transluminal coronary angioplasty (PTCA) balloon catheters were coated with the PM. The deployment processes of the paclitaxel-loaded microcapsules coated balloons (PMCB) under US, PMCB without US and a homogenous matrix of paclitaxel and iopromide coated balloon (PICB) were then placed in healthy and stent implanted porcine coronary arteries. Results: In vitro release assay demonstrated an ability of US (1 MHz, 1.22 W/cm 2 , 1 minute) to affect the release kinetics of paclitaxel from PM by inducing a 76 ± 5.4% increase in the rate of release. The paclitaxel content in target vessels are 203 ± 37 μg/g for PMCB under US, 85 ± 23 μg/g for PMCB without US, and 107 ± 31 μg/g for PICB 1-hr post-surgery. The availability of the drug for the PMCB reaches 27% under US. Conclusions: The US-controlled paclitaxel release balloon significantly improved the drug content of the target vessels in the porcine model. K E Y W O R D S controlled drug release, drug coated balloon, paclitaxel, pharmacokinetics, PLGA microcapsules, US 1 | INTRODUCTION In recent decades, the outcomes of coronary heart disease (CHD) have markedly improved, which can be partly attributed to the evolution of percutaneous coronary intervention (PCI). From percutaneous transluminal coronary angioplasty to bare-metal stent and then to drugeluting stent, every step of PCI is attractive to interventional cardiologist, great progress has been made for patients with CHD. Drug eluting stent (DES) implantation is the first choice of treatment in PCI. The dramatic ability of DES to inhibit neointimal hyperplasia through

Regulatory perspectives of combination products

“…Structural design and carrier material formulations could change the release rate of drugs [ 66 , 69 ,][70]] [] [66] , [69] , [70] []. For combination products that achieve functions by releasing drugs to the intended site (such as sustained release, controlled release or other release methods), such as drug-eluting stents, drug-containing balloon catheters, and silver-containing dressings, drug release studies are needed [ [71] , [72] , [73] , [74] , [75] , [76] , [77] ]. In vitro release study can be used to evaluate the stability of final products and coatings [ [77] , [78] , [79] , [80] ].…”

New Ultrasound-Controlled Paclitaxel Releasing Balloon vs. Asymmetric Drug-Eluting Stent in Primary ST-Segment Elevation Myocardial Infarction ― A Prospective Randomized Trial ―

“…With the acoustic energy (1-10 Hz ultrasound), microcapsules are pushed into the membrane, whose permeability has been changed, and encapsulated paclitaxel is released. 22 The DCBs are available in diameters from 2.0 to 4.0 mm and lengths from 15 to 35 mm. The schematic diagram of drug release by ultrasonic is shown in Figure 1.…”

“…Recently, an ultrasound-controlled paclitaxel releasing balloon (Vasoguard TM ; Rientech, China) was developed and it was found to effectively inhibit restenosis in the treatment of the porcine restenosis model. 22 The current study aimed to test the efficiency and safety of this new DCB vs. DES in the treatment of primary STEMI patients using a 9-month angiographic and a 12-month clinical follow up.…”

“…It has been reported that diagnostic ultrasound can significantly stimulate the rupture of microcapsules to release paclitaxel at a fixed position, thereby achieving the targeted release of paclitaxel. 22 The availability of the drug reaches 27% under ultrasound. The unruptured microcapsules will release paclitaxel through up was 0.24±0.39 mm in the DCB group and 0.31±0.38 mm in the DES group (P>0.05).…”

A novel ultrasound controlled paclitaxel releasing balloon catheter versus plain balloon catheter in the treatment of small coronary vessel stenosis: study protocol of a randomized controlled clinical trial (Vasoguard I Trial)

“…In our previous study, the novel balloon catheter improved the drug content in the target vessel and reduced the drug concentration in the plasma, thus increased the bioavailability of the balloon. It effectively inhibited restenosis after stent implantation in the porcine model [20].…”