A Multilayer Functionalized Drug-Eluting Balloon for Treatment of Coronary Artery Disease

Abstract

Drug-eluting balloons (DEBs) have been mostly exploited as an interventional remedy for treating atherosclerosis instead of cardiovascular stents. However, the therapeutic efficacy of DEB is limited due to their low drug delivery capability to the disease site. The aim of our study was to load drugs onto a balloon catheter with preventing drug loss during transition time and maximizing drug transfer from the surface of DEBs to the cardiovascular wall. For this, a multilayer-coated balloon catheter, composed of PVP/Drug-loaded liposome/PVP, was suggested. The hydrophilic property of 1st layer, PVP, helps to separate drug layer in hydrophilic blood vessel, and the 2nd layer with Everolimus (EVL)-loaded liposome facilitates drug encapsulation and sustained release to the targeted lesions during inflation time. Additionally, a 3rd layer with PVP can protect the inner layer during transition time for preventing drug loss. The deionized water containing 20% ethanol was utilized to hydrate EVL-loaded liposome for efficient coating processes. The coating materials showed negligible toxicity in the cells and did not induce pro-inflammatory cytokine in human coronary artery smooth muscle cells (HCASMCs), even in case of inflammation induction through LPS. The results of hemocompatibility for coating materials exhibited that protein adsorption and platelet adhesion somewhat decreased with multilayer-coated materials as compared to bare Nylon tubes. The ex vivo experiments to confirm the feasibility of further applications of multilayer-coated strategy as a DEB system demonstrated efficient drug transfer of approximately 65% in the presence of the 1st layer, to the tissue in 60 s after treatment. Taken together, a functional DEB platform with such a multilayer coating approach would be widely utilized for percutaneous coronary intervention (PCI).

Reduced restenosis and enhanced re-endothelialization of functional biodegradable vascular scaffolds by everolimus and magnesium hydroxide

“…EVL from the BVS/EVL and BVS/EVL/mMH was burst-released during the initial 3 days, releasing 29.7% and 30.0%, respectively. Subsequently, 72.96% and 83.53% of EVL were released for 28 days, respectively [ 29 , 30 ].

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“…Even after degradation for 7 days, 77.27% of MH remained in BVS/EVL/mMH, which may maintain the neutralizing effect until the BVS is completely degraded. EVL release, measured in PBS solution at 37 °C in an environment similar to the human body can inhibit HCASMC viability for one month after which reduced release is not expected to interfere with re-endothelialization [ 30 ].…”

Endogenous stimulus-responsive nitric oxide releasing bioactive liposome for a multilayered drug-eluting balloon

“…To demonstrate the feasibility of future applications for the multilayer coating system, the drug transfer on the tissue from the multilayer-coated balloon system was simulated ex vivo using a UTM system customized from our lab. 14 On the oppo-…”

“…13 To minimize the major drawbacks of DEBs, including drug loss during insertion to lesions and the low drug delivery rate to the tissue due to vigorous blood flow and short balloon inflation times (within 1 min), we previously suggested a multilayer-coated DEB system composed of a hydrophilic polymer, drug-encapsulated liposome, and hydrophilic polymer, serially. 14 In brief, a biocompatible and biodegradable hydrophilic polymer, polyvinylpyrrolidone (PVP), was coated on the 1st and 3rd layers of the balloon catheter to facilitate drug release to the lesion in hydrophilic environments and inhibit drug loss during the transition time, respectively. Moreover, a `hydrophobic drug (EVL)-encapsulated biocompatible liposome was introduced to the 2nd layer of the balloon catheter to deliver the drug efficiently to the target region.…”

Comparison of Surface Functionalization of PLGA Composite to Immobilize Extracellular Vesicles

“…As a potential alternative for regenerative medicine, EVs have the theoretical advantage of being a safer regenerative tool when compared to cell-based therapies. Recently, surface modification with nanovesicles such as EVs and liposomes is reported to improve the property of implantable medical devices [21][22][23][24][25]. However, one of the major challenges of the application of EVs in medical devices is that free EVs do not allow durable retention at damaged sites, because it is hard to modulate burst release within several hours post-implantation and achieve release in a sustained manner.…”