Pressure-responsive pH-triggered layer-by-layer coating of paclitaxel-eluting balloon catheters for instant high-dose drug delivery for percutaneous coronary artery intervention  

作　　者：Jeong Yu Lee Shonit Nair Sharma Sung-Yu Hong Young-Guk Ko Yangsoo Jang Minjae Do Michael Christopher Stark Qiwen Peng Benjamin Allen Mossburg Bo Chan Seo Yuhan Lee 

机构地区：[1]Department of Materials Science and Engineering,Korea Advanced Institute of Science and Technology,Daejeon 305-701,Republic of Korea [2]Department of Anesthesiology,Perioperative,and Pain Medicine,Center for Accelerated Medical Innovation&Center for Nanomedicine,Brigham and Women’s Hospital,Harvard Medical School,Boston,MA 02115,USA [3]Department of Biological Engineering,Massachusetts Institute of Technology,Cambridge,MA 02139,USA [4]Cardiovascular Product Evaluation Center,Yonsei University College of Medicine,Seoul 120-752,Republic of Korea [5]Division of Cardiology,Department of Internal Medicine,Severance Cardiovascular Hospital,Yonsei University College of Medicine,Seoul 120-752,Republic of Korea

出　　处：《Nano Research》2024年第10期9141-9151,共11页纳米研究（英文版）

基　　金：supported by a grant from the Korea Health Technology R&D Project,Ministry of Health&Welfare(No.A111552),Republic of Korea.

摘　　要：Cardiovascular diseases remain the leading cause of mortality worldwide,with percutaneous coronary interventions(PCI)using drug-eluting stents(DES)as the standard treatment for coronary artery disease.Despite advancements in DES technology,challenges such as restenosis and stent thrombosis still necessitate further interventions and carry considerable risks,highlighting an urgent need for a novel therapeutic approach with lower restenosis rates and reduced reintervention risks.Drugeluting balloons(DEBs)coated with anti-proliferative agents offer a novel method of local drug delivery for reducing restenosis by directly administering drugs to the lesion site.However,efficient delivery of drugs within the brief procedural window while minimizing drug loss during maneuvering to the target site remains a challenge.Herein,we developed a pressure-responsive and pH-triggered,paclitaxel(PTX)coated DEB catheter for rapid and high-dose delivery of paclitaxel to the lesion sites,overcoming the limitations of drug dispersion and inefficiencies associated with conventional DEBs.Using the charge reversion of albumin around its isoelectric point,paclitaxel-loaded human serum albumin nanoparticles(PTX-HSA-NPs)and heparin were coated using a layer-by-layer deposition method at pH 4.0.Upon exposure to physiological pH(i.e.,7.4),the coating is rapidly released from the balloon surface.Combined with a protective shellac coating,the DEB achieved controlled release of high-dose paclitaxel to the arterial tissue in vivo(up to 400μg per gram tissue),exceeding current DEBs in the clinic.These results suggest the pH-responsive,multi-layer coated DEB’s potential for superior procedural outcomes,addressing a critical unmet need in PCI.

关 键 词：drug-eluting balloon layer-by-layer coating coronary artery disease PACLITAXEL 

分 类 号：R541.4[医药卫生—心血管疾病]