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新型脂质体平台共递送治疗药物和生物活性气体用于增强急性动脉损伤治疗

Co-Delivery of Therapeutics and Bioactive Gas Using a Novel Liposomal Platform for Enhanced Treatment of Acute Arterial Injury.

机构信息

Division of Cardiology, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Department of Biomechatronic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

出版信息

Biomolecules. 2023 May 19;13(5):861. doi: 10.3390/biom13050861.

DOI:10.3390/biom13050861
PMID:37238730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10216188/
Abstract

Atherosclerosis is a complex, multi-stage disease characterized by pathological changes across the vascular wall. Endothelial dysfunction, inflammation, hypoxia, and vascular smooth muscle cell proliferation contribute to its progression. An effective strategy capable of delivering pleiotropic treatment to the vascular wall is essential to limit neointimal formation. Echogenic liposomes (ELIP), which can encapsulate bioactive gases and therapeutic agents, have the potential to deliver enhanced penetration and treatment efficacy for atherosclerosis. In this study, liposomes loaded with nitric oxide (NO) and rosiglitazone, a peroxisome proliferator-activated receptor agonist, were prepared using hydration, sonication, freeze-thawing, and pressurization. The efficacy of this delivery system was evaluated in a rabbit model of acute arterial injury induced by balloon injury to the common carotid artery. Intra-arterial administration of rosiglitazone/NO co-encapsulated liposomes (R/NO-ELIP) immediately following injury resulted in reduced intimal thickening after 14 days. The anti-inflammatory and anti-proliferative effects of the co-delivery system were investigated. These liposomes were echogenic, enabling ultrasound imaging to assess their distribution and delivery. R/NO-ELIP delivery exhibited a greater attenuation (88 ± 15%) of intimal proliferation when compared to NO-ELIP (75 ± 13%) or R-ELIP (51 ± 6%) delivery alone. The study demonstrates the potential of echogenic liposomes as a promising platform for ultrasound imaging and therapeutic delivery.

摘要

动脉粥样硬化是一种复杂的、多阶段的疾病,其特征是血管壁发生病理变化。内皮功能障碍、炎症、缺氧和血管平滑肌细胞增殖共同促进其进展。一种能够对血管壁进行多效治疗的有效策略对于限制新生内膜形成至关重要。声振脂(ELIP)能够包裹生物活性气体和治疗剂,具有增强对动脉粥样硬化的穿透和治疗效果的潜力。在这项研究中,使用水合、超声处理、冻融和加压的方法制备了负载一氧化氮(NO)和罗格列酮(一种过氧化物酶体增殖物激活受体激动剂)的脂质体。通过球囊损伤颈总动脉诱导的兔急性动脉损伤模型评估了这种递药系统的疗效。在损伤后立即经动脉内给予罗格列酮/NO 共包封脂质体(R/NO-ELIP),可使 14 天后内膜增厚减少。研究了共递药系统的抗炎和抗增殖作用。这些脂质体具有声振性,可通过超声成像来评估其分布和递送。与单独给予 NO-ELIP(75±13%)或 R-ELIP(51±6%)相比,R/NO-ELIP 给药对内膜增殖的衰减率更高(88±15%)。该研究表明,声振脂质体作为超声成像和治疗性递药的有前途的平台具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/56736606e7fb/biomolecules-13-00861-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/a04be857c722/biomolecules-13-00861-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/3a53a0383d01/biomolecules-13-00861-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/b796a7002338/biomolecules-13-00861-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/025ff0c5d5d3/biomolecules-13-00861-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/f2f816f195a9/biomolecules-13-00861-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/56736606e7fb/biomolecules-13-00861-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/a04be857c722/biomolecules-13-00861-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/3a53a0383d01/biomolecules-13-00861-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/b796a7002338/biomolecules-13-00861-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/025ff0c5d5d3/biomolecules-13-00861-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/f2f816f195a9/biomolecules-13-00861-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac8/10216188/56736606e7fb/biomolecules-13-00861-g006.jpg

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