Co-Delivery of Therapeutics and Bioactive Gas Using a Novel Liposomal Platform for Enhanced Treatment of Acute Arterial Injury.
Co-Delivery of Therapeutics and Bioactive Gas Using a Novel Liposomal Platform for Enhanced Treatment of Acute Arterial Injury.
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DOI：
10.3390/biom13050861
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发表时间：
2023-05-19
期刊：
影响因子：
5.5
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中科院分区：
文献类型：
--
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动脉粥样硬化是一种复杂的、多阶段的疾病，其特征是整个血管壁的病理变化。内皮功能障碍、炎症、缺氧和血管平滑肌细胞增殖有助于其进展。能够向血管壁提供多效治疗的有效策略对于限制新内膜形成至关重要。回声脂质体（ELIP）可以封装生物活性气体和治疗剂，有可能增强动脉粥样硬化的渗透和治疗功效。在这项研究中，通过水合、超声处理、冻融和加压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。该输送系统的功效在由颈总动脉球囊损伤引起的急性动脉损伤兔模型中进行了评估。损伤后立即动脉内注射罗格列酮/NO 共封装脂质体 (R/NO-ELIP)，14 天后可减少内膜增厚。研究了共递送系统的抗炎和抗增殖作用。这些脂质体具有回声性，使得超声成像能够评估它们的分布和递送。与单独的 NO-ELIP (75 ± 13%) 或 R-ELIP (51 ± 6%) 递送相比，R/NO-ELIP 递送表现出更大的内膜增殖衰减 (88 ± 15%)。该研究证明了回声脂质体作为超声成像和治疗递送的有前途的平台的潜力。
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.
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