Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes.
Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes.
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DOI：
10.2147/ijn.s410653
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发表时间：
2023
影响因子：
8
通讯作者：
中科院分区：
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淋巴管功能的激活是解决动脉粥样硬化（AS）这一慢性炎症性疾病的关键。雷帕霉素（Rapamycin，RAPA）作为一种有效的抗动脉粥样硬化药物，近年来受到广泛关注.这项工作的目的是开发一种配体修饰的RAPA负载脂质体，用于靶向递送药物，以改善异常的淋巴结构和功能，从而高效地消退动脉粥样硬化斑块。采用乳化-溶剂挥发法制备透明质酸修饰的RAPA脂质体。对微球的平均粒径、Zeta电位、包封率进行表征，并考察其稳定性和体外释药性能。此外，在淋巴内皮细胞和LDLR−/−小鼠上评估了体外和体内淋巴靶向能力，并证实了该纳米系统在诱导动脉粥样硬化斑块衰减方面的效率。HA-RL粒径约为100 nm，包封率超过90%，贮存稳定性好，从脂质纳米载体中缓慢释放。HA-RL的平均保留时间（MRT）和消除半衰期（t1/2β）分别为100.27±73.08 h和70.74±50.80 h。HA-RL获得了最突出的动脉粥样硬化靶向递送和动脉粥样硬化斑块衰减的功效，这意味着这种新型药物递送系统在体内的成功实施。HA-RL显示出最明显的淋巴靶向能力和最佳的动脉粥样硬化斑块衰减效率，为动脉粥样硬化的治疗开辟了新的范例和有希望的前景。
The activation of lymphatic vessel function is the crux to resolving atherosclerosis (AS), a chronic inflammatory disease. Rapamycin (RAPA) recently has attracted considerable attention as a potent drug to induce atherosclerotic plaque attenuation. The objective of this work was to develop a ligand-decorated, RAPA-loaded liposome for lymphatic-targeted delivery of drugs to improve abnormal lymphatic structure and function, resulting in highly effective regression of atherosclerotic plaques. Hyaluronic acid-decorated, RAPA-loaded liposomes (HA-RL) were fabricated by emulsion-solvent evaporation. The average size, zeta potential, entrapment efficiency were characterized, and the stability and drug release in vitro were investigated. Furthermore, the in vitro and in vivo lymphatic targeting ability were evaluated on lymphatic endothelial cells and LDLR−/− mice, and the efficiency of this nano-system in inducing the attenuation of atherosclerotic plaques was confirmed. HA-RL had a size of 100 nm, over 90% drug encapsulation efficiency, the storage stability was distinguished, demonstrating a slow release from the lipid nano-carriers. The mean retention time (MRT) and elimination half-life (t1/2β) achieved from HA-RL were 100.27±73.08 h and 70.74±50.80 h, respectively. HA-RL acquired the most prominent efficacy of lymphatic-targeted delivery and atherosclerotic plaques attenuation, implying the successful implementation of this novel drug delivery system in vivo. HA-RL exhibited the most appreciable lymphatic targeting ability and best atherosclerotic plaques attenuation efficiency, opening a new paradigm and promising perspective for the treatment of arteriosclerosis.