Hao Cui, Yanchi Liu, Ying Yu, Dong Lv, Sha Ma, Mingju Gao, Ye Yang, Cheng Yuan, Yuan Liu, Chengxiao Wang
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引用次数: 0
摘要
本研究旨在开发脑靶向协同给药脂质体,用于同时给药三七皂苷(PNS)和乙酰水杨酸(ASA),以治疗缺血性中风。在这一系统中,三七皂苷作为胆固醇替代物融入脂质体的磷脂双分子层,而ASA则被包裹在脂质体内部。我们合成了一种聚 2-甲基丙烯酰氧乙基磷酰胆碱(PMPC)聚合物,并将其融入脂质体表面。这种配方显示出更强的 PNS 负荷能力,并促进了关键皂苷成分的同步递送。经 PMPC 改性后,脂质体的循环时间延长,并通过乙酰胆碱受体介导的途径改善了通过血脑屏障(BBB)的转运。此外,在大鼠脑缺血再灌注损伤模型中,联合给药系统通过磷酸肌酸 3- 激酶/蛋白激酶 C 途径提高了疗效。其他分析表明,该药物对神经递质、氨基酸、叶酸和其他各种途径的代谢均有明显影响,显示出多方面的治疗效果。总之,本研究提出了一种创新的研究策略,用于在传统中药配方中全面传递各种成分,突出了传统中药与化学制剂相结合的协同治疗潜力。
Panax notoginseng saponins and acetylsalicylic acid co-delivered liposomes for targeted treatment of ischemic stroke.
In this study, we aimed to develop brain-targeted co-delivery liposomes for the concurrent delivery of Panax notoginseng saponins (PNS) and acetylsalicylic acid (ASA) for the treatment of ischemic stroke. Within this system, PNS served as a cholesterol substitute, integrating into the phospholipid bilayer of the liposomes, while ASA was encapsulated internally. A poly-2-methacryloyloxyethyl phosphorylcholine (PMPC) polymer was synthesized and incorporated into the liposome surface. This formulation demonstrated an enhanced PNS-loading capacity and facilitated the synchronized delivery of key saponin components. Following PMPC modification, the liposomes exhibited prolonged circulation and improved transport across the blood-brain barrier (BBB) through acetylcholine receptor-mediated pathways. Furthermore, the co-delivery system exhibited enhanced therapeutic efficacy in a rat model of cerebral ischemia-reperfusion injury via the phosphoinositide 3-kinase/protein kinase C pathway. Additional analyses revealed significant effects on the metabolism of neurotransmitters, amino acids, folate, and various other pathways, indicating a multi-faceted therapeutic effect. Overall, this study presents an innovative research strategy for the comprehensive delivery of diverse components in traditional Chinese medicine formulations, highlighting the potential for synergistic treatments that combine traditional Chinese medicine with chemical agents.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.