竹节参皂苷Ⅳa纳米体系对脑梗死的靶向治疗

Nanoparticles of Chikusetsu Saponin Ⅳa for Targeting Therapy of Cerebral Infarction

目的:制备和评价以乳铁蛋白修饰的,荷载竹节参皂苷Ⅳa的脂质-聚合物杂化纳米体系(CⅣa/Lf-LPNs),用于脑梗死的靶向治疗。方法:采用纳米沉淀法制备了CⅣa/Lf-LPNs、荷载竹节参皂苷Ⅳa的脂质-聚合物杂化纳米体系(CⅣa/LPNs)、乳铁蛋白修饰的空载脂质-聚合物杂化纳米体系(Lf-LPNs),比较了它们的理化性质、体外释药性质、大鼠血液和脑中药物浓度变化及其对脑梗死模型大鼠的存活率和生化指标的影响。结果:乳铁蛋白修饰为纳米制剂带来正电荷,并附着在纳米体系表面,增大了纳米粒子的直径。三种纳米制剂的包封率均为90%左右。CⅣa/Lf-LPNs具有更持久的药物释放行为。CⅣa/Lf-LPNs组和CⅣa/LPNs组的血药浓度曲线是相似的,但二者脑部药物浓度曲线不同,CⅣa/Lf-LPNs组几乎每个时间点的脑部药物浓度均高于CⅣa/LPNs组(P<0.05)。此外,CⅣa/Lf-LPNs组提高了脑梗死模型大鼠的存活率,大鼠血清LDH含量最低,对脑梗死的改善作用显著优于CⅣa/LPNs和CⅣa溶液组(P<0.05)。结论:本文制备的CⅣa/Lf-LPNs可有效传递药物到达脑部,并持续的发挥改善脑梗死作用,是一种极具潜力的脑靶向治疗体系。

Objective: Lactoferrin-modified lipid-polymer hybrid nanoparticles as a carrier for brain delivery of Chikusetsu saponin Ⅳa(CⅣa/Lf-LPNs)was prepared and evaluated for nano-targeted therapy for cerebral infarction. Methods: CⅣa/Lf-LPNs,lipid-polymer hybrid nanoparticles loaded with CⅣa(CⅣa/LPNs)and lipid-polymer hybrid nanoparticles modified by coating with lactoferrin(Lf-LPNs)were prepared by nano-precipitation method. The physical-chemical characteristics and drug release properties were examined in vitro. The changes of drug concentrations in the blood and brain of cerebral infarction model rats were compared.The survival rates and biochemical indexes in blood were also evaluated. Results: Lactoferrin modification was positively charged in the nanoformulation and attached to the surface of nanoparticle, increasing the diameter of the nanoparticles. The encapsulation efficiencies of three nano-formulations were all about 90%. CⅣa/Lf-LPNs performed a longer lasting drug release behavior. The drug concentration curves of CⅣa/Lf-LPNs group and CⅣa/LPNs group were similar in plasma, but different in brain. The brain drug concentrations in CⅣa/Lf-LPNs group were higher than those in CⅣa/LPNs group at almost every time point(P< 0.05). In addition, CⅣa/Lf-LPNs increased the survival rate and decreased LDH content of cerebral infarction model rats. The improvement effect of CⅣa/Lf-LPNs on cerebral infarction was significantly better than that of CⅣa/LPNs and CⅣa solution groups(P < 0.05). Conclusion: CⅣa/Lf-LPNs effectively delivered drugs to the brain, and played an efficient role in improving cerebral infarction. It might be a promising brain-targeted therapeutic system.