摘要
目的 构建一种丙泊酚-羟丁酸钠脑靶向麻醉双药纳米体系(lactoferrin-modified brain-targeted propofol-sodium hydroxybutyrate dual-anesthetics starch nanocomposite,Lf-SNPs),评估其脑靶向、麻醉增效的性能.方法 本研究选择天然淀粉作为纳米材料,乳铁蛋白作为脑靶向蛋白,采用反相乳液法制备脑靶向纳米体系,分别通过疏水作用力、静电作用力实现麻醉药丙泊酚、羟丁酸钠的联合负载及脑内靶向递送,测定其粒径、电位、体内分布;将20只C57BL/6小鼠随机分为对照组(同浓度混合药物)和Lf-SNPs组,每组各10只,通过尾静脉给药记录小鼠的镇静催眠持续时间,评估其麻醉药效性能.结果 Lf-SNPs粒径(330.6±22.6)nm,平均电位(-23.4±0.5)mV,静脉给药30s即可见脑内分布,3min时达峰值,可持续分布达30min,单次注药镇静催眠持续时间(38.7±5.9)min,较对照组明显延长(P＜0.05),可增强麻醉效果.结论 Lf-SNPs具有丙泊酚、羟丁酸钠联合负载能力,可实现脑内靶向递送,增强麻醉药效.
Abstract
Objective To construct a lactoferrin-modified brain-targeted propofol-sodium hydroxybutyrate dual-anesthetics starch nanocomposite(Lf-SNPs)and evaluate its brain targeting and optimized anesthetic property.Methods In this study,natural starch was selected as the nanomaterial,lactoferrin as the brain targeting protein,and Lf-SNPs was prepared by inverted phase emulsion method.The dual-loading and brain-targeted delivery of propofol and sodium hydroxybutyrate were achieved by hydrophobic and electrostatic forces,respectively.Lf-SNPs'particle size,potential,distribution in vivo were measured.Twenty C57BL/6 mice were randomly divided into two groups:Control group(same concentration of mixed anesthetics)and Lf-SNPs group,with 10 mice in each group.The duration of anesthetic efficacy was recorded after caudal vein administration.Results The Lf-SNPs had a particle size of(330.6±22.6)nm and average potential of(-23.4±0.5)mV,respectively.The distribution of Lf-SNPs in the brain was visible 30s after intravenous administration,the reaching peak at 3 min,and sustainable distributing for 30 min.The duration of anesthetic efficacy of single bolus infusion was(38.7±5.9)min,which was significantly longer than that of the same concentration of control group(P＜0.05).Conclusion Lf-SNPs has the dual-loading capacity of propofol and sodium hydroxybutyrate,which can realize the targeted delivery in brain and enhance the anesthetic effect.
维普
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