内吗啡肽-1类似物HDAPC聚氰基丙烯酸正丁酯纳米粒的镇痛活性

Analgesic activity of polybutylcyanoacrylate nanoparticles of HDAPC,an analog of Endomorphin-1

采用界面聚合法制备聚氰基丙烯酸正丁酯纳米粒,吸附药物内吗啡肽-1类似物HDAPC后孵育包衣聚山梨酯80。采用透射电镜观测纳米粒粒径为(150.00±9.75)nm,高效液相色谱法测定包封率为(87.64±3.02)%。静脉注射后小鼠甩尾镇痛法检测镇痛效果,包衣聚山梨酯80的HDAPC-NP-P80比HDAPC及未包衣聚山梨酯80的HDAPC-NP镇痛效果更有效,最大镇痛时间延后在12.5min,最大可能效应百分数达100,剂量减半在同样时间点最大可能效应百分数也能达到76.64。结果提示纳米粒是一种有效的将肽类药物传递进入大脑的载体,空白纳米粒吸附药物后,必须包衣聚山梨酯80才有镇痛增强的效果。

HDAPC （Tyr-D-Ala-Trp-p-Cl-Phe-OH） nanopaticles were prepared by interfacial polymerization method. The peptide was adsorbed onto the surface of PBCA nanoparticles and coated with polysorbate 80. The transmission electron microscope showed that the particle size of nanoparticles was （150.00±9.75） nm, and the HPLC method measured that the entrapment efficiency was （87.64±3.02）%. After intravenous injection of this formulation to mice, the central analgesia was measured by tai flick test, which showed that HDAPC-NP coated with P80 displayed more effective analgesic effect than HDAPC, or uncoated HDAPC-NP. HDAPC-NP-P80 had a maximum analgesic effect of 100（%MPE） at 12.5 min, and the analgesic effect was 76.64（%MPE） at half of the dose at the same time. The results suggest that nanoparticle is an effective drug vector to carry peptide into brain. The drug was adsorbed onto the surface of nanoparticles, and then the coated with P80 is necessarily.