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目的：采用乳铁蛋白修饰的PEG-PLA纳米粒为递药工具包载α-M，探讨其对快速老化SAMP8小鼠AD相关脑内病理特征的改善作用。方法：用乳化/溶剂蒸发法制备载α-M的PEG-PLA纳米粒NP(α-M)，将巯基化的乳铁蛋白连接于纳米粒表面，得到Lf-NP(α-M)。7月龄SAMP8系小鼠尾静脉给予注射生理盐水、Lf-NP(α-M)或空白纳米粒溶液，每日一次，连续两周。正常老化小鼠SAMR为模型对照组，通过对脑组织进行免疫组化分析，观察Lf-NP(α-M)对SAMP8小鼠脑内炎症、Aβ茁沉积等AD特征性病理变化的影响。结果：0.5、2mg/kg α-M对SAMP8小鼠脑内小胶质细胞激活、星形胶质细胞增生以及Aβ茁沉积均无显著影响；0.5 mg/kg Lf-NP(α-M)可抑制小胶质细胞的激活(P<0.001)，2 mg/mL Lf-NP(α-M)显著抑制星形胶质细胞增生以及Aβ茁沉积(P<0.05)。结论：乳铁蛋白修饰的包载α-M的可降解纳米粒脑靶向递药系统成功有效，显著提高α-M的成药性并改善AD模型小鼠脑内特征性病理改变。
OBJECTIVE: To investigate the effects of PEG-PLA nanoparticles loaded with lactoferrin on drug-loaded brain pathology in AD rats. Methods: PEG-PLA nanoparticles loaded α-M NPs (α-M) were prepared by emulsification / solvent evaporation method. Lf-NP (α-M) was obtained by attaching thiolated lactoferrin to the surface of nanoparticles. Seven-month-old SAMP8 mice were injected intravenously with normal saline, Lf-NP (α-M) or blank nanoparticle solution once a day for two weeks. Normal aging mouse SAMR model control group, through the immunohistochemical analysis of brain tissue to observe Lf-NP (α-M) on SAMP8 mouse brain inflammation, Aβ Zhuo deposition and other AD characteristic pathological changes. Results: 0.5, 2 mg / kg α-M had no significant effect on microglia activation, astrocyte proliferation and Aβ growth in SAMP8 mice; 0.5 mg / kg Lf-NP Inhibition of microglial activation (P <0.001), 2 mg / mL Lf-NP (α-M) significantly inhibited astrocyte proliferation and Aβ growth (P <0.05). CONCLUSION: Lactoferrin modified α-M-loaded biodegradable nanoparticle-targeted delivery system successfully and effectively increases the drug-induced α-M and ameliorates the characteristic pathological changes in the brain of AD model mice.