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研究单甲氧基聚乙二醇聚乳酸羟基乙酸共聚物纳米粒(mPEG-PLGA-NPs)的粒径大小、mPEG相对分子质量及覆盖密度,zeta电位对其在大鼠鼻黏膜转运的影响。以mPEG-PLGA共聚物为载体材料,香豆素-6为荧光标记物,采用纳米沉淀法和乳化溶剂挥发法制备不同理化性质的mPEG-PLGA-NPs及壳聚糖包裹的PLGA-NPs,并测定其粒径大小、zeta电位、香豆素的荧光标记效率、体外泄漏率及在溶菌酶中的稳定性等。采用激光共聚焦显微镜技术研究纳米粒的理化性质对其在大鼠鼻黏膜转运的影响。纳米粒分散均匀,PLGA-NPs表面带负电荷,经mPEG修饰后zeta电位接近电中性,壳聚糖包裹后表面荷正电。香豆素的荧光标记效率均>80%。4 h内香豆素-6纳米粒的泄漏百分率<5%。纳米粒在溶菌酶中基本稳定。结果显示,zeta电位近中性的mPEG-PLGA-NPs在鼻黏膜的转运能力显著高于带正电荷的CS-PLGA-NPs及带负电荷的PLGA-NPs(P<0.05),并且随着mPEG相对分子质量和覆盖密度的增加及粒径的增大,其在鼻黏膜的转运能力增强。mPEG-PLGA-NPs在大鼠鼻黏膜的转运能力与其表面亲水性、zeta电位及粒径大小密切相关。
To investigate the effect of mPEG-PLGA-NPs on the nasal mucosal transport of mPEG-PLGA-NPs, the molecular weight of mPEG, the coverage density and the zeta potential of mPEG-PLGA-NPs. MPEG-PLGA-NPs with different physico-chemical properties and PLGA-NPs encapsulated with chitosan were prepared by mPEG-PLGA copolymer and coumarin-6 as fluorescent labels by nanoprecipitation method and solvent evaporation method Determination of its size, zeta potential, coumarin fluorescent labeling efficiency, in vitro leakage rate and stability in lysozyme and so on. Laser confocal microscopy was used to study the effect of the physicochemical properties of nanoparticles on nasal mucosal transport in rats. The nanoparticles were uniformly dispersed, the surface of PLGA-NPs was negatively charged, and the zeta potential was nearly neutral after mPEG modification. The surface of chitosan coated with chitosan was positively charged. Coumarin fluorescent labeling efficiency> 80%. Coumarin-6 nanoparticle leakage was <5% within 4 h. Nanoparticles basically stable in lysozyme. The results showed that mPEG-PLGA-NPs with near-neutral zeta potential had a higher transport capacity in nasal mucosa than those with positively charged CS-PLGA-NPs and negatively charged PLGA-NPs (P <0.05) Relative molecular mass and coverage density increases and the particle size increases, the transport capacity of the nasal mucosa increased. The transport capacity of mPEG-PLGA-NPs in the nasal mucosa of rats is closely related to their surface hydrophilicity, zeta potential and particle size.