目的制备亲水性多肽类药物神经毒素的自组装核壳型纳米粒,并对其理化性质及体外释药特性进行考察。方法以聚乙二醇-聚氰基丙烯酸乙酯嵌段共聚物(PEG-g-PECA)为载体,乳化聚合法制备神经毒素自组装核壳型纳米粒,采用正交实验优化制备工艺,制得的核壳型纳米粒通过透射电镜、Zeta电位/粒度分布仪考察理化性质,并用透析袋法分别研究其在pH7.4和6.8的PBS缓冲液中的体外释药特性。结果PEG-g-PECA能包埋亲水性多肽神经毒素,制备的神经毒素自组装核壳型纳米粒粒径为(89.6±8.9)nm,多分散系数为(0.110±0.003),包封率为(58.43±0.62)%,Zeta电位为(-38.81±0.47)mV;在pH7.4和6.8的PBS缓冲液中的体外释药行为均符合Weibull方程,分别为lnln[1/(1-Q)]=0.474lnt-1.6121,r=0.9946(pH7.4)及lnln[1/(1-Q)]=0.351lnt-0.8271,r=0.9708(pH6.8)。结论以PEG-g-PECA为载体制备亲水性多肽类药物自组装核壳型纳米粒方法可行,所得纳米粒包封率较高,理化性质稳定,体外释药具有缓释制剂特征。
Abstract
OBJECTIVE To prepare the self-assembled neurotoxin-loaded nanoparticles of core-shell type, and investigate its physicochemical properties and release behavior in vitro. METHODS The self-assembled neurotoxin-loaded nanoparticles of core-shell type were prepared with PEG-g-PECA by emulsion polymerization method. The orthogonal design was used to optimize the preparation technology. The transmission electron microscope(TEM) and Zeta sizer instrument were utilized to investigate the physicochemical properties of the nanoparticles, and the drug release behavior in PBS buffer at pH 7.4 and 6.8 in vitro were studied by dialysis method respectively. RESULTS The mean diameter of the nanoparticles were (89.6±8.9)nm with polydispersity index of (0.110±0.003). The entrapment efficiency was (58.43±0.62)%, and Zeta potential was (-38.81±0.47) mV. The in vitro release profiles of the nanoparticles in pH 7.4 and 6.8 PBS buffer were consistent with Weibull equation, lnln[1/(1-Q)]=0.474lnt-1.612 1,r=0.994 6 (pH 7.4) and lnln[1/(1-Q)]=0.351lnt–0.827 1, r=0.970 8 (pH 6.8) respectively. CONCLUSION PEG-g-PECA is suitable for preparation of self-assembled neurotoxin-loaded nanoparticles of core-shell type with high entrapment efficiency, stable properties and excellent drug sustained release behavior.
关键词
神经毒素 /
自组装核壳型纳米粒 /
聚乙二醇-聚氰基丙烯酸乙酯嵌段共聚物 /
制备 /
体外释药
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Key words
neurotoxin /
self-assembled nanoparticles of core-shell type /
poly(ethylene glycol)-g-polyethylcyanoacrylate block copolymer /
preparation /
in vitro release
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参考文献
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脚注
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基金
国家自然科学基金资助项目(30772793);浙江省新苗人才计划(2007R40G2120044);浙江省卫生高层次创新人才培养工程
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