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用于蛋白质药物递送的可生物消除的聚合物纳米颗粒。

Bioeliminable polymeric nanoparticles for proteic drug delivery.

作者信息

Chiellini Federica, Bartoli Cristina, Dinucci Dinuccio, Piras Anna Maria, Anderson Robert, Croucher Terry

机构信息

BIOlab, UdR INSTM, Department of Chemistry & Industrial Chemistry, University of Pisa, Via Vecchia Livornese 1291, 56122 San Piero a Grado, Pisa, Italy.

出版信息

Int J Pharm. 2007 Oct 1;343(1-2):90-7. doi: 10.1016/j.ijpharm.2007.05.012. Epub 2007 May 16.

Abstract

Bioeliminable co-polymers based on poly(methacryloylglycylglycine-OH(x)-co-hydroxypropylmethacrylamide(y)) were successfully converted into nanoparticles by using the co-precipitation technique. Human serum albumin (HSA) and a modified (beta-cyclodextrin were used, respectively, as model protein drug and stabilizer. Nanoparticles were characterized from a dimensional and morphological point of view by means of laser diffraction granulometry and scanning electron microscopy (SEM). The prepared nanoparticles displayed a monomodal diameter distribution in the range of 130 nm, confirmed by SEM micrographs. Protein loading efficiency and drug release kinetics investigations, carried out on bioeliminable nanoparticles loaded with fluoresceinated HSA (HSA-FITC), showed that protein loading is in the range of 60% with a typical time controlled release profile. In vitro cytotoxicity investigations of the polymer matrices and resulting nanoparticles were carried out by using different assays aimed at the evaluation of the interactions of the materials with cell metabolism and the cell membrane. On the whole, bioeliminable polymers and nanoparticles resulted in high cytocompatibility thus suggesting their suitability for biomedical applications.

摘要

基于聚(甲基丙烯酰甘氨酰甘氨酸 - OH(x)-共 - 羟丙基甲基丙烯酰胺(y))的可生物降解共聚物通过共沉淀技术成功转化为纳米颗粒。分别使用人血清白蛋白(HSA)和一种改性的β-环糊精作为模型蛋白药物和稳定剂。通过激光衍射粒度分析和扫描电子显微镜(SEM)从尺寸和形态角度对纳米颗粒进行了表征。制备的纳米颗粒呈现出单峰直径分布,范围在130 nm,这由SEM显微照片证实。对负载有荧光素标记的HSA(HSA - FITC)的可生物降解纳米颗粒进行的蛋白质负载效率和药物释放动力学研究表明,蛋白质负载量在60%范围内,具有典型的时间控制释放曲线。通过使用旨在评估材料与细胞代谢和细胞膜相互作用的不同测定方法,对聚合物基质和所得纳米颗粒进行了体外细胞毒性研究。总体而言,可生物降解聚合物和纳米颗粒具有高细胞相容性,因此表明它们适用于生物医学应用。

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