RGD 接枝 PMMA-纳米粒子的多聚体系统作为紫杉醇的靶向药物传递系统。

Multimeric System of RGD-Grafted PMMA-Nanoparticles as a Targeted Drug- Delivery System for Paclitaxel.

机构信息

Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac, Estado de Mexico, 52750. Mexico.

Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca S/N., La Marquesa, Ocoyoacac, Estado de Mexico. Mexico.

出版信息

Curr Pharm Des. 2017;23(23):3415-3422. doi: 10.2174/1381612823666170407143525.

DOI:10.2174/1381612823666170407143525

PMID:28403791

Abstract

BACKGROUND

Polymer-based nanoparticles as drug-delivery systems offer new therapeutic opportunities. Among them, ligand-mediated targeting, which increases selectivity and efficacy, allows controllable drug delivery. The aim of the this research was to prepare and characterize poly(methyl methacrylate) (PMMA) nanoparticles grafted with the -Arginine, Glycine, Aspartic Acid (RGD)- peptide sequence as a promising smart drug delivery system for Paclitaxel (PTX), directed at the sites of integrin receptor overexpression.

METHODS

Nanoparticles were characterized by FT-IR and Raman spectroscopy, dynamic light scattering, zeta potential and transmission electron microscopy.

RESULTS

RGD-PMMA-PTX size distribution was 17.58 ± 7.45 nm with a zeta potential of -38.73 ± 5.62 mV. According to the boxLucas Model, PTX was incorporated into nanoparticles with an entrapment efficiency of 100% (evaluated by HPLC analysis). In vitro sustained release was determined, with the maximum release of 55% and 40% after 21 days at pH 5.3 and 7.4, respectively. The highest inhibition on cell proliferation was found with RGD-PMMA-PTX nanoparticles (90 %).

CONCLUSION

The obtained results showed that RGD-PMMA-PTX represents an attractive and suitable therapeutic approach for targeting overexpressed integrins in the cancer cells.

摘要

背景

聚合物基纳米粒子作为药物传递系统提供了新的治疗机会。其中，配体介导的靶向作用提高了选择性和疗效，允许可控的药物传递。本研究的目的是制备和表征接枝有 -精氨酸、甘氨酸、天冬氨酸（RGD）-肽序列的聚甲基丙烯酸甲酯（PMMA）纳米粒子，作为一种有前途的智能药物传递系统，用于紫杉醇（PTX），针对整合素受体过表达的部位。

方法

通过傅里叶变换红外光谱和拉曼光谱、动态光散射、Zeta 电位和透射电子显微镜对纳米粒子进行了表征。

结果

RGD-PMMA-PTX 的粒径分布为 17.58 ± 7.45nm，Zeta 电位为-38.73 ± 5.62mV。根据 BoxLucas 模型，通过 HPLC 分析评估，PTX 以 100%的包封效率被纳入纳米粒子。在 pH 5.3 和 7.4 下分别测定了 21 天后的体外持续释放，最大释放率分别为 55%和 40%。RGD-PMMA-PTX 纳米粒子对细胞增殖的抑制作用最大（90%）。