Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran; Department of Agronomy and Plant Breeding, Faculty of Agriculture and Natural Resources, University of Mohaghegh Ardabili, Ardabil, Iran.
Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Eur J Pharm Sci. 2021 Dec 1;167:106007. doi: 10.1016/j.ejps.2021.106007. Epub 2021 Sep 11.
The self-assembling of various amphipathic copolymers is a simple method that allows the preparation of complex nanoparticles with several useful properties. In the present study, the polylactic acid-polyethylene glycol-folate (PLA-PEG-FA) (PPF), PLA-PEG-T7 peptide (PPT) and PLA-Chitosan-Spermine (PCS) copolymers were synthesized separately.
These copolymers combined with FeO magnetic core and loaded with paclitaxel (PTX)/siRNA-FAM to form magnetic PCS/PPF/PPT/PTX/siRNA micelles (MPCSFT/PTX/siRNA) and were characterized using physicochemical and biological analysis.
The results revealed that the MPCSPFT/PTX/siRNA had spherical morphology with particle size and zeta potential about 197 nm and -7.8 mV, respectively. Release assay was determined under neutral (pH=7.4) and acidic pH (pH=6) conditions to simulate PTX and siRNA release profile from MPCSPFT/PTX/siRNA micelles in normal and cancerous tissues. The ability of MPCSPFT for co-delivery of PTX and siRNA into MCF-7 cells was determined by MTT and flow cytometry tests, respectively. The results revealed that the release rate of siRNA and PTX from MPCSPFT/PTX/siRNA nanoparticles under an acidic environment (pH=6) was significantly higher than that of their release rate in a neutral medium (pH=7.4).
Conjugation of both folic acid and T7-peptide on the surface of micelles compared to separate conjugation of one of these ligands, increased the efficiency of drug and siRNA delivery to breast cancer cells.
各种两亲性共聚物的自组装是一种简单的方法，可以制备具有多种有用性质的复杂纳米粒子。在本研究中，分别合成了聚乳酸-聚乙二醇-叶酸（PLA-PEG-FA）（PPF）、PLA-PEG-T7 肽（PPT）和 PLA-壳聚糖-精胺（PCS）共聚物。
这些共聚物与 FeO 磁核结合，并负载紫杉醇（PTX）/siRNA-FAM，形成磁性 PCS/PPF/PPT/PTX/siRNA 胶束（MPCSFT/PTX/siRNA），并通过物理化学和生物学分析进行了表征。
结果表明，MPCSFT/PTX/siRNA 具有球形形态，粒径和 zeta 电位分别约为 197nm 和-7.8mV。在中性（pH=7.4）和酸性 pH（pH=6）条件下进行释放实验，以模拟 MPCSPFT/PTX/siRNA 胶束在正常和癌组织中 PTX 和 siRNA 的释放曲线。通过 MTT 和流式细胞术试验分别测定 MPCSPFT 共递送 PTX 和 siRNA 进入 MCF-7 细胞的能力。结果表明，在酸性环境（pH=6）下，MPCSFT/PTX/siRNA 纳米粒中 siRNA 和 PTX 的释放率明显高于在中性介质（pH=7.4）中的释放率。
与单独连接其中一种配体相比，叶酸和 T7-肽在胶束表面的连接增加了药物和 siRNA 递送到乳腺癌细胞的效率。
