Faculty of Polymer Engineering, Sahand University of Technology, P.O. Box 51335-1996, 51368 Tabriz, Iran.
Institute of Polymeric Materials, Sahand University of Technology, P.O. Box 51335-1996, 51368 Tabriz, Iran.
Langmuir. 2020 Mar 17;36(10):2683-2694. doi: 10.1021/acs.langmuir.9b03892. Epub 2020 Mar 4.
Smart polymers with extraordinary characteristics are studied in drug-delivery applications. In the current study, temperature-responsive hybrid core-shell nanoparticles were synthesized by precipitation polymerization of -isopropylacrylamide and vinyl-modified silica nanoparticles. These temperature-responsive hybrid core-shells were prepared with different cross-linking densities by using 2, 4, and 8 mol % of ,-methylene bisacrylamide (MBA). Hydrolysis of the silica cores of the hybrid core-shells resulted in hollow poly(-isopropylacrylamide) (PNIPAM) nanogels. Functionalization of silica nanoparticles with vinyl-containing silane modifier of 3-(trimethoxysilyl) propyl methacrylate (MPS) in two different contents was proven by Fourier transform infrared spectroscopy. Preparation of the hybrid PNIPAM nanogels and etching of the silica cores were studied using thermogravimetric analysis and also electron microscopy imaging. Sensitivity of the PNIPAM nanogel samples to temperature was studied using ultraviolet-visible (UV-vis) spectroscopy. In addition, dynamic light scattering was used for investigation of the squeezing and expansion of the hybrid and hollow samples against variation of temperature. The UV-vis spectroscopy results display higher absorption intensities in higher contents of MPS modifier and MBA cross-linker. The swelling content of the nanogels with hollow cavities was higher than that of the hybrid samples. The hybrid nanogels with 2 and 8 wt % silica content and different cross-linking densities and also their hollow nanoparticles were used for loading and release of doxorubicin (DOX). The release characteristics of the DOX-loaded nanogels were studied at different temperatures using UV-vis spectroscopy. The DOX release was higher at temperatures lower than the gel collapse temperature of the PNIPAM network. Although the nanogels with hollow cavities displayed higher loading capacities, the release percentage was higher for the hybrid PNIPAM nanogels, which was confirmed by the experimental release profiles and mathematical models. The most appropriate fitting of the DOX release data from the PNIPAM nanogel samples was observed for the Korsmeyer-Peppas model. Cytotoxicity studies on HeLa cell line showed that drug-loaded hollow samples showed higher toxicity due to loading of a higher amount of DOX.
在药物输送应用中，研究了具有特殊性能的智能聚合物。在当前的研究中，通过沉淀聚合 - 异丙基丙烯酰胺和乙烯改性的硅纳米粒子合成了温度响应性杂化核壳纳米粒子。这些温度响应性杂化核壳纳米粒子通过使用 2、4 和 8 mol %的 - 亚甲基双丙烯酰胺（MBA）来制备不同交联密度的纳米粒子。杂化核壳的硅核的水解导致空心聚（-异丙基丙烯酰胺）（PNIPAM）纳米凝胶。通过傅里叶变换红外光谱证明了硅烷改性剂 3-（三甲氧基硅基）丙基甲基丙烯酸酯（MPS）在两种不同含量下对硅纳米粒子的功能化。通过热重分析和电子显微镜成像研究了杂化 PNIPAM 纳米凝胶的制备和硅核的蚀刻。使用紫外-可见（UV-vis）光谱研究了 PNIPAM 纳米凝胶样品对温度的敏感性。此外，动态光散射用于研究温度变化时杂化和空心样品的挤压和膨胀。UV-vis 光谱结果显示，在更高含量的 MPS 改性剂和 MBA 交联剂中，吸收强度更高。具有空心腔的纳米凝胶的溶胀含量高于杂化样品。具有 2 和 8 wt %硅含量和不同交联密度以及其空心纳米粒子的杂化纳米凝胶被用于载药和阿霉素（DOX）的释放。使用 UV-vis 光谱研究了不同温度下 DOX 载药纳米凝胶的释放特性。DOX 的释放在低于 PNIPAM 网络凝胶塌陷温度的温度下更高。尽管具有空心腔的纳米凝胶具有更高的载药能力，但对于杂化 PNIPAM 纳米凝胶，释放百分比更高，这通过实验释放曲线和数学模型得到证实。从 PNIPAM 纳米凝胶样品中观察到 DOX 释放数据的最适合拟合是 Korsmeyer-Peppas 模型。对 HeLa 细胞系的细胞毒性研究表明，由于负载更高量的 DOX，载药空心样品显示出更高的毒性。
