Department of Materials Science and Engineering, NTNU Norwegian University of Science and Technology, Norway.
Department of Chemical Engineering, NTNU Norwegian University of Science and Technology, Norway.
J Colloid Interface Sci. 2022 Feb;607(Pt 1):76-88. doi: 10.1016/j.jcis.2021.07.139. Epub 2021 Aug 5.
Dual stimuli-responsive nanogels (NGs) have gained popularity in the field of bio medicine due to their versatile nature of applicability. Poly(N-isopropylacrylamide)-co-poly(acrylic acid) (pNIPAm-pAAc)-based NGs provide such dual stimuli-response with pNIPAm and pAAc providing thermal and pH-based responses, respectively. Studying the growth of these NGs, as well as, understanding the effect of the incorporation of pAAc in the NG matrix, is important in determining the physico-chemical properties of the NG. Studies have been conducted investigating the effect of increasing pAAc content in the NGs, however, these are not detailed in understanding its effects on the physico-chemical properties of the pNIPAm-pAAc-based NGs. Also, the biocompatibility of the NGs have not been previously reported using human whole blood model. Herein, we report the effect of different reaction parameters, such as surfactant amount and reaction atmosphere, on the growth of pNIPAm-pAAc-based NGs. It is shown that the size of the NGs can be precisely controlled from ~130 nm to ~400 nm, by varying the amount of surfactant and the reaction atmosphere. The effect of increasing incorporation of pAAc in the NG matrix on its physico-chemical properties has been investigated. The potential of these NGs as drug delivery vehicles is investigated by conducting loading and release studies of a model protein drug, cytochrome C (Cyt C) from the NGs at temperature above the volume phase transition temperature (VPTT) and acidic pH. An ex vivo human whole blood model was used to investigate biocompatibility of the NGs by quantifying inflammatory responses during NG exposure. The NGs did not induce any significant production of chemokine IL-8 or pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and the cell viability in human whole blood was maintained during 4 h exposure. The NGs did neither activate the complement system, as determined by low Terminal Complement Complex (TCC) activation and Complement Receptor 3 (CR3) activation assays, thereby overall suggesting that the NGs could be potential candidates for biomedical applications.
双重刺激响应纳米凝胶（NGs）由于其多功能的适用性，在生物医学领域中得到了广泛的关注。基于聚（N-异丙基丙烯酰胺）-共-聚（丙烯酸）（pNIPAm-pAAc）的 NGs 提供了这种双重刺激响应，其中 pNIPAm 和 pAAc 分别提供了热和 pH 响应。研究这些 NGs 的生长以及了解 pAAc 在 NG 基质中的掺入对 NG 物理化学性质的影响非常重要。已经进行了研究，以研究增加 NGs 中 pAAc 含量的影响，但是，这些研究并没有详细说明其对基于 pNIPAm-pAAc 的 NGs 的物理化学性质的影响。此外，尚未使用人全血模型先前报道过 NGs 的生物相容性。在此，我们报告了不同反应参数（例如表面活性剂用量和反应气氛）对 pNIPAm-pAAc 基 NGs 生长的影响。结果表明，可以通过改变表面活性剂的用量和反应气氛，将 NGs 的尺寸从约 130nm 精确控制至约 400nm。研究了增加 pAAc 在 NG 基质中的掺入对其物理化学性质的影响。通过在高于体积相转变温度（VPTT）和酸性 pH 下从 NGs 中装载和释放模型蛋白药物细胞色素 C（Cyt C）来研究这些 NGs 作为药物输送载体的潜力。使用体外人全血模型通过定量 NG 暴露期间的炎症反应来研究 NGs 的生物相容性。NGs 没有诱导任何趋化因子 IL-8 或促炎细胞因子（IL-1β、IL-6、TNF-α）的产生，并且在 4 小时暴露期间保持人全血中的细胞活力。NGs 既没有激活补体系统，如通过低末端补体复合物（TCC）激活和补体受体 3（CR3）激活测定确定的那样，因此总体上表明 NG 可能是生物医学应用的潜在候选物。
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