Department of Chemical Engineering. Aragon Institute of Nanoscience (INA) and Instituto de Ciencia de Materiales de Aragón (ICMA), Universidad de Zaragoza-CSIC, University of Zaragoza, Campus Río Ebro-Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), 50009, Zaragoza, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, 28029, Madrid, Spain.
Department of Chemical Engineering. Aragon Institute of Nanoscience (INA) and Instituto de Ciencia de Materiales de Aragón (ICMA), Universidad de Zaragoza-CSIC, University of Zaragoza, Campus Río Ebro-Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), 50009, Zaragoza, Spain.
Colloids Surf B Biointerfaces. 2020 Jun;190:110904. doi: 10.1016/j.colsurfb.2020.110904. Epub 2020 Feb 25.
Photopolymerization is a selective technique that takes advantage of light-sensitive molecules to initiate and propagate monomeric structures to render covalently bonded macromolecular materials structures known as polymers. Herein, we present a novel one-step microfluidic synthesis of customized hybrid-thermoresponsive Poly(N-isopropylacrylamide) (PNIPAm) based microparticles (MPs) containing plasmonic hollow gold nanoparticles (HGNPs) and bupivacaine (BVP) used as a model drug. Those hybrid microparticles were prepared using a flow-focusing microreactor coupled to a UV LED device built with a simple outer PTFE tubing and an inner flexible capillary. Different tubing characteristics and flow rate ratios were altered in order to control the size of the resulting microparticles. In addition, components such as monomer, crosslinker and photoinitiator concentrations, as well as LED intensity and irradiation time were tuned to obtain different MPs and their characteristics and polymerization rates were compared by Gel Permeation Chromatography (GPC). Thermoresponsive properties were analyzed and the presence of HGNPs was confirmed in light-activated triggered drug release applications. Bupivacaine loading and release studies were evaluated with the resulting hollow and solid microparticles (which were obtained depending on the polymerization rate used) and their temperature responsiveness was assessed using a NIR laser when HGNPs were present in the constructs. Finally, cytotoxicity studies, cell-cycle arrest and apoptotic induction were carried out to certify their suitability for further biomedical applications to be used as triggerable drug depots.
光聚合是一种选择性技术，利用感光分子引发和传播单体结构，形成共价键合的大分子材料结构，即聚合物。在此，我们提出了一种新颖的一步微流控合成方法，用于定制混合温敏型聚（N-异丙基丙烯酰胺）（PNIPAm）基微球（MPs），其中包含等离子体空心金纳米颗粒（HGNPs）和布比卡因（BVP），BVP 用作模型药物。这些混合微球是使用流聚焦微反应器与 UV LED 装置结合制备的，该装置由简单的外部 PTFE 管和内部柔性毛细管组成。改变不同的管道特性和流速比，以控制所得微球的尺寸。此外，还调整了单体、交联剂和光引发剂浓度以及 LED 强度和辐照时间等成分，以获得不同的 MPs，并通过凝胶渗透色谱（GPC）比较它们的特性和聚合速率。分析了温敏性能，并在光激活触发药物释放应用中证实了 HGNPs 的存在。对所得的空心和实心微球（这取决于所用的聚合速率来获得）进行了布比卡因负载和释放研究，并在构建物中存在 HGNPs 的情况下使用近红外激光评估了其温度响应性。最后，进行了细胞毒性研究、细胞周期阻滞和凋亡诱导，以证明它们适用于进一步的生物医学应用，可用作可触发的药物储存库。
