Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza 50009, Spain; Department of Chemical Engineering, University of Zaragoza, Campus Río Ebro - Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018 Zaragoza, Spain.
Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza 50009, Spain; Department of Chemical Engineering, University of Zaragoza, Campus Río Ebro - Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018 Zaragoza, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, 28029 Madrid, Spain; Aragon Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain.
J Colloid Interface Sci. 2022 Feb;607(Pt 2):1466-1477. doi: 10.1016/j.jcis.2021.09.064. Epub 2021 Sep 17.
The on-demand administration of anaesthetic drugs can be a promising alternative for chronic pain management. To further improve the efficacy of drug delivery vectors, high drug loadings combined with a spatiotemporal control on the release can not only relief the pain according to patient's needs, but also improve the drawbacks of conventional burst release delivery systems. In this study, a hybrid nanomaterial was developed by loading bupivacaine nanocrystals (BNCs) into oligo(ethylene glycol) methyl ether methacrylate (OEGMA)-based thermoresponsive nanogels and coupling them to NIR-absorbing biodegradable copper sulphide nanoparticles (CuS NPs). Those CuS NPs were surface modified with polyelectrolytes using layer-by-layer techniques to be efficiently attached to the surface of nanogels by means of supramolecular interactions. The encapsulation of bupivacaine in the form of nanocrystals allowed to achieve CuS@BNC-nanogels having drug loadings as high as 65.5 wt%. The nanocrystals acted as long-lasting drug reservoirs, leading to an elevated localized drug content, which was useful for their application in prolonged pain relief. The CuS@BNC-nanogels exhibited favorable photothermal transducing properties upon NIR-light irradiation. The photothermal effect granted by the CuS NPs triggered the nano-crystallized drug release to be boosted by the collapse of the thermoresponsive nanogels upon heating. Remote control was achieved for on-demand release at a specific time and place, indicating their potential use as an externally activated triggerable drug-delivery system. Furthermore, cell viability tests and flow cytometry analysis were performed showing satisfactory cytocompatibility in the dose-ranging study having a subcytotoxic concentration of 0.05 mg/mL for CuS@BNC-nanogels. This remotely activated nanoplatform is a promising strategy for long-lasting controlled analgesia and a potential alternative for clinical pain management.
按需给予麻醉药物可能是慢性疼痛管理的一种很有前途的选择。为了进一步提高药物输送载体的疗效，可以将高载药量与药物释放的时空控制相结合，不仅可以根据患者的需求缓解疼痛，还可以改善传统突释型药物输送系统的缺点。在这项研究中，通过将布比卡因纳米晶体（BNCs）负载到聚乙二醇甲基醚甲基丙烯酸酯（OEGMA）基温敏纳米凝胶中，并将其与近红外吸收可生物降解的硫化铜纳米粒子（CuS NPs）偶联，开发了一种混合纳米材料。这些 CuS NPs 通过层层技术用聚电解质进行表面修饰，通过超分子相互作用有效地附着在纳米凝胶的表面上。以纳米晶体的形式包封布比卡因可以使 CuS@BNC-纳米凝胶的药物载药量高达 65.5wt%。纳米晶体充当持久的药物储库，导致局部药物含量升高，这对于延长疼痛缓解时间很有用。CuS@BNC-纳米凝胶在近红外光照射下表现出良好的光热转换特性。CuS NPs 的光热效应触发了纳米凝胶的热响应塌陷，从而增强了纳米结晶药物的释放。可以在特定的时间和地点实现远程控制按需释放，表明它们有可能作为一种外部激活的触发式药物输送系统。此外，进行了细胞活力测试和流式细胞术分析，在剂量范围研究中，CuS@BNC-纳米凝胶的亚细胞毒性浓度为 0.05mg/mL，显示出令人满意的细胞相容性。这种远程激活的纳米平台是一种用于长效控制镇痛的很有前途的策略，也是临床疼痛管理的潜在替代方法。
