Research Center for Analytical Sciences, Northeastern University, Shenyang 110819, China.
Research Center for Analytical Sciences, Northeastern University, Shenyang 110819, China.
J Colloid Interface Sci. 2018 Nov 15;530:465-472. doi: 10.1016/j.jcis.2018.05.102. Epub 2018 May 30.
In this paper, a three-dimensional (3D) poly(lactic-co-glycolic acid) (PLGA)/silica colloidal crystal drug delivery system with sustained drug release and visualized release monitoring was developed. This system had employed silica colloidal crystal microparticles as template skeleton, PLGA as drug carrier and dexamethasone (DEX) as therapeutic agent. The fabrication of the microparticle-based system included droplet formation based-on microfluidics, silica nanoparticle self-assembly and layer-by-layer deposition of PLGA containing DEX. In 370 μm droplets, the silica colloidal nanoparticles could self-assemble orderly into microparticles with a diameter of 187 μm, featuring red structure color. During the deposition of PLGA with the drug into the voids of the template microparticles, the reflection peak red-shifted and weakened until the voids were completely filled. Owing to the gradual degradation of PLGA, the release of DEX was triggered and sustained for 4 weeks with a cumulative release of 94.9%, while the structure color of the microparticles recovered during the release process. The color change could be recognized by the naked eyes, which would benefit the non-invasive monitoring of the drug release. The in vitro cytotoxicity and long-term inhibiting proliferation were investigated on retinal pigment epithelial cells. The inhibition effect of DEX released from the microparticles showed concentration-dependence from 40 to 200 μg mL and time-dependence within 7 days. As a sustained drug delivery system with self-reporting drug release, the particles have potential applications in treatment of intraocular diseases.
本文开发了一种具有持续药物释放和可视化释放监测功能的三维(3D)聚(乳酸-共-乙醇酸)(PLGA)/硅胶体晶体药物递送系统。该系统采用硅胶体晶体微球作为模板骨架,PLGA 作为药物载体,地塞米松(DEX)作为治疗剂。基于微流控技术的液滴形成、硅纳米颗粒自组装和含有 DEX 的 PLGA 的层层沉积,实现了微球的制备。在 370 μm 的液滴中,硅胶体纳米颗粒可以自组装成直径为 187 μm 的微球,呈现红色结构色。在将含药的 PLGA 沉积到模板微球的空隙中时,反射峰发生红移和减弱,直到空隙完全填满。由于 PLGA 的逐渐降解,DEX 的释放被触发并持续 4 周,累积释放率为 94.9%,而微球的结构色在释放过程中恢复。颜色变化可以用肉眼识别,有利于药物释放的非侵入性监测。对视网膜色素上皮细胞进行了体外细胞毒性和长期抑制增殖的研究。微球释放的 DEX 的抑制作用表现出浓度依赖性(40-200μg/mL)和时间依赖性(7 天内)。作为一种具有自报告药物释放功能的持续药物递送系统,该颗粒在治疗眼内疾病方面具有潜在的应用前景。