Istituto Italiano di Tecnologia, IIT - Center for Advanced Biomaterials for Health Care, CABHC@CRIB, Largo Barsanti e Matteucci, 80125, Naples, Italy.
University of Naples Federico II, Department of Chemical Engineering, Materials and Industrial Production, P.le Tecchio 80, 80125, Naples, Italy.
Sci Rep. 2016 Nov 30;6:37906. doi: 10.1038/srep37906.
Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T is observed since a T of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.
最近的成像诊断技术进展集中在使用纳米结构来捕获磁共振成像（MRI）造影剂（CA），而无需对临床批准的化合物进行化学修饰。然而，微流控平台在其受控和连续生产方面的应用仍有待开发。在这里，使用微流控平台合成交联透明质酸纳米颗粒（cHANPs），其中包埋了一种临床相关的 MRI-CA，即钆二乙烯三胺五乙酸（Gd-DTPA）。这种微流控工艺能够高度控制颗粒的合成，从而能够生产出小至 35nm 的单分散颗粒。此外，通过精细调整工艺参数和利用表面活性剂的亲水亲脂平衡（HLB）以及 pH 条件，可以克服 Gd-DTPA 在聚合物沉淀过程中的干扰。对于提出的两种设计载 Gd 的 cHANPs 的生产策略，都观察到弛豫率 T 的提高，因为载 Gd 的 cHANPs 的 T 值为 1562，而在溶液中，相同浓度的临床相关 Gd-DTPA 的 T 值也达到了 1562。该先进的微流控平台用于合成可血管内注射且完全生物相容的水凝胶纳米颗粒，可用于封装临床批准的 CA，从而为诊断和治疗应用提供了简单且可扩展的策略。
