Department of Civil Engineering and Architecture, Via Ferrata 3, Pavia, Italy.
Department of Drug Sciences, University of Pavia, V.le Taramelli 12, Pavia, I, Italy.
Int J Pharm. 2021 Apr 15;599:120447. doi: 10.1016/j.ijpharm.2021.120447. Epub 2021 Mar 5.
Contrast Induced Nephropathy is the most severe side-effect arising after non-ionic iodinated contrast agents (CAs) intravenous administration. The use of antioxidants (i.e., N-Acetylcysteine; NAC) is one of the attempted prevention approaches. Herein, we describe the microfluidic-assisted synthesis of iodinated polymeric nanoparticles (NPs) as new multifunctional blood pool CA. The aim of this research is to co-encapsulate Iohexol (IOX; iodinated CA) and NAC (preventive agent) into poly-D,L-lactide-co-glycolide (PLGA) and PEGylated-PLGA (PLGA-PEG) NPs to exploit CA diagnostic proprieties and NAC preventing antioxidant activity. A microfluidic-assisted nanoprecipitation protocol has been set-up for PLGA and PLGA-PEG NPs, evaluating the effect of formulation and microfluidic parameters by analysing the size, PDI and IOX and NAC encapsulation efficiency. The optimized NPs (PLGA-PEG, L:G 50:50, 5% PEG, Mw 90 kDa) formulated with a size of 67 ± 2.8 nm with PDI < 0.2, spherical shape, and an IOX and NAC encapsulation efficiency of 38% and 20%, respectively. The IOX and NAC encapsulation was confirmed by FTIR and DSC. In vitro release study showed an IOX retention into the polymeric matrix and NAC sustained release up to 24-48 h stating microfluidics as powerful tool for the formulation of multifunctional nanoplatforms. Finally, the protective effect of NPs and NAC were preliminary assessed on human kidney cells.
对比剂肾病是静脉注射非离子型碘造影剂（CAs）后最严重的副作用之一。使用抗氧化剂（如 N-乙酰半胱氨酸；NAC）是一种尝试的预防方法。在此，我们描述了基于微流控的碘聚合纳米颗粒（NPs）的合成，作为新型多功能血池 CA。本研究的目的是将碘海醇（IOX；碘造影剂）和 NAC（预防剂）共包封到聚-D，L-乳酸-共-乙醇酸（PLGA）和聚乙二醇化-PLGA（PLGA-PEG） NPs 中，以利用 CA 的诊断特性和 NAC 的预防抗氧化活性。已经建立了一种基于微流控的纳米沉淀方案来制备 PLGA 和 PLGA-PEG NPs，通过分析粒径、PDI 和 IOX 和 NAC 的包封效率来评估配方和微流控参数的影响。优化的 NPs（PLGA-PEG，L:G 50:50，5%PEG，Mw 90 kDa）的粒径为 67±2.8nm，PDI<0.2，呈球形，IOX 和 NAC 的包封效率分别为 38%和 20%。FTIR 和 DSC 证实了 IOX 和 NAC 的包封。体外释放研究表明，IOX 保留在聚合物基质中，NAC 持续释放长达 24-48 小时，表明微流控技术是制备多功能纳米平台的有力工具。最后，初步评估了 NPs 和 NAC 对人肾细胞的保护作用。
