Microfluidic-assisted synthesis of multifunctional iodinated contrast agent polymeric nanoplatforms

Contrast InducedNephropathy is the most severe side-effect arising after non-ionic iodinatedcontrast 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 polymericnanoparticles (NPs) as new multifunctional blood pool CA. The aim of thisresearch is to co-encapsulate Iohexol (IOX; iodinated CA) and NAC (preventiveagent) into poly-D,L-lactide-co-glycolide (PLGA) and PEGylated-PLGA (PLGA-PEG)NPs to exploit CA diagnostic proprieties and NAC preventing antioxidantactivity. A microfluidic-assisted nanoprecipitation protocol has been set-up forPLGA and PLGA-PEG NPs, evaluating the effect of formulation and microfluidicparameters 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, sphericalshape, and an IOX and NAC encapsulation efficiency of 38% and 20%,respectively. The IOX and NAC encapsulation was confirmed by FTIR and DSC. Invitro release study showed an IOX retention into the polymeric matrix andNAC sustained release up to 24-48h stating microfluidics aspowerful tool for the formulation of multifunctional nanoplatforms. Finally, the protective effect ofNPs and NAC were preliminary assessed on human kidney cells.