Microfluidic-assisted synthesis of multifunctional iodinated contrast agent polymeric nanoplatforms

Enrica Chiesa, Antonietta Greco, Rossella Dorati, Bice Conti, Giovanna Bruni, Dimitrios Lamprou*, Ida Genta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 24-48h 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. 

Original languageEnglish
JournalInternational Journal of Pharmaceutics
Publication statusAccepted - 27 Feb 2021

Keywords

  • contrast-induced nephropathy
  • multifunctional contrast agent
  • iohexol
  • N-acetylcysteine
  • Microfluidics
  • PLGA
  • Nanoparticles

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