Microfluidic-assisted synthesis of multifunctional iodinated contrast agent polymeric nanoplatforms

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

doi:10.1016/j.ijpharm.2021.120447

Microfluidic-assisted synthesis of multifunctional iodinated contrast agent polymeric nanoplatforms

Int J Pharm. 2021 Apr 15:599:120447. doi: 10.1016/j.ijpharm.2021.120447. Epub 2021 Mar 5.

Authors

Enrica Chiesa¹, Antonietta Greco², Rossella Dorati³, Bice Conti⁴, Giovanna Bruni⁵, Dimitrios Lamprou⁶, Ida Genta⁷

Affiliations

¹ Department of Civil Engineering and Architecture, Via Ferrata 3, Pavia, Italy. Electronic address: enrica.chiesa@unipv.it.
² Department of Drug Sciences, University of Pavia, V.le Taramelli 12, Pavia, I, Italy. Electronic address: antonietta.greco01@universitadipavia.it.
³ Department of Drug Sciences, University of Pavia, V.le Taramelli 12, Pavia, I, Italy; Polymerix srl, V.le Taramelli 24, Pavia, I, Italy. Electronic address: rossella.dorati@unipv.it.
⁴ Department of Drug Sciences, University of Pavia, V.le Taramelli 12, Pavia, I, Italy; Polymerix srl, V.le Taramelli 24, Pavia, I, Italy. Electronic address: bice.conti@unipv.it.
⁵ Department of Chemistry - Physical Chemistry Section, University of Pavia, V.le Taramelli 16, Pavia, I, Italy. Electronic address: giovanna.bruni@unipv.it.
⁶ School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK. Electronic address: D.Lamprou@qub.ac.uk.
⁷ Department of Drug Sciences, University of Pavia, V.le Taramelli 12, Pavia, I, Italy; Polymerix srl, V.le Taramelli 24, Pavia, I, Italy. Electronic address: ida.genta@unipv.it.

PMID: 33676989
DOI: 10.1016/j.ijpharm.2021.120447

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 24-48 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.

Keywords: Contrast-induced nephropathy; Iohexol; Microfluidics; Multifunctional contrast agent; N-acetylcysteine; PLGA-PEG nanoparticles.

MeSH terms

Contrast Media
Drug Carriers
Humans
Microfluidics*
Nanoparticles*
Particle Size
Polyethylene Glycols
Polylactic Acid-Polyglycolic Acid Copolymer
Polymers

Substances

Contrast Media
Drug Carriers
Polymers
Polylactic Acid-Polyglycolic Acid Copolymer
Polyethylene Glycols