Hyaluronic acid (HA)-Gd(III) and HA-Fe(III) microgels as MRI contrast enhancing agents

Nurettin Sahiner; Evrim Umut; Selin S Suner; Mehtap Sahiner; Mustafa Culha; Ramesh S Ayyala

doi:10.1016/j.carbpol.2021.118873

Hyaluronic acid (HA)-Gd(III) and HA-Fe(III) microgels as MRI contrast enhancing agents

Carbohydr Polym. 2022 Feb 1:277:118873. doi: 10.1016/j.carbpol.2021.118873. Epub 2021 Nov 8.

Authors

Nurettin Sahiner¹, Evrim Umut², Selin S Suner³, Mehtap Sahiner⁴, Mustafa Culha⁵, Ramesh S Ayyala⁶

Affiliations

¹ Department of Chemistry, Canakkale Onsekiz Mart University, Canakkale, Turkey; Department of Chemical and Biomolecular Engineering, University of South Florida, Tampa, FL 33620, USA; Department of Ophthalmology, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs B. Downs Blv., MDC 21, Tampa, FL 33612, USA. Electronic address: sahiner71@gmail.com.
² Department of Medical Imaging Techniques, School of Healthcare, Dokuz Eylul University, Narlıdere, Izmir 35330, Turkey.
³ Department of Chemistry, Canakkale Onsekiz Mart University, Canakkale, Turkey.
⁴ Department of Fashion Design, Canakkale School of Applied Science, Canakkale Onsekiz Mart University, Terzioglu Campus, Canakkale 17100, Turkey.
⁵ Department of Ophthalmology, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs B. Downs Blv., MDC 21, Tampa, FL 33612, USA; Sabanci University Nanotechnology Research and Application Center (SUNUM), Orta Mh. Universite Cd. No:27/1, Tuzla, Istanbul 34956, Turkey.
⁶ Department of Ophthalmology, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs B. Downs Blv., MDC 21, Tampa, FL 33612, USA.

PMID: 34893278
DOI: 10.1016/j.carbpol.2021.118873

Abstract

Hyaluronic acid (HA) was crosslinked with Gd(III) and Fe(III) ions rendering physically crosslinked HA-metal(III) microgels as magnetic resonance imaging (MRI) enhancing contrast agents. These HA-Gd(III) and HA-Fe(III) microgels are injectable with size range, 50-5000 nm in water. The same isoelectric point, pH 1.2 ± 0.1, was measured for both microgels. HA-Gd(III) and HA-Fe(III) microgels are hemo-compatible biomaterials and can be safely used in intravascular applications up to 1000 μg/mL concentration. Furthermore, no significant toxicity was attained as 95 ± 8 and 81 ± 2% cell viability on L929 fibroblast cells at 100 μg/mL of HA-Gd(III) and HA-Fe(III) microgels were measured. Moreover, HA-Gd(III) microgels were found to afford significant contrast improvement capability in MRI with proton relaxivity, r₁ = 2.11 mM^-1 s^-1, comparable with the values reported for Gd(III) labeled functionalized HA gel systems and commercial Gd based contrast agents.

Keywords: Blood compatible; Fe(II) chelating; HA-Fe(III) microgel; HA-Gd(III) microgel; Hyaluronic acid (HA); Magnetic resonance imaging (MRI).