Magnetic resonance imaging of contrast-enhanced polyelectrolyte complexes

Abstract 

Polyelectrolyte complexes (PECs) assembled from oppositely charged polymers were endowed with gadolinium (Gd) and evaluated to determine cytotoxicity and magnetic resonance image (MRI) contrast enhancement in vivo. Chitosan grafted with Gd diethylenetriaminepentaacetic acid (DTPA) was electrostatically complexed with dextran sulfate, producing particles of about 300 nm possessing a negative surface charge. Alternatively, Gd was ionically trapped within PECs by mixing PECs (with or without Gd-DTPA graft) with gadolinium chloride (GdCl₃). Combinations of these two approaches for including Gd resulted in three particle types: Gd-loaded PECs, Gd-DTPA–conjugated PECs, and PECs containing both ionically trapped Gd and Gd-DTPA grafts. Polyelectrolytes, Gd-DTPA, and PECs were all found to have relatively low cytotoxicity (IC₅₀ > 1 mg/mL) in human umbilical cord vascular endothelial cells. In vivo, MRI revealed that the contrast-enhanced PECs were found to accumulate rapidly in the rat kidney. Some accumulation was also noted in the rat liver; however, negligible enhancement occurred in other tissues. Contrast enhancement was especially intense in or near the renal pelvis. MRI detection of PECs provides a potential approach to rapidly evaluate parameters such as the biodistribution and pharmacokinetics of these established drug and gene delivery vehicles.

Key words: Polyelectrolyte complex, Magnetic resonance imaging, Nanoparticle, Gadolinium, Drug delivery, Chitosan