PAMAM Dendrimers as Potential Carriers of Gadolinium Complexes of Iminodiacetic Acid Derivatives for Magnetic Resonance Imaging

Magdalena Markowicz-Piasecka,Joanna Sikora,Michał Studniarek,Oliwia Kozak,Paweł Szymański,Elżbieta Mikiciuk-Olasik

doi:10.1155/2015/394827

Magdalena Markowicz-Piasecka, Joanna Sikora + Show 4 more

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https://doi.org/10.1155/2015/394827

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Abstract

This is the first study describing the utilization of PAMAM dendrimers as delivery vehicles of novel magnetic resonance imaging (MRI) contrast agents. The purpose of this paper was to establish the potential of G4 PAMAM dendrimers as carriers of gadolinium complexes of iminodiacetic acid derivatives and determine imaging properties of synthesized compounds inin vivostudies. Furthermore, we examined the influence of four synthesized complexes on the process of clot formation, stabilization, and lysis and on amidolytic activity of thrombin. Biodistribution studies have shown that the compounds composed of PAMAM G4 dendrimers and gadolinium complexes of iminodiacetic acid derivatives increase signal intensity preferably in liver in range of 59–116% in MRI studies which corresponds with the greatest accumulation of gadolinium after administration of the compounds. Synthesized compounds affect kinetic parameters of the proces of clot formation, its stabilization, and lysis. However, only one synthesized compound at concentration 10-fold higher than potential plasma concentrations contributed to the increase of general parameters such as the overall potential of clot formation and lysis (↑CLAUC) and total time of the process (↑T). Results of described studies provide additional insight into delivery properties of PAMAM dendrimers but simultaneously underscore the necessity for further research.

Highlights

Over the last quarter of century there has been considerable interest in developing biodegradable nanodevices as effective drug delivery components
In the case of the kidney we reported that gadolinium accumulated therein an amount from 3 to 8 percent, contributing to the contrast enhancement in range of 68–136%
In the presented study we proved that PAMAM dendrimers might be regarded as efficient vehicles of magnetic resonance imaging (MRI) contrast agents

Summary

Introduction

Over the last quarter of century there has been considerable interest in developing biodegradable nanodevices as effective drug delivery components. The drug delivery systems, in relation to the current huge interest in nanotechnology, include liposomes, polymeric micelles, nanoparticles, dendrimers, and nanocrystals [1]. The method of preparation determines the number of properties and release characteristics of the encapsulated, dissolved, absorbed, or attached therapeutic agent [2]. Dendrimers, a relatively new class of compounds, compared to the traditional linear polymers are characterized by unique molecular architecture and dimensions [4, 5]. Dendrimers have, in comparison to linear polymers, welldefined chemical structure and exact molecular mass [4]

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