Abstract
A comprehensive understanding of the behaviour of Glycosaminoglycans (GAGs) combined with imaging or therapeutic agents can be a key factor for the rational design of drug delivery and diagnostic systems. In this work, physical and thermodynamic phenomena arising from the complex interplay between GAGs and contrast agents for Magnetic Resonance Imaging (MRI) have been explored. Being an excellent candidate for drug delivery and diagnostic systems, Hyaluronic acid (HA) (0.1 to 0.7%w/v) has been chosen as a GAG model, and Gd-DTPA (0.01 to 0.2 mM) as a relevant MRI contrast agent. HA samples crosslinked with divinyl sulfone (DVS) have also been investigated. Water Diffusion and Isothermal Titration Calorimetry studies demonstrated that the interaction between HA and Gd-DTPA can form hydrogen bonds and coordinate water molecules, which plays a leading role in determining both the polymer conformation and the relaxometric properties of the contrast agent. This interaction can be modulated by changing the GAG/contrast agent molar ratio and by acting on the organization of the polymer network. The fine control over the combination of GAGs and imaging agents could represent an enormous advantage in formulating novel multifunctional diagnostic probes paving the way for precision nanomedicine tools.
Highlights
Glycosaminoglycans (GAGs) have always attracted the interest of many research groups because of their versatile properties, making them desirable resources for the design of multifunctional materials in biomedicine [1,2,3]
They showed that the administration of a paramagnetic contrast agent, a metal chelate like Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA), can be used to visualize relative GAG distribution in-vivo since the negative charge of the contrast agent will distribute itself within articular cartilage in a spatially inverse relationship to the concentration of the negatively charged GAG molecules [31,32]
In our previous work, Hyaluronic acid (HA)-based nanostructures have been investigated [41] and the impact of the structural properties of the hydrogel matrix on the relaxometric properties of an Magnetic Resonance Imaging (MRI) contrast agent has been explained introducing the concept of hydrodenticity, i.e., the complex equilibrium established by the elastic stretches of polymer chains, water osmotic pressure, and hydration degree of the contrast agent, able to boost the relaxometric properties of the contrast agent itself
Summary
Glycosaminoglycans (GAGs) have always attracted the interest of many research groups because of their versatile properties, making them desirable resources for the design of multifunctional materials in biomedicine [1,2,3]. Compared to other classes of materials, like amino acid sequences, which have been coded and possess well-known properties and characteristics, GAGs represent a still unexplored group of materials, not ascribable to any of the already known chemical and biophysical patterns [1] This stimulates the investigation of their nature and behavior in biological environments, e.g., nanoscale interactions with proteins, lipids, and other GAGs, in order to fully understand and control their potential in the precision nanomedicine field as drug delivery systems and image contrast enhancers. In the foreseeable future, this knowledge can contribute to the innovation of traditional drugs and imaging agents
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