Injectable and In Situ Gelling Dextran Derivatives Containing Hydrolyzable Groups for the Delivery of Large Molecules.

Laura Di Muzio,Chiara Brandelli,Stefania Petralito,Maria Antonietta Casadei,Stefania Cesa,Jordan Trilli,Patrizia Paolicelli

doi:10.3390/gels7040150

Laura Di Muzio, Chiara Brandelli + Show 5 more

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https://doi.org/10.3390/gels7040150

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Journal: Gels	Publication Date: Sep 24, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Sapienza University of Rome

Abstract

Recently, we reported the synthesis and characterization of a new dextran derivative obtained by grafting polyethylene glycol methacrylate to a polysaccharide backbone through a carbonate bond. This moiety was introduced because it allows for the fabrication, through a photo-induced crosslinking reaction, of biodegradable hydrogels particularly suitable for the release of high molecular weight molecules. Here, we investigate the influence of the oxyethylene chain length and the molecular weight of the starting dextran on the main properties of the polymeric solutions as well as those of the corresponding hydrogels. All synthesized polymeric derivatives were characterized by FTIR, NMR, and rheological analyses. The photo-crosslinking reaction of the polymers allowed us to obtain biodegradable networks tested for their mechanical properties, swelling, and degradation behavior. The results showed that both the oxyethylene chain length as well as the molecular weight of the starting dextran influenced swelling and degradation of the hydrogel network. As a consequence, the different behaviors in terms of swelling and degradability were able to affect the release of a large model molecule over time, making these matrices suitable candidates for the delivery of high molecular weight drug substances.

Highlights

A series of DEX derivatives was synthesized with the aim to introduce methacrylic moieties on the polysaccharide backbone through labile carbonate ester groups, in order to modulate biodegradability of the corresponding photo-crosslinked hydrogels, and in this way obtain suitable and tailorable carriers for the delivery of high molecular weight drugs
The oxyethylene chain length was able to affect the rheological properties of the corresponding photocrosslinked hydrogels, and was able to modify the rate of water uptake, which is regulated by the balance between the hydrophilic and hydrophobic portions of the specific polymeric derivative
The rheological properties of the polymers as well as those of the corresponding hydrogels were deeply affected by the molecular weight of the starting DEX

Summary

Introduction

The porous structure of these networks can house large quantities of water-soluble molecules, so the interest in the use of hydrogels as drug delivery systems is constantly growing [6,7]. The release of active molecules physically incorporated into the hydrogel matrix can be governed by multiple mechanisms such as swelling, diffusion, erosion/degradation, or by the combination of two or more of these mechanisms [8,9]. If the hydrogel mesh size is larger than the drug hydrodynamic radius, the diffusion is the driving force for the release process. Instead, the pores are smaller than the radius of the loaded molecule, swelling and/or degradation processes are required to allow for drug release [10,11,12]. Considering the internal structure of hydrogels, the release profile can be modulated by varying the lattice density, and, the polymer architecture, the molecular weight, the concentration, or the chemistry of the system [3]

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