Biodegradable dextran based microgels: a study on network associated water diffusion and enzymatic degradation

Abstract

Sustained drug delivery represents a major challenge in nanomedicine. Solutions to the many requirements posed by this field are not easy to address using a unique delivery vehicle. In recent years, our goal has been to implement such requirements in a single device by manipulating the structural and functional features of “soft” biocompatible drug delivery platforms. In this paper we describe a set of biocompatible drug delivery materials, with controlled structure and dimension, which are both biodegradable in a time frame of interest and designed as drug vectors for therapeutic approaches. These microdevices were obtained using ultrasound assisted “water-in-water” emulsification. The resulting material was a spherical shaped microgel with controlled pore size and water content. The dynamic behaviour of water in these matrixes showed a remarkable supercooling effect, an effect which was more pronounced for those microgels with smaller mesh sizes. The biodegradability of the microgel was monitored by observing the enzymatic breakdown of the material both as a whole, i.e. by observing a large number of microgel particles, and by focussing on single particles. A complex degradation pattern was observed, with the particles first increasing their size followed by a complete structural demolition. The time required to fully degrade a microgel can be tuned by varying the relative enzyme content and/or the degree of crosslinking of the networ

Multiresponsive Hyaluronan‐p(NiPAAm) “Click”‐Linked Hydrogels

“…The inclusion of hyaluronic acid as a constituent of the network enhances the biocompatibility and biodegradability of the construct. We have reported that in dextran/ p (methacrylate‐co‐NiPAAm) microgels the thermoresponsivity can hinder the enzyme biodegradation process above the VPTT . Moreover, high crosslinking degree affects negatively the enzyme catalyzed degradation .…”

“…We have reported that in dextran/ p(methacrylate-co-NiPAAm) microgels the thermoresponsivity can hinder the enzyme biodegradation process above the VPTT. [74] Moreover, high crosslinking degree affects negatively the enzyme catalyzed degradation. [66] Considering that HA is one of the components of the extracellular matrix, which is subject to a degradation catalyzed by metalloproteinases and hyaluronidases, the systems investigated here offer the opportunity to study, preliminarily in vitro, the degradation mechanism as a function of the temperature and of the degree of crosslinking.…”

Biodegradable colloidal microgels with tunable thermosensitive volume phase transitions for controllable drug delivery

“…Frequently used biocompatible and biodegradable polymers include gelatin [22][23][24], chitosan [25,26], alginate acid [27,28], hyaluronic acid [29,30], poly(lactic acid) [31], and dextran [32]. However they do not exhibit a well-characterized thermoresponsive property in general.…”

Imaging-assisted hydrogel formation for single cell isolation

“…Dex-MA hydrogels can be rapidly generated via photo-initiated cross-linking, and the polymer itself is well-characterized and easily accessible [27][28][29] . Importantly, Dex-MA hydrogels can also be degraded under biological conditions using dextran-specific enzyme -dextranase [30][31][32][33][34][35][36][37][38][39][40][41] . Additionally, to ensure the adhesion of fabricated hydrogels to glass surface during rinsing steps, we employed methacrylate-modified glass coverslips, thus leading to covalent bonding of hydrogel objects to the surface.…”