Self-gelling hydrogels based on oppositely charged dextran microspheres

Abstract

This paper presents a novel self-gelling hydrogel potentially suitable for controlled drug delivery and tissue engineering. The macroscopic gels are obtained by mixing dispersions of oppositely charged crosslinked dextran microspheres. These microspheres in turn were prepared by crosslinking of dextran derivatized with hydroxyethyl methacrylate emulsified in an aqueous poly(ethylene glycol) solution. Negatively or positively charged microspheres were obtained by addition of methacrylic acid (MAA) or dimethylaminoethyl methacrylate (DMAEMA) to the polymerization mixture. Rheological analysis showed that instantaneous gelation occurred when equal volumes of oppositely charged microspheres, dispersed in buffer solutions of pH 7, were mixed. The shear modulus of the networks could be tailored from 30 to 6500 Pa by varying the water content of the system. Moreover, controlled strain and creep experiments showed that the formed networks were mainly elastic. Importantly for application of these systems, e.g. as controlled matrix of pharmaceutically active proteins, it was demonstrated that the hydrogel system has a reversible yield point, meaning that above a certain applied stress, the system starts to flow, whereas when the stress is removed, gel formation occurred. Further it was shown that the network structure could be broken by either a low pH or a high ionic strength of the medium. This demonstrates that the networks, formed at pH 7 and at low ionic strength, are held together by ionic interactions between the oppositely charged dextran microspheres. This system holds promise as injectable gels that are suitable for drug delivery and tissue engineering applications. r

Effect of particle size and charge on the network properties of microsphere-based hydrogels

“…as a result of exposure to organic solvent or crosslinking agents, can be avoided when making use of selfassembling systems [13]. In situ formation of hydrogels, mainly based on physical crosslinking between polymer chains can be accomplished through, among others, hydrogen bonding [14,15], crystallization [16], hydrophobic interactions as a result of temperature changes [17], ionic interactions [18][19][20], or stereocomplexes [21,22]. Besides in the protein delivery field, hydrogels have been widely used in tissue engineering applications [23][24][25][26][27].…”

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

“…The addition of a short peptide (Arg-Gly-Asp) as a target ligand to these micelles improved their cell uptake efficacy [315]. Moreover, dextran (Dex) based microgels e.g., dextran-hydroxyethyl methacrylate (Dex-HEMA) could easily be loaded with macromolecules such as proteins and dyes (FITC) as well as latex nanoparticles (NPs, 20kDa) labeled with dyes [316][317][318][319]. The bio-polycation i.e., a poly-Larginine (pARG) labeled with rodamine B isothiocyanate (RITC) or tertramethylrodamine isothiocyanate (TRITC) can form coatings on the Dex-HEMA microgel yielding a clear red fluorescence [320,321].…”

In-Situ Forming Biomimetic Hydrogels for Tissue Regeneration

“…For example, Hennink et al reported on self-gelling hydrogels based on oppositely charged dextran microspheres (Tomme et al, 2005). These charged dextranmicrospheres were prepared by radical polymerization of hydroxyethyl methacrylatederivatized dextran (dex-HEMA) with methacrylic acid (MAA) or dimethylaminoethyl methacrylate (DMAEMA).…”