Enzymatically crosslinked hyaluronic acid microgels as a vehicle for sustained delivery of cationic proteins

Jooybar, Elaheh; Abdekhodaie, Mohammad J.; Mousavi, Abbas; Zoetebier, Bram; Dijkstra, Pieter J.

doi:10.1016/j.eurpolymj.2019.03.032

Cited by 14 publications

(7 citation statements)

References 47 publications

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“…Biomacromolecular drugs, for instance, need such systems to provide conformational stabilization, protect them from degradation, and control their release rate, which causes the reduction in toxicity, thus preventing side-effects [ 80 ]. Besides that, molecules such as growth factors, hormones, enzymes, and antibodies have short half-lives [ 81 ]. The highly hydrophilic nature of most hydrogels is responsible for limiting aggregation and conformational changes of the biomacromolecules.…”

Section: Microgelsmentioning

confidence: 99%

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An Updated Review of Macro, Micro, and Nanostructured Hydrogels for Biomedical and Pharmaceutical Applications

et al. 2020

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Hydrogels are materials with wide applications in several fields, including the biomedical and pharmaceutical industries. Their properties such as the capacity of absorbing great amounts of aqueous solutions without losing shape and mechanical properties, as well as loading drugs of different nature, including hydrophobic ones and biomolecules, give an idea of their versatility and promising demand. As they have been explored in a great number of studies for years, many routes of synthesis have been developed, especially for chemical/permanent hydrogels. In the same way, stimuli-responsive hydrogels, also known as intelligent materials, have been explored too, enhancing the regulation of properties such as targeting and drug release. By controlling the particle size, hydrogel on the micro- and nanoscale have been studied likewise and have increased, even more, the possibilities for applications of the so-called XXI century materials. In this paper, we aimed to produce an overview of the recent studies concerning methods of synthesis, biomedical, and pharmaceutical applications of macro-, micro, and nanogels.

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Section: Microgelsmentioning

confidence: 99%

“…The system was prepared in an inverse microemulsion and crosslinked by and enzyme. In this study, the researchers demonstrated that the drug delivery system could maintain a sustained release for more than four weeks through diffusion and degradation of the microgel [ 81 ].…”

Section: Microgelsmentioning

confidence: 99%

An Updated Review of Macro, Micro, and Nanostructured Hydrogels for Biomedical and Pharmaceutical Applications

et al. 2020

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“…Among microgel manufacture techniques, inverse emulsion (water‐in‐oil emulsion) is employed to obtain polysaccharide‐based microgels. [ 3,9–12 ] For this, mini‐ or microemulsions are achieved by applying high shear forces with suitable water/oil ratio in the presence of surfactant to obtain droplets of sub‐micrometer or micrometer size. [ 2,13 ] The crosslinking reaction inside droplets can be achieved by physical interactions (electrostatic or van der Waals interactions) or covalent chemical reaction.…”

Section: Introductionmentioning

confidence: 99%

“…[ 14–16 ] Enzymes involved in crosslinking reactions are mainly horseradish peroxidase (HRP), transglutaminase, or tyrosinase. [ 17 ] For example, tyramine‐functionalized hyaluronic acid was crosslinked with HRP (in the presence of H 2 O 2 ) to produce microgels for cell culture, [ 18 ] delivery of proteins, [ 12 ] or tissue engineering. [ 19 ]…”

Section: Introductionmentioning

confidence: 99%

Microgels Based on Carboxymethylpullulan Grafted with Ferulic Acid Obtained by Enzymatic Crosslinking in Emulsion for Drug Delivery Systems

Dulong

Morel

Labat

et al. 2021

Macromolecular Bioscience

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Carboxymethylpullulan (CMP) grafted with ferulic acid (FA) is crosslinked with laccase by the reverse water‐in‐oil emulsion technique (with sunflower oil) to obtain microgels with size from 40 to 200 µm. It is demonstrated that laccase activity and dispersion time have an impact on microgels’ size. Fluorescence spectroscopy of different probes (e.g., pyrene, Nile red, and curcumin) shows the nonpolar characteristics of hydrophobic microdomains formed by the FA moieties and its dimers forming the crosslinking nodes. Encapsulation and release of curcumin or lidocaine used as drug models are studied in different buffers. Curcumin is well encapsulated but retained in microgels, while lidocaine is released at 65–70% in 2 h and 30 min in buffer simulating the gastrointestinal tract and at 75–85% in 1 h in acetate buffer pH 5.6 or phosphate‐buffered saline (PBS) pH 6.9.

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“…Microgels are cross-linked polymeric particles with a tunable size from hundreds of nanometers to several micrometers. In recent years, microgels have been widely studied as the means of universal and multifunctional platforms in the fields of targeted drug delivery, sustained protein release, tissue engineering, biomedical implants, bionanotechnology medicine on account of their biocompatibility, biodegradability, tunable size, and a large surface area for multivalent bioconjugation . In general, the microgels are synthesized from naturally occurring polymers or synthetic polymers.…”

Section: Introductionmentioning

confidence: 99%

Dual-Degradable Biohybrid Microgels by Direct Cross-Linking of Chitosan and Dextran Using Azide–Alkyne Cycloaddition

Jain

et al. 2020

Biomacromolecules

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In this work, biocompatible and degradable biohybrid microgels based on chitosan and dextran were synthesized for drug delivery applications. Two kinds of bio-based building blocks, alkyne-modified chitosan and azide-modified dextran, were used to fabricate microgels via single-step cross-linking in water-in-oil emulsions. The cross-linking was initiated in the presence of copper(II) without the use of any extra cross-linkers. A series of pH-responsive and degradable microgels were successfully synthesized by varying the degree of cross-links. The microgels were characterized using 1H NMR and FTIR spectroscopy which proved the successful cross-linking of alkyne-modified chitosan and azide-modified dextran by copper(II)-mediated click reaction. The obtained microgels exhibit polyampholyte character and can carry positive or negative charges in aqueous solutions at different pH values. Biodegradability of microgels was shown at pH 9 or in the presence of Dextranase due to the hydrolysis of carbonate esters in the microgels or 1,6-α-glucosidic linkages in dextran structure, respectively. Furthermore, the microgels could encapsulate vancomycin hydrochloride (VM), an antibiotic, with a high loading of approximately 93.67% via electrostatic interactions. The payload could be released in the presence of Dextranase or under an alkaline environment, making the microgels potential candidates for drug delivery, such as colon-specific drug release.

show abstract

Enzymatically crosslinked hyaluronic acid microgels as a vehicle for sustained delivery of cationic proteins

Cited by 14 publications

References 47 publications

An Updated Review of Macro, Micro, and Nanostructured Hydrogels for Biomedical and Pharmaceutical Applications

An Updated Review of Macro, Micro, and Nanostructured Hydrogels for Biomedical and Pharmaceutical Applications

Microgels Based on Carboxymethylpullulan Grafted with Ferulic Acid Obtained by Enzymatic Crosslinking in Emulsion for Drug Delivery Systems

Dual-Degradable Biohybrid Microgels by Direct Cross-Linking of Chitosan and Dextran Using Azide–Alkyne Cycloaddition

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