“Click” hyaluronan based nanohydrogels as multifunctionalizable carriers for hydrophobic drugs

Manzi, Giuliana; Zoratto, Nicole; Matano, Silvia; Sabia, Rocchina; Villani, Claudio; Coviello, Tommasina; Matricardi, Pietro; Meo, Chiara Di

doi:10.1016/j.carbpol.2017.07.003

Cited by 28 publications

(18 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Copper(I)-catalyzed azide-alkyne click (CuAAC) reactions have been applied for preparing HA-based hydrogel networks for diverse bioapplications [ 47 , 48 , 49 ]. However, upon click reaction, cytotoxic copper traces may remain inside the polymer network, harming encapsulated bioactive compounds, such as DNA, proteins, or cells [ 4 , 50 ].…”

Section: Resultsmentioning

confidence: 99%

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

et al. 2020

View full text Add to dashboard Cite

The demand for tailored, micrometer-scaled biomaterials in cell biology and (cell-free) biotechnology has led to the development of tunable microgel systems based on natural polymers, such as hyaluronic acid (HA). To precisely tailor their physicochemical and mechanical properties and thus to address the need for well-defined microgel systems, in this study, a bottom-up material guide is presented that highlights the synergy between highly selective bio-orthogonal click chemistry strategies and the versatility of a droplet microfluidics (MF)-assisted microgel design. By employing MF, microgels based on modified HA-derivates and homobifunctional poly(ethylene glycol) (PEG)-crosslinkers are prepared via three different types of click reaction: Diels–Alder [4 + 2] cycloaddition, strain-promoted azide-alkyne cycloaddition (SPAAC), and UV-initiated thiol–ene reaction. First, chemical modification strategies of HA are screened in-depth. Beyond the microfluidic processing of HA-derivates yielding monodisperse microgels, in an analytical study, we show that their physicochemical and mechanical properties—e.g., permeability, (thermo)stability, and elasticity—can be systematically adapted with respect to the type of click reaction and PEG-crosslinker concentration. In addition, we highlight the versatility of our HA-microgel design by preparing non-spherical microgels and introduce, for the first time, a selective, hetero-trifunctional HA-based microgel system with multiple binding sites. As a result, a holistic material guide is provided to tailor fundamental properties of HA-microgels for their potential application in cell biology and (cell-free) biotechnology.

show abstract

Section: Resultsmentioning

confidence: 99%

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

et al. 2020

View full text Add to dashboard Cite

show abstract

“…By the reaction of HA-TBA with Rfv-Br, an amphiphilic polymer was obtained [20], capable of self-assembling in aqueous environment under suitable conditions, as nanoprecipitation, ultrasound or autoclave treatments [17,18,19,20,21], thus forming NHs. For the synthesis, the use of the tetrabutiryl-Rfv reagent is due to the low solubility of not-esterified riboflavin in both aqueous and organic solvents; similarly, the TBA + salt of HA was used to carry out the nucleophilic substitution in an aprotic polar solvent (DMSO).…”

Section: Resultsmentioning

confidence: 99%

“…Recently, a new type of amphiphilic HA derivative for NHs formation has been developed, using a riboflavin tetra-ester as hydrophobic moiety [20]. The obtained hyaluronate-riboflavin derivative (HA-Rfv) NHs show an improved stability with respect to HA-cholesterol based nanocarriers, along with an enhanced drug loading capacity; in particular, an excellent behavior is shown in loading hydrophobic molecules, thus leading to their enhanced apparent water-solubility and allowing to obtain aqueous formulations of insoluble drugs [20,21]. For this purpose, piroxicam is selected as model hydrophobic drug.…”

Section: Introductionmentioning

confidence: 99%

Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs

et al. 2018

Self Cite

View full text Add to dashboard Cite

Nanohydrogels based on natural polymers, such as polysaccharides, are gaining interest as vehicles for therapeutic agents, as they can modify the pharmacokinetics and pharmacodynamics of the carried drugs. In this work, hyaluronan-riboflavin nanohydrogels were tested in vivo in healthy rats highlighting their lack of toxicity, even at high doses, and their different biodistribution with respect to that of native hyaluronan. They were also exploited as carriers of a hydrophobic model drug, the anti-inflammatory piroxicam, that was physically embedded within the nanohydrogels by an autoclave treatment. The nanoformulation was tested by intravenous administration showing an improvement of the pharmacokinetic parameters of the molecule. The obtained results indicate that hyaluronan-based self-assembled nanohydrogels are suitable systems for low-soluble drug administration, by increasing the dose as well as the circulation time of poorly available therapeutic agents.

show abstract

“…Hydrogel formation of amphiphilic HA relies on supramolecular self-assembly, with establishment of physical bonds, namely, hydrophobic interactions between polymer chains [65]. Reported HA amphiphilic derivatives comprise the incorporation of riboflavin [66], hexylamine [65], dodecylamine [65] or octadecylamine [65,67,68].…”

Section: Inclusion Complexesmentioning

confidence: 99%

Glycosaminoglycan-Inspired Biomaterials for the Development of Bioactive Hydrogel Networks

et al. 2020

View full text Add to dashboard Cite

Glycosaminoglycans (GAG) are long, linear polysaccharides that display a wide range of relevant biological roles. Particularly, in the extracellular matrix (ECM) GAG specifically interact with other biological molecules, such as growth factors, protecting them from proteolysis or inhibiting factors. Additionally, ECM GAG are partially responsible for the mechanical stability of tissues due to their capacity to retain high amounts of water, enabling hydration of the ECM and rendering it resistant to compressive forces. In this review, the use of GAG for developing hydrogel networks with improved biological activity and/or mechanical properties is discussed. Greater focus is given to strategies involving the production of hydrogels that are composed of GAG alone or in combination with other materials. Additionally, approaches used to introduce GAG-inspired features in biomaterials of different sources will also be presented.

show abstract

“Click” hyaluronan based nanohydrogels as multifunctionalizable carriers for hydrophobic drugs

Cited by 28 publications

References 35 publications

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs

Glycosaminoglycan-Inspired Biomaterials for the Development of Bioactive Hydrogel Networks

Contact Info

Product

Resources

About