Mechanistic investigations into the encapsulation and release of small molecules and proteins from a supramolecular nucleoside gel in vitro and in vivo

Zelzer, Mischa; Márkus, Róbert; Paraskevopoulou, Vasiliki; Foralosso, Rugerro; Clarke, Paula J.; Álvarez, Clara V.; Chenlo, Miguel; Johnson, Litty; Allen, Stephanie; Brasnett, Christopher; Seddon, Annela M.; Marlow, Maria

doi:10.1016/j.jconrel.2019.10.011

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…Erosion-mediated release has been exploited in supramolecular hydrogels for the controlled delivery of proteins that is regulated by degradation of the hydrogel structure (Figure 7b). A self-healing supramolecular hydrogel formed with the N4-octanoyl-2deoxycytidine gelator was used to encapsulate several proteins (BSA, β-lactoglobulin, lysozyme and insulin) and study their release profile [78]. The release profiles of all the model proteins exhibited similar trends within 24 h and were also consistent with the profile of hydrogel degradation, suggesting that degradation might be the dominated mechanism for release regardless of the properties of loaded proteins.…”

Section: Erosion-controlled Releasementioning

confidence: 80%

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Lyu

Azevedo

2021

Molecules

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Therapeutic proteins, such as growth factors (GFs), have been used in tissue engineering (TE) approaches for their ability to provide signals to cells and orchestrate the formation of functional tissue. However, to be effective and minimize off-target effects, GFs should be delivered at the target site with temporal control. In addition, protein drugs are typically sensitive water soluble macromolecules with delicate structure. As such, hydrogels, containing large amounts of water, provide a compatible environment for the direct incorporation of proteins within the hydrogel network, while their release rate can be tuned by engineering the network chemistry and density. Being formed by transient crosslinks, afforded by non-covalent interactions, supramolecular hydrogels offer important advantages for protein delivery applications. This review describes various types of supramolecular hydrogels using a repertoire of diverse building blocks, their use for protein delivery and their further application in TE contexts. By reviewing the recent literature on this topic, the merits of supramolecular hydrogels are highlighted as well as their limitations, with high expectations for new advances they will provide for TE in the near future.

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Section: Erosion-controlled Releasementioning

confidence: 80%

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Lyu

Azevedo

2021

Molecules

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“…The fluorescence studies conducted in sodium acetate at pH 7.4, along wi concentration-dependent experiments, provide essential contributions to understa the dynamics of self-assembly. To universally excite the two aromatic amino acids nylalanine and tyrosine, embedded within the peptide backbone, an excitation length of 275 nm was employed [39]. As represented in Figure 5, the noticeable dec fluorescence intensity at 304 nm, coupled with the concurrent decrease in the sho within the 322-335 nm range after 20 min, alongside a reduction in fluorescence int in the violet-blue region (390-450 nm), collectively signifies significant changes microenvironment enveloping the aromatic amino acids (phenylalanine and tyro These observed alterations strongly suggest a compelling correlation with the ge process [40].…”

Section: Fluorescence Studiesmentioning

confidence: 99%

Self-Assembly of a Novel Pentapeptide into Hydrogelated Dendritic Architecture: Synthesis, Properties, Molecular Docking and Prospective Applications

Jitaru,

Enache,

Cojocaru

et al. 2024

Gels

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Currently, ultrashort oligopeptides consisting of fewer than eight amino acids represent a cutting-edge frontier in materials science, particularly in the realm of hydrogel formation. By employing solid-phase synthesis with the Fmoc/tBu approach, a novel pentapeptide, FEYNF-NH2, was designed, inspired by a previously studied sequence chosen from hen egg-white lysozyme (FESNF-NH2). Qualitative peptide analysis was based on reverse-phase high performance liquid chromatography (RP-HPLC), while further purification was accomplished using solid-phase extraction (SPE). Exact molecular ion confirmation was achieved by matrix-assisted laser desorption–ionization mass spectrometry (MALDI-ToF MS) using two different matrices (HCCA and DHB). Additionally, the molecular ion of interest was subjected to tandem mass spectrometry (MS/MS) employing collision-induced dissociation (CID) to confirm the synthesized peptide structure. A combination of research techniques, including Fourier-transform infrared spectroscopy (FTIR), fluorescence analysis, transmission electron microscopy, polarized light microscopy, and Congo red staining assay, were carefully employed to glean valuable insights into the self-assembly phenomena and gelation process of the modified FEYNF-NH2 peptide. Furthermore, molecular docking simulations were conducted to deepen our understanding of the mechanisms underlying the pentapeptide’s supramolecular assembly formation and intermolecular interactions. Our study provides potential insights into amyloid research and proposes a novel peptide for advancements in materials science. In this regard, in silico studies were performed to explore the FEYNF peptide’s ability to form polyplexes.

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“…Reports on nucleic acids ‐ based hydrogels in drug delivery include oligomer cytosine‐polypropylene glycol comprising hydrogen‐bonded Cy moieties, [118a] DNA comprising un‐methylated cytosine‐phosphate‐guanine dinucleotides, [118b] Ge containing DNA, [118c] glyconucleoside bolaamphiphiles having stilbene, [118d] N4‐octanoyl‐2‐deoxycytidine, [118e] and nucleotide‐lipid salt [118f] …”

Section: Supramolecular Gelsmentioning

confidence: 99%

Recent Updates on Supramolecular‐Based Drug Delivery – Macrocycles and Supramolecular Gels

Saji

2022

The Chemical Record

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Supramolecules‐based drug delivery has attracted significant recent research attention as it could enhance drug solubility, retention time, targeting, and stimuli responsiveness. Among the different supramolecules and assemblies, the macrocycles and the supramolecular hydrogels are the two important categories investigated to a greater extent. Here, we provide the most recent advancements in these categories. Under macrocycles, reports on drug delivery by cyclodextrins, cucurbiturils, calixarenes/pillararenes, crown ethers and porphyrins are detailed. The second category discusses the supramolecular hydrogels of macrocycles/polymers and low molecular weight gelators. The updated information provided could be helpful to advance R & D in this vital area.

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Mechanistic investigations into the encapsulation and release of small molecules and proteins from a supramolecular nucleoside gel in vitro and in vivo

Cited by 11 publications

References 48 publications

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

Self-Assembly of a Novel Pentapeptide into Hydrogelated Dendritic Architecture: Synthesis, Properties, Molecular Docking and Prospective Applications

Recent Updates on Supramolecular‐Based Drug Delivery – Macrocycles and Supramolecular Gels

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