Nanogel Particles Based on Modified Nucleosides and Oligosaccharides as Advanced Delivery System.

This work addresses the challenge of delivering bioactive molecules by designing biocompatible nanogel particles (NGPs) utilizing rationally modified nature-sourced building blocks: capryl-oligochitosan and oxidized inosine. Capryl substituents endowed the resultant NGPs with membrane-penetration capabilities, while purine-containing inosine allowed H-bond/π-π/π-cation interactions. The prepared NGPs were complexed with carboxyfluorescein-labeled single-stranded oligonucleotide (FAM-oligo) and DsRed-encoding plasmid DNA. The successful delivery of FAM-oligo to the cell cytoplasm of the Nicotiana benthamiana plant was observed. Alexa 555-labeled bovine serum albumin (Alexa 555-BSA) was also efficiently encapsulated and delivered to the plant. In addition to delivering FAM-oligo and Alexa 555-BSA separately, NGPs also successfully co-delivered both biomolecules to the plant. Finally, NGPs successfully encapsulated the drug amphotericin B and reduced its toxicity while maintaining its efficacy. The presented findings suggest that NGPs may become a promising platform for the advanced delivery of bioactive molecules in various applications.

Oligochitosan and oxidized nucleoside-based bioderived hydrogels for wound healing.

Herein, we report biocompatible hydrogel for wound healing that was prepared using nature-sourced building blocks. For the first time, OCS was employed as a building macromolecule to form bulk hydrogels along with the nature-sourced nucleoside derivative (inosine dialdehyde, IdA) as the cross-linker. A strong correlation was obtained between the mechanical properties and stability of the prepared hydrogels with a cross-linker concentration. The Cryo-SEM images of IdA/OCS hydrogels showed an interconnected spongy-like porous structure. Alexa 555 labeled bovine serum albumin was incorporated into the hydrogels matrix. The release kinetics studies under physiological conditions indicated that cross-linker concentration could also control the release rate. The potential of hydrogels in wound healing applications was tested in vitro and ex vivo on human skin. Topical application of the hydrogel was excellently tolerated by the skin with no impairment of epidermal viability or irritation, determined by MTT and IL-1α assays, respectively. The hydrogels were used to load and deliver epidermal growth factor (EGF), showing an increase in its ameliorating action, effectively enhancing wound closure inflicted by punch biopsy. Furthermore, BrdU incorporation assay performed in both fibroblast and keratinocyte cells revealed an increased proliferation in hydrogel-treated cells and an enhancement of EGF impact in keratinocytes.

Nucleoside-Based Cross-Linkers for Hydrogels with Tunable Properties.

Herein, we report bioderived cross-linkers to create biopolymer-based hydrogels with tunable properties. Nucleosides (inosine and uridine) and ribose (pentose sugar lucking the nitrogenous base) were partially oxidized to yield inosine dialdehyde (IdA), uridine dialdehyde (UdA), and ribose dialdehyde (RdA). The dialdehydes were further used as cross-linkers with polysaccharide chitosan to form hydrogels. Depending on the cross-linker type and concentration, the hydrogels showed tunable rheological, mechanical, and liquid holding properties allowing the preparation of injectable, soft, and moldable hydrogels. Computational modeling and molecular dynamics simulations shed light on hydrogel formation and revealed that, in addition to covalent bonding, noncovalent interactions (π-π stacking, cation-π, and H-bonding) also significantly contributed to the cross-linking process. To demonstrate various application possibilities, the prepared hydrogels were used as a growth platform for plant cells, as injectable inks for layer-by-layer 3D printing applications, and as moldable hydrogels for soft lithography to replicate the microstructure of the plant. These findings suggest that the obtained tunable biocompatible hydrogels have the potential to be good candidates for various biotechnological applications.