Accelerated full-thickness skin wound tissue regeneration by self-crosslinked chitosan hydrogel films reinforced by oxidized CNC-AgNPs stabilized Pickering emulsion for quercetin delivery.

BACKGROUND: The non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs. RESULTS: The DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice. CONCLUSION: Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.

ThermOxshield ion pair self assembly unleashing suppressed release.

Poly (acrylic acid) (PAA), an anionic polymer was used to prepare ion pair self-assembly (IPSAM) with 4-(methylthio)aniline (MTA), a hydrophobic counter ion, which is responsive to temperature and oxidation. The IPSAM was formed when the carboxylic to amino group molar ratio was 7/3-5/5. The structure of the IPSAM nanoparticle was spherical whose diameter was 30-40 nm on the TEM images. The PAA/MTA ion pair showed the upper critical solution temperature (UCST) that hiked with increasing MTA content. When the MTA of the ion pair was oxidized by H2O2, the UCST was also increased. The amphiphilic property of the ion pair was responsible for interface activity which declined upon the oxidation of the MTA. The surface tension was low for the ratio of PAA/MTA (5/5), which made the 5/5 ratio suitable for further studies. The interaction between PAA and MTA, which was ionic, and the oxidation of MTA was confirmed by FT-IR spectroscopy. The release of payload (i.e. Nile red) in IPSAM was restrained below the UCST but it was triggered above the phase transition temperature possibly due to the disintegration of the IPSAM whereas on MTA oxidation the release was shielded due to more hydrophobicity. The release was found to be higher in tumor environment temperature which could be controlled with the input concentration of H2O2 giving a stable IPSAM. The cell viability results showed that IPSAM has no significant cytotoxicity and can serve as a drug carrier for stimulus-response.