Introduction The cutting-edge innovations in dermatology entail the combination of antinflammatory, antioxidant, antimicrobial, biocompatible and moisturizing features in composite, green systems. Nevertheless, it is uncommon to get such performances from environmentally sustainable, biodegradable materials [1]. Skin moisturization is an essential requirement for wound care materials, as well as for skin drug delivery systems, patches and beauty masks. In this respect, hydrogel-based formulations provide the right water content for skin issues management, while ensuring tunable loading and release properties [2]. In this work, it is described the development and characterization of an eco-friendly composite hydrogel, based on a mixture of polysaccharides and clays. The hydrogel has been loaded with berberine, a polyphenolic extract with antioxidant, antinflammatory and antimicrobial properties, already used to treat several skin conditions. The physico-chemical properties of the hydrogel have been extensively studied, as well as its cytocompatibility and berberine skin permeation kinetics. Experimental methods CMC-based hydrogels have been developed from our patented technology with modifications [3]. Berberine loading has been achieved through direct dissolution in water employed for hydrogel preparation or through prior intercalation in bentonite, one of the clays included in the composite. The hydrogel chemical composition and thermal properties have been assessed by FT-IR/ATR, XPS, XRD and TGA. Furthermore, hydrogels water uptake, gel fraction and berberine in vitro skin permeation have also been investigated. In vitro assessment has been performed on HaCaT and NhDF cells, evaluating viability and changes in cytoskeletal organization. Results and discussion The optimization of the hydrogel composition and crosslinking procedure enabled to tune the gel stiffness, as well as its water uptake. In particular, gallium ions were used as source of ionic crosslinking of the polysaccharide-based hydrogel composite, for the first time. The obtained hydrogels, after 24 hours, displayed a water uptake above 100 g/g. Transdermal permeations studies, performed by Franz diffusion cell, highlighted that both berberine containing hydrogels provided a gradual berberine release, reaching a plateau after 24h. Our results showed that at 48 h cells indirectly exposed to the hydrogels, with or without berberine, modify their behavior. In HaCaT, migratory features with the presence of lamellipodia and filopodia, as well as cell-cell separation with total or partial loss of intercellular junctions were observed. Conclusion The developed hydrogels, after a careful optimization of their composition, have been able to tune berberine release and water uptake, while being nontoxic for human keratinocytes. Overall, these systems represent a promising tool for future applications to treat both intact and damaged skin.
Polysaccharide-based hydrogels for local berberine delivery: an innovative strategy for wound healing
Loris Pinto;Federico Baruzzi;
2021
Abstract
Introduction The cutting-edge innovations in dermatology entail the combination of antinflammatory, antioxidant, antimicrobial, biocompatible and moisturizing features in composite, green systems. Nevertheless, it is uncommon to get such performances from environmentally sustainable, biodegradable materials [1]. Skin moisturization is an essential requirement for wound care materials, as well as for skin drug delivery systems, patches and beauty masks. In this respect, hydrogel-based formulations provide the right water content for skin issues management, while ensuring tunable loading and release properties [2]. In this work, it is described the development and characterization of an eco-friendly composite hydrogel, based on a mixture of polysaccharides and clays. The hydrogel has been loaded with berberine, a polyphenolic extract with antioxidant, antinflammatory and antimicrobial properties, already used to treat several skin conditions. The physico-chemical properties of the hydrogel have been extensively studied, as well as its cytocompatibility and berberine skin permeation kinetics. Experimental methods CMC-based hydrogels have been developed from our patented technology with modifications [3]. Berberine loading has been achieved through direct dissolution in water employed for hydrogel preparation or through prior intercalation in bentonite, one of the clays included in the composite. The hydrogel chemical composition and thermal properties have been assessed by FT-IR/ATR, XPS, XRD and TGA. Furthermore, hydrogels water uptake, gel fraction and berberine in vitro skin permeation have also been investigated. In vitro assessment has been performed on HaCaT and NhDF cells, evaluating viability and changes in cytoskeletal organization. Results and discussion The optimization of the hydrogel composition and crosslinking procedure enabled to tune the gel stiffness, as well as its water uptake. In particular, gallium ions were used as source of ionic crosslinking of the polysaccharide-based hydrogel composite, for the first time. The obtained hydrogels, after 24 hours, displayed a water uptake above 100 g/g. Transdermal permeations studies, performed by Franz diffusion cell, highlighted that both berberine containing hydrogels provided a gradual berberine release, reaching a plateau after 24h. Our results showed that at 48 h cells indirectly exposed to the hydrogels, with or without berberine, modify their behavior. In HaCaT, migratory features with the presence of lamellipodia and filopodia, as well as cell-cell separation with total or partial loss of intercellular junctions were observed. Conclusion The developed hydrogels, after a careful optimization of their composition, have been able to tune berberine release and water uptake, while being nontoxic for human keratinocytes. Overall, these systems represent a promising tool for future applications to treat both intact and damaged skin.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
