Keloid is a kind of unique human fibroproliferative dermal disease, and there are still no optimal treatment methods for it. In the present study, a thermosensitive hydroxybutyl chitosan (HBC) hydrogel as a co-delivery matrix for 5-fluorouracil (5-FU) and dexamethasone sodium phosphate (DEXSP) in keloid treatment was developed. The gelation temperature of the HBC hydrogel was observed to be 25.7 °C by rheology analysis. The HBC hydrogel showed sustained drug release capacity (5-FU, 89.3 ± 3.4%; DEXSP, 95.6 ± 3.9%) for drug delivery. The HBC hydrogel was shown to be cytocompatible, while the dual drug-loaded HBC hydrogel could suppress the proliferation of keloid fibroblasts (KFs). The keloid biopsies treated with the dual drug-loaded hydrogel could be inhibited through the efficient suppression of VEGF expression within 7 days. The results suggested that the HBC hydrogel could be applied as a potential co-delivery matrix for drugs in the keloid therapy field.

The aim of this study was to present a non-trypsin 3D cell culture method with a reversible thermosensitive HBCS hydrogel. In this study, hydroxybutyl chitosan (HBCS) was synthesized by grafting hydroxybutyl groups on chitosan molecule chains. The prepared HBCS was water-soluble, and the reversible phase transformation temperature was 26 °C. Scanning electron microscope images illuminated the 3-D network of hydrogel formed irregular porous structure which ranged from 50–250 μm. Cell viability assay indicated that HBCS solution could promote the proliferation of human umbilical vein endothelial cells (HUVECs), and the boost of proliferation was enhanced with the increase of HBCS concentration. HBCS had no harm to the nitric oxide (NO) synthesis functionality of HUVECs. HUVECs could grow and reproduce inside the hydrogel, and showed good vitality after 14-days culture. Meanwhile, cells cultured inside the hydrogel could be passaged successively through the reversible phase transformation process of HBCS. The results revealed that HBCS have the potential to be used for 3-D cell culture without the use of trypsin.

Oleoyl-carboxymethy-chitosan (OCMCS) nanoparticles based on chitosan with various molecular weights were prepared using coacervation process, which demonstrated particle size of 150–350 nm, zeta potential of 10–20 mV, and high encapsulation efficiency of fluorescein isothiocyanate dextran (FD4). OCMCS nanoparticles were found to be adsorbed onto the excised carp intestinal mucosa, the extent of adsorption increased with increasing chitosan molecular weight. In comparison to FD4 solution, OCMCS nanoparticles promoted FD4 transport through excised carp intestinal mucosa by 3.26–6.52 folds, which were observed via fluorescence microscope. The OCMCS nanoparticulate systems that interacted with the Caco-2 cells decreased the transepithelial electric resistance (TEER) and induced increasing the apparent permeability coefficient (Papp) of FD4 by 3.61–6.32 folds. Cytotoxicity studies in Caco-2 monolayers verified the safety of the delivery system. The improvement of mucoadhesive ability and permeability enable the OCMCS nanosystems suitable carriers for the intestinal absorption of protein drugs.Graphical abstractHighlights► OCMCS was investigated for the mucoadhesion and permeation enhancement at neutral pH. ► OCMCS nanoparticles showed high adhesion tendency onto carp intestinal mucosa. ► OCMCS nanoparticles promoted FD4 transport through excised carp intestinal mucosa. ► The improvement of permeability was further verified via Caco-2 cell monolayer. ► Cytotoxicity studies in Caco-2 monolayers verified the safety of the delivery system.

Layer-by-layer (LbL) alginate beads, which were prepared by multi-phase emulsion technique, had been fabricated via the ionic crosslinking between calcium ion (Ca2+) and the carboxylic group of alginate. The prepared beads were spherical, smooth-surfaced and non-aggregated. The SEM analysis displayed the LbL structure of the beads clearly. It had been demonstrated that the size of the beads was controllable and had a correlation with concentration of sodium alginate (SA) and CaCl2, ratio of water phase and oil phase (W/O), stirring speed, pH value of the water phase, viscosity of SA as well as the temperature for solidification. Stability studies showed that the beads degraded slowly in simulated gastric fluid and simulated intestinal fluid but degraded sharply when they were moved to simulated colonic fluid. Cytotoxicity study by MTT assay indicated that the prepared beads are slightly toxic. It is hoped that this kind of novel beads could be used in pharmaceutical area and cell culture area.

Keloid is a kind of unique human fibroproliferative dermal disease, and there are still no optimal treatment methods for it. In the present study, a thermosensitive hydroxybutyl chitosan (HBC) hydrogel as a co-delivery matrix for 5-fluorouracil (5-FU) and dexamethasone sodium phosphate (DEXSP) in keloid treatment was developed. The gelation temperature of the HBC hydrogel was observed to be 25.7 °C by rheology analysis. The HBC hydrogel showed sustained drug release capacity (5-FU, 89.3 ± 3.4%; DEXSP, 95.6 ± 3.9%) for drug delivery. The HBC hydrogel was shown to be cytocompatible, while the dual drug-loaded HBC hydrogel could suppress the proliferation of keloid fibroblasts (KFs). The keloid biopsies treated with the dual drug-loaded hydrogel could be inhibited through the efficient suppression of VEGF expression within 7 days. The results suggested that the HBC hydrogel could be applied as a potential co-delivery matrix for drugs in the keloid therapy field.