Construction and functional evaluation of oral long-acting insulin hydrogel microparticles based on physical and chemical double crosslinking.

The objective of this study was to enhance the convenience and effectiveness of diabetes treatment by developing hydrogel microparticles as an oral insulin delivery system, aiming to reduce the necessity for frequent treatments. The hydrogel microparticles were prepared with polysaccharides through a combination of physical and chemical crosslinking method, they achieved good results in insulin loading efficiency (70 %), insulin release efficiency (98 %) and sustained release time (>20 h). The effective transmembrane transport was validated using an intestinal epithelial cell model, which demonstrated a continuous hypoglycemic effect lasting from 6 to 26 h in a type 2 diabetes mouse model. Additionally, the relative bioavailability of insulin reached 30.14 ± 2.62 %, representing a significant breakthrough in the field of oral insulin delivery carriers. Furthermore, oral insulin hydrogel exhibited a substantial improvement in insulin resistance, organ damage, and diabetes-related complications stemming from hyperglycemia. These compelling findings underscore the potential of hydrogel microparticles as a cost-effective and valuable strategy for oral drug delivery in diabetes treatment.

A composite hydrogel scaffold based on collagen and carboxymethyl chitosan for cartilage regeneration through one-step chemical crosslinking.

The number of cases of cartilage damage worldwide is increasing annually and this problem severely limits an individual's physical activities, subsequently contributing to additional medical problems. Hydrogels can repair cartilage defects and promote cartilage regeneration. In this study, a composite hydrogel scaffold was prepared with collagen (COL), carboxymethyl chitosan (CMC), and the Arg-Gly-Asp (RGD) peptide through one-step chemical crosslinking, in which the three compositions ratio was especially investigated. The hydrogel scaffold performed well in cell adhesion and biocompatibility experiments, mainly due to the favorable porosity (the aperture was concentrated at 100 µm and the porosity was >70 %) and RGD concentration (2 mM RGD was the optimal concentration, which could effectively improve the attachment of BMSCs to the stent). Moreover, bone marrow mesenchymal stem cells (BMSCs) filled in the hydrogel scaffold, together with transforming growth factor TGF-ß3, which was applied to evaluate the feasibility on the repair of the injured cartilage of the rat. In vitro and in vivo study, according to the results of cell proliferation and cytotoxicity, the hydrogel material had no toxic effect on cells, and the COL2/CMC1 hydrogel scaffold had the most obvious role in promoting cell proliferation. The results of pathological section showed that the cell scaffold complex group provided good mechanical properties for the wound and supplemented the stem cells derived from chondrocytes and showed good cartilage defect repair effect; In the scaffold group, the surface fibrosis of the injured area was mainly filled with fibrocartilage and other collagen fibers The hydrogel/BMSCs complex based on COL and CMC can be beneficial for the regeneration of cartilage.