ß-Cyclodextrin/dialdehyde glucan-coated keratin nanoparticles for oral delivery of insulin.

Successful oral insulin administration can considerably enhance the quality of life (QOL) of diabetes patients who must frequently take insulin injections. However, Oral insulin administration is seriously hampered by gastrointestinal enzymes, wide pH range, mucus and mucosal layers, which limit insulin oral bioavailability to ≤2 %. Herein, we developed a simple, inexpensive and safe dual ß-cyclodextrin/dialdehyde glucan-coated keratin nanoparticle (ß-CD-K-IN-DG). The resulted ß-CD-K-IN-DG not only gave the ultra-high insulin loading (encapsulation efficiency (98.52 %)), but also protected insulin from acid and enzymatic degradation. This ß-CD-K-IN-DG had a notable hypoglycemic effect, there was almost 80 % insulin release after 4 h of incubation under hyperglycemic conditions. Ex vivo results confirmed that ß-CD-K-IN-DG possessed high mucus-penetration ability. Transepithelial transport and uptake mechanism studies revealed that bypass transport pathway and endocytosis promoted ß-CD-K-IN-DG entered intestinal epithelial cells, thus increased the bioavailability of insulin (12.27 %). The improved stability of insulin during in vivo transport implied that ß-CD-K-IN-DG might be a potential tool for the effective oral insulin administration.

Modulating the gut microbiota is involved in the effect of low-molecular-weight Glycyrrhiza polysaccharide on immune function.

Low molecular weight (6.5 kDa) Glycyrrhiza polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4+, CD8+ T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-ß3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Alistipes, Lachnospiraceae_NK4A136_group, Ligilactobacillus, and Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria and CTX-derived bacteria (Clostridiales_unclassified, Candidatus_Arthromitus, Firmicutes_unclassified, and Clostridium). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.