Metal-polyphenol microgels for oral delivery of puerarin to alleviate the onset of diabetes.

Puerarin (Pue) is a naturally bioactive compound with many potential functions in regulating blood glucose and lipid metabolism. However, the low bioavailability and rapid elimination in vivo limit the application of Pue in diabetic treatment. Here, we developed a metal-polyphenol-functionalized microgel to effectively deliver Pue in vivo and eventually alleviate the onset of diabetes. Pue was initially encapsulated in alginate beads through electrospray technology, and further immersed in Fe3+ and tannic acid solution from tannic acid (TA)-iron (Fe) coatings (TF). These constructed Pue@SA-TF microgels exhibited uniform spheres with an average size of 367.89 ± 18.74 µm and high encapsulation efficiency of Pue with 61.16 ± 1.39%. In vivo experiments proved that compared with free Pue and microgels without TF coatings, the biological distribution of Pue@SA-TF microgels specifically accumulated in the small intestine, prolonged the retention time of Pue, and achieved a high effectiveness in vivo. Anti-diabetic experimental results showed that Pue@SA-TF microgels significantly improved the levels of blood glucose, blood lipid, and oxidative stress in diabetic mice. Meanwhile, histopathological observations indicated that Pue@SA-TF microgels could significantly alleviate the damage to the liver, kidney, and pancreas in diabetic mice. Our study provided an effective strategy for oral delivery of Pue and achieved high anti-diabetic efficacy.

Phosphatidylserine-functionalized liposomes-in-microgels for delivering genistein to effectively treat ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory disease involving ulcers in the colon and rectum. The conventional treatments for UC still have many limitations, such as non-specific release, adverse effects and low absorption, resulting in the poor bioavailability of therapeutic agents. To address these challenges, targeting delivery systems are required to specifically deliver drugs to the colonic site with controlled release. Herein, we present a novel microgel oral delivery system, loaded with liposome nanoparticles (Li NPs) containing a natural anti-inflammatory compound genistein (Gen) into alginate microgels, thereby achieving the targeted release of Gen in the colonic region and ameliorating UC symptoms. Initially, Gen was loaded into phosphatidylserine (PS)-functionalized Li NPs to form Gen@Li NPs with an average size of 245.9 ± 9.6 nm. In vitro assessments confirmed that Gen@Li NPs efficiently targeted macrophages and facilitated the internalization of Gen into cells. To prevent rapid degradation in the harsh gastrointestinal tract, Gen@Li NPs were further encapsulated into alginate microgels through electric spraying technology, forming Gen@Li microgels. In vivo distribution tests demonstrated that Gen@Li microgels possessed long-term retention in the colon and gradual release characteristics compared to Gen@Li NPs. Furthermore, in vivo experiments confirmed that Gen@Li microgels significantly alleviated UC symptoms in mice induced by dextran sulfate sodium salt (DSS) mainly through reducing the expression levels of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) and promoting colonic mucosal barrier repair through upregulation of mucosal protein expression. This study shed light on the potential of utilizing oral administration of natural compounds for UC treatment.

Helical-Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus.

Oral delivery of antidiabetic active components promises to free millions of people from daily suffering who require routine injections. However, oral insulin (Ins) and other short-acting compounds such as nateglinide (NG) in harsh gastrointestinal tract still face great challenging, including low bioavailability, and rapid elimination. In this study, inspired by the self-assembly of phenylalanine-based peptides in nature, it is showed that NG a small phenylalanine derivative, assembles into left-handed helical nanofibers in the presence of Ca2+ . These helical NG nanofibers functioned as a coating layer on the surface of Ca2+ -linked alginate (Alg) microgels for the effective encapsulation of Ins. As expected, the sustained release and prolonged circulation of Ins and NG from the Ins-loading Alg/NG microgels (Ins@Alg/NG) in the intestinal tract synergistically maintain a relatively normal blood glucose level in streptozotocin-induced diabetic mice after oral administration of Ins@Alg/NG. This further confirms that Ins@Alg/NG ameliorated Ins resistance mainly through activating Insreceptor substrate 1 (IRS1), protein kinase B (AKT), and AMP-activated protein kinase (AMPK), as well as by repressing glycogen synthase kinase-3ß (GSK-3ß). The strategy of using the assembly of NG as a coating achieves the oral delivery of insulin and showcases a potential for the treatment of diabetes.