Biocompatible hydrophobic cross-linked cyclodextrin-based metal-organic framework as quercetin nanocarrier for enhancing stability and controlled release.

Cyclodextrin-based metal-organic framework (CD-MOF) has been widely used in various delivery systems due to its excellent edibility and high drug loading capacity. However, its typically bulky size and high brittleness in aqueous solutions pose significant challenges for practical applications. Here, we proposed an ultrasonic-assisted method for rapid synthesis of uniformly-sized nanoscale CD-MOF, followed by its hydrophobic modification through ester bond cross-linking (Nano-CMOF). Proper ultrasound treatment effectively reduced particle size to nanoscale (393.14 nm). Notably, carbonate ester cross-linking method significantly improved water stability without altering its cubic shape and high porosity (1.3 cm3/g), resulting in a retention rate exceeding 90% in various media. Furthermore, the loading of quercetin did not disrupt cubic structure and showcased remarkable storage stability. Nano-CMOF achieved controlled release of quercetin in both aqueous environments and digestion. Additionally, Nano-CMOF demonstrated exceptional antioxidant (free radical scavenging 82.27%) and biocompatibility, indicating its significant potential as novel nutritional delivery systems in food and biomedical fields.

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.