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.

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.

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.

Tendon-inspired hybrid hydrogel based on polyvinyl alcohol and gallic acid-lysozyme for promoting wound closure and healing.

Noninvasive wound closure remains a challenge in the field of wound healing. In this study, we report the development of a cross-linked P-GL hydrogel constructed from polyvinyl alcohol (PVA) and GL (a hydrogel consisting of gallic acid and lysozyme) that effectively promotes wound closure and healing. The P-GL hydrogel exhibited a unique lamellar and tendon-like fibrous network structure, providing good thermo-sensitivity and tissue adhesiveness up to 60 MPa, as well as retaining autonomous self-healing and acid resistance capacities. In addition, the P-GL hydrogel exhibited sustained release characteristics lasting >100 h, excellent biocompatibility both in vitro and in vivo, as well as good antibacterial activity and mechanical properties. The in vivo full-thickness skin wounds model revealed the positive wound closure and healing therapeutic effects of the P-GL hydrogels were confirmed, showing a promising potential as a noninvasive wound closure and healing bio-adhesive hydrogel.

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.

A novel magnetic solid-phase extraction method for detection of 14 heterocyclic aromatic amines by UPLC-MS/MS in meat products.

The current study developed a cheap and effective method for the simultaneous extraction of 14 heterocyclic aromatic amines (HAAs) in food matrix. Core-shell Fe3O4@PDA nanoparticles were constructed and acted as the magnetic solid-phase extraction adsorbent to separate and purify HAAs from meat products for the first time. Then, UPLC-MS/MS technique was employed to identify and quantify the HAAs easily. Fe3O4@PDA nanoparticles were synthesized and characterized successfully. Totally 14 HAAs were completely separated in 19.99 min with good regression coefficients. LODs and LOQs were in the range of 0.013-0.247 ng/g and 0.056-0.803 ng/g, respectively. The intra-day precisions and inter-day precisions were below 9%. Except for IQ[4,5-b], Phe-p-1, PhIP, other 11 types of HAAs (DMIP, 1,5,6-TMIP, IQ, IQx, MeIQ, MeIQx, 7,8-DiMeIQx, AαC, MeAαC, Harman, Norharman) could acquire relatively high recoveries (71.06%-108.49%). The proposed method was successfully devoted to the evaluation of HAAs levels in 8 commercial meat products to verify the adaptability.

Construction of Ginsenoside Nanoparticles with pH/Reduction Dual Response for Enhancement of Their Cytotoxicity Toward HepG2 Cells.

The aim of this study is to construct a pH- and reduction-responsive nanodrug delivery system to effectively deliver a ginsenoside (Rh2) and enhance its cytotoxicity against human hepatocarcinoma cells (HepG2). Here, pullulan polysaccharide was grafted by urocanic acid and α-lipoic acid (α-LA) to obtain a copolymer, α-LA-conjugated N-urocanyl pullulan (LA-URPA), which was expected to have pH and redox dual response. Then, the copolymer LA-URPA was used to encapsulate ginsenoside Rh2 to form Rh2 nanoparticles (Rh2 NPs). The results showed that Rh2 NPs exhibited an average size of 119.87 nm with a uniform spherical morphology. Of note, Rh2 NPs showed a high encapsulation efficiency of 86.00%. Moreover, Rh2 NPs possessed excellent pH/reduction dual-responsive drug release under acidic conditions (pH 5.5) and glutathione (GSH) stimulation with a low drug leakage of 14.8% within 96 h. Furthermore, Rh2 NPs with pH/reduction dual response had higher cytotoxicity than Rh2 after incubation with HepG2 cells for 72 h, indicating that Rh2 NPs had a longer circulation time. After the treatment with Rh2 NPs, the excessive increase of reactive oxygen species and the decrease of superoxide dismutase, glutathione (GSH), and mitochondrial membrane potential suggested that the mitochondrial pathway mediated by oxidative stress played a role in this Rh2 NP-induced apoptosis. In conclusion, this study provides a new strategy for improving the application of ginsenoside Rh2 in the food and pharmaceutical fields.

Enzymatic Synthesis of Polyglycerol Fatty Acid Esters and Their Application as Emulsion Stabilizers.

Polyglycerol ester is considered an excellent kind of food emulsifier. The aim of the current study was to synthesize polyglycerol fatty acid esters (PGFEs) with different-sized long-chain fatty acids (i.e. long-carbon fatty acid polyglycerol esters, L-PGFEs; medium-carbon fatty acid polyglycerol esters, M-PGFEs; and short-carbon fatty acid polyglycerol esters, S-PGFEs), using Lipozyme 435 as a catalyst in a solvent-free system. Thereafter, the physicochemical properties of the newly synthesized PGFEs and their potential applications as food emulsifiers were investigated. The maximum esterification efficiencies of L-PGFEs, M-PGFEs, and S-PGFEs were 69.37, 67.34, and 71.68%, respectively, at the optimum conditions: a reaction temperature of 84.48 °C, a reaction time of 6 h, a molar ratio of polyglycerol to fatty acid of 1.35:1, and 1.41 wt % enzyme usage (based on the total substrate mass). A high-performance liquid chromatograph equipped with an evaporative light-scattering detector (HPLC-ELSD) and an electrospray-ionization mass spectrometer (ESI-MS) were employed to identify the synthesized products. The results demonstrated that the main components of these PGFEs were dimeric glycerides (68.3%), triglycerides (13.13%), and a small amount of tetraglycerides (3.18%). The properties of the PGFEs were characterized by physical and chemical methods. Compared with M-PGFEs and S-PGFEs, L-PGFEs had the best physicochemical properties without any obvious odor. Further, the emulsion capabilities of these different long-chain PGFEs were evaluated via examining the particle sizes and storage stabilities and comparing them with those of glycerin monostearate (GMS). The results showed that the emulsions prepared with L-PGFEs had the best stability and the smallest particle sizes (16.8 nm) compared with those of M-PGFEs, S-PGFEs, and GMS, and they were not prone to oil-droplet coalescence or the separation of oil and water. From the current study, the newly synthesized PGFEs with long-chain fatty acids showed the best advantages as a food emulsifier compared with M-PGFEs, S-PGFEs, and even glycerin monostearate.