Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.

AIMS: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. METHODS: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated. RESULTS: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 µg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group. CONCLUSION: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

Piperine alleviates nonalcoholic steatohepatitis by inhibiting NF-κB-mediated hepatocyte pyroptosis.

PURPOSE: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), which has a high risk of cirrhosis, liver failure, and hepatocellular carcinoma. Piperine (Pip) is an extract of plants with powerful anti-inflammatory effects, however, the function of Pip in NASH remains elusive. Here, we aim to explore the role of Pip in NASH and to find the possible mechanisms. METHODS: Methionine and choline-deficient (MCD) diets were used to induce steatohepatitis, methionine- and choline-sufficient (MCS) diets were used as the control. After Pip treatment, H&E staining, Oil Red O staining, hepatic triglyceride (TG) content and F4/80 expression were performed to analysis liver steatosis and inflammation; Masson's staining, COL1A1 and α-SMA were detected liver fibrosis. Lipopolysaccharide (LPS) -treated AML12 cells were used to as the cell model to induce pyroptosis. Then, pyroptosis-related proteins, IL-1ß and LDH release were detected in vivo and in vitro. Finally, NF-κB inhibitor, BAY11-7082, was used to further demonstrate the mechanism of Pip in NASH. RESULTS: The study found that Pip alleviated liver steatosis, inflammation, hepatocyte injury, and fibrosis in mice fed with MCD diets. Moreover, the pyroptosis markers (NLRP3, ASC, caspase-1 p20, and GSDMD), IL-1ß and LDH release were decreased by Pip treatment. NF-κB activation was suppressed by Pip treatment and pyroptosis-related proteins were down regulated by BAY11-7082. CONCLUSION: Pip ameliorates NASH progression, and the therapeutical effect was associated with inhibition of hepatocyte pyroptosis induced by NF-κB.

Effect and potential mechanism of oncometabolite succinate promotes distant metastasis of colorectal cancer by activating STAT3.

To investigate the effect of Oncometabolite succinate on colorectal cancer migration and invasion and to initially explore the underlying mechanism.Succinate acid detection kit detected the succinate content in tissues. The growth of colorectal cancer cells was measured by cck-8 assay, wound-healing migration assay and transwell migration and invasion assays, and then explored the level of epithelial-mesenchymal transition (EMT) and STAT3/ p-STAT3 expression by western blot analysis and quantitative real-time PCR for mRNA expression. We found that succinate levels were significantly higher in carcinoma tissues than paracancerous tissues. After succinate treatment, the colorectal cancer cell lines SW480 and HCT116 had enhanced migration and invasion, the expression of biomarkers of EMT was promoted, and significantly increased phosphorylation of STAT3. In vivo experiments also showed that succinate can increase p-STAT3 expression, promote the EMT process, and promote the distant metastasis of colorectal cancer in mice.Succinate promotes EMT through the activation of the transcription factor STAT3, thus promoting the migration and invasion of colorectal cancer.

PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer.

Tumor-associated macrophages (TAMs) are the predominant cells that express programmed cell death ligand 1 (PD-L1) within human tumors in addition to cancer cells, and PD-L1+ TAMs are generally thought to be immunosuppressive within the tumor immune microenvironment (TIME). Using single-cell transcriptomic and spatial multiplex immunofluorescence analyses, we show that PD-L1+ TAMs are mature and immunostimulatory with spatial preference to T cells. In contrast, PD-L1- TAMs are immunosuppressive and spatially co-localize with cancer cells. Either higher density of PD-L1+ TAMs alone or ratio of PD-L1+/PD-L1- TAMs correlate with favorable clinical outcome in two independent cohorts of patients with breast cancer. Mechanistically, we show that PD-L1 is upregulated during the monocyte-to-macrophage maturation and differentiation process and does not require external IFN-γ stimulus. Functionally, PD-L1+ TAMs are more mature/activated and promote CD8+ T cells proliferation and cytotoxic capacity. Together, our findings reveal insights into the immunological significance of PD-L1 within the TIME.

Preparation of astaxanthin-loaded composite micelles with coaxial electrospray technology for enhanced oral bioavailability and improved antioxidation capability.

BACKGROUND: Astaxanthin (AST) is approved by the US Food and Drug Administration (FDA) as a safe dietary supplement for humans. As a potent lipid-soluble keto-carotenoid, it is widely used in food, cosmetics, and the pharmaceutical industry. However, its low solubility limits its powerful biological activity and its application in these fields. This study aims to develop a delivery system to address the low solubility and bioavailability of AST and to enhance its antioxidant capacity. RESULTS: Astaxanthin-loaded composite micelles were successfully prepared via coaxial electrospray technology. Astaxanthin existed in the amorphous state in the electro-sprayed formulation with an approximate particle size of 186.28 nm and with a polydispersity index of 0.243. In this delivery system, Soluplus and copovidone (PVPVA 64) were the main polymeric matrix for AST, which then released the drug upon contact with aqueous media, resulting in an overall increase in drug solubility and a release rate of 94.08%. Meanwhile, lecithin, and Polyethylene glycol-grafted Chitosan (PEG-g-CS) could support the absorption of AST in the gastrointestinal tract, assisting transmembrane transport. The relative bioavailability reached about 308.33% and the reactive oxygen species (ROS) scavenging efficiency of the formulation was 44.10%, which was 1.57 times higher than that of free astaxanthin (28.10%) when both were at the same concentration level based on astaxanthin. CONCLUSION: Coaxial electrospray could be applied to prepare a composite micelles system for the delivery of poorly water-soluble active ingredients in functional food, cosmetics, and medicine. © 2023 Society of Chemical Industry.

Preparation, characterization, pharmacokinetics and ulcerative colitis treatment of hyperoside-loaded mixed micelles.

At present, ulcerative colitis (UC) has become a global disease due to its high incidence. Hyperoside (HYP) is a naturally occurring flavonoid compound with many pharmacological effects. This study aimed to develop HYP-loaded mixed micelles (HYP-M) to improve oral bioavailability of HYP and to evaluate its therapeutic effect on UC. The prepared HYP-M exhibited stable physical and chemical properties, smaller particle size (PS) (21.48 ± 1.37 nm), good polydispersity index (PDI = 0.178 ± 0.013), negative Zeta potential (ZP) (- 20.00 ± 0.48 mV) and high entrapment rate (EE) (89.59 ± 2.03%). In vitro release and in vivo pharmacokinetic results showed that HYP-M significantly increased the releasing rate of HYP, wherein its oral bioavailability was 4.15 times higher than that of free HYP. In addition, HYP-M was more effective in the treatment of UC than free HYP. In conclusion, HYP-M could serve as a novel approach to improve bioavailability and increase anti-UC activity of HYP.

Enhancing Anticancer Efficacy of Formononetin Microspheres via Microfluidic Fabrication.

Formononetin is a flavonoid compound with anti-tumor and anti-inflammatory properties. However, its low solubility limits its clinical use. We employed microfluidic technology to prepare formononetin-loaded PLGA-PEGDA microspheres (Degradable polymer PLGA, Crosslinking agent PEGDA), which can encapsulate and release drugs in a controlled manner. We optimized and characterized the microspheres, and evaluated their antitumor effects. The microspheres had uniform size, high drug loading efficiency, high encapsulation efficiency, and stable release for 35 days. They also inhibited the proliferation, migration, and apoptosis. The antitumor mechanism involved the induction of reactive oxygen species and modulation of Bcl-2 family proteins. These findings suggested that formononetin-loaded PLGA-PEGDA microspheres, created using microfluidic technology, could be a novel drug delivery system that can overcome the limitations of formononetin and enhance its antitumor activity.

Virtual Screening and Binding Analysis of Potential CD58 Inhibitors in Colorectal Cancer (CRC).

Human cell surface receptor CD58, also known as lymphocyte function-associated antigen 3 (LFA-3), plays a critical role in the early stages of immune response through interacting with CD2. Recent research identified CD58 as a surface marker of colorectal cancer (CRC), which can upregulate the Wnt pathway and promote self-renewal of colorectal tumor-initiating cells (CT-ICs) by degradation of Dickkopf 3. In addition, it was also shown that knockdown of CD58 significantly impaired tumor growth. In this study, we developed a structure-based virtual screening pipeline using Autodock Vina and binding analysis and identified a group of small molecular compounds having the potential to bind with CD58. Five of them significantly inhibited the growth of the SW620 cell line in the following in vitro studies. Their proposed binding models were further verified by molecular dynamics (MD) simulations, and some pharmaceutically relevant chemical and physical properties were predicted. The hits described in this work may be considered interesting leads or structures for the development of new and more efficient CD58 inhibitors.

Photothermal Therapy Mediated Hybrid Membrane Derived Nano-formulation for Enhanced Cancer Therapy.

Emodin is applied as an antitumor drug in many tumor therapies. However, its pharmacology performances are limited due to its low solubility. Herein, we fused erythrocyte and macrophage to form a hybrid membrane (EMHM) and encapsulated emodin to form hybrid membrane-coated nanoparticles. We employed glycyrrhizin to increase the solubility of emodin first and prepared the hybrid membrane nanoparticle-coated emodin and glycyrrhizin (EG@EMHM NPs) which exhibited an average particle size of 170 ± 20 nm and encapsulation efficiency of 98.13 ± 0.67%. The half-inhibitory concentrations (IC50) of EG@EMHM NPs were 1.166 µg/mL, which is half of the free emodin. Based on the photosensitivity of emodin, the reactive oxygen species (ROS) results disclosed that ROS levels of the photodynamic therapy (PDT) section were higher than the normal section (P < 0.05). Compared to the normal section, PDT-mediated EG@EMHM NPs could induce an early stage of apoptosis of B16. The western blot and flow cytometry results verified that PDT-mediated EG@EMHM NPs can significantly improve the solubility of emodin and perform a remarkably antitumor effect on melanoma via BAX and BCL-2 pathway. The application of the combined chemical and PDT therapy could provide an improving target therapy for cutaneous melanoma and also may offer an idea for other insoluble components sources of traditional Chinese medicine. Schematic of EG@EMHM NPs formulation.

In-vitro and in-vivo evaluation and anti-colitis activity of esculetin-loaded nanostructured lipid carrier decorated with DSPE-MPEG2000.

OBJECTIVE: Encapsulation of esculetin into DSPE-MPEG2000 carrier was performed to improve its water solubility and oral bioavailability, as well as enhance its anti-inflammatory effect on a mouse model of ulcerative colitis that was induced with dextran sulphate sodium (DSS). METHODS: We determined the in-vitro and in-vivo high-performance liquid chromatographic (HPLC) analysis method of esculetin; Esculetin-loaded nanostructure lipid carrier (Esc-NLC) was prepared using a thin-film dispersion method, wherein a particle size analyser was used to measure the particle size (PS) and zeta potential (ZP) of the Esc-NLC, while a transmission electron microscope (TEM) was employed to observe its morphology. Also, HPLC was used to measure its drug loading (DL), encapsulation efficiency (EE) and the in-vitro release of the preparation, as well as investigate the pharmacokinetic parameters. In addition, its anti-colitis effect was evaluated via histopathological examination of HE-stained sections and detection of the concentrations of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (ß), and IL-6 in serum with ELISA kits. RESULTS: The PS of Esc-NLC was 102.29 ± 0.63 nm with relative standard deviation (RSD) of 1.08% (with poly-dispersity index-PDI of 0.197 ± 0.023), while the ZP was -15.67 ± 1.39 mV with RSD of 1.24%. Solubility of esculetin was improved coupled with prolonged release time. Its pharmacokinetic parameters were compared with that of free esculetin, wherein the maximum concentration of the drug in plasma was increased by 5.5 times. Of note, bioavailability of the drug was increased by 1.7 times, while the half-life was prolonged by 2.4 times. In the anti-colitis efficacy experiment, the mice in Esc and Esc-NLC groups exhibited significantly reduced levels of TNF-α, IL-1ß, and IL-6 in their sera comparable to the DSS group. Colon histopathological examination revealed that mice with ulcerative colitis in both Esc and Esc-NLC groups displayed improved inflammation, amid the Esc-NLC groups having the best prophylactic treatment effect. CONCLUSION: Esc-NLC could ameliorate DSS-induced ulcerative colitis by improving bioavailability, prolonging drug release time and regulating cytokine release. This observation confirmed the potential of Esc-NLC to reduce inflammation in ulcerative colitis, albeit the need for follow-up research to verify the application of this strategy to clinical treatment of ulcerative colitis.

Progress and Challenges of Immunotherapy Predictive Biomarkers for Triple Negative Breast Cancer in the Era of Single-Cell Multi-Omics.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with a poor prognosis. Despite conventional treatments, including surgery, radiation, and chemotherapy, the overall response rate to PD-1/PD-L1 immune checkpoint inhibitors remains low, with limited predictive significance from current biomarkers such as PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and tumor mutational burden (TMB). To address this challenge, recent advancements in single-cell sequencing techniques have enabled deeper exploration of the highly complex and heterogeneous TNBC tumor microenvironment at the single-cell level, revealing promising TNBC predictive biomarkers for immune checkpoint inhibitors. In this review, we discuss the background, motivation, methodology, results, findings, and conclusion of multi-omics analyses that have led to the identification of these emerging biomarkers. Our review suggests that single-cell multi-omics analysis holds great promise for the identification of more effective biomarkers and personalized treatment strategies for TNBC patients.

Microfluidic fabricated bisdemethoxycurcumin thermosensitive liposome with enhanced antitumor effect.

Bisdemethoxycurcumin (BDMC) is the main active ingredient that is isolated from Zingiberaceae plants, wherein it has excellent anti-tumor effects. However, insolubility in water limits its clinical application. Herein, we reported a microfluidic chip device that can load BDMC into the lipid bilayer to form BDMC thermosensitive liposome (BDMC TSL). The natural active ingredient glycyrrhizin was selected as the surfactant to improve solubility of BDMC. Particles of BDMC TSL had small size, homogenous size distribution, and enhanced cultimulative release in vitro. The anti-tumor effect of BDMC TSL on human hepatocellular carcinomas was investigated via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, live/dead staining, and flowcytometry. These results showed that the formulated liposome had a strong cancer cell inhibitory, and presented a dose-dependent inhibitory effect on migration. Further mechanistic studies showed that BDMC TSL combined with mild local hyperthermia could significantly upregulate B cell lymphoma 2 associated X protein levels and decrease B cell lymphoma 2 protein levels, thereby inducing cell apoptosis. The BDMC TSL that was fabricated via microfluidic device were decomposed under mild local hyperthermia, which could beneficially enhance the anti-tumor effect of raw insoluble materials and promote translation of liposome.

Vitexin loaded mixed polymeric micelles: preparation, optimization, evaluation and anti-osteoporotic effect.

In this regard, we developed vitexin (Vi)-loaded D-ɑ-tocopherol polyethylene glycol succinate, polyvinylpyrrolidone K30 and sodium cholate mixed micelles (Vi-MMs) mainly for improving oral bioavailability and enhancing anti-osteoporotic effect of Vi. Thin layer dispersion method was employed to prepare Vi-MMs, and then the optimal prescription was optimized by the orthogonal design-response surface method, wherein encapsulation efficiency (EE) was used as optimizing index. The physical properties of Vi-MMs such as appearance morphology, particle size, and zeta potential were also characterized. We further analyzed thein-vitrorelease of Vi and Vi-MMs in three media and investigated the pharmacokinetics of Vi and Vi-MMs in rats. Anti-osteoporotic activity of Vi and Vi-MMs was assessed by establishing a zebrafish osteoporosis model with prednisone. Drug loading, EE, particle size and zeta potential of the optimized Vi-MMs were 8.58 ± 0.13%, 93.86 ± 1.79%, 20.41 ± 0.64 nm and -10 ± 0.56 mV, respectively. The optimized Vi-MMs were shaped spherically as exhibited by transmission electron microscopic technique, with evident core shell nano-structure, well dispersed. In all three media, the release rate of Vi-MMs was significantly higher than that of free Vi. The oral bioavailability of Vi-MMs was increased by 5.6-fold compared to free Vi. In addition, alleviation of prednisone induced osteoporosis in zebrafish by Vi-MMs further demonstrated good anti-osteoporotic effect. In summary, Vi-MMs exhibited enhanced bioavailability and anti-osteoporotic effect, which is expected to be potential nanocarrier for Vi applications in drug development.

The applications of 3D printing in wound healing: The external delivery of stem cells and antibiosis.

As the global number of chronic wound patients rises, the financial burden and social pressure on patients increase daily. Stem cells have emerged as promising tissue engineering seed cells due to their enriched sources, multidirectional differentiation ability, and high proliferation rate. However, delivering them in vitro for the treatment of skin injury is still challenging. In addition, bacteria from the wound site and the environment can significantly impact wound healing. In the last decade, 3D bioprinting has dramatically enriched cell delivery systems. The produced scaffolds by this technique can be precisely localized within cells and perform antibacterial actions. In this review, we summarized the 3D bioprinting-based external delivery of stem cells and their antibiosis to improve wound healing.

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy.

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro. (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes.

Enhanced oral bioavailability of capsaicin-loaded microencapsulation complex via electrospray technology: Preparation, in vitro and in vivo evaluation.

The purpose of this work was to fabricate the microencapsulation of capsaicin using electrospray technology and polyvinylpyrrolidone (PVP) K30 as a carrier. The morphological characteristics of capsaicin-PVP electrosprayed microencapsulation complex under different processing parameters were observed by scanning electron microscope (SEM), while the best process was determined, wherein it comprised of 10 KV (voltage), 0.8 ml·h-1 (solution flow rate), 0.9 mm (the inner diameter of the needle), and 10 cm (receiving distance). The X-ray diffraction results of the electrosprayed complex showed that capsaicin was present in the carrier in an amorphous form. The drug release properties of capsaicin powder and electrosprayed complex in different media were investigated. The results showed that in vitro release rates of the capsaicin complex in different media were much higher than that of capsaicin powder, with correspondingly improved bioavailability, defined by intravenous and oral dosing in rats in vivo, for the electrosprayed complex compared to that of capsacin powder. The dose absorbed of the electrosprayed complex was 2.2-fold that of the capsaicin powder. In short, electrospray technology can be used to prepare capsaicin-loaded electrosprayed microencapsulation complex. This technique can improve the solubility and bioavailability of capsaicin, and provide a new idea for the solubilization of other insoluble drugs.

Preparation and evaluation of astaxanthin-loaded 2-hydroxypropyl-beta-cyclodextrin and Soluplus® nanoparticles based on electrospray technology.

BACKGROUND: Astaxanthin is a type of food-derived active ingredient with antioxidant, antidiabetic and non-toxicity functions, but its poor solubility and low bioavailability hinder further application in food industry. In the present study, through inclusion technologies, micellar solubilization and electrospray techniques, we prepared astaxanthin nanoparticles before optimizing the formulation to regulate the physical and chemical properties of micelles. We accomplished the preparation of astaxanthin nanoparticle delivery system based on single needle electrospray technology through use of 2-hydroxypropyl-ß-cyclodextrin and Soluplus® to improveme the release behavior of the nanocarrier. RESULTS: Through this experiment, we successfully prepared astaxanthin nanoparticles with a particle size of approximately 80 nm, which was further verified with scanning electron microscopy and transmission electron microscopy. Furthermore, the encapsulation of astaxanthin molecules into the carrier nanoparticles was verified via the results of attenuated total reflectance intensity and X-ray powder diffraction techniques. The in vitro release behavior of astaxanthin nanoparticles was different in media that contained 0.5% Tween 80 (pH 1.2, 4.5 and 6.8) buffer solution and distilled water. Also, we carried out a pharmacokinetic study of astaxanthin nanoparticles, in which it was observed that astaxanthin nanoparticle showed an effect of immediate release and significant improved bioavailability. CONCLUSION: 2-hydroxypropyl-ß-cyclodextrin and Soluplus® were used in the present study as a hydrophilic nanocarrier that could provide a simple way of encapsulating natural function food with repsect to improving the solubility and bioavailability of poorly water-soluble ingredients. © 2023 Society of Chemical Industry.

[Resting-state electroencephalogram relevance state recognition of Parkinson's disease based on dynamic weighted symbolic mutual information and k-means clustering].

At present, the incidence of Parkinson's disease (PD) is gradually increasing. This seriously affects the quality of life of patients, and the burden of diagnosis and treatment is increasing. However, the disease is difficult to intervene in early stage as early monitoring means are limited. Aiming to find an effective biomarker of PD, this work extracted correlation between each pair of electroencephalogram (EEG) channels for each frequency band using weighted symbolic mutual information and k-means clustering. The results showed that State1 of Beta frequency band ( P = 0.034) and State5 of Gamma frequency band ( P = 0.010) could be used to differentiate health controls and off-medication Parkinson's disease patients. These findings indicated that there were significant differences in the resting channel-wise correlation states between PD patients and healthy subjects. However, no significant differences were found between PD-on and PD-off patients, and between PD-on patients and healthy controls. This may provide a clinical diagnosis reference for Parkinson's disease.

Preparation, Physical Characterization, Pharmacokinetics and Anti-Hyperglycemic Activity of Esculetin-Loaded Mixed Micelles.

Despite its low water solubility, esculetin (EC) have been described to demonstrate various health benefits. Thus, we sought to develop esculetin-loaded mixed micelles (EC-M) delivery system to purposively improve biological availability and anti-hyperglycemia activity of EC. Thin-film hydration method was employed to fabricate EC-M, amid characterization with transmission electron microscopic analysis (TEM), coupled with physical properties such as particle size (PS), poly-dispersity index (PDI), zeta-potential (ZP) and stability testing. We analyzed in-vitro release and studied EC-M pharmacokinetics in rats. The hyperglycemic mice model was established with streptozotocin (STZ) to evaluate anti-hyperglycemic activity of EC-M. The PS, PDI and ZP of EC-M were 47.97 ± 0.41 nm, 0.189 ± 0.005 and -25.55 ± 0.28 mV, respectively. The release rate of EC-M increased comparable to free EC in the three media. The oral biological availability and half-life of EC-M increased respectively by 3.06 and 1.45 folds compared to free EC. Besides, we observed 46.21% decrease in blood glucose of mice in EC-M group comparable to the model control, wherein, the anti-hyperglycemic effect of EC-M was better compared to free EC. Conclusively, EC-M may ideally serve as a novel approach to enhance biological availability and increased anti-hyperglycemic activity of EC.

Synthesis and Characterization of Benzoxazine Resin Based on Furfurylamine.

This paper presents an investigation of the modification of natural oxazines to traditional bisphenol A benzoxazines. Eugenol was reacted with furfurylamine to synthesize a new type of benzoxazine (eugenol-furfurylamine benzoxazine), with a yield of 77.65%; and another new type of benzoxazine (bisphenol A-furfurylamine benzoxazine) was generated from bisphenol A and furfurylamine, with the highest yield of 93.78%. In order to analyze and study the target molecules, IR (infrared radiation) spectroscopy, GPC (gel-permeation chromatograph), mass spectrometry, 1H-NMR (nuclear magnetic resonance), DSC (differential scanning calorimetry), and DMA (dynamic mechanical analysis) tests were conducted. Eugenol-furfurylamine benzoxazine and conventional bisphenol A-aniline benzoxazine (BZ) composite was also analyzed and cured at different mass ratios of 2:98, 5:95, 10:90, 20:80, and 40:60. When the content of eugenol furfurylamine in the blend reached 5%, the strength of the composite was greatly enhanced, while the strength decreased with the increase in eugenol furfurylamine oxazine content. Moreover, octamaleimide phenyl POSS (OMPS, polyhedral oligomeric silsesquioxane) and bisphenol A furamine benzoxazine were mixed at different molar ratios of 1:16, 1:8, 1:4, 1:2, and 1:1. The curing temperature sharply decreased with the increase in OMPS content. When the molar ratio reached 1:1, the curing temperature decreased from 248 to 175℃. A further advantage of using eugenol and furfurylamine is that they are renewable resources, which is important in terms of utilizing resources effectively and developing environmentally friendly products.