Formulation design and characterization of silymarin liposomes for enhanced antitumor activity.

Liposomes, a nanoscale carrier, plays an important role in the delivery of drug, affects the in vivo efficacy of drugs. In this paper, silymarin(SM)-loaded liposomes was optimized using the response surface method (RSM), with entrapment efficiency (EE%) as an index. The formulation was optimized as follow: lecithin (7.8mg/mL), SM/lecithin (1/26) and lecithin/cholesterol (10/1). The optimized SM liposomes had a high EE (96.58 ±3.06%), with a particle size of 290.3 ±10.5nm and a zeta potential of +22.98 ±1.73mV. In vitro release tests revealed that SM was released in a sustained-release manner, primarily via diffusion mechanism. In vitro cytotoxicity studies demonstrated that the prepared SM liposomes had stronger inhibitory effects than the model drug. Overall, these results indicate that this liposome system is suitable for intravenous delivery to enhance the antitumor effects of SM.

Yam paste in glycemic preloads curbs peak glycemia of rice meals in apparent healthy subjects.

BACKGROUND AND OBJECTIVES: People with dental problems and dysphagia frequently consume foods in paste form. A strategy is required to mitigate the glycemic responses of these foods. METHODS AND STUDY DESIGN: The effect of yam paste ingestion on postprandial glycemic responses was assessed using a two-arm study design for yam paste ingestion: (1) as low- and medium-glycemic index food and (2) as preload and coingested food in a rice meal. In a randomized crossover trial, 18 healthy volunteers consumed (1) low-intensity-cooked yam paste; (2) medium-intensity-cooked yam paste; (3) cooked white rice; (4) coingested low-intensity-cooked yam paste with rice; (5) coingested medium-intensity-cooked yam paste with rice; (6) a preload of low-intensity-cooked yam paste before rice; (7) a preload of medium-intensity-cooked yam paste before rice. Postprandial glycemic responses and satiety assessments were conducted for each food approach. The glycemic characteristics of yam paste were manipulated with the preparatory treatment. RESULTS: Ingesting a preload of 10 g of yam paste before a rice meal resulted in better glycemic responses for 0-60 min in terms of peak glucose value and positive increments under the curve than co-ingesting yam paste with rice, with no adverse effect on satiety, irrespective of the glycemic index of the yam paste. CONCLUSIONS: Regarding isocarbohydrates, both low- and medium-glycemic index yam paste preloads curbed the glucose peak value of a rice meal and lowered the glycemic index value of mixed meals in young healthy people.

G-Quadruplex DNA with an Apurinic Site as a Soft Molecularly Imprinted Sensing Platform.

Molecularly imprinted polymers (MIPs) provide versatile sensor platforms to recognize targets by shape complementarity. However, the rigid structure of the classic MIPs compromises the signal transduction with necessary polymer and target modifications. Herein, we tried to use a flexible DNA that has a perfectly structured folding as the soft molecularly imprinted polymer (SMIP) for a straightforward sensor. As a proof of concept, the guanosine SMIP recognition was achieved by removal of a guanosine from a G-quadruplex-forming sequence (G4). The G4 folding structure with such an apurinic site (AP site) provides a well-defined MIP binding accommodation for guanosine according to the shape complementarity. The guanosine binding at the AP site subsequently leads to a conformation change suitable for remote readout using a G4-specific fluorescent ligand. The G4 sequence and AP site position were optimized for this SMIP behavior. Due to the G4 compact structure and the remaining hydrogen bonding pattern, nucleosides other than guanosine and negatively charged nucleotides exhibit no binding with the AP site, suggesting a high selectivity in the SMIP recognition. The proposed rationale was then convinced by the alkaline phosphatase-catalyzed GMP hydrolysis. Our work will inspire more interest in exploring nucleic acids as the SMIP frameworks due to their variant conformations and well-established molecular engineering.

Reversible Regulating the Substrate Specificity of Enzymes in Microgels by a Phase Transition in Polymer Networks.

Here, we report a distinct approach for regulating the substrate specificity of enzymes immobilized in microgels by a phase transition in polymer networks. The finding is demonstrated on glucose oxidase that is immobilized in thermoresponsive poly(N-isopropylacrylamide)-based microgels. Laser light scattering and enzymatic oxidation tests indicate that the broadened specificity appears at low temperatures, at which the gel matrix is in the relatively swollen state relative to its state at microgel synthesis temperature; upon heating to the relative higher temperatures, the gel matrix is not able to shrink further that offers a tight space in which the enzyme resides to retain high glucose specificity. It is proposed that polymer phase transition in the gel matrix mainly alter protein gates that control passage of substrates into active sites, making them open or close to a certain extent that enable reversible regulating the substrate specificity. The finding is also observed on bulk gels under a rational design, making it of potential interest in enzymatic biofuel cell applications.

Biocompatible micelles based on comb-like PEG derivates: formation, characterization, and photo-responsiveness.

A novel comb-like derivative CPEG-g-DNQ was prepared by incorporating light responsive 2-diazo-1,2-naphthoquinone (DNQ) groups into the structure of comb-like poly(ethylene glycol) (CPEG). DLS and TEM results showed that CPEG-g-DNQ self-assembled into spherical micelles with an average size of about 135 nm in water. Upon exposure to light, the micelles could be disrupted because of the conversion of hydrophobic DNQ to hydrophilic 3-indenecarboylic acid. Additionally, hydrophobic coumarin 102 was successfully loaded into the micelles and photo-induced ON-OFF release was demonstrated by fluorescence spectroscopy. MTT assay revealed that the micelles are biocompatible. These photo-responsive micelles might have great potential for controlled release of hydrophobic drugs.

Development of curcumin-loaded composite phospholipid ethosomes for enhanced skin permeability and vesicle stability.

Ethosomes are widely applied as the carriers for the transdermal delivery of hydrophobic and hydrophilic drugs. Herein, curcumin-loaded ethosomes (CE) with different phospholipid composition were formulated and thoroughly compared. A significant interaction between the unsaturated phosphatidylcholine (PC) and saturated hydrogenated phosphatidylcholine (HPC) was found by molecular simulation and differential scanning calorimetry (DSC), which led to the reduction of PC peroxidation with the presence of HPC. Subsequently, the composite phospholipid ethosomes containing curcumin were prepared for the first time to evaluate their properties in comparison with the conventional ethosomes composed of PC (CE-P) or HPC (CE-H). CE with PC/HPC ratio of 1:1 (CE-P1H1) with the best vesicle stability and flexibility significantly decreased the uptake by HaCaT cells compared to CE-H and free curcumin, indicating reduced skin cell toxicity. Compared with free curcumin, CE-P1H1 had the highest transdermal efficiency (p < 0.001), followed by CE-P (p < 0.05), partly due to the fact that CE-P1H1 could disturb lipid domain of stratum corneum (SC). Moreover, CE-P1H1 was found to promote curcumin for deep penetration of the skin via the hair follicles route. Our study has shown that using composite phospholipid ethosomes as lipid vesicular carriers could enhance transdermal penetration of drugs and increase in the vesicle stability.

Identification of Candidate Genes Associated with Charcot-Marie-Tooth Disease by Network and Pathway Analysis.

Charcot-Marie-Tooth Disease (CMT) is the most common clinical genetic disease of the peripheral nervous system. Although many studies have focused on elucidating the pathogenesis of CMT, few focuses on achieving a systematic analysis of biology to decode the underlying pathological molecular mechanisms and the mechanism of its disease remains to be elucidated. So our study may provide further useful insights into the molecular mechanisms of CMT based on a systematic bioinformatics analysis. In the current study, by reviewing the literatures deposited in PUBMED, we identified 100 genes genetically related to CMT. Then, the functional features of the CMT-related genes were examined by R software and KOBAS, and the selected biological process crosstalk was visualized with the software Cytoscape. Moreover, CMT specific molecular network analysis was conducted by the Molecular Complex Detection (MCODE) Algorithm. The biological function enrichment analysis suggested that myelin sheath, axon, peripheral nervous system, mitochondrial function, various metabolic processes, and autophagy played important roles in CMT development. Aminoacyl-tRNA biosynthesis, metabolic pathways, and vasopressin-regulated water reabsorption were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network, suggesting that these pathways may play key roles in CMT occurrence and development. According to the crosstalk, the biological processes could be roughly divided into a correlative module and two separate modules. MCODE clusters showed that in top 3 clusters, 13 of CMT-related genes were included in the network and 30 candidate genes were discovered which might be potentially related to CMT. The study may help to update the new understanding of the pathogenesis of CMT and expand the potential genes of CMT for further exploration.

Initiated Chemical Vapor Deposition of Graded Polymer Coatings Enabling Antibacterial, Antifouling, and Biocompatible Surfaces.

We report initiated chemical vapor deposition of model-graded polymer coatings enabling antibacterial, antifouling, and biocompatible surfaces. The graded coating was constructed by a bottom layer consisting of bactericidal poly(dimethyl amino methyl styrene) and a surface layer consisting of both dimethyl amino methyl styrene (DMAMS) and hydrophilic vinyl pyrrolidone (VP) moieties. Fourier transform infrared spectra showed existence of both DMAMS and VP in the coating with DMAMS as the major component, while X-ray photoelectron spectroscopy analysis and water contact angle measurement revealed a VP-enriched coating surface. The resultant coating exhibited more than 99.9% killing rate against both Gram-negative Escherichia coli and Gram-positive Bacillus subtilis despite the incorporation of VP on the surface. We believe that such bactericidal capability resulted because of its high surface zeta potential, which could be originated from the DMAMS units distributed both on the top surface and underneath. The graded coating achieved more than 85% bacterial fouling resistance than the pristine substrate, as well as improved biocompatibility, owing to the abundant surface lactam groups from the VP moiety. Furthermore, the graded coating maintained good bactericidal capability after multicycle challenges of bacterial solutions and was durable against continuous rigorous washing, suggesting potential applications in biomedical devices.

Plasma treated polyethylene terephthalate/polypropylene films assembled with chitosan and various preservatives for antimicrobial food packaging.

In this study, polyethylene terephthalate/polypropylene (PET/PP) films were treated via atmospheric pressure plasma, assembled with chitosan and various preservatives and applied for antimicrobial food packaging. Surface properties of these obtained films were studied by contact angle measurement, atomic force microscopy (ATM), X-ray photoelectron spectroscopy (XPS), Fourier transformed infrared spectroscopy (FT-IR) and dynamic laser scattering (DLS). The above results showed that the surface hydrophilicity and roughness of the films increased after the plasma treatment. Besides, chitosan and the preservatives were successfully assembled onto the surface of the films. In addition, the antimicrobial activities of the films against three kinds of microorganisms (Staphylococcus aureus, Bacillus subtilis and Escherichia coli) were investigated and the results indicated that the inhibition ratios against B. subtilis and E. coli reached almost 100% while the inhibition ratios against S. aureus were lower than 85%. Moreover, the accumulative release profiles of the antimicrobial substances migrating from the assembled films into the release solutions revealed that their release speed increased with the increment of temperature and acidity, but decreased with enhancing the ionic strength regulated by sodium chloride or with lowering the ionic mobility regulated by sucrose.

Silver ions/ovalbumin films layer-by-layer self-assembled polyacrylonitrile nanofibrous mats and their antibacterial activity.

The CN groups of polyacrylonitrile (PAN) can strongly adsorb silver ions. The possibility of using this attraction as a layer-by-layer (LBL) self-assembly driving force was investigated. Firstly, the surface of the PAN nanofibrous mats was modified by silver ions to make sure it was positively charged. Then oppositely charged ovalbumin (OVA) and silver ions in aqueous media were alternatively deposited onto the surface of the obtained composite mats by layer-by-layer self-assembly technique. The morphology of the LBL films coating mats was observed by field emission scanning electron microscope (FE-SEM). The deposition of silver ions and OVA was confirmed by X-ray photoelectron spectroscopy (XPS) and wide-angle X-ray diffraction (XRD). The thermal degradation properties were investigated by thermo-gravimetric analysis (TGA). Besides these, the cytotoxicity and antibacterial activity of the prepared mats were studied via flow cytometry (FCM) and inhibition zone test, respectively. The results showed that the composite mats after LBL self-assembly processing exhibited improved thermal stability, slightly decreased cytotoxicity, and excellent antibacterial activity against Escherichia coil and Staphylococcus aureus.