Designing amorphous formulations of polyphenols with naringin by spray-drying for enhanced solubility and permeability

Naringin (NAR), a major flavanone (FVA) glycoside, is a component of food mainly obtained from grapefruit. We used NAR as a food additive to improve the solubility and permeability of hydrophobic polyphenols used as supplements in the food industry. The spray-dried particles (SDPs) of NAR alone show an amorphous state with a glass transition temperature (T_g) at 93.2 °C. SDPs of hydrophobic polyphenols, such as flavone (FVO), quercetin (QCT), naringenin (NRG), and resveratrol (RVT) were prepared by adding varying amounts of NAR. All SDPs of hydrophobic polyphenols with added NAR were in an amorphous state with a single T_g, but SDPs of hydrophobic polyphenols without added NAR showed diffraction peaks derived from each crystal. The SDPs with NAR could keep an amorphous state after storage at a high humidity condition for one month, except for SDPs of RVT/NAR. SDPs with NAR enhanced the solubility of hydrophobic polyphenols, especially NRG solubility, which was enhanced more than 9 times compared to NRG crystal. The enhanced solubility resulted in the increased membrane permeability of NRG. The antioxidant effect of the hydrophobic NRG was also enhanced by the synergetic effect of NAR. The findings demonstrated that NAR could be used as a food additive to enhance the solubility and membrane permeability of hydrophobic polyphenols.     

In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Synthesis and characterization of poly (linoleic acid)-g-poly(methyl methacrylate) graft copolymer with applying in Au/PLiMMA/n-Si diode

Poly (linoleic acid)-g-poly(methyl methacrylate) (PLiMMA) graft copolymer was synthesized and characterized. PLiMMA graft copolymer was synthesized from polymeric linoleic acid peroxide (PLina) possessing peroxide groups in the main chain by free radical polymerization of methyl methacrylate. Later, PLiMMA was characterized by proton nuclear magnetic resonance (¹H NMR), gel permeation chromatography (GPC), thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. Furthermore, Au/PLiMMA/n-Si diode was fabricated for the purpose of investigating PLiMMA׳s conformity in diodes. The main electrical characteristics of this diode were investigated using experimental current–voltage (I–V) measurements in dark and at room temperature. Obtained results, such as sufficiently high rectifying ratio of 4.5×10⁴, indicate that PLiMMA is a promising organic material for electronic device applications.     

Mechanical properties of polyethylene mixtures crystallized under high pressure

The mechanical properties of a medium molecular weight polyethylene (MMW‐PE) and an ultrahigh molecular weight PE (UHMW‐PE) binary mixture with different weight fractions crystallized from the melt at 0.1 and 450 MPa were studied. The tensile modulus, yield stress, and strain were obtained as a function of the weight fractions in the PE mixtures at 25 and 85°C. The tensile modulus in the sample crystallized at 0.1 MPa decreased from 1.5 GPa of pure MMW‐PE to about 0.4 GPa of pure UHMW‐PE with the UHMW‐PE content but it did not decrease with the UHMW‐PE in the sample crystallized at 450 MPa in testing at 25°C. A decreasing rate of the storage modulus E′ of UHMW‐PE in a dynamic measurement for the sample crystallized at 0.1 MPa with the temperature is larger than that of the sample crystallized at 450 MPa. These experimental facts are interpreted in relation to the molecular motion and crystallinity of the sample. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1962–1968, 2003     

Structural changes in isothermal crystallization process of polyoxymethylene investigated by time-resolved FTIR, SAXS and WAXS measurements

Structural evolution in the isothermal crystallization process of polyoxymethylene from the molten state has been investigated by carrying out the time-resolved measurements of infrared spectra and synchrotron small angle X-ray scattering (SAXS) and wide angle X-ray scattering. In case of isothermal crystallization at 130 °C, for example, the infrared bands intrinsic of folded chain crystal (FCC) morphology appeared at first, and then the bands of extended chain crystal (ECC) morphology were detected with time delay of ca. 150 s. In the SAXS experiment at 130 °C, the lamellar stacking structure of the long period of ca. 15 nm was observed at first, which changed rapidly to ca. 12 nm in a short time. The SAXS peak with the long period of ca. 6 nm started to appear with a time delay of ca. 150 s after the initial lamellae appeared and coexisted with the initially-observed 12 nm peak. Judging from the timing to detect these characteristic infrared and SAXS signals, a good correspondence was found to exist between the stacked lamellar structure of 12 nm long period and FCC morphology and between the structure of 6 nm long period and ECC morphology. The quantitative analysis was made for the SAXS data on the basis of the lamellar insertion model combined with the paracrystalline theory of the second-kind of disorder. The following structural evolution was deduced from all these results. Immediately after the temperature jump from the melt to 130 °C, the stacked lamellar structure of FCC morphology was generated at first. New lamellae were formed from the amorphous region in between the originally-existing lamellae about 150 s later, where the random chain segments bridging the adjacent lamellae were extended to form the taut tie chains, giving infrared bands of ECC morphology. This inserted lamellar structure of 6 nm long period coexisted at a population of ca. 6% with the initially-formed lamellar stacking structure of 12 nm long period. When the experiment was made at 150 °C, only the formation of stacked lamellar structure of FCC morphology was observed and the insertion of new lamella did not occur.     

锰铜基高阻尼合金中锌量的测定──硫氰酸盐萃取分离络合滴定法

基于甲基异丁基甲酮于稀盐酸介质中定量地萃取Ｚｎ￣（２＋）与ＣＮＳ￣－形成的络阴离子。从而达到与共存的锰、镍、铝、铬的完全分离。在有氟化物、硫脲存在时Ｆｅ￣（３＋）、Ｃｎ￣（２＋）和Ａｇ￣＋也不被萃取。有机相中的锌于ＰＨ５．５“六胺”缓冲介质中返萃取回水相，用ＥＤＴＡ滴定。在文中给定的条件下锌的一次被萃取率可达９９％以上，成功地解决了锰铜基高阻尼合金中共存离子对锌量测定的干扰问题。     

电位滴定法快速测定洗衣粉中的聚磷酸盐含量

用强酸分解洗衣粉中的聚磷酸盐，以电位滴定法间接测定其中的聚磷酸盐含量。该法简便，快速，结果可靠。     

Further study on the cooling correction in bomb calorimetry: Theoretical aspects of approximate formulae

On the basis of the compensation of errors it is postulated that the most accurate correction may not always give the most accurate result for calorific value, and experimental evidence for this is presented. A new criterion is therefore suggested for judging the best (not necessarily the most accurate) cooling correction. Using this principle the cooling correction formula previously proposed is improved which results in higher accuracy whilst retaining the original simplicity.