Ae-Jin Choi

Microemulsion-based Hydrogel Formulation of Itraconazole for Topical Delivery

The present study was aimed at preparing microemulsion-based hydrogel (MBH) for the skin delivery of itraconazole. Microemulsion prepared with Transcutol as a surfactant, benzyl alcohol as an oil and the mixture of ethanol and phasphatidyl choline (3:2) as a cosurfactant were characterized by solubility, phase diagram, particle size. MBHs were prepared using 0.7 % of xanthan gum (F1-1) or carbopol 940 (F1-2) as gelling agents and characterized by viscosity studies. The in vitro permeation data obtained by using the Franz diffusion cells and hairless mouse skin showed that the optimized microemulsion (F1) consisting of itraconazole (1% w/w), benzyl alcohol (10% w/w), Transcutol (10% w/w) and the mixture of ethanol and phospahtidylcholine (3:2) (10% w/w) and water (49% w/w) showed significant difference in the flux (~1 µg/ cm 2 /h) with their corresponding MBHs (0.25-0.64 µg/cm 2 /h). However, the in vitro skin drug content showed no significant difference between F1 and F1-1, while F1-2 showed significantly low skin drug content. The effect of the amount of drug loading (0.02, 1 and 1.5% w/w) on the optimized MBH (F1-2) showed that the permeation and skin drug content increased with higher drug loading (1.5%). The in vivo study of the optimized MBH (F1-2 with1.5% w/w drug loading) showed that this formulation could be used as a potential topical formulation for itraconazole. Key wordsItraconazole, Benzyl alcohol, Microemulsion-based gel, Topical skin delivery

Activation of the GP130-STAT3 axis and its potential implications in nonalcoholic fatty liver disease

The status of the GP130-STAT3 signaling pathway in humans with nonalcoholic fatty liver disease (NAFLD) and its relevance to disease pathogenesis are unknown. The expression of the gp130-STAT3 axis and gp130 cytokine receptors were studied in subjects with varying phenotypes of NAFLD including nonalcoholic steatohepatitis (NASH) and compared with lean and weight-matched controls without NAFLD. Gp130 and its downstream signaling element (Tyk2 and STAT3) expression were inhibited in obese controls whereas they were increased in NAFLD. IL-6 levels were increased in NASH and correlated with gp130 expression (P < 0.01). Palmitate inhibited gp130-STAT3 expression and signaling. IL-6 and palmitate inhibited hepatic insulin signaling via STAT3-dependent and independent mechanisms, respectively. STAT3 overexpression reversed palmitate-induced lipotoxicity by increasing autophagy (ATG7) and decreasing endoplasmic reticulum stress. These data demonstrate that the STAT3 pathway is activated in NAFLD and can worsen insulin resistance while protecting against other lipotoxic mechanisms of disease pathogenesis.

Anticancer activity of ferulic acid-inorganic nanohybrids synthesized via two different hybridization routes, reconstruction and exfoliation-reassembly.

We have successfully prepared nanohybrids of biofunctional ferulic acid and layered double hydroxide nanomaterials through reconstruction and exfoliation-reassembly routes. From X-ray diffraction and infrared spectroscopy, both nanohybrids were determined to incorporate ferulic acid molecules in anionic form. Micrsocopic results showed that the nanohybrids had average particle size of 150 nm with plate-like morphology. As the two nanohybridization routes involved crystal disorder and random stacking of layers, the nanohybrids showed slight alteration in z-axis crystallinity and particle size. The zeta potential values of pristine and nanohybrids in deionized water were determined to be positive, while those in cell culture media shifted to negative values. According to the in vitro anticancer activity test on human cervical cancer HeLa cells, it was revealed that nanohybrids showed twice anticancer activity compared with ferulic acid itself. Therefore we could conclude that the nanohybrids of ferulic acid and layered double hydroxide had cellular delivery property of intercalated molecules on cancer cell lines.

Electrophoretically prepared hybrid materials for biopolymer hydrogel and layered ceramic nanoparticles

BackgroundIn order to obtain biomaterials with controllable physicochemical properties, hybrid biomaterials composed of biocompatible biopolymers and ceramic nanoparticles have attracted interests. In this study, we prepared biopolymer/ceramic hybrids consisting of various natural biopolymers and layered double hydroxide (LDH) ceramic nanoparticles via an electrophoretic method. We studied the structures and controlled-release properties of these materials.Results and discussionX-ray diffraction (XRD) patterns and X-ray absorption spectra (XAS) showed that LDH nanoparticles were formed in a biopolymer hydrogel through electrophoretic reaction. Scanning electron microscopic (SEM) images showed that the ceramic nanoparticles were homogeneously distributed throughout the hydrogel matrix. An antioxidant agent (i.e., ferulic acid) was loaded onto agarose/LDH and gelatin/LDH hybrids, and the time-dependent release of ferulic acid was investigated via high-performance liquid chromatography (HPLC) for kinetic model fitting.ConclusionsBiopolymer/LDH hybrid materials that were prepared by electrophoretic method created a homogeneous composite of two components and possessed controllable drug release properties according to the type of biopolymer.

Physicochemical analysis methods for nanomaterials considering their toxicological evaluations

Based on increasing interest and demands for nanomaterials in both industrial and academic fields, concerns for their potential toxicity emerged. In order to evaluate their potential toxicity as well as their interaction towards biological substances, it is important to comprehend and to precisely determine their physicochemical properties. In this review, we demonstrate current state-of-art on analytical methods for determining physicochemical parameters of nanomaterials in both powder and suspension states. A brief introduction on the operating principles of each instrument along with literature examples is given.

693 The gp130/STAT3 Axis Is Modulated by Lipotoxic Stress and Activated in Humans With Nonalcoholic Fatty Liver Disease

A S L D A b st ra ct s random-effects model; Q-statistic with p-value 50% for both estimates). SVR rates in HCV-6 patients were 79.1% (CI=73.2-84.0%) if treated for 48 weeks and 58.7% (CI=46.0-70.2%) if treated for 24 weeks. When compared to HCV-1 patients, those with HCV-6 treated for 48 weeks had higher SVR, OR 2.73 (1.69-4.41, p<0.001) (Figure 1). This difference was not statistically significant when comparing HCV-6 patients treated for only 24 weeks to HCV-1 patients, OR 1.80 (0.72-4.48, p=0.206). SVR in patients with early virologic response (EVR, undetectable HBV RNA PCR at week 12 of therapy) was 66% (CI=54.2-76.4%) for HCV-1 and 81.6% (CI=75.3-86.6%) for HCV-6 patients treated for 48 weeks. There was no statistically significant difference in SVR between HCV-6 patients treated for 48 weeks versus patients with HCV-1 if they all had EVR, OR 2.02 (CI=0.864.76, p=0.106). Conclusions: Patients with HCV-6 treated for 48 weeks had higher SVR than patients with HCV-1 (79.1% vs. 71.8%, OR=2.73, p<0.001); however, SVR for Asian HCV-1 appeared much higher than SVR to PEG IFN+RBV for HCV-1 in pivotal registration trials with mostly Western patients. In patients with EVR, there is no difference in SVR rates between HCV-1 and HCV-6 who were treated for 48 weeks.