Hyun-Jae Shin

Improved oral bioavailability of alendronate via the mucoadhesive liposomal delivery system

This study aimed to design the chitosan coated liposomes of alendronate and optimize their in vitro/in vivo characteristics to improve the bioavailability as well as potentially to reduce the mucosal irritation of alendronate. Liposomes of alendronate were prepared with DSPC/DSPG by using thin layer film hydration method and then the surface of anionic liposomes was coated by chitosan. In vitro characteristics of liposomes (e.g., stability in various biological media, mucoadhesiveness and cellular uptake profiles) were evaluated along with the pharmacokinetic studies in rats. Lipid vesicles of 200 nm size were obtained with narrow size distribution (PI<0.1) and subsequently coated with chitosan. Chitosan coated liposomes were stable for 24 h without either size change or drug leakage in various biological fluids including simulated gastric fluids and intestinal fluids. Furthermore, it exhibited strong mucoadhesive properties. Compared to the untreated drug (non-liposome), the chitosan coated liposomes indicated significantly (p<0.05) increased cellular uptake of alendronate in Caco-2 cells and also 2.6-fold enhancement in oral bioavailability of alendronate in rats. Taken all together, the mucoadhesive liposomes for the oral delivery of alendronate was prepared by using DSPC and DSPG with narrow size distribution and appeared to be effective to enhance the bioavailability of alendronate in rats.

Removal of malachite green by adsorption and precipitation using aminopropyl functionalized magnesium phyllosilicate.

We report a method for the removal of malachite green (MG) by adsorption and precipitation using nano-sized aminopropyl functionalized magnesium phyllosilicate (AMP) clay. MG, which is used in aquaculture and fisheries, is a carcinogenic and mutagenic compound. In response to these health risks, many efforts have been focused on adsorption of MG onto various adsorbents, which is a versatile and widely used technique for removing MG from water. Herein, we describe the adsorption and precipitation of MG using AMP clay, as well as the alkaline fading phenomenon of MG. In this study, prepared AMP clay and the precipitate product after the reaction of MG-AMP clay mixture were characterized. In addition, adsorption isotherms and kinetics, as well as thermodynamic studies are presented. Based on the results, we suggest a macro- and microscopic removal mechanism for the adsorption and precipitation of MG using AMP clay. An AMP clay dosage of 0.1 mg mL(-1) exhibited a maximum removal capacity of 334.80 mg g(-1) and 81.72% MG removal efficiency. With further increases of the AMP clay dosage, removal capacity by AMP clay gradually decreased; at dosage above 0.2 mg mL(-1) of AMP clay, the removal efficiency reached 100%.

Harvesting of oleaginous Chlorella sp by organoclays

In microalgae-based biorefinement, one of the highest practical priorities is to reduce the costs of downstream processes. As one potential solution, microalgae harvesting by organoclays has received particularly keen research interest. In the present study, cationic charged aluminum- and magnesium-backboned organoclays were synthesized and solubilized in aqueous solution due to their high-density of amino sites. Each, within 30 min of its injection into 1.7 g/L-concentration microalgal feedstocks, effected harvesting efficiencies of almost 100% at concentrations above 0.6 g/L while maintaining a neutral pH. Conclusively, organoclays, if recycled efficiently, can be uniquely effective microalgae harvesting agents.

Magnesium and calcium organophyllosilicates: synthesis and in vitro cytotoxicity study.

Synthesis of multifunctional hybrid nanomaterials for biomedical applications has received great attention. Herein, we examine the potential toxicity of organophyllosilicates on cells from different organs such as A549 (lung epithelial cancer), HT-29 (colon epithelial cancer), MRC-5 (lung fibroblast) and CCD-986sk (skin fibroblast) cells. For this, aminopropyl functionalized magnesium phyllosilicate (AMP clay) and aminopropyl functionalized calcium phyllosilicate (ACP clay) were prepared using one-pot direct sol-gel method. Toxic effects of these organoclays on normal fibroblast and tumor cells were examined under varying concentrations and exposure times. MTT and LDH assays indicated that both organoclays had little cytotoxicity in all of the cells tested at concentrations as high as 500 μg/mL. Even at high concentration (1000 μg/mL), the toxicity of both organoclays on cell viability and membrane damage was not severe and appeared to be cell type specific. In addition, organoclays did not induce apoptosis at concentrations as high as 1000 μg/mL.

Lipid extractions from docosahexaenoic acid (DHA)-rich and oleaginous Chlorella sp. biomasses by organic-nanoclays

Microalgae biorefinement has attracted in intensive academic and industrial interest worldwide for its potential to replace petrol biofuels as economically and environmentally advantageous alternatives. However, harvesting and lipid extraction remain as critical and difficult issues to be resolved. In the present study, four amino-groups functionalized organic-nano clays were prepared. Specifically, Mg or Al or Ca backboned and covalently linked with 3-aminopropyltriethoxysilane or 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane by sol-gel reaction under ambient conditions, resulted in Mg-APTES clay, Al-APTES clay, Ca-APTES clay, and Mg-N3 clay, respectively. Each organic-nanoclay was utilized for lipid extraction from wet microalgae biomass. As a result, the lipid-extraction efficiency of paste docosahexaenoic acid (DHA)-rich Chlorella sp. with low lipid content was high, while one of paste oleaginous Chlorella sp. with high lipid content was relatively low. Despite the low lipid-extraction efficiencies in all of the wet microalgae biomass, the conversion of the extracted lipids fatty acids to biodiesel was nearly 100%.

Galacto-oligosaccharide production byβ-galactosidase in hydrophobic organic media

SummaryProduction of galacto-oligosaccharide (GO), including trisaccharide and tetrasaccharide, was performed using a β-galactosidase in water-hydrophobic solvent mixtures. A maximum GO concentration of 45% (w/w) was attained in a 95% cyclohexane/5% water mixture from a 55% (w/w) of lactose at 60°C and pH 6.0, while a maximum of 38% GO in aqueous media. GO production decreased with an increase in surfactant concentration. The optimum water content for GO production showed a broad range from 2.5 to 10% (v/v). Solvent properties, such as log P and the dipole moment, had no relation to GO production.

Optical Properties of Fluorescein‐labeled Organoclay

We report the preparation of aminopropyl‐functionalized magnesium phyllosilicate (Mg‐organoclay) conjugated to fluorescein isothiocyanate (FITC) functionality (FITC‐organoclay) by one‐pot sol‐gel synthesis. The physical characteristics of the Mg‐ and FITC‐organoclays were examined by scanning electron microscopy (SEM), X‐ray diffraction (XRD), FT‐IR and UV–Vis spectrophotometry. X‐ray fluorescence and elemental analysis were conducted to confirm the composition of the Mg‐organoclay. The FITC‐organoclay particles were polydispersed with an average particle size of ∼50u2003nm, as determined from SEM images. The XRD patterns of FITC‐organoclay exhibited broad peaks and reduced basal d001 indicating a less condensed and more disordered structure than was observed for Mg‐organoclay. The conjugation between FITC‐ and Mg‐organoclay was characterized by FT‐IR spectroscopy. Fluorescence excitation and emission spectral data demonstrated the successful conjugation of FITC dye molecules to the Mg‐organoclay. The time‐resolved fluorescence measurements revealed that FITC had a lifetime of 4.58u2003ns, whereas the lifetime of FITC‐organoclay required a double exponential fit (τ1,2u2003=u20030.72 and 2.68u2003ns). As a result, the lifetime of the FITC‐organoclay was shorter than that of FITC in ethanol and indicated moderate photostability in the solution state. The cellular uptake of FITC‐organoclay in human lung alveolar carcinoma epithelial cells (A549) was quantified and characterized.

Enhanced systemic exposure of fexofenadine via the intranasal administration of chitosan-coated liposome.

The present study aimed to develop the intranasal delivery system of fexofenadine for the prolonged drug release via the preparation of mucoadhesive liposome. By using thin layer film hydration method, liposome of fexofenadine was prepared with DPPC/DPPG, resulting in the small lipid vesicles (359 ± 5.5 nm) with narrow size distribution (PI<0.1). Subsequently, the surface of anionic liposome was coated by chitosan and in vitro characteristics of liposomes were evaluated along with the pharmacokinetic studies in rats. Chitosan coated liposomes were stable for 6-month storage at 4 °C without any significant size change and drug leakage. Furthermore, it exhibited strong mucoadhesive properties in mucin adsorption test, which was 3-fold higher than uncoated liposomes. Compared to the oral delivery of powder formulation, the intranasal delivery of fexofenadine significantly (p<0.05) increased systemic exposure of fexofenadine in rats. Particularly, the intranasal administration of chitosan coated liposome exhibited approximately 5 fold enhancement of AUC with more sustained drug release in rats compared to the oral delivery. In conclusion, intranasal administration of chitosan coated liposome appeared to be effective to enhance the bioavailability as well as prolonged exposure of fexofenadine in rats.

Wrinkle-Directed Self-Assembly of Block Copolymers for Aligning of Nanowire Arrays

Highly aligned metal nanowire arrays with feature sizes approaching 10 nm are fabricated. This is made possible by the self-assembly of block copolymers (BCPs) on graphene-wrinkle arrays. Thickness-modulated BCP films confined on the wrinkled reduced graphene oxide (rGO) surface promote the strict alignment of the self-assembled BCP lamellae in the direction of the film thickness gradient.

High-yield production of biosugars from Gracilaria verrucosa by acid and enzymatic hydrolysis processes

Gracilaria verrucosa, the red alga, is a suitable feedstock for biosugar production. This study analyzes biosugar production by the hydrolysis of G. verrucosa conducted under various conditions (i.e., various acid concentrations, substrate concentrations, reaction times, and enzyme dosages). The acid hydrolysates of G. verrucosa yielded a total of 7.47g/L (37.4%) and 10.63g/L (21.26%) of reducing sugars under optimal small (30mL) and large laboratory-scale (1L) hydrolysis processes, respectively. Reducing sugar obtained from acid and enzymatic hydrolysates were 10% higher, with minimum by-products, than those reported in other studies. The mass balance for the small laboratory-scale process showed that the acid and enzymatic hydrolysates had a carbohydrate conversion of 57.2%. The mass balance approach to the entire hydrolysis process of red seaweed for biosugar production can be applied to other saccharification processes.