• Asian-Australasian Journal of Animal Sciences
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• v.27 no.11
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• pp.1577-1583
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• 2014

Encapsulation is a method used to protect material from certain undesirable environments, for controlled release at a more favorable time and place. Animal productivity would be enhanced if feed additives are delivered to be utilized at their site of action, bypassing the rumen where they are likely to be degraded by microbial action. A novel method of encapsulation with sesame gum was used to coat nitrate, a known enteric methane mitigating agent, and tested for the effect on methane reduction and other in vitro fermentation parameters using rumen fluid from cannulated Hanwoo steers. Orchard grass was used as basal diet for fermentation. The treatments were matrix (1.1 g sesame gum+0.4 g sesame oil cake) only, encapsulated nitrate (matrix+nitrate [21 mM]), free nitrate (21 mM), and a control that contained no additive. Analyses of fermentation parameters were done at 0, 3, 6, 9, 12, 24, and 48 h time periods. In comparison to control, both free and encapsulated nitrate produced significantly reduced (p<0.01) methane (76% less) and also the total volatile fatty acids were reduced. A significantly higher (p<0.01) concentration of ammonia nitrogen was obtained with the encapsulated nitrate treatment (44%) compared to the free form (28%) and matrix only (20%) (p = 0.014). This might suggest slow release of encapsulated nitrate so that it is fully reduced to ammonia. Thus, this pioneering study found a significant reduction in methane production following the use of sesame gum encapsulated nitrate that shows the potential of a controlled release system in enhancing sustainability of ruminant production while reducing/eliminating the risk of nitrite toxicity.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.511-519
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• 1993

The short and variabke transit of drug throught GI tracj and the inter-and intra-subject variations of the transit restrict the sustained drug absorption after oral adminstration. These restrictions may be solved by retaining the dosage forms in the stomach. Then the dosage form will act as a platform which releases the drug slowly and makes the GI absorption occur for a long time. In this study, as the platforms, PVP hydrogels were synthesized by chemical and y-irradiation method in the cylindrical test tube. The chemical method means the synthesis of the hydrogel by heating the mixed solution of N-vinyl-2-pyrrolidone [monomer], acrylated albumin [crosslinking agent], 2, 2'-agobis(2-methylpropionitrile) [initiator] and proxyphylline [drug] at $65^{\circ}C$ for 5 hr. The $\gamma$-irradiation method means the synthesis of the hydrogel by irradiation with $^{60}$ Co $\gamma$-ray of the mixed solution of the monomer, acrylated albumin, and flurbiprofen [drug] at room temperature with total 0.2 Mrad for 3 hr. Our intention is to design the hydrogel tablet (diameter : 1.20 cm, thickness : 0.60 cm) which swells in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the period of drug release. After releasing drug, the hydrogel should be degraded by the enzymeatic digestion in the stomach, or by hydrolysis and eventually solubilized. Thus, in votro tests were performed to examine the factors that affect swelling and drug release from the PVP hydrogels. Experimental results show that the hydrogels swell to a size larger than the diameter of the pylorus(l.3$\pm$0.7 cm) and the hydrogel prepared by the chemical method is digested by pepsin. But the hydrogel prepared by the $\gamma$-irradiation method was not digested by the pepsin and just collapsed with time. Thus, the swelling of the hydrogel synthesized by $\gamma$-irradiation was independent albumin acrylation time and pepsin concentration. But drug content and radiation dose affected the swelling and drug release kinetics of the hydrogel. Drug release from the hydrigels was prolonged up to about 24 hr. Therefore, it was concluded that by adjusting these factors, the albumin-crosslinked PVP hydrogel synthesized by $\gamma$-irradiation method is expected to be retained in the stomach for up to 60hr and be a potential platform of drugs for long-term GI absorption.

• 한국유가공학회:학술대회논문집
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• 2005.06a
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• pp.37-61
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• 2005

Microcapsules consisting of natural, biodegradable polymers for controlled and/or sustained core release applications are needed. Physicochemical properties of whey proteins suggest that they may be suitable wall materials in developing such microcapsules. The objectives of the research were to develop water-insoluble, whey protein-based microcapsules containing a model water-soluble drug using a chemical cross-linking agent, glutaraldehyde, and to investigate core release from these capsules at simulated physiological conditions. A model water soluble drug, theophylline, was suspended in whey protein isolate (WPI) solution. The suspension was dispersed in a mixture of dichloromethane and hexane containing 1% biomedical polyurethane. Protein matrices were cross-linked with 7.5-30 ml of glutaraldehyde-saturated toluene (GAST) for 1-3 hr. Microcapsules were harvested, washed, dried and analyzed for core retention, microstructure, and core release in enzyme-free simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) at 37$^{\circ}C$, A method consisting of double emulsification and heat gelation was also developed to prepare water-insoluble, whey protein-based microcapsules containing anhydrous milkfat (AMF) as a model apolar core. AMF was emulsified into WPI solution (15-30%, pH 4.5-7.2) at a proportion of 25-50% (w/w, on dry basis). The oil-in-water emulsion was then added and dispersed into corn oil (50 $^{\circ}C$)to form an O/W/O double emulsion and then heated at 85$^{\circ}C$ for 20 min for gelation of whey protein wall matrix. Effects of emulsion composition and pH on core retention, microstructure, and water-solubility of microcapsules were determined. Overall results suggest that whey proteins can be used in developing microcapsules for controlled and sustained core release applications.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.350-356
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• 2017

We previously reported that the CopA3 peptide (LLCIALRKK, ${\small{D}}-form$) originally isolated from the Korean dung beetle has antimicrobial and immunosuppressive effects. However, the high cost of producing the synthetic peptide, especially the ${\small{D}}-form$, has limited the development of CopA3 for therapeutic purposes. Here, we investigated whether the CopA3 deletion derivative, CopA5, which is composed of only five amino acids (LLCIA) and has the ${\small{L}}-form$ structure, could inhibit the lipopolysaccharide (LPS)-induced activation of macrophages. Peritoneal exudate macrophages (PEM) were isolated from mice and exposed to LPS in the presence or absence of CopA5, and biomarkers of macrophage activation were measured. Our results revealed that LPS-induced nitric oxide (NO) production, tumor necrosis factor $(TNF)-{\alpha}$ secretion, and phagocytic activity of PEM were significantly inhibited by CopA5 treatment. Similar to CopA3, the structurally modified CopA5 peptide had no cell toxicity (as assessed by measurement of cell viability loss and apoptosis) in PEM. Moreover, the LPS-induced upregulation of the activating phosphorylation of signal transducer and activator of transcription 1 (STAT1) was markedly inhibited by CopA5 treatment. These results suggest that, similar to CopA3, CopA5 inhibits macrophage activation by inhibiting STAT1 phosphorylation and blocking the release of NO and $TNF-{\alpha}$. CopA5 may therefore prove therapeutically useful in the realm of immune suppression.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.1939-1943
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• 2014

Solid dispersion (SD) system of everolimus (EVR) with Gelucire 50/13 (Stearoyl polyoxyl-32 glycerides) was prepared using melt granulation technique with the aim of improving the physicochemical properties and dissolution rate. The solid state characterization using scanning electron microscopy and X-ray powder diffraction, indicated that the drug was homogeneously distributed in the surfactant carrier in a stable amorphous form. The dissolution rate of EVR from the optimized SD composed of the drug, Gelucire 50/13 and microcrystalline cellulose in a weight ratio of 1:5:10, was markedly rapid and higher than that from the drug powder and the market product (Afinitor$^{(R)}$, Novartis Pharmaceuticals) in all dissolution mediums tested from pH 3.0 to pH 6.8. The results of this study suggest that formulation of SD with Gelucire 50/13 using melt granulation procedure may be a simple and promising approach for improving the dissolution rate and oral absorption of the anti-cancer agent without the need for using an organic solvent.

• Journal of Radiation Protection and Research
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• v.17 no.2
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• pp.49-59
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• 1992

A new model was developed in order to investigate the effects of chelating agents on the migration of a radionuclide in the form of ion or chelate. The migration behavior of the chelated radionuclide was analyzed by formulating a convective-dispersion transport equation which included a degradation of chelating agent and chelated radionuclide. The mathematical model was analytically solved and checked with the existing retardation factor. The results show that the migration velocity of the chelated radionuclide was much faster than the ionic one due to the decreased retardation. Therefore, it was concluded that a new remedial action should be developed to reduce the generation and release of chelating agents from the nuclear power plant into the environment.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.76-82
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• 2003

Drug releasing porous poly($\varepsilon$-caprolactone) (PCL)-chitosan matrices were fabricated for bone regenerative therapy. Porous matrices made of biodegradable polymers have been playing a crucial role as bone substitutes and as tissue-engineered scaffolds in bone regenerative therapy. The matrices provided mechanical support for the developing tissue and enhanced tissue formation by releasing active agent in controlled manner. Chitosan was employed to enhance hydrophilicity and biocompatibility of the PCL matrices. PDGF-BB was incorporated into PCL-chitosan matrices to induce enhanced bone regeneration efficacy. PCL-chitosan matrices retained a porous structure with a 100-200 $\mu$m pore diameter that was suitable for cellular migration and osteoid ingrowth. $NaHCO_3$ as a porogen was incorporated 5% ratio to polymer weight to form highly porous scaffolds. PDGF-BB was released from PCL-chitosan matrices maintaining therapeutic concentration for 4 week. High osteoblasts attachment level and proliferation was observed from PCL-chitosan matrices. Scanning electron microscopic examination indicated that cultured osteoblasts showed round form and spread pseudopods after 1 day and showed broad cytoplasmic extension after 14 days. PCL-chitosan matrices promoted bone regeneration and PDGF-BB loaded matrices obtained enhanced bone formation in rat calvarial defect. These results suggested that the PDGF-BB releasing PCL-chitosan porous matrices may be potentially used as tissue engineering scaffolds or bone substitutes with high bone regenerative efficacy.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.167-172
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• 2000

The purpose of this study is to develop a transurethral liquid suppository containing prostaglandin $E_1\;(PGE_1)-loaded$ microemulsion, which undergoes a phase transition to gels at body temperature. The effects of oils, ethanol as solvent and HCl as pH-controlling agent on the physicochemical properties of liquid suppositories composed of poloxamer P 407, P 188 and carbopol was investigated. The stability of $PGE_1$ and release of $PGE_1$ from liquid suppository were evaluated. Oils such as Neobee and soybean oil significantly decreased the gelation temperature but increased the gel strength of liquid suppository due to their strongly binding with the components of liquid suppository base. However, ethanol slightly did the opposite. The pH of liquid suppositories hardly affected the gelation temperature and gel strength due to addition of very small HCl (0.005-0.01%). A liquid suppository [$PGE_1/P$ 407/P 188/carbopol/Neobee/ethanol/HCl (0.2/14/14/0.4/7/2/0.005%)], which had the gelation temperature $(34.2{\pm}0.6^{\circ}C)$ and gel strength $(31.35{\pm}4.37\;sec)$ suitable for liquid suppository system, was easily administered and not leak out from the body. About 60% of $PGE_1$ was released out within 2 h from this formulation. It was shown that the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppository by Fickian diffusion. It was stable at $4^{\circ}C$ for at least 2 months. The results suggest that transurethral liquid suppository containing prostaglandin $E_1-loaded$ microemulsion is thought to be a convenient, safe and effective dosage form for $PGE_1$. However, it should be further developed as a more convenient and stable dosage form for $PGE_1$.

• Macromolecular Research
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• v.13 no.2
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• pp.135-140
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• 2005

Poly(vinyl alcohol) (PVA) membranes crosslinked with poly(acrylic acid-co-maleic acid) (PAM) were prepared to investigate the effect of aging on their morphology by swelling them for up to 7 days. PAM was used both as a crosslinking agent and as a donor of the hydrophilic-COOH group. A $30 wt\%$ weight loss of the dry membrane was observed in the swelling test after 6 days. The surface of the membrane was dramatically changed after the swelling test. The surface roughness of the PVA/PAM membrane was increased, as determined by atomic force microscopy (AFM). The swelling loosened the polymer structure, due to the release of the unreacted polymer and the decomposition of the ester bond, thereby resulting in an increase in the free volume capable of containing water molecules. The water molecules present in the form of free water were determined by differential scanning calorimetry (DSC). The fraction of free water increased with increasing swelling time. The swelling of the membrane may provide space for the transport of protons and increase the mobility of the protonic charge carriers. The proton conductivity of the membranes measured at T= 30 and $50^{\circ}C$ was in the range of $10^{-3} to 10^{-2} S/cm$, and slightly increased with increasing swelling time and temperature.

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.264-269
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• 2003

5-Aminosalicylic acid (5-ASA) is an active ingredient of therapeutic agents used for Crohn s disease and ulcerative colitis. Because it is absorbed rapidly and extensively in the upper intestine, delivery of the agent specifically to the colon is necessary. We selected taurine as a colon-specific promoiety and designed 5-aminosalicyltaurine (5-ASA-Tau) as a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA). It was expected that introduction of taurine would restrict the absorption of the prodrug and show additive effect to the anti-inflammatory action of 5-ASA after hydrolysis. 5-ASA-Tau was prepared in good yield by a simple synthetic route. The apparent partition coefficient of 5-ASA-Tau in 1-octanol/pH 6.8 phosphate buffer or $CHCl_3$/pH 6.8 phosphate buffer was 0.10 or 0.18, respectively, at $37^{\circ}C$. To determine the chemical and biochemical stability in the upper intestinal environment, 5-ASA-Tau was incubated in pH 1.2 and 6.8 buffer solutions, and with the homogenates of tissue and contents of stomach or small intestine of rats at $37^{\circ}C$. 5-ASA was not detected from any of the incubation medium with no change in the concentration of 5-ASA-Tau. On incubation of 5-ASA-Tau with the cecal and colonic contents of rats, the fraction of the dose released as 5-ASA was 45% and 20%, respectively, in 8 h. Considering low partition coefficient and stability in the upper intestine, 5-ASA-Tau might be nonabsorbable and stable in the upper intestine. After oral administration, it would be delivered to the colon in intact form and release 5-ASA and taurine. These results suggested 5-ASA-Tau as a promising colon-specific prodrug of 5-ASA.