• YAKHAK HOEJI
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• v.54 no.5
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• pp.323-327
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• 2010

Translationally controlled tumor protein (TCTP) activates basophils to release histamine and causes chronic inflammation. It was also reported that TCTP significantly reduced in brain of Alzheimer's Disease and Down Syndrome as compared to normal person, suggesting that TCTP might be involved in cognitive function. We wondered whether TCTP could act as a general inducer in neurotransmitters release in brain. We, therefore, investigated the role of TCTP in PC12 cell line which expressed neuronal properties. We found that TCTP could activate JNK, and the activity was inhibited by pretreatment of dicoumarol, a JNK inhibitor. However, TCTP could not activate ERK that has known to be involved in neurotransmitter release. These suggest TCTP did not participate in neurotransmitter release from PC12 cells, and TCTP might not be a general inducer in neurotransmitter release.

• Macromolecular Research
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• v.16 no.5
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• pp.429-433
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• 2008

Alginate/carboxymethyl scleroglucan (CMSG) hydrogels were suggested as a novel carrier for the controlled release of protein drugs. The drug release characteristics of alginate hydrogels were improved by CMSG addition. Scleroglucan (Sclg) was carboxymethylated using monochloroacetic acid in aqueous alkaline medium. Alginate/CMSG hydrogels were prepared by dropping the mixture solution of alginate/CMSG into calcium chloride solution. The swelling behaviors and drug release characteristics of the hydrogels were investigated in the buffers of pH 1.2 or 7.4. As the CMSG content increased in the hydrogels, the swelling ratio of the alginate/CMSG hydrogel increased rapidly in the buffer of pH 7.4. At pH 1.2, however, the swelling ratio significantly decreased compared to that at pH 7.4. According to in vitro release tests, only 15% of ovalbumin, investigated as a model protein drug, was released from the alginate/CMSG hydrogels at pH 1.2 within 6 h. At pH 7.4, however, the drug release significantly increased due to the rapid swelling of the hydrogels. The release and swelling behaviors of the hydrogels could be controlled by changing the CMSG content in the hydrogels. These results supported the use of alginate/CMSG hydrogels as a suitable carrier for the controlled release of protein drugs in a pH responsive manner.

• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.5
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• pp.326-331
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• 2001

With the aim of developing of pH-sensitive controlled drug release system, a poly(Llysine) (PLL) based cationic semi-interpenetrating polymer network (semi-IPN) has been synthesized. This cationic hydrogel was designed to swell at lower pH and de-swell at higher pH and therefore be applicable for achieving regulated drug release at a specific pH range. In addition to the pH sensitivity, this hydrogel was anticipated to interact with an ionic drug, providing another means to regulate the release rate of ionic drugs. This semi-IPN hydrogel was prepared using a free-radical polymerization method and by crosslinking of the polyethylene glycol (PEG)-methacrylate polymer through the PLL network. The two polymers were penetrated with each other via interpolymer complexation to yield the semi-IPN structures. The PLL hydrogel thus prepared showed dynamic swelling/de-swelling behavior in response to pH change, and such a behavior was influenced by both the concentrations of PLL and PEG-methacrylate. Drug release from this semi-IPN hydrogel was also investigated using a model protein drug, streptokinase. Streptokinase release was found to be dependent on its ionic interaction with the PLL backbones as well as on the swelling of the semi-IPN hydrogel. These results suggest that a PLL semi-IPN hydrogel could potentially be used as a drug delivery platform to modulate drug release by pH-sensitivity and ionic interaction.

• Journal of Dairy Science and Biotechnology
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• v.23 no.2
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• pp.115-123
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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${\sim}$30%, pH 4.5-7.2) at a proportion of 25${\sim}$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.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.385-390
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• 2000

To demonstrate the effect of formulation conditions on the controlled release of protein from poly(lactide-co-glycolide) (PLGA) microspheres for use as a parenteral drug carrier, ovalbumin (OVA) microspheres were prepared using the W/O/W multiple emulsion solvent evaporation and extraction method. Methylene chloride or ethyl acetate was applied as an organic phase and poly(vinyl alcohol) as a secondary emulsion stabilizer. Low loading efficiencies of less than 20％ were observed and the in vitro release of OVA showed a burst effect in all batches of different microspheres, followed by a gradual release over the next 6 weeks. Formulation processes affected the size and morphology, drug content, and the controlled release of OVA from PLGA microspheres.

• 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.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.251-256
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• 2000

Sterically stabilized liposomes (SSL) composed of distearoylphosphatidylcholine, cholesterol, dicetylphosphate and distearoylphosphatiodylethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG 2000) were made by reverse phase evaporation method to prolong biological half-life and decrease toxic side effect of drug. Streptozocin (572), a water-soluble antitumor agent with short half-life, was selected as a model drug. The size of SSL was controlled by polycarbonate extrusion to 100 nm which is adequate size for long circulation in plasma. The release rate of drugs from SSL in PBS was evaluated. And the stability of STZ-containing liposomes against drug leakage into rat plasma was evaluated in order to investigate the interaction of liposome and plasma protein. Incorporation of DSPE-PEG 2000 into conventional liposomes significantly decreased the drug leakage into rat plasma.

• Biomedical Science Letters
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• v.12 no.4
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• pp.443-450
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• 2006

To demonstrate their possibilities as an enhanced vaccine delivery system, protein-loaded Poly lactide glycolide copolymer (PLGA) microspheres were prepared with different physical characteristics. Ethyl acetate (EA) solvent extraction process was employed to prepare microspheres and the effects of process parameters on drug release properties were evaluated. The biodeuadability of microspheres was also evaluated by the pH change and GPC (Gel permeation chromatography). Primary IgG antibody responses in BALB/c mice were compared with protein saline solutions as negative controls and adsorbed alum suspensions as positive controls after single subcutaneous injection for in vivo studies. The microspheres showed a erosion with a highly porous structure and did not keep their spherical shape at 45 days and this result could be confirmed by GPC. In vitro release of proteinous drug showed initial burst effect in all batches of microspheres, followed by gradual release over the next 4 weeks. PLGA microspheres were degraded until 45 days and the secondary structure of OVA was not affected by the preparation method. Enzyme-linked immunosorbent assays demonstrated that the single subcutaneous administrations of OVA-loaded PLGA microspheres induced enhanced serum IgG antibody response in comparison to negative and positive controls. These results demonstrated that microspheres providing the controlled release of antigens might be useful in advanced vaccine formulations for the parenteral carrier system.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.43-47
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• 2001

Sterically stabilized liposomes (SSL) have been introduced for longer circulation in blood than conventional liposomes (CL). However, there are a couple of problems in SSL preparation due to the instability of phospholipid and the degradation of drug in aqueous conditions. To solve these problems, it is necessary to go through lyophilization process. Therefore, in this study, effects of lyophilization on SSL were evaluated for physical characteristics changes upon rehydration of lyophilized SSL such as the particle size, efficiency of drug entrapment, turbidity and drug release. SSL containing streptozocin, a water-soluble anticancer drug as a model compound, were prepared with DSPC and DSPE-PEG 2000. The size was controlled to 100 nm by extrusion with polycarbonate membrane, and sucrose was used as a cryoprotectant for lyophilization at the 1:3 (lipid:sucrose) ratio. Upon rehydration of lyophilized SSL, the average size was in the range of $50{\sim}200\;nm$ which is adequate for longer circulation in blood, and the encapsulation efficiency was kept as its initial state. Rehydrated SSL were not adsorbed to rat plasma protein and revealed a similar drug release profile to that of fresh SSL before lyophilization. Therefore, lyophilization could be introduced efficiently to overcome aqueous instability problems of SSL.

• Polymer(Korea)
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• v.29 no.5
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• pp.468-474
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• 2005

PLGA and PCL copolymers initiated by carbitol as drug carriers were synthesized by ring-opening polymerization of L-lactide (LA), glycolide (GA), and $\varepsilon-caprolactone(\varepsilon-CL)$. Implantable wafers were simply fabricated by direct compression method after physical mixing of copolymers and bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) as a model protein drug. The release amounts of BSA-FITC from wafers were determined by fluorescence intensity using the fluorescence spectrophotometer. Also, the release behavior of BSA-FITC on wafers was controlled by adding the additives such as collagen, small intestinal submucosa (SIS), poly(vinyl pyrrolidone) (PVP), and poly(thylene glycol) (PEG). The wafer prepared by PLGA and PCL exhibited slow release within $10\%$ for 30 days. But, those prepared by a variety of additives exhibited the controlled BSA release patterns with a dependence on the additive contents. furthermore, the wafers containing natural materials such as collagen and SIS showed more zero-order release profile than that with synthetic materials such as PVP and PEG. It was confirmed that the release of BSA from implantable wafers could be easily controlled by adding natural additives.