• Journal of Powder Materials
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• v.30 no.6
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• pp.493-501
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• 2023

This study aimed to develop a solid self-nanoemulsifying drug delivery system (solid-SNEDDS) to enhance the formulation of ketoconazole (KTZ), a BCS Class II drug with poor solubility. Ketoconazole, which is insoluble above pH 3, requires solubilization for effective delivery. This SNEDDS comprises oil, surfactant, and co-surfactant, which spontaneously emulsify in the gastrointestinal tract environment to form nanoemulsions with droplet sizes less than 100 nm. The optimal SNE-vehicle composition of oleic acid, TPGS, and PEG 400 at a 10:80:10 weight ratio was determined based on the smallest droplet size achieved. This composition was used to prepare liquid SNEDDS containing ketoconazole. The droplet size and polydispersity index (PDI) of the resulting liquid SNEDDS were analyzed. Subsequently, solid-SNEDDS was fabricated using a spray-drying method with solidifying carriers such as silicon dioxide, crospovidone, and magnesium alumetasilicate. The physicochemical properties of the solid-SNEDDS were characterized by scanning electron microscopy and powder X-ray diffraction, and its solubility, droplet size, and PDI were evaluated. In particular, the solid-SNEDDS containing ketoconazole and crospovidone in a 2:1 weight ratio exhibited significantly enhanced solubility, highlighting its potential for improved medication adherence and dissolution rates.

• Journal of Integrative Natural Science
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• v.10 no.1
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• pp.1-6
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• 2017

Demand for a new anti-malarial drug has been dramatically increasing in the recent years. Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR) plays a vital role in fatty acid elongation process, which now emerged as a new important target for the development of anti-microbial and anti-parasitic molecules. In the present study, 19 compounds namely alginic acid, atropine, chlorogenic acid, chrotacumine A & B, coenzyme $Q_1$, 4-coumaric acid, curcumin, ellagic acid, embelin, 5-O-methyl embelin, eugenyl glucoside, glabridin, hyoscyamine, nordihydroguaiaretic acid, rohitukine, scopolamine, tlatlancuayin and ursolic acid were evaluated on their docking behaviour on P. falciparum enoyl-acyl carrier protein reductase (PfENR) using Auto dock 4.2. The docking studies and binding free energy calculations exhibited that glabridin gave the highest binding energy (-8.07 kcal/mol) and 4-coumaric acid in contrast showed the least binding energy (-4.83 kcal/mol). All ligands except alginic acid, ellagic acid, hyoscyamine and glabridin interacted with Gln409 amino acid residue. Interestingly four ligands namely coenzyme $Q_1$, 4-coumaric acid, embelin and 5-O-methyl embelin interacted with Gln409 amino acid residue present in both chains (A & B) of PfENR protein. Thus, the results of this present study exhibited the potential of these 19 ligands as P. falciparum enoyl-acyl carrier protein reductase (PfENR) inhibitory agents and also as anti-malarial agents.

• Journal of Pharmaceutical Investigation
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• v.41 no.6
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• pp.323-329
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• 2011

In order to develop new protein carrier replacing poly(DL-lactic acid-co-glycolic acid) (PLGA) microspheres, succinylated pullulan acetate (SPA) was investigated to fabricate a long term protein delivery carrier. SPA microspheres loaded with lysozyme (Lys) as a model protein drug were prepared by a water/oil/water (W/O/W) double emulsion method. An acidity test of SPA copolymers after hydrolysis was performed to estimate the change of protein stability during releasing proteins from the microspheres. There was no pH change of SPA copolymers, but pH of PLGA polymers after hydrolysis was significantly decreased to around pH 2, indicating that the long-term stability of proteins released from SPA microspheres can be guaranteed. Loading efficiency of proteins into SPA microspheres was three times higher than those into conventional PLGA microspheres, indication of inducing stronger charge interaction between proteins and succinyl groups in SPA microspheres. Although initial burst behaviors were monitored in Lys-loaded SPA microspheres due to relatively strong hydrophilic succinyl segments in SPA microspheres, initial burst issues would be circumvented if the ratio of charge density of succinyl moieties and hydrophobic acetate groups is harmonically controlled. Therefore, in this study, a new attempt of protein delivery system was made and functional SPA was successfully confirmed as a new protein carrier.

• Journal of Pharmaceutical Investigation
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• v.40 no.4
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• pp.219-223
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• 2010

The hyaluronic acid (HA) conjugate bearing $\alpha$-cyclodextrin ($\alpha$-CD) was synthesized as the potential carrier of poly(ethylene glycol) (PEG)-drug conjugates. The HA conjugate was prepared by the reaction between the carboxylic acid of HA and the primary amine of $\alpha$-CD in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and 1-hydroxybenzotriazole. The chemical structure of the conjugate was confirmed using $^1H$ NMR and FT-IR spectroscopy. The conjugate could form nano-sized particles in the presence of PEG by forming the inclusion complexes between $\alpha$-CD at the backbone of HA, which was demonstrated using electrophoretic light scattering and field emission transmission electron microscopy. It is anticipated that this novel kind of nanoparticles can serve as a useful delivery system for PEGylated drugs.

• Prospectives of Industrial Chemistry
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• v.20 no.6
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• pp.40-53
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• 2017

나노전달체 관련 기술은 다양한 질병 치료에 사용되어 단위세포 수준의 치료를 가능하게 할 뿐 아니라 영상 진단과 접목되어 질병의 진단 및 치료가 동시에 가능한 기술로 진화하고 있다. 본지에서는 이러한 연구 중 하나로 생체모사 나노전달체에 대해 다룬다. 다양한 면역세포 및 백혈구, 적혈구 등의 살아있는 세포의 기능을 나노전달체에 부여하여 전달효율 및 치료효과를 높이고자 하는 기술이다. 지금까지의 나노전달체 연구 및 개발 동향에 대하여 간략하게 살펴보고 특별히 최근 주목 받고 있는 생체모사 나노전달체의 개념, 제조 방법, 응용 및 앞으로의 전망에 대하여 논하였다.

• Polymer(Korea)
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• v.29 no.1
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• pp.36-40
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• 2005

Poly(amino acid) derivatives have been widely investigated as a drug carrier in drug delivery system. Particularly,polysuccinimide (PSI) is one of the most promising drug carriers since it possesses suitable physicochemical characteristics for development of macromolecular prodrugs, due to biocompatibility and biodegradability. In this study, we deal with the synthesis of polyaspartamide having various functional groups such as methoxy-poly(ethylene glycol) (MPEG) via ring closing of PSI. PSI was synthesized by polyonensation polymerization of spartic acid. The variety of average molecular weight was confirmed with reacion time and catalyst content to observe the optimum condition of synthesis. MPEG, hydrophilic chain, was bonded to fabricate polymeric micell composed of hydrophilic and hydrophobic polymer. All materials were characterized by 1H-NMR, FT-IR and GPC. In addition, the formation of nanoparticle micelle as drug carrier were also examined. Micelle size was measured by ELS and AFM. The functionalized polysparamide formed nanoparticle micelle whose size ranged from 90 to 130 nm. In conclusion, we prepared polyaspartamide functionalized with PEG examined the possibility as drug carriers.

• Journal of the Korean Chemical Society
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• v.57 no.4
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• pp.493-498
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• 2013

Liposomes, which can deliver payload at target site, have been studied as drug carrier. However, conventional liposomes have limitation for drug release at target site. Therefore, we developed hydroxyapatite (HA) coated ultrasound sensitive liposomes to increase drug release at target site and to enhance stability in blood stream. Control liposome was prepared using hydrogenated soy phosphatidylcholine (HSPC) and cholesterol, and then we assessed HA coating on the surface of control liposomes using calcium acetate, phosphoric acid, and 25% ammonium solution. Doxorubicin was used as a model drug. Size of HA coated liposomes was 120 nm and encapsulation efficiency of doxorubicin in liposomes was up to 95%. Size of HA coated liposomes are not changed in 30% serum solution, however, the control liposomes was 1.4 fold increased. After ultrasound triggered drug release from liposomes, intracellular efficiency of drug released from HA coated liposomes was 3 fold increased compared to control liposomes. In this study, we developed ultrasound sensitive liposomes to enhance drug release, which will be applied in controlled drug release at disease site.

• Journal of Pharmaceutical Investigation
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• v.39 no.6
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• pp.393-400
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• 2009

PHEA (hydroxyethyl-aspartamide)-mPEG (methoy-polyethyleneglycol)-$C_{16}$ (hexadecylamine)-ED (ethylenediamine) was prepared as a drug delivery carrier. The structure and molecular weight of polymers were characterized by $^1H$-NMR and gel permeation chromatography. Micelle size and shape were measured by electro-photometer light scattering and transmission electron microscope. The mean diameter of micelles was 23 nm in aqueous solution. To evaluate the potential of these polymeric micelles as a drug carrier, PSI-mPEG-$C_{16}$-ED was conjugated with Cy5.5 for Near-Infrared Fluorescent (NIRF) based optical imaging. PSI-mPEG-$C_{16}$-ED-Cy5.5 was injected intravenously into mice (n=5) and in vivo NIRF imaging was performed during 48 h after injection. The biodistribution study at 24 h after injection showed the longcirculation property of PSI-mPEG-$C_{16}$-ED-Cy5.5. Therefore, PSI-mPEG-$C_{16}$-ED micelles could be a promising drug carrier and imaging agent.

• Polymer(Korea)
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• v.33 no.4
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• pp.389-395
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• 2009

To develop the carrier of hydrophobic antifungal agents based on low molecular weight water-soluble chitosan (LMWSC), LMWSC was chemically modified with deoxycholic acid (DA) which is one of the bile acid as a hydrophobic group. The nanoparticles (WSCDA) using DA conjugated LMWSC were characterized using dynamic light scattering (DLS) and transmittance electron microscope (TEM). The particle size of WSCDA ranged from 250 to 350 nm and increased with the number of DA substitution. The loaded itraconazole as an antifungal agent WSCDA nanoparticles (WSCDA-ITCN) were prepared by solvent evaporation method. The drug content and the loading efficiency were investigated approximately $9{\sim}10%$ and $61{\sim}68%$ by UV spectrophotometer, respectively. The release of drug from nanoparticles was slow and showed sustained release characteristics. Based on the results of release study that the higher DA contents in WSCDA, the slower the releasing rate, the WSCDA-ITCN could be used as an excellent antifungal agent.

• Bulletin of the Korean Chemical Society
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• v.34 no.6
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• pp.1800-1808
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• 2013

Dual-responsive amphiphilic block copolymers were synthesized by combining enzymatic ring-opening polymerization (eROP) of ${\varepsilon}$-caprolactone (CL) and ATRP of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA). The obtained block copolymers were characterized by gel permeation chromatography (GPC), $^1H$ NMR and FTIR-IR. The critical micelle concentration (CMC) of copolymer was determined by fluorescence spectra, it can be found that with hydrophilic block (PDMAEMA) increasing, CMC value of the polymer sample increased accordingly, and the CMC value was 0.012 mg/mL, 0.025 mg/mL and 0.037 mg/mL for $PCL_{50}$-b-$PDMAEMA_{68}$, $PCL_{50}$-b-$PDMAEMA_{89}$, $PCL_{50}$-b-$PDMAEMA_{112}$, $PCL_{50}$-b-$PDMAEMA_{89}$ was chosen as drug carrier to study in vitro release profile of anti-cancer drug (taxol). The temperature and pH dependence of the values of hydrodynamic diameter (Dh) of micelles, and self-assembly of the resulting block copolymers in water were evaluated by dynamic light scattering (DLS). The result showed that with the temperature increasing and pH decreasing, the Dh decreased. Drug-loaded nanoparticles were fabricated using paclitaxel as model. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) had been explored to study the morphology of the hollow micelles and the nanoparticles, revealing well-dispersed spheres with the average diameters both around 80 nm. In vitro release kinetics of paclitaxel from the nanoparticles was also investigated in different conditions (pH and temperature, etc.), revealing that the drug release was triggered by temperature changes upon the lower critical solution temperature (LCST) at pH 7.4, and at $37^{\circ}C$ by an increase of pH.