• YAKHAK HOEJI
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• v.55 no.1
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• pp.69-74
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• 2011

Hyaluronic acid (HA) is a natural polymer consisting of disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. It has a great potential and success in cosmetic and biomedical applications. However, native HA is highly soluble and easily metabolized by enzymes such as hyaluronidase. Thus, various studies have been reported on modifying the physicochemical properties of HA, while maintaining its biocompatibility. For controlled drug delivery, many trials for fabricating HA microspheres were achieved under chemical reaction. The HA microspheres fabricated to improve the physical stability of HA using adipic acid dihydrazide (ADH) by cross-linking reaction has been reported earlier, however it lacks the desired physical stability and rapidly decomposes by swelling or enzymes. Therefore, we prepared double cross-linked HA microspheres (DC-HA microspheres) and alginate containing HA microspheres (AC-HA microspheres) to enhance its physicochemical properties. DC-HA microspheres were prepared using trisodium trimetaphosphate (STMP) under crosslinking reaction after ADH cross-linking reaction. AC-HA microspheres were prepared by adding alginate as a networking polymer. These microspheres were characterized by morphology, particle size, zeta potential, stability against hyaluronidase. Results showed that the DC-HA and AC-HA microspheres are more stable than that of HA microspheres.

• Macromolecular Research
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• v.16 no.1
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• pp.15-20
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• 2008

The enhanced permeability and retention (EPR) effect is used extensively for the passive targeting of many macromolecular drugs for tumors. Indeed, the EPR concept has been a gold standard in polymeric anticancer drug delivery systems. This study investigated the tumoral distribution of self-assembled nanoparticles based on the EPR effect using fluorescein and radio-labeled nanoparticles. Self-assembled nanoparticles were prepared from amphiphilic chitosan derivatives, and their tissue distribution was examined in tumor-bearing mice. The size of the nanoparticles was controlled to be 330 run, which is a size suited for opening between the defective endothelial cells in tumors. The long-circulating polymer nanoparticles were allowed to gradually accumulate in the tumors for 11 days. The amount of nanoparticles accumulated in the tumors was remarkably augmented from 3.4%ID/g tissue at 1 day to 25.9%ID/g tissue at 11 days after i.v. administration. The self-assembled nanoparticles were sustained at a high level throughout the 14 day experimental period, indicating their long systemic retention in the blood circulation. The ${\gamma}$-images provided clear evidence of selective tumor localization of the $^{131}I$-labeled nanoparticles. Confocal microscopy revealed the fluorescein-labeled nanoparticles to be preferentially localized in the perivascular regions, suggesting their extravasation to the tumors through the hyperpermeable angiogenic tumor vasculature. This highly selective tumoral accumulation of nanoparticles was attributed to the leakiness of the blood vessels in the tumors and their long residence time in the blood circulation.

• Journal of Dairy Science and Biotechnology
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• v.23 no.1
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• pp.9-17
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• 2005

Nanotechnology has penetrated into the various branches of research and development and it is particularly of benefit to the particle size engineering. It has been widely known that the particle size of an active pharmaceutical ingredient (API) is critical in determining the bioavailability and processability of pharmaceutical formulation. However, the window of appropriate particle size has been limited mainly due to related processing difficulties. The windows have been widened by the recent development of nanotechnologies, resulting in diversified drug delivery systems. The impact of this development is far more fundamental than what can be expected from conventional particle size engineering. It is the case that the preparation and use of nanoparticles will soon be a common task in the particle engineering step of pharmaceutical unit operations. In this chapter, the basic principles of variouspreparation techniques will be discussed in detail. Regardless of processing details, the preparation methods of pharmaceutical nanoparticles mainly concern how to deal with the extra energy related with particle size. Depending on the ways of treating the e103 energy, preparation methods can be classified into two major classes, i.e.. thermodynamic and kinetic approaches. The recent progresses have shown the possibilities of much more complex combinations of different approaches and the use of new types of energy and nanostructures.

• Journal of Pharmaceutical Investigation
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• v.25 no.4
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• pp.353-363
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• 1995

The purpose of this study was to investigate the intestinal and nasal absorption enhancement of cefotaxime (CTX) by ion-pairing with counterions and to design an effective oral and intranasal drug delivery system for antibiotics. Counterions for absorption promotion were cationic surfactants [cetylpyridinium chloride (CP), cetrimide (CT) and benzalkonium chloride (BA)]. In the presence of counterions, the apparent partition coefficient of cefotaxime was increased depending on the molar concentration of the counterions. Anion interference was observed for ion-pairing of cefotaxime with counterions because of the counterbalance between an anion and counterions. The present study employed the in situ simultaneous nasal and intestinal perfusion technique in rats. The apparent permeabilities $(P_{app})$ of cefotaxime were $1.43{\pm}0.04{\times}10^{-5}\;cm/sec(mean{\pm}S.E)$ in the nasal cavity and 0 in the jejunum, respectively, which indicated that the intrinsic absorptivity of cefotaxime was greater in the nasal cavity than in the jejunum. When ionupairing formers were used, the decreasing order of apparent cefotaxime permeability $(P_{app},\;10^{-5}\;cm/sec)$, corrected for surface area of absorption, was as followings: $BA\;(7.50{\pm}0.36)\;>\;CT\;(4.92{\pm}0.24)\;>\;CP\;(3.01{\pm}0.17)$ in the jejunum and $BA\;(22.31{\pm}1.36)\;>\;CP\;(18.24{\pm}0.81)\;>\;CT \;(16.22{\pm}1.87)$ in the nasal cavity. The increase in permeability of cefotaxime was about 13-fold in the rat nasal cavity and was marked in the rat jejunum for ion-pairing with counterions as compared to those without ion-pairing. The damages of jejunal and nasal mucosal membrane by counterions were observed within approximately 2hrs after removal of ion-pair of cefotaxime with counterions from the nasal cavity and jejunum. These results suggest that CP can be used as an ion-pairing former in the jejunum and CP and CT can be used as ion-pairing formers in the nasal cavity for cefotaxime, as well as for poorly absorbed drugs with a negative charge due to ionization.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.125-142
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• 2011

Solid dispersion, defined as the dispersion of one or more active ingredient in a carrier or matrix at solid state, is an efficient strategy for improving dissolution of poorly water-soluble drugs for enhancement of their bioavailability. Compared to other conventional formulations such as tablets or capsules, solid dispersion which can be prepared by various methods has many advantages. However, despite numerous studies which have been carried out, limitations for commercializing these products remain to be solved. For example, during the manufacturing process or storage, amorphous form of solid dispersion can be converted into crystalline form. That is, the dissolution rate of solid dispersion would continuously decrease during storage, resulting in a product of no value. To resolve these problems, studies have been conducted on the effects of excipients. In fact, modification of the solid dispersions to overcome these disadvantages has progressed from the first generation to the recent third generation products. In this review, an overview on solid dispersions in general will be given with emphasis on the various manufacturing processes which include the use of polymers and on the stabilization strategies which include methods to prevent crystallization.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.147-151
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• 2011

This paper demonstrates the development of a method for preparing micropatterned microdiscs in order to increase contact area with cells and to change the release pattern of drugs. The microdiscs were manufactured with hot embossing, where a polyurethane master structure was pressed onto both solid and porous microparticles made of polylactic-co-glycolic acid at various temperatures to form a micropattern on the microdiscs. Flat microdiscs were formed by hot embossing of porous microparticles; the porosity allowed space for flattening of the microdiscs. Three types of micro-grooves were patterned onto the flat microdiscs using prepared micropatterned molds: (1) 10 ${\mu}M$ deep, 5 ${\mu}M$ wide, and spaced 2 ${\mu}M$ apart; (2) 10 ${\mu}M$ deep, 9 ${\mu}M$ wide, and spaced 5 ${\mu}M$ apart; and (3) 10 ${\mu}M$ deep, 50 ${\mu}M$ wide, and spaced 50 ${\mu}M$ apart. This novel microdisc preparation method using hot embossing to create micropatterns on flattened porous microparticles provides the opportunity for low-cost, rapid manufacture of microdiscs that can be used to control cell adhesion and drug delivery rates.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.353-356
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• 2010

Although liposomes have been applied as drug delivery systems in various fields, the usage was limited due to the low encapsulation efficiency compared to other carrier systems. Here, cationic liposomes were prepared by mixing 1,2-dioleoyl-3-trimethylammoniopropane (DOTAP) as a cationic lipid, 1,2-dioleoyl-sn-glycerol-phosphoethanolamine (DOPE) and cholesterol (CH), and the liposomes were hydrated by varying the aqueous phases such as phosphate-buffered saline (PBS), 5% dextrose, and 10% sucrose in order to improve the encapsulation efficiency of bovine serum albumin (BSA). The particle size and zeta potential were determined by dynamic light scattering method and in vitro release patterns were investigated by spectrophotometry. Particle size and zeta potential of liposomes were varied depending on the ratio of DOTAP/DOPE/CH in range of 270-350 nm and 0.8-9.7 mV, respectively. Moreover, the addition of polyethylene glycol (PEG) improved the encapsulation efficiency from 37% to 43% as well as reduced particle sizes of liposomes while the liposomes were hydrated in PBS. When the liposomes were hydrated with 10% sucrose, the encapsulation efficiency of BSA was higher than any other groups. Whereas PBS was used as hydration solution, lower encapsulation efficiency was obtained compared with other groups. More than 60% of BSA was released from the liposomes hydrated with 10% sucrose; thereafter another 20% of BSA was released. Therefore, release pattern of BSA from cationic liposomes was extended release in this study. From the results, cationic liposomes dispersed in 10% sucrose would be potential carrier with high encapsulation efficiency.

• Journal of Periodontal and Implant Science
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• v.38 no.1
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• pp.15-22
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• 2008

Purpose: The attachment level is strongly associated with tooth loss and provides useful information on patterns of destruction of the periodontium. The presence of horizontal attachment loss would not be detected in clinical measurement. Therefore, the purpose of the present study was to estimate the patterns of periodontal destruction based on the attachment area and horizontal attachment loss in extracted teeth due to severe periodontitis. Materials and Methods: 307 teeth satisfied the criteria for assessment. An indirect method, based on digital images obtained from a digital camera and an image analysis program, was used to calculate the area of root surface and attachment loss and the extent of horizontal attachment loss. The data were analysed using SPSS. Results: No statistically significant differences among root surfaces were observed in anterior teeth on the loss of attachment area. However, in posterior teeth statistically significant differences in palatal surfaces of maxillary and mandibular premolar and molar surfaces compared with buccal surfaces were observed. Horizontal attachment loss was observed in 21.5% of the teeth examined. Frequency of horizontal attachment loss was highest in the maxillary first premolar (34.8%), followed by the maxillary second premolar (27.3%) and maxillary canine (25%). The mean length of horizontal attachment loss was 1.5mm. Conclusion: More meticulous examination will be needed of the palatal surfaces of maxillary and mandibular premolar and molar teeth. The percentage of teeth with horizontal attachment loss greater than 2.1 mm was 5.2%. Considering the length of curette blades, about 5.2% of teeth were not properly debrided. Therefore, Additional supportive therapy such as local drug delivery has to be considered in treatment of the first maxillary, second premolar and canine due to the high prevalence of horizontal attachment loss.

• Korean Chemical Engineering Research
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• v.51 no.5
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• pp.597-601
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• 2013

In this study, we present simple microfluidic approach for the synthesis of monodisperse microcapsules by using droplet-based system. We generate double emulsion through single step in the microfluidic device having single junction while conventional approaches are limited in surface treatment for the generation of double emulsion. First, we have injected disperse fluid containing FC-77 oil and photocurable ethoxylated trimethylolpropane triacrylate (ETPTA) and water containing 3 wt% poly(vinyl alcohol) (PVA) as continuous phase into microfluidic device. Under the condition, we easily generate double emulsion with high monodispersity by using flow focusing. The double emulsion droplets are transformed into microcapsules under the UV irradiation via photopolymerization. In addition, we control thickness of double emulsion's shell by controlling flow rate of ETPTA. We also show that the size of double emulsions can be controlled by manipulation of flow rate of continuous phase. Furthermore, we synthesize microcapsules encapsulating various materials for the application of drug delivery systems.

• Korean Chemical Engineering Research
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• v.55 no.2
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• pp.225-229
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• 2017

Micron-sized dextran particles, which now attract wide attention as a promising drug delivery systems, can be prepared via the supercritical anti-solvent (SAS) process. In SAS process, dextran particles are obtained as a result of recrystallization of dissolved dextran in dimethyl sulfoxide (DMSO) on addition of supercritical $CO_2$ as an anti-solvent. In this work, with an intention to provide information on the feasible operating conditions of the process, the phase behavior of Dexran/DMSO/$CO_2$ is observed by measuring the cloud point in favor of a variable volume cell. From the experimental study, it is concluded that a feasible operating condition of the SAS process for preparation of dextran particles would be 300.15 K~330.15 K and 90 bar~130 bar, respectively, and solute concentration ranges from 5mg/ml to 20 mg/ml.