• Title/Summary/Keyword: drug release control

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Fabrication of Biodegradable Disc-shaped Microparticles with Micropattern using a Hot Embossing Process with Porous Microparticles

  • Hwang, Ji-Yea;Choy, Young-Bin;Seo, Soon-Min;Park, Jung-Hwan
    • 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.

Development of Aloin Loaded PVA/CMC Hydrogel for Wound Healing (알로인이 함유된 창상치료제용 PVA/CMC 하이드로젤의 개발)

  • Kim, Jin;Lee, Chang Moon;Kim, Dong-Woon;Lee, Ki-Young
    • Polymer(Korea)
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    • v.37 no.6
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    • pp.802-808
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    • 2013
  • The purpose of this study was to develop an aloin-loaded wound dressing with an enhanced healing effect. The cross-linked hydrogel films were prepared with poly(vinyl alcohol) (PVA) and carboxyl methyl cellulose (CMC) using a freeze-thawing (F-T) method. Their gel properties, release of drug, in vivo wound healing effect and histopathology were then evaluated. In the wound healing test, this aloin loaded PVA/CMC hydrogel showed faster healing of the wound made in rat dorsum than the aloin carbomer 934 gel or the control (carbomer 934 gel) due to phytochemical activity of aloin and moisture of CMC. In conclusion, the aloin-loaded wound dressing composed of 5% PVA, 5% CMC and 0.125% aloin is a potential wound dressing with enhanced wound healing effect.

Experimental Studies on Antitumor Activity of Herb Drugs (I)-Effectiveness on Rat Natural Killer Cell Activity- (수종(數種)의 생약(生藥)에 대(對)한 항암효과(抗癌效果)의 실험적(實驗的) 연구(硏究)(I) -백서(白鼠)의 자연살해세포활성(自然殺害細胞活性)에 미치는 영향(影響)-)

  • Kang, Yun-Ho;Kim, Byung-Woon;Ha, Youn-Mun;Park, Jai-Kyung;Nam, Sang-Yun;Choi, Kyu-Chul;Choi, Yong-Mook
    • Korean Journal of Pharmacognosy
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    • v.18 no.2
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    • pp.118-126
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    • 1987
  • Natural Killer cells are considerd to play an important role in antitumor immune surveilance mechanism. In this study, 21 putative anticancer drugs selected from reference were assessed by evaluating the effect on rat Natural Killer cell activity (NKCA). All 21 herb drugs were extracted in boiling water, lyophilized, autoclaved, and then used for experiment. Culture supernatant of concanavalin-A (Con-A)-stimulated rat spleen cells as a source of lymphokine was also used as a control of comparison. Rat spleen cells were used as effector and NKCA was measured in 4hr $^{51}Cr-release$ assay against Yac-1 mouse lymphoma cell line. In order to determine the optimal conditions for NKCA augmentation, effector cells were treated with 3 different concentrations of each drug for 24, or 48 hrs before testing of NKCA, In optimal conditions determined from previous results, the effect of herb drugs on NKCA were assessed in 3 to 5experiments. NKCA was significantly enhanced by treatment with 4 herb drugs(Ponciri Fructus, Houttuyniae Herba, Aurantii Pericarpium, Nepetae Herba). Culture supernatant of Con-A-stimulated spleen cells also augmented the rat NKCA more significantly. The results show that 4 of the herb medicines supposed to display anticancer effect may have activity as a biological response modifier through augmentation of NKCA.

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Dietary total sugar intake of Koreans: Based on the Korea National Health and Nutrition Examination Survey (KNHANES), 2008-2011 (한국인의 총 당류 섭취실태 평가: 2008~2011년 국민건강영양조사 자료를 이용하여)

  • Lee, Haeng-Shin;Kwon, Sung-Ok;Yon, Miyong;Kim, Dohee;Lee, Jee-Yeon;Nam, Jiwoon;Park, Seung-Joo;Yeon, Jee-Young;Lee, Soon-Kyu;Lee, Hye-Young;Kwon, Oh-Sang;Kim, Cho-Il
    • Journal of Nutrition and Health
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    • v.47 no.4
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    • pp.268-276
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    • 2014
  • Purpose: The aim of this study is to estimate total sugar intake and identify major food sources of total sugar intake in the diet of the Korean population. Methods: Dietary intake data of 33,745 subjects aged one year and over from the KNHANES 2008-2011 were used in the analysis. Information on dietary intake was obtained by one day 24-hour recall method in KNHANES. A database for total sugar content of foods reported in the KNHANES was established using Release 25 of the U.S. Department of Agriculture National Nutrient Database for Standard Reference, a total sugar database from the Ministry of Food and Drug Safety, and information from nutrition labeling of processed foods. With this database, total sugar intake of each subject was estimated from dietary intake data using SAS. Results: Mean total sugar intake of Koreans was 61.4 g/person/day, corresponding to 12.8% of total daily energy intake. More than half of this amount (35.0 g/day, 7.1% of daily energy intake) was from processed foods. The top five processed food sources of total sugar intake for Koreans were granulated sugar, carbonated beverages, coffee, breads, and fruit and vegetable drinks. Compared to other age groups, total sugar intake of adolescents and young adults was much higher (12 to 18 yrs, 69.6 g/day and 19 to 29 yrs, 68.4 g/day) with higher beverage intake that beverage-driven sugar amounted up to 25% of total sugar intake. Conclusion: This study revealed that more elaborated and customized measures are needed for control of sugar intake of different subpopulation groups, even though current total sugar intake of Koreans was within the range (10-20% of daily energy intake) recommended by Dietary Reference Intakes for Koreans. In addition, development of a more reliable database on total sugar and added sugar content of foods commonly consumed by Koreans is warranted.

Suppression of Cocaine Intake by Acupuncture at HT7

  • Lee, Bong-Hyo;Kim, Sung-Hwan;Lim, Sung-Chul;Kim, Jae-Su;Lee, Yun-Kyu;Lee, Ji-Hye;Jung, Tae-Young;Yang, Chae-Ha;Yoon, Seong-Shoon;Han, Chang-Hyun;Lee, Kyung-Min
    • The Journal of Korean Medicine
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    • v.31 no.3
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    • pp.17-27
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    • 2010
  • Objectives: Cocaine has been well known as a representative drug of abuse for its strong reinforcing effect linked to the mesolimbic reward system including dopamine, and such reinforcement leads to the addiction. Acupuncture has been used widely in eastern Asia for the treatment of various diseases including mental disorders and psychiatric problems, and is gathering more interest as one of the complementary and alternative medicines in western countries. In a previous study, we demonstrated that acupuncture at HT7 could affect dopamine release in the mesolimbic system of rats sensitized to alcohol and morphine. This study was designed to investigate whether acupuncture at HT7 could attenuate cocaine intake or not. Material & Methods: Male Sprague-Dawley rats weighing 270-300 g at the start of experiment were trained to self-administer food pellets under a fixed ratio 1 schedule. After the success of acquisition of 100 pellets within 3 h for 3 consecutive days, animals were subjected to surgery whereby Silastic tubing was implanted into right jugular vein and secured with mesh under the anesthetization using pentobarbital injection (50 mg/kg, i.p.). Following recovery, rats were trained to self-administer cocaine (0.25 mg/kg) in daily 2 h sessions under fixed ratio 1 schedule over 10 days. Each treatment was performed on the next day of each establishment of baseline. Results: Results show that acupuncture at HT7, but not at control points, reduced cocaine intake significantly. Acupuncture at HT7 decreased selectively active lever response from $63.15{\pm}3.35$ to $51.46{\pm}3.99$ corresponding $82.12{\pm}5.31%$ compared to basal level. Also, it was demonstrated that the effect of acupuncture was mainly occurred at the half period. Nevertheless, acupuncture at HT7 did not influence the food taking behavior. Conclusions: From the results of this study, it may be suggested that acupuncture at HT7, at least in part, could contribute to the treatment of cocaine abuse.

Preparation of Alzheimers Animal Model and Brain Dysfunction Induced by Continuous $\beta$-Amyloid Protein Infusion

  • Akio Itoh;Kiyofumi Yamada;Kim, Hyoung-Chun;Toshitaka Nabeshima
    • Toxicological Research
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    • v.17
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    • pp.47-57
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    • 2001
  • Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and its pathology is characterized by the presence of numerous numbers of senile plaques and neurofibrillary tangles. Several genetic and transgenic studies have indicated that excess amount of $\beta$-amyloid protein (A$\beta$) is produced by mutations of $\beta$TEX>$\beta$-amyloid precursor protein and causes learning impairment. Moreover, $A\beta$ has a toxic effect on cultured nerve cells. To prepare AD model animals, we have examined continuous (2 weeks) infusion of $A\beta$ into the cerebral ventricle of rats. Continuous infusion of $A\beta$ induces learning impairment in water maze and passive avoidance tasks, and decreases choline acetyltransferase activity in the frontal cortex and hippocampus. Immunohistochemical analysis revealed diffuse depositions of $A\beta$ in the cerebral cortex and hippocampus around the ventricle. Furthermore, the nicotine-evoked release of acetylcholine and dopamine in the frontal cortex/hippocampus and striatum, respectively, is decreased in the $A\beta$-infused group. Perfusion of nicotine (50 $\mu\textrm{M}$) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the control group, but not in those of the $A\beta$-infused group, suggesting the impairment of nicotinic signaling in the $A\beta$-infused group. In fact, Kd, but not Bmax, values for [$^3H$] cytisine binding in the hippocampus significantly increased in the $A\beta$-infused rats. suggesting the decrease in affinity of nicotinic acetylcholine receptors. Long-term potentiation (LTP) induced by tetanic stimulations in CA1 pyramidal cells, which is thought to be an essential mechanism underlying learning and memory, was readily observed in the control group, whereas it was impaired in the $A\beta$-infused group. Taken together, these results suggest that $A\beta$ infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of LTP induction and may lead to learning and memory impairment. We also found the reduction of glutathione- and Mn-superoxide dismutase-like immunoreactivity in the brains of $A\beta$-infused rats. Administration of antioxidants or nootropics alleviated learning and memory impairment induced by $A\beta$ infusion. We believe that investigation of currently available transgenic and non-transgenic animal models for AD will help to clarify the pathogenic mechanisms and allow assessment of new therapeutic strategies.

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Wound Healing Effects of Rose Placenta in a Mouse Model of Full-Thickness Wounds

  • Kim, Yang Woo;Baek, Seung Ryeol;Lee, Eun Sook;Lee, Sang Ho;Moh, Sang Hyun;Kim, Soo Yun;Moh, Ji Hong;Kondo, Chieko;Cheon, Young Woo
    • Archives of Plastic Surgery
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    • v.42 no.6
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    • pp.686-694
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    • 2015
  • Background Rosa damascena, a type of herb, has been used for wound healing in Eastern folk medicine. The goal of this study was to evaluate the effectiveness of rose placenta from R. damascena in a full-thickness wound model in mice. Methods Sixty six-week-old C57BL/6N mice were used. Full-thickness wounds were made with an 8-mm diameter punch. Two wounds were made on each side of the back, and wounds were assigned randomly to the control and experimental groups. Rose placenta ($250{\mu}g$) was injected in the experimental group, and normal saline was injected in the control group. Wound sizes were measured with digital photography, and specimens were harvested. Immunohistochemical staining was performed to assess the expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), and CD31. Vessel density was measured. Quantitative analysis using an enzyme-linked immunosorbent assay (ELISA) for EGF was performed. All evaluations were performed on postoperative days 0, 2, 4, 7, and 10. Statistical analyses were performed using the paired t-test. Results On days 4, 7, and 10, the wounds treated with rose placenta were significantly smaller. On day 2, VEGF and EGF expression increased in the experimental group. On days 7 and 10, TGF-${\beta}1$ expression decreased in the experimental group. On day 10, vessel density increased in the experimental group. The increase in EGF on day 2 was confirmed with ELISA. Conclusions Rose placenta was found to be associated with improved wound healing in a mouse full-thickness wound model via increased EGF release. Rose placenta may potentially be a novel drug candidate for enhancing wound healing.

Comparisons of 12-Hour and 24-Hour Sustained-Release Theophyllines in the Management of Asthma (천식치료에서 서방형 Theophylline의 1일 1회 제형과 1일 2회 제형의 비교)

  • Lee, Yang-Deok;Park, Seoung-Ju;Lee, Heung-Bum;Lee, Yong-Chul;Rhee, Yang-Keun
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.3
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    • pp.293-299
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    • 2001
  • Background : Sustained-release theophylline, which is generally prescribed as a twice-daily equal-dose regimen, is one of the more common asthma treatments. The development of a sustained-release drug delivery technology that enables improved control of the theophylline blood levels represents a significant advancement in both the efficacy and safety of dosing. Method : A crossover study was conducted with 25 adult chronic asthmatic patients requiring daily bronchodilator therapy. The study group included thirteen males and twelve females with ages ranging from 19 to 71 years. The overall approach was to place the patients first on the twice-daily preparation($Etheophyl^{(R)}$) for 28 days at 8 AM and 8 PM, and measure the pulmonary function and theophylline level on the 28th day. The patients were subsequently switched to the once-daily preparation($Uniphyl^{(R)}$) in the same daily dose at 8 PM on the 29th day and the same parameters were measured on the 56th day. Results : The mean serum levels of theophylline were $8.18{\pm}1.66\;{\mu}g/ml$ in the $Etheophyl^{(R)}$-treated period and $8.00{\pm}1.75\;{\mu}g/ml$ in the $Uniphyl^{(R)}$-treated period. ln addition, the $FEV_1$ showed $71.40{\pm}7.48$ percent in the $Etheophyl^{(R)}$-treated and $69.18{\pm}9.00$ percent in the $Uniphyl^{(R)}$-treated period. Thus there were no significant differences between the once-daily and twice-daily preparation. Conclusion : The results indicated little clinical differences between the two medications. The two drugs are equally effective in controlling asthma over the four weeks of treatment.

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Study on Anti-allergic Effect and Safety of Bangpung-galgeun-tang (방풍갈근탕(防風葛根湯)의 항알레르기효과에 관한 연구)

  • Lee, Joo-Eun;Park, Seong-Ha;Kang, Kyung-Hwa;Lee, Yong-Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.5
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    • pp.1118-1126
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    • 2007
  • The purpose of this study was to examine the anti allergic effect in vivo and in vitro, and to observe single and four weeks repeated toxicity in mice of Bangpung-galgeun-tang (BGT). We investigated anti DNP IgE-mediated passive cutaneous anaphylaxis in rodents and compound 48/80-induced active systemic anaphylatic shock in mice after oral administration with BGT of 0.4 g/kg and 0.8 g/kg for 8 days, and also examined MTT assay, ${\beta}-hexosaminidase$ activity, IL-4 and $TNF-{\alpha}$ from RBL-2H3 and $TNF-{\alpha}$ from Raw264.7 after pre-treatment with BGT of 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml and 2 mg/ml. To ascertain safety and toxicity of BGT, we divided into single and four weeks repeated administration test. In single test, three groups were administrated different dosages and routes (2 g/kg/i.p., 4 g/kg/i.p. and 15 g/kg /p.o.) of BGT, and in four weeks repeated test, 0.8 g/kg BGT was administrated. Control groups were administrated with only saline according to on Korean Food and Drug Administration, respectively. We observed attentively motality, abnormal clinical sign, body weight change, organ weight, AST and ALT of mice after BGT administration. BGT inhibited passive cutaneous anaphylaxis and active systemic anaphylatic shock by oral administration. All the concentrations of BGT from 0.25 to 2 mg/ml didn't have an effect on cell viability and cytotoxicity. In RBL-2H3, ${\beta}-hexosaminidase$ release, IL-4 and $TNF-{\alpha}$, and in Raw264.7, $TNF-{\alpha}$ were significantly reduced by treated all concentrations of BGT. During toxicity experiment period, there was no difference in body weight change, organ weight, AST and ALT among different dose groups. Death were found 3 mice from day 2 to day 3 in single test i.p. group. (2 g/kg, 4 g/kg). Several individuals of single test i.p. group were observed that decreased locomotor activity, exophthalmos, bloodshot eyes, loss of eyesight and so on in early period after administration. But there was no difference in clinical signs among p.o. group. These results indicate that BGT have inhibition effects on allergy and suggest that no observable effect level of the test orally administration was considered to be more than 2 g/kg in mice under the conditions employed in this study.

Self-Assembled Nanoparticles of Bile Acid-Modified Glycol Chitosans and Their Applications for Cancer Therapy

  • Kim Kwangmeyung;Kim Jong-Ho;Kim Sungwon;Chung Hesson;Choi Kuiwon;Kwon Ick Chan;Park Jae Hyung;Kim Yoo-Shin;Park Rang-Won;Kim In-San;Jeong Seo Young
    • Macromolecular Research
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    • v.13 no.3
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    • pp.167-175
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    • 2005
  • This review explores recent works involving the use of the self-assembled nanoparticles of bile acid-modified glycol chitosans (BGCs) as a new drug carrier for cancer therapy. BGC nanoparticles were produced by chemically grafting different bile acids through the use of l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). The precise control of the size, structure, and hydrophobicity of the various BGC nanoparticles could be achieved by grafting different amounts of bile acids. The BGC nanoparticles so produced formed nanoparticles ranging in size from 210 to 850 nm in phosphate-buffered saline (PBS, pH=7.4), which exhibited substantially lower critical aggregation concentrations (0.038-0.260 mg/mL) than those of other low-molecular-weight surfactants, indicating that they possess high thermodynamic stability. The SOC nanoparticles could encapsulate small molecular peptides and hydrophobic anticancer drugs with a high loading efficiency and release them in a sustained manner. This review also highlights the biodistribution of the BGC nanoparticles, in order to demonstrate their accumulation in the tumor tissue, by utilizing the enhanced permeability and retention (EPR) effect. The different approaches used to optimize the delivery of drugs to treat cancer are also described in the last section.