• Transactions of the Korean Society of Mechanical Engineers B
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• v.31 no.1 s.256
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• pp.21-28
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• 2007

The use of drug-eluting stents has dramatically reduced the incidence of restenosis however, much remains to be teamed about the performance of these stouts. In the present study, we tested the hypothesis that the design of drug-eluting stents influences the efficacy of local drug delivery to the arterial wall and that this effect depends on both arterial geometry and the prevailing flow conditions. We performed computational simulations in which the coupled Navier-Stokes and advection-diffusion equations were solved to determine the flow field and drug concentration in the vicinity of model drug-eluting stouts It is found that the characteristics of flow phenomena can be influenced greatly by the ratio of stent diameter to vessel diameter. The presence of drug-eluting stent may have profound effect on wall shear stresses, recirculation sizes and drug distributions. The results show that recirculation zone is influenced by the imposed flow conditions and stent diameter. In pulsatile flow, the low wall shear stress and high drug concentration occur along the arterial wall during the decelerating flow conditions. These results could provide the guideline for future drug-eluting stent designs toward reducing restenosis by affecting local wall shear stress distributions associated with neointimal hyperplasia.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.453-460
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• 2005

4-Aminopyridine (AP) is a potassium channel blocker used in the treatment of neurological disorders such as multiple sclerosis and Alzheimer disease. AP‘s window of therapeutic effect appears to correlate with its plasma halflife (3.5 hours). It demonstrates pH-dependent solubility because of a weakly basic drug. In addition, the resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study is to design sustained release matrix tablet containing AP, overcoming this problem. $Eudragit^{\circledR}$ L 100 (EuL) and sodium alginate were used in an effort to achieve pH independent drug release. The effect of sodium alginate and EuL on drug release from matrix tablet was investigated. The drug release behavior from the different tablets was analyzed by $t_{20%},\;t_{40%},\;t_{60%}$, The exponential diffusion coefficient n, kinetic constant K were calculated according to the Korsmeyer-Peppas equation. The drug release from matrix tablets prepared with sodium alginate was decreased with increasing the content of sodium alginate in pH 7.4 while there is no significant difference in pH 1.2. The exponent n values were determined to be approximately 0.5 and 0.8 respectively, in both pH 1.2 and 7.4. These values indicate diffusion-based anomalous mechanism and erosion-based anomalous mechanism, respectively. The drug release from sodium alginate matrix tablets prepared with solid dispersion of EuL containing drug showed a slow drug release in an acidic medium and a more fast drug release in phosphate medium, compared with sodium alginate matrix tablets prepared with physical mixture. These results may be attributed to the gel forming ability of sodium alginate and pH dependent solubility of EuL. Therefore, sustained-release AP matrix tablets using sodium alginate and EuL were successfully prepared.

• Journal of the Korean Chemical Society
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• v.53 no.6
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• pp.653-662
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• 2009

Developing effective tools for predicting absorption, distribution, metabolism, excretion properties and toxicity (ADME/T) of new chemical entities in the early stage of drug design is one of the most important tasks in drug discovery and development today. As one of these attempts, support vector machines (SVM) has recently been exploited for the prediction of ADME/T related properties. However, two problems in SVM modeling, i.e. feature selection and parameters setting, are still far from solved. The two problems have been shown to be crucial to the efficiency and accuracy of SVM classification. In particular, the feature selection and optimal SVM parameters setting influence each other, which indicates that they should be dealt with simultaneously. In this account, we present an integrated practical solution, in which genetic-based algorithm (GA) is used for feature selection and grid search (GS) method for parameters optimization. hERG ion-channel inhibitor classification models of ADME/T related properties has been built for assessing and testing the proposed GA-GS-SVM. We generated 6 different models that are 3 different single models and 3 different ensemble models using training set - 1891 compounds and validated with external test set - 175 compounds. We compared single model with ensemble model to solve data imbalance problems. It was able to improve accuracy of prediction to use ensemble model.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.92-93
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• 2002

With the recent development of combinatorial chemistry, recombinant biotechnology and rational drug design, millions of compounds are being produced in the laboratories of pharmaceutical companies. These new drug candidates are evaluated their efficacy and toxicity through in vivo animal model studies which is very important in drug development. From these studies, very successful drug candidates are selected. (omitted)

• Macromolecular Research
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• v.8 no.5
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• pp.199-208
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• 2000

The recent development of biodegradable polymers for drug delivery system (DDS) has been investigated. The biodegradable polymers for DDS are mainly discussed in two categories: one category is natural biodegradable polymers such as polysaccharides, modified celluloses, poly(${\alpha}$-amino acid)s, modified proteins, and microbial biodegradable polymers; the other is synthetic biodegradable polymers such as poly(ester)s, poly(ortho ester)s, poly(phosphazene)s, poly(anhydride)s, poly(alkyl cyanoacrylate)s, and multiblock copolymers. The bioconjugate polymeric drug delivery systems have been also proposed for the design of biocompatible polymeric controlled drug delivery.

• Journal of Integrative Natural Science
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• v.5 no.4
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• pp.229-232
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• 2012

The pharmaceutical industry has an ongoing need for new, safe medicines with genuine biomedical effects. Most of the candidate molecules are far from becomes a drug, because of their pharmacokinetic and pharmacodynamic properties. The introduction of bioisostere to improve properties of molecules and to obtain new class of compound is currently increased. Silicon substitution of carbon of existing drugs is an attractive strategy to search a new candidate with improved biological and physicochemical properties. The fundamental differences between carbon and silicon can lead to improved profile of the silicon containing candidate, and could be exploited to get further benefit in drug design process.

• Journal of Pharmaceutical Investigation
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• v.24 no.2
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• pp.49-55
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• 1994

Bioequivalence test of commercially available rifampicin capsules was performed. Sixteen volunteers were divided into 2 groups and the reference and test drug were given orally (450 mg) by cross-over design. Statistical evaluation of AUC, $C_{max}\;and\;T_{max}$ involved an analysis of variance (ANOVA). The differences of mean value in AUC, $C_{max}\;and\;T_{max}$ between the reference and test drug were within 20% with reference drug. ANOVA showed no significant differences for ‘between group’, ‘drug’ and ‘period’, but not for ‘between subjects’. The power of test $(1-{\beta})\;of\;AUC\;and\;$C_{max}$ was larger than 0.8 and the confidence of bioavailability was $within\;{\pm}20%$. From these results, it was concluded that the two preparations were bioequivalent for AUC and $C_{max}$, but was not for $T_{max}$.

• Journal of Integrative Natural Science
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• v.6 no.1
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• pp.16-20
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• 2013

G-protein-coupled receptor (GPCR) superfamily is the largest known receptor family, characterized by seven transmembrane domains and considered to be an important drug target. In this study we focused on an orphan GPCR termed as GPR18. As there is no X-ray crystal structure has been reported for this receptor, we report on a homology model of GPR18. Template structure with high homology was used for modeling and ten models were developed. A model was selected and refined by energy minimization. The selected model was further validated using various parameters. Our results could be a starting point for further structure based drug design.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.375-385
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• 2010

Conventional cancer chemotherapy is seriously limited by tumor cells exhibiting multidrug resistance (MDR), which is caused by changes in the levels or activity of membrane transporters that mediate energy-dependent drug efflux and of proteins that affect drug metabolism and/or drug action. Cancer scientists and oncologists have worked together for some time to understand anticancer drug resistance and develop pharmacological strategies to overcome such resistance. Much focus has been on the reversal of the MDR phenotype by inhibition of ATP-binding cassette (ABC) drug transporters. ABC transporters are a family of transporter proteins that mediate drug resistance and low drug bioavailability by pumping various drugs out of cells at the expense of ATP hydrolysis. Many inhibitors of MDR transporters have been identified, and though some are currently undergoing clinical trials, none are in clinical use. Herein, we briefly review the status of MDR in human cancer, explore the pathways of MDR in chemotherapy, and outline recent advances in the design and development of MDR modulators.

• International Journal of Precision Engineering and Manufacturing
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• v.9 no.2
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• pp.81-83
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• 2008

The Rapid Prototyping (RP) technology has advanced in many application areas. In this research, two different types, cylinder and scaffold, of implantable Drug Delivery System (DDS) were fabricated using Nano Composite Deposition System (NCDS), one of the RP systems. The anti-cancer drug (5-fluorouracil, 5-FU), biodegradable polymer (PLGA(85: 15)), and bio ceramic (Hydroxyapatite, HA) were used to form drug-polymer composite material. Both types of DDS were evaluated in vivo environment for two weeks. For evaluation, the cumulative drug release and shape stability were measured. Test results showed that the scaffold DDS provide higher cumulative drug release and has better stability than cylinder DDS.