• Archives of Pharmacal Research
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• 제20권4호
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• pp.318-323
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• 1997

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethyinitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life $(t_{1/2})$ in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL $(8.67{\pm}4.85%)$ decreased about four-folds, but in DMNA $(73.00{\pm}9.85%)$ similar result war observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.

• 약학회지
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• 제46권2호
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• pp.102-107
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• 2002

The particle size of medicinal materials is an important physical property which affects the pharmaceutical behaviors such as dissolution, chemical stability, compressibility and bioavailability of solid dosage forms. The size reduction of raw pharmaceutical powder is needed to formulize insoluble drugs or slightly soluble drugs and to improve the pharmaceutical properties such as the solubility, the pharmaceutical mixing and the dispersion. The objective of the present study is to evaluate the grinding characteristics of ursodeoxycholic acid(UDCA) as a model of insoluble drugs. The effects of the grinding time and the amount of additive on particle size distribution of ground UDCA were investigated. Grinding of insoluble drug, UDCA and a series of dry co-grinding experiments of UDCA with sodium lauryl sulfate(SLS) as an additive were carried out using a planetary ball mill. It was measured that the median diameter and the particle size distribution of ground products with grinding UDCA and additive SLS by Mastersizer. As a result of co-grinding of UDCA and SLS, the particle size of co-grinding products was decreased more than single grinding one. However, it was observed that co-grinding products were reaggregated to larger particles after 120 min.

• Toxicological Research
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• 제23권4호
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• pp.289-299
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• 2007

Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane of Gram-negative bacteria. LPS is usually used as an inflammatory animal model. During the inflammation, diarrhea and changes in plasma proteins, in hepatic and/or intestinal microsomal cytochrome P450 (CYP) isozymes, and in the renal and/or biliary excretion of drugs have been reported. Thus, in rats pretreated with lipopolysaccharide endotoxin isolated from Klebsiella pneumoniae (KPLPS rats), the absorption, distribution, metabolism, and excretion of drugs could be expected to be altered. Interestingly time-dependent effects on the hepatic CYP isozymes have been reported in KPLPS rats. Thus, in KPLPS rats, the pharmacokinetics of drugs which are mainly metabolized via CYP isozymes could be expected to be time-dependent. In this review, an attempt to explain changes in pharmacokinetics of drug reported in the literature was made in terms of CYP isozyme changes or urinary and/or biliary excretion changes in KPLPS rats.

• 한국기계가공학회지
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• 제17권5호
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• pp.111-116
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• 2018

Thermal fusion bonding is a method to enclose open microchannels fabricated on polymer chips for use in lab-on-a-chip (LOC) devices. Polymethyl methacrylate (PMMA) is utilized in various biomedical-microelectromechanical systems (bio-MEMS) applications, such as medical diagnostic kits, biosensors, and drug delivery systems. These applications utilize PMMAs biochemical compatibility, optical transparency, and mold characteristics. In this paper, we elucidate both the conformational entanglement of PMMA molecules at the contact interfacial regime, and the qualitative nature of the thermal fusion bonding phenomena through systematic molecular dynamics simulations.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.4983-4988
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• 2013

Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

• The Journal of Asian Finance, Economics and Business
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• 제8권2호
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• pp.583-593
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• 2021

The purpose of this study was to examine the relationship between transformational leadership and organizational performance with readiness to change and empower knowledge sharing quality as mediating variables. The survey was conducted by collecting the respondents' data by filling up forms which were designed using the google form application and collecting it using WhatsApp. This was performed on 400 respondents, encompassing employees from the National Agency of Drug and Food Control in Indonesia. The research model adopted was validated using Structural Equation Modeling technique with AMOS tool. The findings showed transformational leadership as a significant predictor of readiness to change and it proved relevant in empowering knowledge sharing quality, which in turn affects organizational performance. Furthermore, the effects of both two mediating variables was also examined, and only readiness to change significantly influenced the relationship between predictors of transformational leadership and organizational performance. The findings of this study showed the need for transformational leaders as the research focused on understanding the differences in employee character. This is required to encourage better performance by empowering quality knowledge dissemination mechanisms, with continuous in-house training activities. Therefore, the model adopted in this research and the hypotheses prove the direct effect of transformational leadership on organizational performance, achievable through the mediating role of readiness to change.

• Journal of Ginseng Research
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• 제42권4호
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• pp.512-523
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• 2018

Background: 20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD. Methods: MEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model. Results: A Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient $r^2=0.929-0.947$). Conclusion: The MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.

• 생명과학회지
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• 제31권5호
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• pp.527-535
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• 2021

라이소좀은 산성가수분해 효소를 가진 세포 내 소기관으로 단백질 및 고분자를 분해한다. 영양분 상태에 따라 세포 내 다양한 신호 전달 경로를 조절하는 신호 경로 중추로, 세포 항상성 조절에 중요한 역할을 한다. 따라서 이러한 라이소좀의 기능 이상은 라이소좀 저장질환, 퇴행성 신경질환 및 암을 발생시킬 수 있다. 암세포에서는 다양한 자극에 의한 lysosomal membrane permeabilization (LMP)가 일어날 수 있으며, 카텝신과 같은 라이소좀 내 효소 및 내용물이 세포질로 유출되어 다양한 형태의 라이소좀 의존적인 암세포사멸을 유도한다. 본 보고에서는 LMP 증가를 통한 다양한 형태의 세포사멸 유도 기전 및 항암제 민감성 증진에 대해 서술하였다. 미미한 LMP 유도는 일부 카텝신이 세포질로 유출되어 전형적인 세포사멸(apoptosis)을 일으키는 반면 강력한 LMP 유도는 라이소좀의 파열로 많은 카텝신 및 활성산소의 유출로 non-apoptotic 세포사멸을 일으킨다. 이러한 LMP 유도는 라이조솜 내에 포획된 항암제가 세포질로 유출되어 다른 타겟 소기관으로 작용하여 항암제에 대한 내성을 극복하고 민감성을 증진시킬 수 있다. 따라서, LMP 유도제 및 라이소좀 항성 작용제(lysosomotropic agent)에 의한 라이소좀 막 분열은 종양치료에 있어 새로운 전략이 될 수 있다.

• 한국임상약학회지
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• 제13권2호
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• pp.55-58
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• 2003

Astromicin is an aminoglycoside antiviotic that is structually different from conventional aminoglycosides. Astromicin has been shown to be active against aerobic Gram-negative bacilli. The pharmacokinetics of astromicin were determined in 12 healthy volunteers ($65.5\pm5.23\;kg$ of body weight) following a 30-min continuous intravenous infusion at a dose of 200 mg. The plasma and urine samples were collected up to 24 h and drug concentrations were measured by a bioassay using Bacillus subtilis. Pharmacokinetic parameters were calculated by fitting individual concentration-time curve to a one-exponential decay model. The plasma levels were $16.9\pm1.68\;and\;1.05\pm0.346\l{\mu}g/ml$ at 0 h and 8 h after the infusion, respectively. The elimination half-life of astromicin was $1.86\pm0.360\;h$ The volume of distribution was $0.182\pm0.0164\;L/kg$, and the total body clearance was $5.25\pm1.74\;L/h$. These pharmacokinetic parameters were similar to these of gentamicin, tobramycin, and amikacin. Therefore, it is recommended that therapeutic drug monitoring of astromicin could be conducted in a similar fashion as the other aminoglycosides.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.109-114
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• 2006

Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were developed for sustained delivery of water-soluble macromolecules. PLGA nanoparticles were fabricated by spontaneous emulsification solvent diffusion method generating negatively charged particles and heterogeneous size distribution. As a model drug, blue dextran was encapsulated in PLGA nanoparticles. In addition, nanoparticles were also prepared with varying ratio of poloxamer 188 (P188) and poloxamer 407 (P407), and coating with poly(vinyl alcohol) (PVA). Then, the particle size, zeta potential and encapsulation efficiency of nanoparticles containing blue dextran were studied. In vitro release of blue dextran from nanoparticles was also investigated. The surface and morphology of nanoparticles were characterized by scanning electron microscopy (SEM). In case of nanoparticles prepared with PLGA, P407, and different organic solvents, particle size was in the range of $230{\sim}320\;nm$ and zeta potentials of nanoparticles were negative. The SEM images showed that ethyl acetate is suitable for the formulation of PLGA nanoparticles with good appearance. Moreover, ethyl acetate showed higher encapsulation efficiency than other solvents. The addition of P188 to formulation did not affect the particle size of PLGA nanoparticles but altered the release patterns of blue dextran from nanoparticles. However, PVA, as a coating material, altered the particle size with increasing the PVA concentration. The nanoparticles were physically stable in the change of particle size during long-term storage. From the results, the PLGA nanoparticles prepared with various contents of poloxamers and PVA, could modulate the particles size of nanoparticles, in vitro release pattern, and encapsulation of water-soluble macromolecules.