• Archives of Pharmacal Research
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• v.5 no.2
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• pp.61-70
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• 1982

Sulfisoxazole, a chemotherapeutic agent, was microencapsulated with ethylcellulose by means of phase separation form cyclohexane by temperatture change. The size distribution was determined by use of standard sieves and the effect of core to wall ratio was noted. To examine their shapes and usrface characteristics, the microcapsules were observed with a scanning electron microscope. Release of the drug from microcapsules into pH 7.5 buffer medium was studied. The release pattern was found to have similar properties to the release of a drug from an insoluble porous matrix reported. The apparent diffusion coefficient of sulfisoxazole was measured for the transport of the drug from the core of microcapsules into the surronding sink condition. The apparent diffusion coefficient increased with increasing capsule size.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.49-57
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• 1994

The objective of this study was to determine whether Pz-peptide, an enhancer of hydrophilic solute permeability in the intestine, could elevate the paracellular permeability of the cornea and conjunctiva in the pigmented rabbit. The in vitro penetration of four hydrophilic solutes, mannitol (MW 182), fluorescein (MW 376), FD-4 (FITC-dextran, 4 KDa), and FD-10 (FITC-dextran, 10 KDa) across the pigmented rabbit cornea and conjunctiva was studied either in the presence or absence of 3 mM enhancers. Drug penetration was evaluated using the modified Ussing chamber. The conjunctiva was more permeable than the cornea to all four markers. EDTA and cytochalasin B showed higher effects on marker transport than Pz-peptide, but Pz-peptide elevated the corneal transport of mannitol, fluoresein, and FD-4 by 50%, 26%, and 50%, respectively, without affecting FD-10 transport. Possibly due to the leakier nature of the conjunctiva, 3 mM Pz-peptide elevated the transport of only FD-4 by about 45%, without affecting the transport of other markers. Furthermore, the transport of Pz-peptide itself across the cornea and conjunctiva increased with increasing concentration in the 1-5 mM range, suggesting that Pz-peptide enhanced its own permeability, possibly by elevating paracellular permeability. Effects of ion transport inhibitors on Pz-peptide transport were then investigated. PZ-peptide penetration was not changed by mucosal addition of $10\;{\mu}M$ amiloride or $10\;{\mu}M$ hexamethylene amiloride, inhibiting serosal $Na^{+}$ exit by $100\;{\mu}M$ ouabain, or replacing $Na^{+}$ with choline chloride in the mucosal side buffer. These results seggested that Pz-peptide enhanced the paracellular permeability of rabbit cornea and conjunctiva and further indicate that ion transporters were not involved in the Pz-peptide induced elevation of paracellular marker permeability.

• Journal of Ginseng Research
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• v.42 no.3
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• pp.370-378
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• 2018

Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.6
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• pp.516-521
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• 2005

Drug delivery to the lymphatic system may be important in terms of the treatment with lymphatic involvement, such as tumor metastases and immunization. Especially, drug transport via the intestinal lymphatics after oral administration has been attracted lots of interests. The purpose of this study was to prepare cyclosporin A (CSA)-loaded liposomes, with different characteristics, and evaluate their mucoadhesivity. Three liposome preparations were formulated: cationic stearylamine liposomes (SA-Lip), anionic phosphatidylserine liposomes (PS-Lip), Polymer (chitosan)-coated liposomes (CS-Lip), and characterized. The liposome preparations were found to be spherical in shape, with PS-Lip being the smallest. The liposome preparations exhibited entrapment efficiencies in the order: PS-Lip $(52.5{\pm}2.9%)$ > SA-Lip $(48.8{\pm}3.3%)$ > CS-Lip $(41.7{\pm}4.2%)$. Finally, mucoadhesive tests were carried out using rat intestine, with SA-Lip (67%) showing the best adhesive rate of the three preparations (PS-Lip: 56%, CS-Lip: 61%). These results suggest that a positive charge on the surface of drug carriers may be an important factor for the intestinal drug delivery.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.136-136
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• 1998

L-asparaginyl and L- aspartyl residues in proteins are subject to spontaneous degradation reactions generating isomerized and racemized aspartyl derivatives. Proteins containing L-isoaspartyl and D-aspartyl residues usually have altered structures and diminished biological activities. These residues can be recognized and be repaired to normal L-aspartyl residues by protein L-isoaspartyl methyltransferase(PIMT), which is present at high levels in testis. Although testicular PIMT have been shown to be involved in either sperm motility or sperm maturation, it may play an important role in the repair of damaged sperm proteins during the prolonged period of epididymal transport and storage. In the present study, as a initial step toward elucidating the function of protein carboxylmethylation in testis, we purified PIMT from porcine testicular cytosol as a momeric 27,000 Da species by ammonium sulfate precipitation, DEAE-sephacel chromatography, SAH-liganded affinity chromatography, and gel filtration chromatography. The optimum pH for the reaction was 6.0. $K_{m}$ values of the enzyme for the S-adenosyl-L-methionine (SAM), synthetic oligopeptide(VYP-L-isoD-HA) and histone type II-As were 1.0 ${\mu}$M, 33.2 ${\mu}$M and 276 ${\mu}$M respectively. Consequently, properties of the porcine testicular PIMT is similar to that of other mammalian PIMTs.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.165-172
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• 1999

In the present work , the transport mechanism of a capsaicin derivative, DA-5018, through blood-brain barrier (BBB) has been investigated to evaluate the feasibility of potential drug development. The result of pharmacokinetic parameters obtained from the intravenous injection of plasma volume marker,$[3^H]RSA$ and $[{14}^C]DA-5018$, indicated that both AUC, area under the plasma concentration curve and VD, volume of distribution in brain of $[3^H]RSA$ agreed with those reported ($1620{\pm}10 $percentage injected dose minute per milliliter (%IDmin/ml) and $12.0{\pm}0.1{\mu}l/g$, respectively). Elimination half-life and AUC of $[{14}^C]DA-5018$is corrected by the PHLC analysis, 19.6$\pm$1.2 min and 7.69$\pm$0.85% IDmin/ml, respectively. The metabolic rate of $[{14}^C]DA-5018$was very rapid. The blood-brain barrier permeability surface area (PS) product of $[{14}^C]DA-5018$ was calculated to be 0.24$\pm$0.05 $\mu$l/min/g. The result of internal carotid artery perfusion and capillary depletion suggested that [14C]DA-5018 pass through BBB with the time increasingly. Investigation of transport mechanism of $[{14}^C]DA-5018$ using agonist and antagonist suggested that vanilloid (capsaicin) receptor did not exist in the BBB, and nutrient carrier system in the BBB has no effect on the transport of DA-5018. In conclusion, despite the fact that penetration of DA-5018 through BBB is significant, the intact drug found in the brain tissue is small because of a rapid metabolism. Therefore, for the central analgesic effect of DA-5018, the method to increase the metabolic stability in plasma and the brain permeability should be considered.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.36 no.5
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• pp.545-551
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• 2012

We investigated the diffusive transport of bupivacaine HCl through the microchannels of microfluidic drug delivery devices. In the biodegradable microfluidic drug delivery devices developed in this research, the drug release rate can be controlled by simply modulating the geometrical parameters of the microchannels, such as the length, number, and cross-sectional area of the microchannels, when the microchannels are used as paths for drug release. However, the hydrophobic nature of a biodegradable polymer, 85/15 poly(lactic-co-glycolic acid), hinders the infiltration of a release medium (phosphate-buffered saline) through the microchannels into the reservoir of a device that contains bupivacaine HCl, at the early stage of drug release. This can have an adverse effect on the early stage release of local analgesic compounds from the device. In this study, microfluidic channels were surface-treated with surfactants such as PEG600 and Tween80, and the effects of the surfactants on the release performance are presented and analyzed.

• Journal of Nutrition and Health
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• v.33 no.6
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• pp.660-667
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• 2000

Previous studies on the effect of age on intestinal taurine transport in animals have invariably shown a decline in the activity of the transport system with increasing age. In the present study changes in taurine transporter activity were observed during cell differentiation in the human colon carcinoma cell line HT-29 This cell line exhibits various enterocytic characteristics when differentiated and therefore has frequently been used to study the characteristcs and regulation of nutrient and drug absorption in the small intestine at the cellular level. Pre-treatment of the cells with $\beta$-alanine(10mM) reduced the taurine transport activity to 33% of the value for the control cells(p<0.05) which implies that taurine and $\beta$-alanine share a common $\beta$-amino acid transport system for their celluar uptake in the HI-29 was continued until 21 days post seeding. Kinetic studies of the taurine transporter were conducted in the HT-29 cell line with varying taurine concentration(5-60$\mu$M) in the uptake medium Both Vmax and the Michaelis-Menten constant(Km) of taurine transporter were decreased as differentiation of the HT-29 cell line was progressed ; Vmax of the taurine transporter in cells incubated for 4, 14 and 21 days post seeding was 2.79$\pm$3.4m 16.89$\pm$1.74, and 0.85$\pm$0.08 and 0.32$\pm$0.01nmol.mg protein-1 .30min-1 respectively(p<0.001) and Km was 42.3$\pm$3.4, 16.89$\pm$1.74, and 11.2$\pm$3.0$\mu$M respectively (p<0.01) These results indicate that the activity of sodium dependent active taurine transport system in the HT-29 cell line is decreased as confluent cells are differentiated. This phenomenon in cell culture system corresponds well with the earlier observation of lower intestinal taurine transport activity in suckling rats compared to that in adult animals although direct relationship of cell differentiation with in vivo aging process needs further verification.

• BMB Reports
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• v.49 no.1
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• pp.18-25
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• 2016

Recent evidence has indicated that nano-sized vesicles called "exosomes" mediate the interaction between cancer cells and their microenvironment and play a critical role in the development of cancers. Exosomes contain cargo consisting of proteins, lipids, mRNAs, and microRNAs that can be delivered to different types of cells in nascent as well as distant locations. Cancer cell-derived exosomes (CCEs) have been identified in body fluids such as urine, plasma, and saliva from patients with cancer. Although their content depends on tumor type and stage, CCEs merit consideration as prognostic and diagnostic markers, as vehicles for drug delivery, and as potential therapeutic targets because they could transport various oncogenic elements. In this review, we summarize recent advances regarding the role of CCEs in cancer invasion and metastasis, as well as its potential clinical applications. [BMB Reports 2016; 49(1): 18-25]

• YAKHAK HOEJI
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• v.27 no.1
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• pp.21-28
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• 1983

Distribution volume (Vd$_{ss}$ ) of a model basic drug, tetraethylammonium bromide (TEA) at a steady-state decreased sinificantly in glycerol and uranium-renal failure rats. Assuming carrier-mediated transport of TEA into tissues, the theoretical $Vd_{ss}$ of TEA decreases in an exponential way as the plasmal concentration of TEA increases. The relationship between $Vd_{ss}$ and plasma concentration of TEA in the experimental renal failure (ERF)-rats was similar. Therefore, the decrease in $Vd_{ss}$ of TEA in the ERF-rats seemed to be due to the saturation of the carrier system that are responsible for the tissue distribution of TEA, by the elevated plasma concentration of TEA in the ERF-rats. ERF was induced to rats with glycerol, folate, salicylate, uranium and gentamicin, respectively..