• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5191-5197
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• 2015

A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5659-5665
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• 2014

Background: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro. Materials and Methods: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively. Results: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): $2.25{\pm}0.02$ mmol trolox / mmol and $1.96{\pm}0.04$ mmol trolox / mmol respectively) and DPPH ($IC_{50}=3.75{\pm}0.04mg/mL$ and $IC_{50}=2.28{\pm}0.02mg/mL$ respectively). Both MTG and SRM demonstrate equal potency ($IC_{50}=25.20{\pm}1.53$ and $IC_{50}=22.19{\pm}1.06$ respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) ($IC_{50}24.40{\pm}1.26$). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > $100{\mu}M$ towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60). Conclusions: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.

• Journal of Food Hygiene and Safety
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• v.25 no.4
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• pp.325-332
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• 2010

The bactericidal efficacy of three common sanitizers (100 or 200 ppm of sodium hypochlorite, 100 or 200 ppm of n-alkyl($C_{12}-C_{18}$)benzyldimethyl ehloride, and 50 or 100 ppm of peroxyacetie acid) against Escherichia coli ATCC 10536 and Staphylococcus aureus ATCC 6538 was studied using the suspension test method at various exposure temperatures (4~$40^{\circ}C$) and times(1~60min) under both dirty and clean conditions, respectively. During the suspension tests, sodium hypochlorite (200 ppm) showed higher bactericidal activity than the other sanitizers under clean conditions, with 5 log reductions against E. coli as well as S. aureus in the first 1 min of treatments at $4^{\circ}C$, However, the efficacy of sodium hypochlorite decreased markedly under dirty conditions due to its susceptibility to interfering substances. The efficacy of the n-alkyl($C_{12}-C_{18}$)benzyldimethyl chloride increased considerable as the exposure temperature and time increased. The bactericidal efficacy of the n-alkyl($C_{12}-C_{18}$)benzyldimethyl chloride might be less effective on low temperature, however, the longer time the sanitizer is in contact, the more effective the sanitization effect. Treatment with peroxyacetic acid (100 ppm) showed at least 5 log reduction against E. coli and S. aureus for 5 min at $4^{\circ}C$ under both clean and dirty conditions. The efficacy of the peroxyacetic acid was not much altered by interfering substances and aflected by changes in temperature or time.

• 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.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.357-363
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• 2011

In relieving local pains, ropivacaine has been widely used. In case of their application such as ointments and creams, it is difficult to expect their effects for a significant period of time, because they are easily removed by wetting, movement and contacting. Therefore, the new formulations that have suitable bioadhesion were needed to enhance local anesthetic effects. The effect of drug concentration and temperature on drug release was studied from the prepared 1.5% Carboxymethyl cellulose (CMC) (150MC) gels using synthetic cellulose membrane at $37{\pm}0.5^{\circ}C$. As the drug concentration and temperature increased, the drug release increased. A linear relationship was observed between the logarithm of the permeability coefficient and the reciprocal temperature. The activation energy of drug permeation was 3.16 kcal/mol for a 1.5% loading dose. To increase the skin permeation of ropivacaine from CMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the ropivacaine-CMC gels. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects. For the efficacy study, the anesthetic action of the formulated ropivacaine gel containing an enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. According to the rat tail-flick test, 1.5% drug gels containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed the best prolonged local analgesic effects. In conclusion, the enhanced local anesthetic gels containing penetration enhancer and vasoconstrictor could be developed using the bioadhesive polymer.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.355-361
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• 2006

Intraarticular corticosteroid injections for therapy of rheumatic arthritis are administered with the aim of optimal local anti-inflammatory effect at the injection site. Since the side effects of corticosteroidal drug, dexamethasone(DEX), administered at hish dose limited the therapeutic efficacy, there was a need to design a new drug delivery system for controlled release of dexamethasone. As a prodrug for continuous therapeutic efficacy, dexamethasone-21-palmitate(DEX-PAL) was prepared via esterification of palmitoyl chloride and dexamethasone. DEX-PAL was identified by NMR and MASS analysis. DEX-PAL or DEX was entrapped in lipid nanosphere which could be prepared by using a self emulsification-solvent evaporation method. Physicochemical characteristics such as mean particle diameter, zeta potential and drug loading efficiency of the lipid nanospheres were investigated with variation of either the kind of lipid or the lipid composition. The lipid nanospheres had a mean diameter $83{\sim}95$ nm and DEX-PAL loading efficiency of up to 95%. The drug loading efficiency increased with the increase of aliphatic chain length attached to the phospholipid. The incorporation of cationic lipid was very efficient for both reducing particle size of lipid nanospheres and enhancing drug loading efficiency. The lipid nanospheres containing DEX-PAL may be a promising novel drug carrier for the controlled release of the poorly water-soluble drugs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5977-5981
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• 2015

Background: Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin, a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2-neu receptors, but it is an expensive drug with only 20% beneficial rate of survival. This study introduces a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study. Materials and Methods: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) according to the supplier's guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader. Results: Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group. Conclusions: Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor.

• Journal of the Korean Applied Science and Technology
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• v.29 no.4
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• pp.552-560
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• 2012

Drug delivery technologies are patent protected formulation technologies that modify drug release profile, absorption, distribution, and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. The most commonly used transdermal system is the skin patch using various types of technologies. Compared with other method of dosage, it is possible to use for a long term. It is also possible to stop the drug dosage are stop if the drug dosage lead to side effect. Polysaccharide, such as karaya gum and locust bean gum(LBG)/water-soluble chitosan oligomer(WSCO) were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers, tacrine contents. Among these polysaccharide, the permeation rate of karaya gum matrix was fastest in tacrine such as lipophilic drug in vitro. We used glycerin, PEG 400, and PEG 800 as enhancers. Therefore, transdermal absorption of tacrine could be improved by changing vehicle composition or by using penetration enhancers. Especially it would be anticipated that the high permeation efficacy could be obtained by using vehicle that has enhancing effect for itself and by adding enhancers to it.

• Journal of Food Hygiene and Safety
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• v.12 no.3
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• pp.228-233
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• 1997

Drug Dclivcry system (DDS) purpose to getting better remedial result by improving medication from ordinary methods. Applied for DDS, to improve selectivity and comtinuity during absorbing and delivery step, polmer drug (prodrug) was prepared by the esterification with dextran in such of biodegradable polymer and phthalylsulfathiazole with is efficient for entilitis. The polymer durg was prepared with dextran and phthalylsulfathiazole by the esterification. The synthetic procedures of polymer drug was performed by acid chloride and DCC methods. Polymer drug was synthesized in high yield by acid chloride method than DCC method. The antibiotic activities of polymer drug exhibited growth-inhibitory activity against Staphylococcus aureus, Staphylococcus epidermidis, E. coli, Salmonella typhimurium, Klebsiella pneumoniae at the concentration of 500 *g/m* in general through in vitro. As a result of test, polymer drug has 1/2 MIC than phthalylsulfathiazole. Also, it has high level MIC as much as phthalylsulfathiazole with Proteus, Pseudomonas. We conducted possibility of DDS as an applied for medicine with synthesized polymer drug by using natrural polymer. We consider that clinical research must be followed to verify safety and efficacy for controlled release, activity and toxicity.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.3-5
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• 1997

Properties of a good drug include safety, efficacy, half-life and bioavailability. With the current approach to drug discovery based on receptor-based and cell-based screening methods, compounds are frequently moved into development with poor bioavailability. With low bioavailability, drug administration is typically limited to parenteral routes, thus limiting the potential wide-spread utility of these therapeutic agents. The first and most important factor limiting a drug's bioavailability is the intestinal membrane permeability which in turn determines the maximum fi:action of the dose administered that can be absorbed. We have recently utilized new intubation methods for performing permeability measurements in humans and establishing a fundamental human data base for correlating intestinal jejunal membrane permeabilities with permeabilities determined in other systems, e.g., animals, tissue culture, as well as physical chemical properties.