• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.385-392
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• 2006

Paclitaxel is an important chemotherapeutic agent for the treatment of human solid tumors. Multicellular resistance(MCR) is considered to be a major mechanism of resistance of human solid tumors to chemotherapeutic agent such as paclitaxel, which includes barriers to drug penetration through tumor tissues. Multicellular layers(MCL) cultures resemble in vivo tumor condition in terms of MCR and has been used successfully to produce clinically relevant data. In the present study, we evaluated the penetration characteristics and post-penetration anti-proliferative activity of paclitaxel using MCL of human colorectal cancer cells(DLD-1 and HT-29) grown in Transwell inserts. The penetration of $[^{14}C]-paclitaxel$ was slower than that of mannitol which penetrates via paracellular pathway in DLD-1 MCL. The penetration of $[^{14}C]-paclitaxel$ was faster in HT-29 MCL compared to DLD-1 MCL, i.e., at 10 ${\mu}M$ 100% and 40% penetration were observed after 48 hr incubation for HT-29 and DLD-1 cells, respectively. When calculated using anti-proliferative activity in the conditioned media of bottom chamber, the penetration after 24 hr was very limited(less than 50%) and concentration-dependent at the concentrations tested in both MCL's. These results suggest that limited and differential penetration of paclitaxel in tumor tissues may contribute to lower and differential efficacy against human solid tumors.

• Korean Journal of Clinical Pharmacy
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• v.11 no.2
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• pp.62-67
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• 2001

Paclitaxel과 vancomycin을 $5\%$ 포도당주사액, $0.9\%$ 염화나트륨주사액 또는 하트만용액과 함께 Y-Site 장치를 써서 환자에게 주입할 때 두 약물의 안정성에 관하며 면구하였다. Paclitaxel 0.3 mg/ml 및 1.2 mg/ml과 vancomycin 1 mg/ml, 5 mg/ml 및 10 mg/ml을 각각 1 : 1로 혼합한 후 0, 1, 2, 4, 12시간 시점에서 두 약물의 농도를 HPLC로 분석하였다, 방해물질에 의한 분석오차를 줄이기 위해 분석법을 여러상태에서 확인하였으며 각 농도에서 3차례씩 실험하였고 각 샘플은 반복하여 HPLC로 분석하였다. 분석전에 각 시료의 투명도, 색의 변화, 침전상태 및 pH를 검사하였다. Paclitaxel 0.3 mg/ml 및 1.2 mg/ml와 vancomycin 1 mg/ml, 5 mg/ml 및 10 mg/mt를 각각 혼합하였을 때 12시간 동안 안정하였으며 주사액의 혼탁이나 색의 변화 및 침전은 나타나지 않았으며 pH도 변하지 않았다.

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.501-504
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• 2003

A novel prepurification method was developed aiming at increasing yield and purity, also reducing solvent usage for purification of paclitaxel. This method was a simple and efficient procedure, for the isolation and prepurification of paclitaxel from the biomass of Taxus chinensis, consisting of micelle formation, followed by two steps of precipitation. The use of a micelle and precipitation in the prepurification process allows for rapid separation of paclitaxel from interfering compounds and dramatically reduces solvent usage compared to alternative methodologies. This prepurification process serves to minimize the size and complexity of the HPLC operations for paclitaxel purification. This process is readily scalable to a pilot plant and eventually to a production environment where multikilogram quantities of material are expected to be produced. As much as possible, the process has been optimized to minimize solvent usage, complexity, and operating costs.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04a
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• pp.27-31
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• 2002

Samyang Genex succeeded in commercialization of anticancer agent-paclitaxel by plant cell culture technology. The core technology of Samyang Genex relating paclitaxel production includes cell line development, cell line preservation, cell culture, scale-up technology, and purification technology. On the basis of the research, Samyang Genex built the factory operated by CGMP (current good manufacturing practice). The $paclitaxel-Genexol^{TM}$ is commercially available in Korea, and it will be launched to world market including USA after approval US FDA.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04b
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• pp.27-31
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• 2002

Samyang Genex succeeded in commercialization of anticancer agent-paclitaxel by plant cell culture technology. The core technology of Samyang Genex relating paclitaxel production includes cell line development, cell line preservation, cell culture, scale-up technology, and purification technology. On the basis of the research, Samyang Genex built the factory operated by CGMP (current good manufacturing practice). The $paclitaxel-Cenexol^{TH}-is$ commercially available in Korea, and it will be launched to world market including USA after approval of US FDA.

• Journal of Plant Biotechnology
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• v.29 no.1
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• pp.59-62
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• 2002

Samyang Genex succeeded in commercialization of anticancer agent-paclitaxel by plant cell culture technology. The core technology of Samyang Genex relating paclitaxel production includes cell line development, cell line preservation, cell culture, scale-up technology, and purification technology. On the basis of the research, Samyang Genex built the factory operated by CGMP (current good manufacturing practice). The paclitaxel-Genexol$^{TM}$-is commercially available in Korea, and it will be launched to world market including USA after approval of US FDA.

• Journal of Korean Neurosurgical Society
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• v.65 no.2
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• pp.180-185
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• 2022

Objective : Drug-eluting stents and balloons are occasionally used to reduce restenosis in medically intractable intracranial atherosclerotic stenosis. The authors aimed to determine whether such drugs can cause neurotoxicity due to local effects in a rat model. Methods : Intra-arterial catheters were placed in the right common carotid artery of rats. Mannitol was injected to transiently open the brain-blood barrier (BBB), followed by high-dose drug (paclitaxel and rapamycin) injection. The optimal time interval of transient BBB opening for maximal drug penetration was determined to be 10 minutes. Paclitaxel and rapamycin were intra-arterially administered in various doses. All the rats were neurologically evaluated, and their brain tissues were histologically examined. Results : Neither neurological deficits nor histological abnormalities were observed in all the rats. Conclusion : Paclitaxel and rapamycin did not cause neurotoxicity in a rat model with transient BBB opening.

• KSBB Journal
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• v.16 no.3
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• pp.233-236
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• 2001

Because of casehardenign effect of amorphous paclitaxel, residual solvents, methylene chloride and emthanol could not be reduced to the maximum value allowed, 600 ppm and 3,000 ppm, in accord with the guidelines issued by the International Conference on Harmonization (ICH, 1997), using rotary evaporation and successive drying in a vacuum oven. However, methylene chloride and methanol were reduced to 486 ppm and 403 ppm, respectively using supercritical $CO_2$ on purified paclitaxel. The optimum pressure and operating time were 80 bar and 30 min at fixed operating temperature ($40^{circ}C$). This approach serves as a novel application of supercritical fluid extraction to remove residual solvents from active pharmaceutical ingredients.

• Journal of Pharmaceutical Investigation
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• v.38 no.5
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• pp.331-334
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• 2008

The objectives of this study were to formulate oral paclitaxel microemulsion and to compare the bioavailability of paclitaxel in the microemulsion formulation from the commercially available $Taxol^{(R)}$ formulation. Paclitaxel microemulsion was formulated with much less amount of Cremophor $EL^{TM}$ as compared with $Taxol^{(R)}$ to reduce severe adverse reactions produced by Cremophor $EL^{TM}$. The area under the plasma concentration-time curve from 0 hr to 24 hr ($AUC_{0-24}$), maximum plasma concentration ($C_{max}$), and relative bioavailability of palcitaxel microemulsion were increased as compared with $Taxol^{(R)}$ after oral administration. The time required to reach $C_{max}\;(T_{max})$ of palcitaxel microemulsion was significantly shorter than $Taxol^{(R)}$ following oral administration. These results suggest the faster intestinal absorption and the enhanced oral bioavailability of paclitaxel in the microemulsion formulation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2967-2971
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• 2012

Objective: To explore whether monoclonal antibodies against stathmin and the chemotherapuetic agent paclitaxel have synergenic effects in inhibiting growth and inducing apoptosis in human QG-56 cells. Methods: QG-56 cells were treated with monoclonal antibodies against stathmin or paclitaxel alone or in combination, with untreated cells used as controls. After 24, 48, 72 and 96 hours the cell growth condition was observed under an inverted microscope and inhibition was studied by MTT assay; apoptosis was analyzed by flow cytometry. Results: The populations decreased and cell shape and size changed after the various treatments. Monoclonal antibodies against stathmin and paclitaxel used alone or incombination inhibited the proliferation of QG-56 cells, especially in combination with synergism (P<0.05). Combined treatment also resulted in a significantly higher apoptosis rate than in the other groups (P<0.05). Conclusions: Monoclonal antibodies against stathmin and paclitaxel used alone or in combination can inhibit proliferation of QG-56 cells and induce apoptosis when applied together. The observed synergistic effects may have important implications for clinical application.