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백혈병 세포주에 대한 (±)-ar-Turmerone, 자근 및 황금추출물에 의한 항암제의 세포독성 증강효과
이윤영,유관희,김삼용,안병준 충남대학교부설 생명공학연구소 1992 생물공학연구지 Vol.2 No.-
Using the colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide](MTT)assay, we evaluated the chemosensitivity of 8 anticancer drugs{vincristine(VCR), vinblastine(VBL), adriamycin(ADR), cisplatin(CPDD), etoposide(VP-16), cytosine arabinoside(ara-C), bleomycin(Bleo) and cyclophosphamide(CYC)} and the cytotoxicity-enhancing effects of (±)-ar-turmerone and the extracts of the crude drugs {Lithospermum erythrorhizon(LE) and Scutellaria baicalensis(SB)}on the above mentioned anticancer drugs against HL-60 and KG-1 cells among 8 anticancer drugs, VCR, VBL, ADR, and CPDD inhibited the growth of both cell lines by more than 50% while VP-16, ara-C, Bleo, and CYC were less effective. (±)-ar-Turmerone had significant inhibitory effects against both cell lines, showing the ID_50 values of 11.730 ㎍/㎖ and 0.292 ㎍/㎖ for HL-60 and KG-1 cells. respectively. But the extracts of LE and SB roots showed no significant cytotoxic effects. According to ID_50 values, the cytotoxicities of VCR, VBL and ADR against HL-60 were enhanced two, eight and three times by mixing (±)-ar-turmerone, five, seven and three times by adding the extract of LE root, and twenty, six and three times by mixing the extract of SB root, respectively. The cytotoxicities of the above mentioned drugs against KG-1 cell were enhanced two, seven and three times by mixing (±)-ar-turmerone, two, three and three times by conbining wilth the extract of LB root, and two, five and two times by adding the extract of SB root, respectively. The cytotoxicity-potentiating effects of (±)-ar-turmerone and the extracts of LE and SB roots against HL-60 cell were greater than KG-1 cell.
Jeon, Yong Hyun,Ahn, Sohn Joo,Lee, Yong Jin,Lee, You La,Lee, Sang-Woo,Park, Seung-Yoon,Kim, In-San,Ahn, Byeong-Cheol,Ha, Jeoung-Hee,Lee, Jaetae Mary Ann Liebert 2010 Cancer Biotherapy & Radiopharmaceuticals Vol.25 No.6
<P>Abstract The objective of this study was to investigate the therapeutic potential of (131)I added to doxorubicin therapy in multidrug resistance (MDR) mouse colon cancer coexpressing the MDR1 small hairpin RNA (shRNA) and human sodium iodide symporter (hNIS) gene in a single gene construct and to visualize the antitumor effects using molecular nuclear imaging. HCT-15 coexpressing shRNA for MDR1 gene (MDR1 shRNA) and hNIS gene with a single construct was established (referred to as MN61 cell). Inhibition of P-gp function by MDR1 shRNA and functional activity of hNIS gene was assessed using a (99m)Tc sestamibi uptake and (125)I uptake, respectively. Cytotoxic effects by a combination of doxorubicin and (131)I were determined in parental (HCT-15) or MN61 cells using an in vitro clonogenic assay. Therapeutic effect of either combination therapy (doxorubicin and (131)I) or single therapy (doxorubicin or (131)I alone) was evaluated by tumor volume measurement. (99m)Tc-sestamibi, (123)I, and (99m)Tc-pertechnetate images of mice were acquired to evaluate functional assessment in vivo. Cellular uptake of (99m)Tc-sestamibi and (125)I was approximately 2-fold and 100-fold higher in MN61 cells than in parental cells, respectively. Combination of (131)I and doxorubicin resulted in higher cytotoxcity in MN61 cells as compared with parental cells. Scintigraphic imaging showed higher uptake of (99m)Tc-sestamibi and (123)I in MN61 tumor as compared with parental tumor. In mice treated with doxorubicin, there was a slight delay in tumor growth in the MN61 tumor but not in the parental tumor. Cancer treatment with (131)I or doxorubicin induced a rapid reduction of tumor volume in the MN61 tumor but not in the parental tumor. Combination therapy further generated a rapid reduction of tumor volume as compared with (131)I therapy alone (p??lt;??.05). A combination hNIS mediated radioiodine gene therapy added to MDR1 shRNA treatment improved the effects of cancer treatment in a MDR cancer model and could enable visualization of the antitumor effects with nuclear imaging.</P>
아시클로비어와 수용성 고분자를 이용한 고체분산체 제조 및 생체외 방출
안용산,이하영,홍금덕,정성범,조선행,이종문,이해방,강길선 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.3
Acyclovir(ACV) is an important antiviral drug used extensively against infections caused by herpes viruses, especially herpes simplex and varicella zoster. Because of high crystallinity and large particle size, solubility of intact ACV is very low in water(1.3 ㎎/㎖). The goal of this work is to enhance the solubility of ACV. To make solid dispersion, Polyethyleneglycol. Hydroxyprophylmethyleelluose and Polyvinylpyrrolidone were used as polymer carriers in this work. Polymer carriers and drug were dissolved in acetic acid. And then spray drying method and freeze drying method were used as solvent extraction. Morphology, crystallization and functional group were characterized using SEM. XRD and ET-IR. The result of in vitro test showed the sample using PVP as polymer carrier had higher dissolution rate(up to 466%) than intact ACV.
아시클로비어 고체분산체의 용해도에 대한 수용성 고분자의 종류 및 배합 비율에 따른 효과
안용산,이하영,홍금덕,정성범,조선행,이종문,이해방,강길선 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.4
Acyclovir (ACV) is one of the most effective and selective agents against viruses of the herpes group. Because of low solubility, bioavailability of ACV has shown below 30% with oral dosage form. In our previous study, we reported that the fabrication of solid dispersion of ACV was possible and the solid dispersion of ACV and PVP was the most useful in all samples. In this study, we examined the effect of mixture ratio of polymers (PEG and PVP) to ACV. Solubility of ACV was dramatically increased up to 25 mg/ml in 80°C distilled water. So water was used as a solvent to eliminate problem of residual solvent. Spray drying method was used for the solid dispersion of ACV as solvent extraction. Different scanning calorimeter was used to check degradation of drug. Polymer carriers were PEG 6,000 and PVP. In summary, ACV-PVP (1:3) showed the best solubility in distilled water.
자가미세유화를 이용한 이부프로펜 액상제제의 제조와 특성
안용산,송지희,강복기,김문석,조선행,이종문,이해방,강길선 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.1
Ibuprofen (IBU), is a non-steroidal anti-inflammatory drug, used to treat rheumatoid arthritis, removal of fever and mild to moderate pain. Because of small dosage and very low accumulation in the body, IBU has been used to heal children's fever. However, IBU was very low solubility in a low pH and water (in water 0.03∼2.5 ㎎/ml). A nanoemulsion containing IBU by means of self-micromulsion drug delivery system (SMEDDS) was prepared in order to enhance the solubility of IBU. The SMEDDS was composed of cosurfactant, oil and surfactant. The solubility of IBU in various components such as cosurfactant, oil and surfactant was examined. Carbitol^(??) (389.99±20.5 ㎎/ml) as a cosurfctant, Labrafil^(??) M1944CS (90.16±1.60 ㎎/ml) as an oil and Cremopher^(??) RH-40(239.01±2.8 ㎎/ml) as a surfactant were used in this study for preparing SMEDDS. Optimized formulation of SMEDDS was obtained by phase diagram which express the section of nanoemulsion formation. The SMEDDS containing IBU had higher dissolution rate than conventional IBU sirups. Thus the SMEDDS was a potential candidate of stable conventional and effective oral dosage form for IBU.