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目的 观察脂质体Dotap包裹反义脱氧寡核苷酸对酪氨酸酶(TYR)的调控效果和降解时间的影响,寻找适合于临床应用的高效转染、低降解率的载体和应用方法。方法 应用DNA合成仪合成针对TYR的反义脱氧寡核苷酸,32P标记、脂质体包埋,加入黑色素细胞培养体系进行点杂交,行黑素含量、酪氨酸酶mRNA表达量检测以及降解时间的同位素液闪检测。结果 经脂质体包埋的反义脱氧寡核苷酸使细胞黑素含量由(64±2.3)pg/cell下降至(23±1.5)pg/cell,并可使基因表达水平由160%降低至82%;同位素液闪显示经脂质体包埋的反义脱氧寡核苷酸能使其半衰期由8 h延长至12 h。结论 脂质体可以明显增强反义核酸的调控效果,并可延长其作用半衰期。 相似文献
3.
TONG Saixiong PANG jinzhong SUO Tao JIN Haiying 《美国中华健康卫生杂志》2005,8(4):41-44
Objective To evaluate preliminarily the effect of HSV - tk/GCV system on gallhladder carcinoma cells in vitro.Methods Recombinant retroviral vector PLtkSN containing tk suicide gene was transfacted into gallbladder carcinoma cells, mediated by LipofectAMINETM 2000 liposome, and the growth - inhibiting rotes of GBC, SD/tk cells in the different GCV concentrations were measured by MTr methods; GBC - SD cells were mixed in the different proportions, and death rotes of the mixed cells treated with GCV were detected to verify by stander effect. Resuts GCV could lead GBC - SD/tk cells to significant death, and there was striking difference compared with the control cells (p〈0.01). When the concentration of GCV was 1,10, 50,100,500ug/ml, the killing rate of GBC - SD/tk cells was respecfively 6.8%, 2.5.2%, 54.5%, 66.3%, 89.3%, indicating dose - dependent phenomenon; With GBC - SD/tk cells in the proportion of 0, 10%, 20% ,50%, 70%, 100%, the killing rate of the mixed cells treated with GCV was 0, 19.7%, 40.3%, 77.7%, 88.0%, 93.5%, respectively. It was apparent that bystander effect was observed in the experiment. Condusion HSV - tk/GCV system could be a potential tool for the treatment of carcinoma. 相似文献
4.
Purpose. To determine whether the non-toxic pentameric B subunit of Cholera toxin (CTB) binding to ganglioside GM1 on both the lipid vesicles and epithelial cells may provide a means to target lipid vesicles to mucosal cells expressing surface GM1.
Methods. Sonicated lipid vesicles containing ganglioside GM1 were prepared. Inter-vesicle cross-linking due to pentameric CTB binding to these GM1 vesicles was determined with a sub-micron particle analyzer. Association of CTB to GM1 vesicles was analyzed with continuous sucrose gradient centrifugation. CTB-mediated binding of GM1 vesicles to human mucosal epithelial cells (Caco-2 and HT-29), mucous membranes of mouse trachea, and nasal tissues were detected with fluorescent labeled vesicles.
Results. An increase in lipid particle size due to binding of CTB to lipid vesicles and inter-vesicles cross-linking was detected. At a 30-to-1 mole ratio of membrane-bound GMl-to-CTB, optimum increase in GM1 vesicle aggregation, was detected. Under such conditions, all the added CTB molecules were associated with GM1 vesicles. Time course analysis showed that inter-vesicles cross linking by CTB was detectable within 10 min. and reached a maximum value at 60 min. CTB associated GM1-vesicles bind to mucosal epithelial cells HT-29 and Caco-2 with similar affinity [Kd = 7.8 × 10–4 M lipid (Caco-2) and 7.6 × 10–4 M lipid (HT-29)]. GM1 mediated binding specificity was demonstrated by blocking with anti-GMl antibody and the insignificant degree of CTB-associated GM1 vesicle binding to GM1 deficient C6 cells.
Conclusions. The CTB-mediated GM1 binding to multiple membrane surfaces provides selective localization of GM1 vesicles to GM1 expressing mucosal cells and tissues. The strategy may be useful in localizing drugs and proteins to gut and respiratory tract mucosa. 相似文献
5.
本文采用去垢剂透析法成功制备出携载SOD的脂质体(L-SOD),其直径为102nm,对SOD的包裹率为21%,90%以上酶活性存在于脂质体内部。将L-SOD注射到大鼠静脉血中,其半衰期超过4h,明显长于天然SOD(8min)。表明L-SOD优于天然SOD,具有临床应用前景。 相似文献
6.
Intraperitoneal injection of free valproic acid (VPA) suppressed amygdaloid-kindled seizure 1 h after injection in rats, but had no effect at 24 h. VPA entrapped in positively charged liposomes showed a prolonged anticonvulsant effect lasting for 2 days, while the effect evaluated at 1 h was not different from that with free VPA. VPA entrapped in negatively charged liposomes exerted a significantly stronger effect at 1 h than did free VPA, while it had no significant effect at 24 h. These results suggest that surface charges on liposomes play an important role in modifying the anticonvulsant effect of VPA. 相似文献
7.
高效液相色谱法检测血中表阿霉素的研究 总被引:2,自引:0,他引:2
用ZorbaxC-8柱成功地分离了阿霉素、表阿霉素及其代谢产物。在此基础上建立了用阿霉素作内标物定量测定表阿霉素的分析方法,其最低检测限为2ng/ml,线性范围10-300ng/ml。 相似文献
8.
MARION FRANKENBERGER BARBARA HOFMANN BERTOLD EMMERICH CHRISTOPH NERL RETO A. SCHWENDENER & H.W. LÖMS ZIEGLER -HEITBROCK 《British journal of haematology》1997,98(1):186-194
The vitamin D3 derived hormone 1,25 (OH)2 vitamin D3 (1,25 D3 ) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1,25 D3 reduced proliferation as measured by 3 H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D3 65% inhibition was achieved at 48 n M . The MC 1288 stereoisomer of 1,25 D3 was more potent and had the same activity at 48 n M .
The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4.
The antiproliferative effect of liposomal 1,25 D3 was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33.
When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)2 vitamin D3 may offer a novel approach to treatment of myelomonocytic leukaemia. 相似文献
The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4.
The antiproliferative effect of liposomal 1,25 D
When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)
9.
Takeuchi Hirofumi Yamamoto Hiromitsu Niwa Toshiyuki Hino Tomoaki Kawashima Yoshiaki 《Pharmaceutical research》1996,13(6):896-901
Purpose. The mucoadhesiveness of polymer-coated liposomes was evaluated to develop a novel drug carrier system for oral administration of poorly absorbed drugs such as peptide drugs.
Methods. Multilamellar liposomes consisting of dipalmitoylphosphatidylcholine (DPPC) and dicetyl phosphate (DCP) (DPPC:DCP = 8:2 in molar ratio) were coated with chitosan (CS), polyvinyl alcohol having a long alkyl chain (PVA-R) and poly (acrylic acid) bearing a cholesteryl group. The adhesiveness of the resultant polymer-coated liposomes to the rat intestine was measured in vitro by a particle counting method with a Coulter counter. The CS-coated liposomes containing insulin were administered to normal rats and the blood glucose level was monitored.
Results. The existence of polymer layers on the surface of liposomes was confirmed by measuring the zeta potential of liposomes. The CS-coated liposomes showed the highest mucoadhesiveness and the degree of adhesion was dependent on the amount of CS on the surface of the liposomes. The blood glucose level of rats was found to be significantly decreased after administration of the CS-coated liposomes containing insulin. The lowered glucose level was maintained for more than 12h after administration of the liposomal insulin, which suggested mucoadhesion of the CS-coated liposomes in the intestinal tract of the rats. 相似文献
10.
脂质体阿苯达唑及主要代谢产物的HPLC法和药代动力学研究 总被引:2,自引:0,他引:2
作者报道了动物(鼠)口服脂质体阿苯达唑后血浆、肝脏、包虫囊组织和囊液中阿苯达唑及主要代谢产物阿苯达唑砜和阿苯达唑亚砜的反相HPLC法。同时进行了药物动力学研究和并用西咪替丁后对血、肝药物浓度的影响。结果表明,阿苯达唑在血浆、囊液中的检出限为0.05μg/ml,在肝脏和囊组织中为0.10μg/g;砜和亚砜在血浆、囊液中均为0.01μg/ml,在肝脏和囊组织中均为0.02μg/g。药物动力学结果显示,阿苯达唑脂质体、混悬液及脂质体并用西咪替丁后的体内过程均符合二室模型,混悬液并用西咪替丁后符合单室模型。阿苯达唑脂质体具有一定的缓释及靶向的作用,西咪替丁可能增强阿苯达唑的缓释作用,同时可能加速阿苯达唑亚砜的代谢。 相似文献