Objective:To evaluate the tumor load and adverse reactions of nedaplatin combined with paclitaxel liposome and with paclitaxel treatment of advanced esophageal cancer.Methods:A total of 68 patients with advanced esoph...Objective:To evaluate the tumor load and adverse reactions of nedaplatin combined with paclitaxel liposome and with paclitaxel treatment of advanced esophageal cancer.Methods:A total of 68 patients with advanced esophageal cancer who were treated in our hospital between August 2013 and March 2016 were collected and divided into the paclitaxel liposome group (n=34) who received nedaplatin combined with paclitaxel liposome therapy and the paclitaxel group (n=34) who received nedaplatin combined with paclitaxel therapy according to the double-blind randomized control method, and both therapies lasted for 8 weeks. Before treatment and after 8 weeks of treatment, RIA method was used to determine serum esophageal cancer-related tumor marker levels, enzyme-linked immunosorbent assay was used to determine serum angiogenesis index levels, and flow cytometry was used to measure cellular immunity indexes.Results: Before treatment, the differences in serum tumor marker and angiogenesis index levels as well as cellular immune function indexes were not statistically significant between the two groups. After 8 weeks of treatment, serum tumor markers CY211, CEA, SCC, CA724 and CA125 levels of observation group were lower than those of control group, angiogenesis indexes HIF-α, VEGF and MMP-9 levels were lower than those of control group, and peripheral blood cellular immunity indexes CD4+ and CD4+/CD8+ levels were higher than those of control group while CD8+ level was lower than that of control group. Conclusion: Nedaplatin combined with paclitaxel liposome can more effectively reduce the tumor load, causes less adverse effects, and has good curative effect and security.展开更多
Paclitaxel(PTX) is an important cancer chemotherapeutic drug. To ameliorate the disadvantages of paclitaxel, this study designed liposomes to load paclitaxel, adding the acidsensitive material cholesteryl hemisuccinat...Paclitaxel(PTX) is an important cancer chemotherapeutic drug. To ameliorate the disadvantages of paclitaxel, this study designed liposomes to load paclitaxel, adding the acidsensitive material cholesteryl hemisuccinate(CHEMS) to increase the accumulation of the drug in the tumor site. To begin, we used a high-performance liquid chromatography(HPLC)method to determine the content of PTX and the encapsulation efficiency. Then, we prepared paclitaxel-loaded acid-sensitive liposomes(PTX ASLs) by a thin-film dispersion method.We investigated the physical and chemical properties of the liposomes. The particle size was 210.8 nm, the polydispersity index(PDI) was 0.182 and the ζ-potential was-31.2 mV.The liposome shape was observed by transmission electron microscopy(TEM), and the results showed that the liposomes were round with a homogenous size distribution. The release characteristics of the liposomes in vitro were studied via a dynamic dialysis method. The results showed that the prepared liposomes had acid sensitivity and sustained release properties. An in vitro cellular uptake assay of MCF-7 cells showed that the cell uptake of coumarin-6-loaded acid-sensitive liposomes was significantly higher than that of free coumarin-6. The cytotoxicity of the PTX ASLs was significantly higher than that of paclitaxel. In conclusion,these results showed that the prepared liposomes had clear acid-sensitive release characteristics and a higher cell uptake rate and cytotoxicity than free PTX. The system is very suitable for targeted cancer therapy with paclitaxel.展开更多
The combination of paclitaxel(PTX)and doxorubicin(DOX)has been widely used in the clinic.However,it remains unsatisfied due to the generation of severe toxicity.Previously,we have successfully synthesized a prodrug PT...The combination of paclitaxel(PTX)and doxorubicin(DOX)has been widely used in the clinic.However,it remains unsatisfied due to the generation of severe toxicity.Previously,we have successfully synthesized a prodrug PTX-S-DOX(PSD).The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX.Thus,we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation.Due to the fact that copper ions(Cu2+)could coordinate with the anthracene nucleus of DOX,we speculate that the prodrug PSD could be actively loaded into liposomes by Cu2+gradient.Hence,we designed a remote loading liposomal formulation of PSD(PSD LPs)for combination chemotherapy.The prepared PSD LPs displayed extended blood circulation,improved tumor accumulation,and more significant anti-tumor efficacy compared with PSD NPs.Furthermore,PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil,indicating better safety.Therefore,this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.展开更多
文摘Objective:To evaluate the tumor load and adverse reactions of nedaplatin combined with paclitaxel liposome and with paclitaxel treatment of advanced esophageal cancer.Methods:A total of 68 patients with advanced esophageal cancer who were treated in our hospital between August 2013 and March 2016 were collected and divided into the paclitaxel liposome group (n=34) who received nedaplatin combined with paclitaxel liposome therapy and the paclitaxel group (n=34) who received nedaplatin combined with paclitaxel therapy according to the double-blind randomized control method, and both therapies lasted for 8 weeks. Before treatment and after 8 weeks of treatment, RIA method was used to determine serum esophageal cancer-related tumor marker levels, enzyme-linked immunosorbent assay was used to determine serum angiogenesis index levels, and flow cytometry was used to measure cellular immunity indexes.Results: Before treatment, the differences in serum tumor marker and angiogenesis index levels as well as cellular immune function indexes were not statistically significant between the two groups. After 8 weeks of treatment, serum tumor markers CY211, CEA, SCC, CA724 and CA125 levels of observation group were lower than those of control group, angiogenesis indexes HIF-α, VEGF and MMP-9 levels were lower than those of control group, and peripheral blood cellular immunity indexes CD4+ and CD4+/CD8+ levels were higher than those of control group while CD8+ level was lower than that of control group. Conclusion: Nedaplatin combined with paclitaxel liposome can more effectively reduce the tumor load, causes less adverse effects, and has good curative effect and security.
文摘Paclitaxel(PTX) is an important cancer chemotherapeutic drug. To ameliorate the disadvantages of paclitaxel, this study designed liposomes to load paclitaxel, adding the acidsensitive material cholesteryl hemisuccinate(CHEMS) to increase the accumulation of the drug in the tumor site. To begin, we used a high-performance liquid chromatography(HPLC)method to determine the content of PTX and the encapsulation efficiency. Then, we prepared paclitaxel-loaded acid-sensitive liposomes(PTX ASLs) by a thin-film dispersion method.We investigated the physical and chemical properties of the liposomes. The particle size was 210.8 nm, the polydispersity index(PDI) was 0.182 and the ζ-potential was-31.2 mV.The liposome shape was observed by transmission electron microscopy(TEM), and the results showed that the liposomes were round with a homogenous size distribution. The release characteristics of the liposomes in vitro were studied via a dynamic dialysis method. The results showed that the prepared liposomes had acid sensitivity and sustained release properties. An in vitro cellular uptake assay of MCF-7 cells showed that the cell uptake of coumarin-6-loaded acid-sensitive liposomes was significantly higher than that of free coumarin-6. The cytotoxicity of the PTX ASLs was significantly higher than that of paclitaxel. In conclusion,these results showed that the prepared liposomes had clear acid-sensitive release characteristics and a higher cell uptake rate and cytotoxicity than free PTX. The system is very suitable for targeted cancer therapy with paclitaxel.
基金supported by National Science and Technology Major Projects for Major New Drugs Innovation and Development(No.2017ZX09101-001-005,Beijing,China)Science and Technology Plan Project of Shenyang(No.18-400-4-08,Z17-5-064,China)the Career Development Program for Young and Middle-aged Teachers in Shenyang Pharmaceutical University(Shenyang,China)
文摘The combination of paclitaxel(PTX)and doxorubicin(DOX)has been widely used in the clinic.However,it remains unsatisfied due to the generation of severe toxicity.Previously,we have successfully synthesized a prodrug PTX-S-DOX(PSD).The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX.Thus,we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation.Due to the fact that copper ions(Cu2+)could coordinate with the anthracene nucleus of DOX,we speculate that the prodrug PSD could be actively loaded into liposomes by Cu2+gradient.Hence,we designed a remote loading liposomal formulation of PSD(PSD LPs)for combination chemotherapy.The prepared PSD LPs displayed extended blood circulation,improved tumor accumulation,and more significant anti-tumor efficacy compared with PSD NPs.Furthermore,PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil,indicating better safety.Therefore,this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.
文摘目的采用p H梯度法制备重酒石酸长春瑞滨长循环脂质体并进行表征。方法以粒径为指标,考察水化温度和挤出次数对空白脂质体粒径的影响;以粒径及包封率为指标,考察孵化温度和孵化时间对载药脂质体粒径和包封率的影响。并采用Malvern粒度仪测定脂质体的粒径分布、多分散系数及Zeta电位,透射电镜考察其形态,并考察脂质体稳定性。结果重酒石酸长春瑞滨长循环脂质体粒径(96.4±27.2)nm,多分散系数(0.162±0.042),Zeta电位(-26.7±3.5)m V;透射电镜显示脂质体粒径均一,成单层膜球状分布;长期稳定性研究显示,脂质体在5℃条件下放置3个月稳定。结论 p H梯度法可以用于重酒石酸长春瑞滨长循环脂质体的制备。
