Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are...Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle （ADM-PBCA-NP） in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver. Methods One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group （5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group）. A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin cOncentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector. Results Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups （P〈0.05）. The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of （22.3 ±6.2） nm （P〈0.05）. The ADM-PBCA-NP in （101.0±20.3） nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of （143.0±23.5） run diameter （P〈0.05）. Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBC展开更多
Background Hepatocellular carcinoma （HCC） ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies b...Background Hepatocellular carcinoma （HCC） ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide （DATS） is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide （DATS-PBCA-NP） on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice. Methods DATS-PBCA-NP were detected by transmission electron microscope （TEM） and high-performance liquid chromatography （HPLC）. The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models （n=29） were divided into 4 groups： normal saline （NS）, empty nanoparticles （EN）, DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL） assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism. Results DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice （compared with the other three groups, all P〈0.05） without causing weight loss （P〉0.05）. TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice exh展开更多
目的对阿霉素纳米囊(adriamyc in nanocapsu les,ADM-NC)的制备工艺进行研究,优化最佳制备工艺,并对ADM-NC进行了急性毒性试验。方法以可生物降解的聚氰基丙烯酸正丁酯(polybutylcyanoacrylate,PBCA)为囊材,采用乳化聚合法(emu lsion po...目的对阿霉素纳米囊(adriamyc in nanocapsu les,ADM-NC)的制备工艺进行研究,优化最佳制备工艺,并对ADM-NC进行了急性毒性试验。方法以可生物降解的聚氰基丙烯酸正丁酯(polybutylcyanoacrylate,PBCA)为囊材,采用乳化聚合法(emu lsion polym erization m ethod)制备ADM-NC;以NC粒度和包封率为评价指标,通过正交试验设计(orthogonal design)优化制备工艺。以小鼠尾静脉注射方式分别测定空白纳米囊及载药纳米囊的半数致死量LD50。结果优化制备工艺后ADM-NC冻干前后的粒径分别为110nm和130nm;Zeta电位为114.6mV;以凝胶色谱法测得ADM-NC中药物的包封率达53.5%;测得空白纳米囊的LD50为(238.1±40.0)mg/kg,载药纳米囊ADM-NC的LD50为(36.6±6.2)mg/kg。结论利用乳化聚合法可制备具有较高包封率的ADM-NC;与ADM普通制剂的LD50(8.7±0.3)mg/kg相比,ADM-NC的毒性明显降低。展开更多
基金This study was supported by a grant from the National 863 Program of China (No. 2002AA216011).
文摘Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle （ADM-PBCA-NP） in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver. Methods One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group （5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group）. A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin cOncentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector. Results Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups （P〈0.05）. The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of （22.3 ±6.2） nm （P〈0.05）. The ADM-PBCA-NP in （101.0±20.3） nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of （143.0±23.5） run diameter （P〈0.05）. Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBC
基金a fund of the Natural Science Foundation of Shandong(No.Y2004C34)
文摘Background Hepatocellular carcinoma （HCC） ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide （DATS） is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide （DATS-PBCA-NP） on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice. Methods DATS-PBCA-NP were detected by transmission electron microscope （TEM） and high-performance liquid chromatography （HPLC）. The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models （n=29） were divided into 4 groups： normal saline （NS）, empty nanoparticles （EN）, DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL） assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism. Results DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice （compared with the other three groups, all P〈0.05） without causing weight loss （P〉0.05）. TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice exh
文摘目的对阿霉素纳米囊(adriamyc in nanocapsu les,ADM-NC)的制备工艺进行研究,优化最佳制备工艺,并对ADM-NC进行了急性毒性试验。方法以可生物降解的聚氰基丙烯酸正丁酯(polybutylcyanoacrylate,PBCA)为囊材,采用乳化聚合法(emu lsion polym erization m ethod)制备ADM-NC;以NC粒度和包封率为评价指标,通过正交试验设计(orthogonal design)优化制备工艺。以小鼠尾静脉注射方式分别测定空白纳米囊及载药纳米囊的半数致死量LD50。结果优化制备工艺后ADM-NC冻干前后的粒径分别为110nm和130nm;Zeta电位为114.6mV;以凝胶色谱法测得ADM-NC中药物的包封率达53.5%;测得空白纳米囊的LD50为(238.1±40.0)mg/kg,载药纳米囊ADM-NC的LD50为(36.6±6.2)mg/kg。结论利用乳化聚合法可制备具有较高包封率的ADM-NC;与ADM普通制剂的LD50(8.7±0.3)mg/kg相比,ADM-NC的毒性明显降低。
