| Tumor chemotherapy drugs can kill tumor cells and play a powerful role in the destruction of the growing endothelial cells of tumor blood vessels. The purpose of this work was to prepare Adriamycin stealth liposomes for tumor low-dose chemotherapy. Low-dose chemotherapy (Metronomic Chemotherapy) is a new type of chemotherapy. Compared to traditional chemotherapy, it has many characteristics. Traditional tumor chemotherapy is generally known as the maximum tolerated dose therapy using a longer time interval (eg 2-3 weeks) administration to ensure that human normal tissues in the interval between administrations could recover. However, the longer delivery intervals make it possible for tumor blood vessel formation to result in tumor nutrition supply recovered and make the tumor continue to grow. This is one of the reasons for the failure of the traditional tumor chemotherapy. In contrast, low-dose chemo- therapy is the use of very small doses, such as one-tenth of the traditional dose and shortens the delivery time interval, that is, more frequent dosing. Low-dose chemotherapy fundamental purpose is to extend the chemotherapy drugs circulation time in the blood and inhibit the tumor vascular endothelial cell growth by blocking the tumor's nutrient supply, and achieve the "starving to death" of cancer tissue. Therefore, low-dose chemotherapy is also known as a type of anti-tumor angiogenesis therapy. However, there is no specific principle how to choose the appropriate drug for tumor low-dose chemotherapy. We have reported that Adriamycin stealth liposomes (Doxorubicin Stealth Liposomes) can significantly extend the doxorubicin circulation time in the blood, and could significantly promote doxorubicin to be distributed into tumor tissue. Therefore, we predict doxorubicin stealth liposomes have may be more applicable to low-dose cancer chemotherapy. The purpose of this paper is to prepare doxorubicin stealth liposomes for tumor of low-dose chemotherapy and evaluate its acute toxicity and anti-tumor effects. PEG-DSPE) oleic acid, vitamin E and cholesterol were used to prepare stealth liposomes. Lipid bilayer mosaic has acid molecules. When the pH was increased to 7.4, some oleic acid molecules could be changed into positively charged ones and attracts doxorubicin molecules into the liposomes. Laser Particle Size / Zeta potential analyzer was used to characterize Doxorubicin Stealth Liposomes. The loading efficiency for Doxorubicin was determined using the Sephadex G50 column chromatography method. The acute toxicity of Doxorubicin Stealth Liposomes was evaluated using mice. The long time blood circulation role of Doxorubicin Stealth Liposomes was evaluated by measuring blood drug concentration at different times after administration. The anti-tumor effect of Doxorubicin Stealth Liposomes was studied in S180 animal tumor model by small-dose chemotherapy administration. The results: Doxorubicin Stealth Liposomes mean diameter 116.7±0.8 nm, Zeta potential of the average -29.9±1.5 mv, drug-loading rate of 98.5±0.5%. Doxorubicin Stealth liposomes Doxorubicin significantly prolonged the blood circulation time (p <0.01), while reducing the acute toxicity of Doxorubicin. Following low-dose chemotherapy, both Doxorubicin Stealth Liposomes and Doxorubicin have stronger anti-tumor effects than the corresponding high-dose chemotherapy, but the anti-cancer effect of Doxorubicin Stealth Liposomes was much greater than that of Doxorubicin in low dose chemotherapy(p <0.01). Conclusion: Compared with Doxorubicin, Doxorubicin Stealth Liposomes has fewer adverse effects, but much more antitumor action, which indicates Doxorubicin Stealth Liposome, is applicable to tumor low-dose chemotherapy.
|
PDF Full Text Request