Drug formulations for cancer treatment
a technology for cancer and formulations, applied in the field of compounding and pharmaceutical compositions for cancer treatment, can solve the problems of difficult treatment of liposomes, low median survival time for patients treated with these regimens, etc., and achieve the effect of reducing or preventing tumor growth in cancer patients and limiting the toxicity of active agents
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example 1
ting Drug Ratio Suitable for Synergy and Encapsulation of Drugs into Liposomes
[0137]Materials and Methods
[0138](i) Cell Culture
[0139]All cell lines were obtained by ATCC and maintained in a humidified CO2 incubator at 37° C. BT-474 human breast cancer cells were cultured in Hybri-Care medium (ATCC) supplemented with 10% fetal bovine serum (FBS; Thermo Scientific), and 4T1 murine breast cancer cells were cultured in RPMI-1640 medium (Thermo Scientific) supplemented with 10% FBS and 1% penicillin / streptomycin (Thermo Scientific). MCF10A human breast epithelial cells were cultured in Mammary Epithelial Basal Medium (MEBM; Lonza) supplemented with BPE, hydrocortisone, hEGF, insulin, and 100 ng / mL cholera toxin (Sigma-Aldrich), and bEnd.3 mouse brain endothelial cells were cultured in Dulbecco's Modified Eagle's medium (DMEM; ATCC) supplemented with 10% FBS and 1% penicillin / streptomycin. For all experiments, cells were maintained in the exponential growth phase by subcultivation.
[0140](...
example 2
harmacokinetics
[0189](i) In Vivo Tumor Growth Inhibition
[0190]To assess tumor growth inhibition in vivo, a 4T1 murine breast carcinoma model was adopted. Female BALB / c mice six to eight weeks in age (Charles River Laboratories) were injected subcutaneously with 1×105 4T1 cells in the abdominal mammary gland. In preparation for inoculation, 4T1 cells were washed twice in PBS and finally suspended in sterile saline (0.9 wt / vol. % NaCl). Post-inoculation, mice were randomized into experimental and control groups, and were monitored daily for tumor growth and weight changes. Mice were treated with i.v. tail injections of either synPFD-L or free 5FURW combined with free DOX, at drug-equivalent doses of 3 mg / kg DOX and 0.6 mg / kg 5FURW diluted in sterile saline. Treatments began on day 3 post tumor inoculation, and were repeated every other day for a total of 4 injections. Tumor volumes were calculated as V=1 / 2 (1)×(w)2, where / and w correspond to the longest and shortest tumor diameters, r...
example 3
ic Study of 5FU and DOX Synergy Via the Generation of Reactive Oxygen Species (ROS)
[0199]Materials and Methods
[0200]Reactive Oxygen Species Studies
[0201]To understand the cause of synergistic interactions between 5FU and DOX, one of the mechanisms DOX utilizes to induce cell death was investigated: reactive oxygen species (ROS) generation. DOX is known to induce apoptosis in endothelial and tumor cells by different mechanisms. In endothelial cells, DOX induces cell death by ROS generation, whereas in tumor cells, DOX induces apoptosis by activating the p53 tumor suppressor gene (Wang, et al., The Journal of Biological Chemistry 2004,279(24), 25535-43). By comparing ROS generation in cancer cells exposed to 5FU and DOX rather than DOX alone, one can investigate the impact of 5FU on DOX cancer cell cytotoxicity.
[0202]To visualize and assess the production of reactive oxygen species (ROS), cells were seeded in an 8-well chambered borosilicate coverglass (Nunc Lab-Tek) at a density of 8...
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