Antitumor efficacy of EDTA co-treatment with cisplatin in tumor-bearing mice

Ethylenediamine tetraacetic acid (EDTA) is used in various medical applications. The aim of this study is to investigate the antitumor efficacy of EDTA alone or with cisplatin (Cis). Fifty male albino mice were used to assess the median lethal dose (LD50) of EDTA via intraperitoneal (i.p) injection. To determine the antitumor activity, fifty female albino mice were divided into five groups as the following; Group 1 (Gp1) was negative control; (Gp2-5) inoculated i.p with 2×106 Ehrlich Ascites Carcinoma (EAC) cells/mouse. After one day, Gp3, Gp4 and Gp5 injected with Cis (2 mg/kg), EDTA (25 mg/kg) and Cis (2 mg/kg)/EDTA (25 mg/kg) for six days, respectively. At day 14, all groups were sacrificed to assess the tumor profile, liver enzymes (alanine transaminases and aspartate transaminases), kidney function (urea and creatinine) and electrolytes (Na+, K+ and Ca2+). The results showed that the i.p LD50 of EDTA was 250 mg/kg. Treatment with EDTA alone did not show any antitumor activity and did not interfere with the antitumor efficacy of Cis. Biochemical findings revealed that EDTA had mild toxicity on liver and kidneys functions. In summary, EDTA had no antitumor effect and did not alter the Cis efficacy.

Development, in vitro biocompatibility, and antitumor efficacy of acetic acid-modified Cordyceps sinensis polysaccharide nanoparticle drug delivery system

Docetaxel-loaded acetic acid conjugated Cordyceps sinensis polysaccharide (DTX-AA-CSP) nanoparticles were prepared through dialysis and their release rates in vitro, particle sizes, zeta potentials, drug loading capacities, and encapsulation efficiencies were characterized for the synthesis of AA-modified CSPs from traditional Chinese medicine Cordyceps sinensis (Berk.) Sacc. Then, the AA-modified CSPs were characterized by 1H-NMR and FT-IR. Furthermore, the biocompatibility of the delivery carrier (AA-CSP nanoparticles) was assessed on human umbilical vein endothelial cells. In vitro antitumor activity studies on DTX-AA-CSP nanoparticles were conducted on the human liver (HepG2) and colon cancer cells (SW480). The DTX-AA-CSP nanoparticles were spherical and had an average size of 98.91±0.29 nm and zeta potential within the −19.75±1.13 mV. The encapsulation efficiency and loading capacity were 80.95%±0.43% and 8.09%±0.04%, respectively. In vitro, DTX from the DTX-AA-CSP nanoparticles exhibited a sustained release, and the anticancer activities of DTX-AA-CSP nanoparticles against SW480 and HepG2 were significantly higher than those of marketed docetaxel injection (Taxotere®) in nearly all the tested concentrations. The AA-CSP nanoparticles showed good biocompatibility. This study provided a promising biocompatible delivery system for carrying antitumor drugs for cancer therapy

Investigation of the antitumor activity and toxicity of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in a murine breast cancer animal model.

To associate paclitaxel (PTX) with doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Despite the high response rates for this combination, it presents a cardiotoxic synergism, attributed to pharmacokinetic interactions between PTX and both DXR and its metabolite, doxorubicinol. One of the main strategies to minimize the cardiotoxicity of the combination is to extend the interval of time between DXR and PTX administration. However, it has been previously suggested that their co-administration leads to better efficacy compared to their sequential administration. In the present study, we investigated different molar ratio combinations of PTX:DXR (10:1; 1:1, and 1:10) against the 4T1 murine breast cancer cell line and concluded that there is no benefit of enhancing PTX concentration above that of DXR on the combination. Therefore, we obtained a long-circulating and fusogenic liposomal formulation co-encapsulating PTX and DXR (LCFL-PTX/DXR) at a molar ratio of 1:10, respectively, which maintained the in vitro biological activity of the combination. This formulation was investigated for its antitumor activity and toxicity in Balb/c mice bearing 4T1 breast tumor, and compared to treatments with free PTX, free DXR, and the mixture of free PTX:DXR at 1:10 molar ratio. The higher tumor inhibition ratios were observed for the treatments with free and co-encapsulated PTX:DXR in liposomes (66.87 and 66.52%, respectively, P>0.05) as compared to the control. The great advantage of the treatment with LCFL-PTX/DXR was its improved cardiac toxicity profile. While degeneration was observed in the hearts of all animals treated with the free PTX:DXR combination, no signs of cardiac toxicity were observed for animals treated with the LCFL-PTX/DXR. Thus, LCFL-PTX/DXR enables the co-administration of PTX and DXR, and might be considered valuable for breast cancer management.

Long-circulating and fusogenic liposomes loaded with a glucoevatromonoside derivative induce potent antitumor response.

Cancer is an important public health problem, being one of the leading causes of death worldwide. Most antineoplastic agents cause severe toxic effects and some types of cancer do not respond or are resistant to the existing pharmacotherapy, necessitating the research and development of new therapeutic strategies. Cardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells. Glucoevatromonoside containing peracetylated glucose hydroxyl groups (GEVPG) is a cardenolide derivative that has low solubility in aqueous media, which constitutes a barrier to its potential biological applications. In this context, the use of liposomes represents a promising strategy to deliver GEVPG, thus allowing its intravenous administration. In this study, long-circulating and fusogenic liposomes containing GEVPG (SpHL-GEVPG) were developed, and their chemical and physicochemical properties were evaluated. SpHL-GEVPG presented adequate properties, including a mean diameter of 182.2 ± 2.7 nm, a polydispersity index equal to 0.36 ± 0.03, a zeta potential of -2.37 ± 0.31 mV, and a GEVPG entrapment of 0.38 ± 0.04 mg/mL. Moreover, this formulation showed a good stability after having been stored for 30 days at 4 °C. The cytotoxic studies against breast (MDA-MB-231, MCF-7, and SKBR-3) and lung (A549) cancer cell lines demonstrated that SpHL-GEVPG treatment significantly reduced the cell viability. In addition, the SpHL-GEVPG formulation presented a good selectivity toward these cancer cells. The evaluation of the therapeutic efficacy of the treatment with SpHL-GEVPG showed a potent anticancer effect in an A549 human lung cancer xenograft model. SpHL-GEVPG administered at doses of 1.0 and 2.0 mg/kg (i.v.) induced antitumor effect comparable to paclitaxel given at dose of 10 mg/kg (i.v.) to mice. Therefore, the results of the present work indicate the potential applicability of SpHL-GEVPG as a new anticancer formulation.