Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model

Abstract

Small unilamellar vesicles from camel milk phospholipids (CML) mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were prepared, and anticancer drugs doxorubicin (Dox) or etoposide (ETP) were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98%) in liposomes (Lip) prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).

Safety and Therapeutic Efficacy of Thymoquinone-Loaded Liposomes against Drug-Sensitive and Drug-Resistant Acinetobacter baumannii

“…The stability of Lip-TQ was determined at 37 °C as described earlier [ 26 ]. A sample (1 mL) of the liposomal suspension was placed in the cellulose dialysis tubing in 25 mL of sterile distilled water in a water bath maintained at 37 °C with constant slow stirring.…”

“…The release kinetics of TQ from the liposomal formulation was determined by incubating the mixture consisting of one volume of Lip-TQ with nine volumes of human serum. The reaction mixtures were incubated for 1, 2, 3, 6, 12 and 24 h at 37 °C as described earlier [ 26 ]. The mixture was centrifuged at 12,000× g for 15 min.…”

Research Development on Anti-Microbial and Antioxidant Properties of Camel Milk and Its Role as an Anti-Cancer and Anti-Hepatitis Agent

“…The anti-cancer drug etoposide (ETP), which was embedded in liposomes isolated from camel milk phospholipids, slowed down tumor growth and increased survival [ 104 ]. Likewise, the anti-cancer agent doxorubicin (Dox) or ETP loaded with camel milk phospholipid showed strong anti-cancer activity in a murine model [ 126 ]. The phosphatase and tensin homolog (PTEN) gene with anti-cancer efficacy was lower in tumor-induced cells; however, the PTEN gene was found to be higher in phospholipid-embedded doxorubicin-treated cancer cells.…”

Therapeutic Applications of Camel’s Milk and Urine against Cancer: Current Development Efforts and Future Perspectives

“…In vitro [110] PMF (Cesium (Cs) and Rubidium (Rb) nanoparticles) [132][133][134]. Liposomes prepared from these phospholipids were used as drug delivery systems for various anticancer drugs, and have shown promising anticancer activity in the murine/mouse model.…”

“…Etoposide entrapped in camel milk phospholipid liposomes has showed greater anticancer activity against fibrosarcoma in a murine model compared to free etoposide or etoposide entrapped in 1,2-Dipalmitoyl-snglycero-3-phosphatidylcholine (DPPC) liposomes [132]. Combination of doxorubicin (Dox) and etoposide (ETP) loaded into camel milk phospholipids liposomes (CML-Lip) is found also to increase survival and to reduce tumor growth in the mice than the combination of Dox and ETP in DPPC-Lip [133]. The presence of PE in camel milk phospholipid liposomes could play important role in increasing the anticancer efficacy of etoposide.…”