Menadione (Vitamin K3) and Doxorubicin loaded liposomes for enhanced anticancer effect by dual treatment

Akkad, Suzan
Chemotherapy is the first line of cancer treatment, but due to its adverse effects, it is set to be limited. Therefore, liposomes are mainly extensively studied to be employed as nanocarriers as they are more advantageous than traditional therapy. They overcome the obstacle of cellular and tissue uptake and improve drugs’ bioavailability, biodistribution and pharmacokinetics. Doxorubicin, an anthracycline drug, is widely used to treat hematological malignancies and solid tumors, to ameliorate its usage a liposomal formulation DOXIL, is commercially available and used in clinical settings. Vitamin K3, also known as menadione, have shown to possess anticancer effects through the production of reactive oxygen species (ROS) and mitochondrial damage. To enhance the anticancer effect of both agents, liposomal formulations of the drugs were synthesized. Both drugs are hydrophilic, they were encapsulated within the core of PEGylated liposomes to improve their anticancer effects. Doxorubicin was loaded within liposomes using ammonium sulfate method, achieving a high encapsulation efficiency (96.2 ±1.1 %), vitamin K3 was loaded passively by dissolving it in the hydrating solution its encapsulation efficiency was around 53.81±14 %. Liposomal formulations produced were ranging between the sizes 128-150 nm. In vitro release profiles of the liposomal formulations showed controlled release of the drugs the release of DOX was faster than that of the VitK3. In vitro cell cytotoxicity was done to evaluate the potency of both drugs on human breast cancer cells (MCF-7) and mouse fibroblasts (L929), firstly free drugs were administered alone and then after that in a dual manner. DOX IC50 on MCF-7 cells was lower than that for L929 cells, when Vitamin K3 was administered with doxorubicin, it inhibited the cytotoxicity of doxorubicin, therefore coloaded liposomes were not produced. For the anticancer enhancement cells were pretreated with vitamin K3 for 72 hours prior the treatment with doxorubicin for 24 hours there was no effect on the cytotoxicity of the drugs. Pretreatment was also done with liposomal vitamin K3 for 3 days followed by liposomal DOX for another 3 days, the results were unanticipated, and it showed a decrease in the cytotoxicity. As the liposomal formulations did not perform as expected, future works might be paved for trial of simultaneous administration of the liposomal drug formulations.


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The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore we investigated GST activity and the protein expression of glutathione S-transferases (GSTs) isoenzymes known to be involved in the metabolism of endogenous and exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression.
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Chemotherapy is one of the well-known treatments in cancer therapy. The effectiveness of chemotherapy is limited by several factors one of which is the emergence of multidrug resistance (MDR). One of the major mechanisms of MDR is the activity of several ATP binding cassette (ABC) transporters that pump drugs out of the cells. Doxorubicin intercalates and inhibits DNA replication; it is a powerful chemotherapeutic agent. However, it causes development of MDR in tumor cells. Vimentin is a type III intermedia...
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Citation Formats
S. Akkad, “Menadione (Vitamin K3) and Doxorubicin loaded liposomes for enhanced anticancer effect by dual treatment,” M.S. - Master of Science, Middle East Technical University, 2022.