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In this study, citric acid-functionalized Fe 3 O 4 magnetic nanoparticles (CA-MNPs) were prepared via a coprecipitation method and were fully characterized. Doxorubicin (DOX) and melittin (MEL), as anticancer agents, were loaded onto CA-MNPs surface through electrostatic interactions with the aim to achieve an effective co-delivery system for cancer therapy. The loading efficiency and in vitro release profiles of DOX and MEL were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The MS/MS step was performed in the selected reaction monitoring (SRM) mode which enabled simultaneous quantification of the analytes with high specificity and sensitivity. An excellent loading efficiency of about 100% was achieved for DOX and MEL in a drug to nanocarrier ratio of 1:10. The in vitro release of the drugs from CA-MNPs was evaluated for 8 h at pH 7.4, 5.5 and 4.5. The experimental results revealed that the release behaviour of both of the anticancer agents was strongly pHdependent and significantly enhanced at pH 4.5. The in vitro MTT assay on MCF-7 breast cancer cell line exhibited a synergistic effect between DOX and MEL which led to substantially greater antitumor efficacy, compared to single administration of these anticancer agents at equivalent doses. The results indicated that the co-delivery system of (DOX/MEL)-loaded CA-MNPs is highly capable to be used in magnetically targeted cancer therapy.

Oxidation is a chemical reaction that occurs in lubricants upon exposure to an oxidizing agent such as oxygen and can be catalyzed by copper and iron. Antioxidants are a group of chemicals that can be used in the formulation of lubricants to stop or reduce the rate of oxidation. Based on the mechanism of action, antioxidants are categorized as primary antioxidants (radical scavengers), secondary antioxidants (Peroxide decomposers), and metal deactivators (complex-forming or chelating agents). Selection of the antioxidants in a formulation is a critical decision that depends on the base oil, application and other ingredients in the formulations. Presence of some other ingredients in the product with antagonistic behavior may suppress the role of antioxidants; however, optimal application of antioxidants with synergistic behavior would increase the stabilization impact of the ingredients on the base oil.

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