[Optimization of Cytotoxic Properties of Magnetic Nanoparticle- Based Doxorubicin Delivery System].

Abstract

Doxorubicin (DOX) is a widely used cytotoxic drug known for its high antitumor activity; however, its use is associated with side effects. The development of DOX delivery systems that can minimize systemic toxicity and enhance therapeutic efficacy is an urgent task in modern oncology. We studied the process of loading nanoparticles (NPs) with DOX under conditions that promote DOX precipitation to achieve maximum sorption efficiency. For this purpose, polymer-stabilized magnetic NPs were synthesized, and the efficiency of loading and sedimentation was examined based on the buffer type, DOX concentration, and incubation time with the drug. Our findings indicated that in solutions with the most pronounced DOX sedimentation (phosphate and borate buffers), loading was most effective. In a phosphate buffer with an initial DOX concentration of 667 μg/mL, the loading was 886 mg DOX/g NP. The sorption of DOX on NPs under these conditions reached 85% within the first hour and increased to 90% within 3 hours. The release of DOX from NPs was 25% at pH 7.4 and 96% at pH 5.4. Analysis of the survival of EMT-HER2 breast cancer cells demonstrated that the cytotoxicity of NPs loaded with DOX under sedimentation conditions was eight times higher than that of NPs loaded at a concentration of 20 μg/mL, where DOX did not form a sediment. These results suggest that NPs loaded with DOX under sedimentation conditions can be considered an effective delivery system that not only maintains the cytotoxic properties of DOX but also significantly enhances the content and release of the delivered drug.