A Novel Nanoantibiotic Formulation With Magnetic and Targeting Potential: Ampicillin‐Conjugated L ‐glu–Fe 3 O 4 NPs

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Abstract
Magnetic nanoparticles (NPs) are maintained in the body for a significantly longer duration than small molecule antibiotics, potentially facilitating prolonged therapeutic effects. In this study, a novel nanoantibiotic formulation ( l ‐glu–Fe 3 O 4 –Amp NPs) was prepared, and its antibacterial efficacy was evaluated. For this purpose, l ‐glutamic acid ( l ‐glu) was used for surface modification of iron oxide nanoparticles (Fe 3 O 4 NPs), and ampicillin (Amp) was then conjugated l ‐glu–Fe 3 O 4 NPs structure. Fourier transform infrared analyses revealed that the final nanoantibiotic formulation l ‐glu–Fe 3 O 4 –Amp NPs was successfully prepared. The size distribution of the formulation was determined to be 164 nm by ZETAsizer. It exhibited a controlled drug release profile over a certain period of time, with a slightly increased release and then exhibited a stable profile. Agar well diffusion assay and the LIVE/DEAD BacLight fluorescent assay showed that the formulation had an antibacterial effectiveness against both Bacillus cereus and Staphylococcus aureus . The formulation has a lower minimal inhibitory concentration value against S. aureus . It significantly increased the accumulation of reactive oxygen species in both bacteria when compared with the Amp group. Its cellular uptake and bacterial interaction were confirmed by confocal and transmission electron microscopy images. The in vitro assay revealed that this formulation is nontoxic to fibroblast cells. This study highlights the potential of l ‐glu–Fe 3 O 4 –Amp NPs conjugate as a potentially effective antibacterial agent. This is the first report on the use of l ‐glu as a surface modifier of Fe 3 O 4 NPs and Amp. Use of l ‐glu increases the drug‐carrying capacity of NPs and reduces the possible side effects of Amp.

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