The lack of optimal methods employing nanoparticles to administer local anesthesia often results in posing severe risks such as non-biocompatibility, in vivo cytotoxicity, and drug overdose to patients. Here, we employed magnetic field-induced hyperthermia to achieve localized anesthesia. We synthesized iron–gold alloy nanoparticles (FeAu Nps), conjugated an anesthetic drug, Lidocaine, and coated the product with gelatin to increase the biocompatibility, resulting in a FeAu@Gelatin–Lidocaine nano-complex formation. The biocompatibility of this drug–nanoparticle conjugate was evaluated in vitro, and its ability to trigger local anesthesia was also evaluated in vivo. Upon exposure to high-frequency induction waves (HFIW), 7.2 ± 2.8 nm sized superparamagnetic nanoparticles generated heat, which dissociated the gelatin coating, thereby triggering Lidocaine release. MTT assay revealed that 82% of cells were viable at 5 mg/mL concentration of Lidocaine, indicating that no significant cytotoxicity was induced. In vivo experiments revealed that unless stimulated with HFIW, Lidocaine was not released from the FeAu@Gelatin–Lidocaine complex. In a proof-of-concept experiment, an intramuscular injection of FeAu@Gelatin–Lidocaine complex was administered to the rat posterior leg, which upon HFIW stimulation triggered an anesthetic effect to the injected muscle. Based on our findings, the FeAu@Gelatin–Lidocaine complex can deliver hyperthermia-induced controlled anesthetic drug release and serve as an ideal candidate for site-specific anesthesia administration.
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