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Effects and safety of magnetic lidocaine microsphere as novel strategy to targeted long-acting peripheral nerve blocks
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DOI：10.1186/s12967-026-08752-4.png)
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Abstract
En 中文
Local anesthetics have been a cornerstone in the field of anesthesia for over a century, yet they face ongoing challenges in providing sustained postoperative analgesia. The ideal duration for such analgesia is 48–72 hours, a benchmark that current formulations often fail to meet. There is a recognized need for long-acting local anesthetics that can maintain their presence at the periphery of target nerves, thereby extending their therapeutic window. Despite advancements, traditional methods for prolonging nerve blockade—such as adjuvant addition, nerve catheter placement, and repetitive blocks—each have their limitations. The specific gap is the development of a targeted, long-acting peripheral nerve block that can prolong the duration of action of local anesthetics without significant toxic side effects. In this study, we developed magnetic lidocaine microspheres using an ultrasonic W1/O/W2 re‑emulsion method, incorporating nano‑iron oxide (Fe₃O₄) and poly(lactic‑co‑glycolic acid) (PLGA). The microspheres were characterized for morphology, magnetic properties, and in vitro drug release. Pharmacokinetics and pharmacodynamics were evaluated in animal models, including electrophysiological and behavioral assessments of peripheral nerve block and analgesia. Blood concentrations were measured by liquid chromatography‑mass spectrometry (LC‑MS), and drug distribution was observed by MRI. Toxicity was assessed via sciatic nerve pathology and cytotoxicity tests on rat Schwann cells. Under a static magnetic field, the magnetic lidocaine microspheres prolonged peripheral nerve blockade for up to 60 hours, with the compound action potential amplitude suppressed to <20% of baseline for 48 hours. In vitro release reached 97.3 ± 2.1% at 60 hours with an initial burst of 76% at 24 hours. The formulation exhibited concentration‑dependent cytotoxicity on Schwann cells, with significantly higher cell viability compared to free lidocaine at clinically relevant concentrations (≥250 μM, p < 0.01; 500 μM, p < 0.05). Pharmacokinetic analysis revealed that the MLM‑M group had a 21.33‑fold longer Tₘₐₓ and a 15.62‑fold longer t₁/₂ compared to free lidocaine, with AUC₀‑₄₈ reduced to approximately 4.5% of that in the free lidocaine groups (0.341 ± 0.034 vs. 7.566 ± 0.302 μg·h/mL), confirming sustained local delivery with minimal systemic exposure. The magnetic lidocaine microspheres effectively prolonged peripheral nerve blocks under the influence of a static magnetic field, achieving sustained drug release over 60 hours with significantly reduced systemic absorption compared to conventional lidocaine. Notably, this targeted approach demonstrated concentration‑dependent cytotoxicity on Schwann cells and maintained therapeutic concentrations at the nerve site while limiting systemic exposure, as evidenced by pharmacokinetic and MRI analyses. These findings demonstrate that magnetic lidocaine microspheres can achieve prolonged, site-targeted nerve blockade in a preclinical model, with reduced systemic exposure and favorable local tissue compatibility. While these results are encouraging, further studies in postoperative pain models and large-animal studies are needed before clinical translation can be considered. If successfully translated, this technology could potentially offer a new approach to prolonged regional analgesia with reduced reliance on systemic opioids. This study is not a randomized controlled trial and therefore was not registered in a public clinical trials registry. This study introduces magnetic lidocaine microspheres that provide targeted, sustained peripheral nerve blockade for over 60 hours under a magnetic field, significantly prolonging analgesia while reducing systemic toxicity and offering a safer alternative to opioids for postoperative pain management.
Keywords:
Magnetic microspheres
Lidocaine
Peripheral nerve block
Sustained-release
Targeted drug delivery
Regional anaesthesia
Postoperative pain
PLGA
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