RESUMO
OBJECTIVE: This study aimed to optimize the formulation of magnetically targeted lidocaine microspheres, reduce the microsphere particle size, and increase the drug loading and encapsulation rate of lidocaine. The optimized microspheres were characterized, and their pharmacokinetics and effective radii of action were studied. METHODS: The preparation of magnetically targeted lidocaine microspheres was optimized using ultrasonic emulsification-solvent evaporation. The Box-Behnken design method and response surface method were used for optimization. The optimized microspheres were characterized and tested for their in vitro release. Blood concentrations were analyzed using a non-compartment model, and the main pharmacokinetic parameters (half-life (t1/2 ), maximum blood concentration, area under the blood concentration-time curve (AUC), time to peak (Tmax ), and mean retention time (MRT) were calculated. Pathological sections were stained to study the safety of the microsphere tissues. A rabbit sciatic nerve model was used to determine the "standard time (t0 )" and effective radius of the microspheres. RESULTS: The optimized lidocaine microspheres exhibited significantly reduced particle size and increased drug loading and encapsulation rates. Pharmacokinetic experiments showed that the t1/2 , Tmax , and MRT of magnetically targeted lidocaine microspheres were significantly prolonged in the magnetic field, and the AUC0-48 and AUC0-∞ were significantly decreased. Its pharmacodynamic radius was 31.47 mm. CONCLUSION: Magnetically targeted lidocaine microspheres provide sustained long-lasting release, neurotargeting, nerve blocking, and high tissue safety. This preparation has a significantly low blood concentration and a slow release in vivo, which can reduce local anesthetic entry into the blood. This may be a novel and effective method for improving postoperative comfort and treating chronic pain. This provides a countermeasure for exploring the size of the magnetic field for the application of magnetic drug-carrying materials.
RESUMO
PURPOSE: Lidocaine microspheres can prolong the analgesic time to 24-48 h, which still cannot meet the need of postoperative analgesia lasting more than 3 days. Therefore, we added Fe3O4 to the lidocaine microspheres and used an applied magnetic field to attract Fe3O4 to fix the microspheres around the target nerves, reducing the diffusion of magnetic lidocaine microspheres to the surrounding tissues and prolonging the analgesic time. METHODS: Fe3O4-lidocaine-PLGA microspheres were prepared by the complex-emulsion volatilization method to characterize and study the release properties in vitro. The neural anchoring properties and in vivo morphology of the drug were obtained by magnetic resonance imaging. The nerve blocking effect and analgesic effect of magnetic lidocaine microspheres were evaluated by animal experiments. RESULTS: The mean diameter of magnetically responsive lidocaine microspheres: 9.04 ± 3.23 µm. The encapsulation and drug loading of the microspheres were 46.18 ± 3.26% and 6.02 ± 1.87%, respectively. Magnetic resonance imaging showed good imaging of Fe3O4-Lidocain-PLGA microspheres, a drug-carrying model that slowed down the diffusion of the microspheres in the presence of an applied magnetic field. Animal experiments demonstrated that this preparation had a significantly prolonged nerve block, analgesic effect, and a nerve anchoring function. CONCLUSION: Magnetically responsive lidocaine microspheres can prolong analgesia by slowly releasing lidocaine, which can be immobilized around the nerve by a magnetic field on the body surface, avoiding premature diffusion of the microspheres to surrounding tissues and improving drug targeting.