Magnetically targeted lidocaine sustained-release microspheres: optimization, pharmacokinetics, and pharmacodynamic radius of effect

Abstract

ObjectiveThis 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.MethodsThe 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.ResultsThe optimized lidocaine microspheres exhibited significantly reduced particle size and increased drug loading and encapsulation rates. Pharmacokinetic experiments showed that thet1/2,Tmax, and MRT of magnetically targeted lidocaine microspheres were significantly prolonged in the magnetic field, and the AUC0-48and AUC0-∞were significantly decreased. Its pharmacodynamic radius was 31.47 mm.ConclusionMagnetically 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.