{"title":"Magnetically targeted lidocaine sustained-release microspheres: optimization, pharmacokinetics, and pharmacodynamic radius of effect.","authors":"Ling-Xi Zheng, Qian Yu, Lin Peng, Qiang Li","doi":"10.1136/rapm-2024-105634","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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 (<i>t<sub>1/2</sub></i> ), maximum blood concentration, area under the blood concentration-time curve (AUC), time to peak (<i>T<sub>max</sub></i> ), 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 (<i>t<sub>0</sub></i> )\" and effective radius of the microspheres.</p><p><strong>Results: </strong>The optimized lidocaine microspheres exhibited significantly reduced particle size and increased drug loading and encapsulation rates. Pharmacokinetic experiments showed that the <i>t<sub>1/2</sub></i> , <i>T<sub>max</sub></i> , and MRT of magnetically targeted lidocaine microspheres were significantly prolonged in the magnetic field, and the AUC<sub>0-48</sub> and AUC<sub>0-∞</sub> were significantly decreased. Its pharmacodynamic radius was 31.47 mm.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":54503,"journal":{"name":"Regional Anesthesia and Pain Medicine","volume":" ","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regional Anesthesia and Pain Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/rapm-2024-105634","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}
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Abstract
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.
期刊介绍：
Regional Anesthesia & Pain Medicine, the official publication of the American Society of Regional Anesthesia and Pain Medicine (ASRA), is a monthly journal that publishes peer-reviewed scientific and clinical studies to advance the understanding and clinical application of regional techniques for surgical anesthesia and postoperative analgesia. Coverage includes intraoperative regional techniques, perioperative pain, chronic pain, obstetric anesthesia, pediatric anesthesia, outcome studies, and complications.
Published for over thirty years, this respected journal also serves as the official publication of the European Society of Regional Anaesthesia and Pain Therapy (ESRA), the Asian and Oceanic Society of Regional Anesthesia (AOSRA), the Latin American Society of Regional Anesthesia (LASRA), the African Society for Regional Anesthesia (AFSRA), and the Academy of Regional Anaesthesia of India (AORA).
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