Construction of injectable micron-sized polymorphic vesicles for prolonged local anesthesia with weekly sustained release of ropivacaine

• Published in: International journal of pharmaceutics Vol. 661; p. 124378
• Main Authors: Tan, Xin, Ke, Peng, Chen, Ziying, Zhou, Yi, Wu, Linjie, Bao, Xiaoyan, Qin, Yaxin, Jiang, Ruolin, Han, Min
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2024
• Subjects: Amides - administration & dosage; Amides - chemistry; Anesthesia, Local - methods; Anesthetics, Local - administration & dosage; Anesthetics, Local - chemistry; Animals; Decanoic Acids - administration & dosage; Decanoic Acids - chemistry; Delayed-Action Preparations; Drug Delivery Systems; Drug Liberation; Hydrophobic and Hydrophilic Interactions; Hydrophobic ion pairing; Injections; Lecithins - chemistry; Lipids - chemistry; Liposomes; Long-acting analgesia; Male; Pain management; Pain, Postoperative - drug therapy; Pain, Postoperative - prevention & control; Particle Size; Rats; Rats, Sprague-Dawley; Ropivacaine; Ropivacaine - administration & dosage; Ropivacaine - chemistry; Ropivacaine - pharmacokinetics; Long-acting analgesia; Hydrophobic ion pairing; Ropivacaine; Pain management
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124378

[Display omitted] Currently, to overcome the short half-life of the local anesthetic ropivacaine, drug delivery systems such as nanoparticles and liposomes have been used to prolong the analgesic effect, but they are prone to abrupt release from the site of administration or have poor slow-release effects, which increases the risk of cardiotoxicity. In this study, injectable lipid suspensions based on ropivacaine-docusate sodium hydrophobic ion pairing (HIP) were designed to significantly prolong the duration of analgesia. The resulting ion-paired lipid suspension (HIP/LIPO) had a micrometer scale and a high zeta potential, which facilitates stable in situ retention. The strong interaction between docusate sodium and ropivacaine was verified using thermal and spectroscopic analyses, and the formation of micron-sized polymorphic vesicles was attributed to the mutual stabilizing interactions between ropivacaine-docusate sodium HIP, docusate sodium and lecithin. The HIP/LIPO delivery system could maintain drug release for more than 5 days in vitro and achieve high analgesic efficacy for more than 10 days in vivo, reducing the side effects associated with high drug doses. The stable HIP/LIPO delivery system is a promising strategy that offers a clinically beneficial alternative for postoperative pain management and other diseases.