Injectable Hydrogel Delivery System with High Drug Loading for Prolonging Local Anesthesia

Author:

Li Yongchun1,Chen You2,Xue Yifan2,Jin Jinlong2,Xu Yixin1,Zeng Weian1,Liu Jie2,Xie Jingdun1ORCID

Affiliation:

1. Department of Anesthesiology Sun Yat‐Sen University Cancer Center State Key Laboratory of Oncology in Southern China Guangdong Provincial Clinical Research Center for Cancer Guangzhou Guangdong 510060 China

2. School of Biomedical Engineering Shenzhen Campus of Sun Yat‐sen University Guangming District Shenzhen Guangdong 518107 China

Abstract

AbstractPeripheral nerve block is performed for precise pain control and lesser side effects after surgery by reducing opioid consumption. Injectable hydrogel delivery systems with high biosafety and moisture content have good clinical application prospects for local anesthetic delivery. However, how to achieve high drug loading and long‐term controlled release of water‐soluble narcotic drugs remains a big challenge. In this study, heterogeneous microspheres and an injectable gel‐matrix composite drug delivery system are designed in two steps. First, heterogeneous hydrogel microspheres loaded with ropivacaine (HMS‐ROP) are prepared using a microfluidic chip and in situ alkalization. An injectable self‐healing hydrogel matrix (Gel) is then prepared from modified carboxymethylcellulose (CMC‐ADH) and oxidized hyaluronic acid (OHA). A local anesthetic delivery system, Gel/HMS‐ROP/dexmedetomidine (DEX), with long‐term retention and drug release in vivo is prepared by combining HMS‐ROP and Gel/DEX. The drug loading of HMS‐ROP reached 41.1%, with a drug release time of over 160 h in vitro, and sensory and motor blockade times in vivo of 48 and 36 h, respectively. In summary, the sequential release and synergistic analgesic effects of the two anesthetics are realized using core‐shell microspheres, DEX, and an injectable gel, providing a promising strategy for long‐acting postoperative pain management.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

Publisher

Wiley

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