Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia

Abstract

Rationale : Peripheral nerve block is a traditional perioperative analgesic method for its precise pain control and low systemic toxicity. However, a single low dose of local anesthetic merely provides a few hours of analgesia, and high dose results in irreversible toxicity, whereas continuous infusion of anesthetics is expensive and complicated. Therefore, it is necessary to develop a long-acting and sensory-selective local anesthetic for safe perioperative analgesia. Methods : An injectable composite comprising ropivacaine-loaded poly (ε-caprolactone) electrospun fiber and clonidine-loaded F127 hydrogel (Fiber-Rop/Gel-Clo composite) was developed for long-acting and walking regional analgesia with barely one dose. The peripheral nerve blockade effect of the composite was evaluated in a rat sciatic nerve block model. Also, the biodegradability and biosafety of the composite was evaluated. Results : The preferentially released Clo from the hydrogel rapidly constricted the peripheral arterial vessels, reducing the blood absorption of Rop and thus enhancing the local Rop accumulation at the injection site. The subsequently sustainable release of Rop from the fiber, significantly prolonged the sciatic nerve block of rats. Remarkably, an amazing sensorimotor segregation effect was achieved, as the sensory blockade (32.0 ± 1.4 h) lasted significantly longer than the motor blockade (20.3 ± 0.9 h). Additionally, the Fiber-Rop/Gel-Clo composite presented good biodegradability and biosafety in vivo . Conclusions : Our designed Fiber-Rop/Gel-Clo composite with minimal invasion, prolonged synergistic analgesia, and strikingly sensorimotor segregation effect, posted a promising prospect for regional long-term walking analgesia in clinical treatment.

The potential value of exosomes as adjuvants for novel biologic local anesthetics

“…Interestingly, a new composite material consisting of poly electrospun fibers of ropivacaine and colistin-containing hydrogel was used in a rat sciatic nerve block model. This anesthetic composite was found to accelerate the onset of action and allow sensory and motor blockade for more than 32 h, thus significantly prolonging the duration of analgesia compared to the single application of ropivacaine ( Chen et al, 2022 ). Colistin also has a sedative effect, but unlike midazolam, it achieves sedation primarily by decreasing sympathetic nervous system activity and level of consciousness ( Fernandes et al, 2018 ).…”

Analgesic nanomedicines for the treatment of chronic pain

“…Furthermore, the GEL/MS composite demonstrated commendable biodegradability and biocompatibility, as indicated by histological analyses. Subsequently, Chen et al [36] engineered an injectable composite comprising ropivacaine-loaded poly (εcaprolactone) electrospun fiber and clonidine-loaded F127 hydrogel, referred to as the Fiber-Rop/Gel-Clo composite. This nanomaterial was employed for analgesia, with Clonidine and Ropivacaine functioning similarly to DEX and BUP, respectively (Figure 7a).…”

“…(b) Schematic illustration of the preparation process of Silicene@MSNs loading with Ropivacaine (RP) and their application as a local anesthesia system. Reproduced with permission [36] . Copyright 2022 Wiley‐VCH.…”

Ropivacaine-loaded hydrogels for prolonged relief of chemotherapy-induced peripheral neuropathic pain and potentiated chemotherapy

“…However, currently available LAs cannot entirely ful ll the demand for long-lasting anesthesia and high doses result in irreversible toxicity [8,9]. In order to overcome these de ciencies, Chen et al developed an injectable electrospun ber-hydrogel composite loaded with clonidine and ropivacaine for long-term walking analgesia [10]. Zhao et al designed hydrogel microneedles to deliver lidocaine hydrochloride and enhance local long-lasting analgesia [11].…”