Thermosensitive hydroxypropyl chitin-based microneedle patch for long-term management of neuropathic pain

Neuropathic pain caused by neurological lesions seriously affects patients' quality of life. To overcome this clinical challenge, we developed a microneedle patch based on thermosensitive hydroxypropyl chitin (HPCH) for transdermal delivery of ropivacaine (Rop) with adjuvant dexmedetomidine (DEX) to enhance and prolong analgesic efficacy. Neither organic solvents nor crosslinking agents were used in the whole drug-loaded microneedle fabrication process, being "green" and eco-friendly avoiding safety concerns. This dual-drug-loaded microneedle patch (Rop/DEX@HPCH) exhibited sufficient mechanical strength (≥0.5 N per needle) for stable skin penetration, showing a slower drug release up to 72 h at physiological temperature based on real time and simultaneous tracking of both fluorescent model drug and fluorescein-labeled HPCH carrier in vitro and in vivo. The Rop/DEX@HPCH patch provided significant, prolonged and consistent relief of neuropathic pain without affecting motor function in a spared nerve injury rat model, lasting up to 48 h (6 times longer as the Rop/DEX injection control group) after single application. Moreover, once-daily administration for one week indicated that Rop/DEX@HPCH patch could effectively and stably alleviate neuropathic pain without negative effect on the health of the rats, showing great potential for long-term, minimally invasive and painless management of neuropathic pain.