Lee, D. Nah, H. Ko, W.-K. Jun, Kim S. Han, G.H. Jeong, D. Lee, D. Han, I. Sheen, S.H. Heo, D.N. Lee, S.J. NAM, YUN SIK Kwon, I.K. Sohn, S. 2024-01-19T12:32:44Z 2024-01-19T12:32:44Z 2022-01-26 2022-03 1385-8947 https://pubs.kist.re.kr/handle/201004/115598 To treat neuropathic pain, dexamethasone (DEX, an anti-inflammatory agent) and ropivacaine (RVC, a local anesthetic) are injected into the epidural space of the patient's spine in clinics. This combinatorial drug treatment is short-acting and subjected to uncontrolled drug flow to the motor nerve. To overcome these limitations, we developed thiolate poly(lactic-co-glycolic acid) (PLGA-SH) nanofibers conjugated with mono-(6-mercapto-6-deoxy)-β-cyclodextrin (SH-β-CD) containing DEX and RVC. The anti-inflammatory effect in the PGLA-CD-DEX-RVC nanofibers was assessed using bone marrow-derived macrophages (BMMs) in vitro. We injured the sciatic nerve in Sprague Dawley (SD) rats to create a Chronic constriction injury (CCI) model for an in vivo assessment. Neuropathic pain was evaluated by testing the cold allodynia response, and by Immunofluorescence (IF) staining of transient receptor potential vanilloid 1 (TRPV1, a nociceptor marker) and ionized calcium-binding adaptor molecule 1 (iba1, a microglia marker). In this study, the synthesized PLGA-CD-DEX-RVC nanofibers sustainably released RVC and DEX for more than 48 h. The PLGA-CD-DEX-RVC nanofibers suppressed polarized M1 macrophages and increased polarized M2 macrophages. The allodynia cold sensitivity was consistently relieved in the PLGA-CD-DEX-RVC group for 14 days. Moreover, the expressions of the TRPV1 and iba1 were remarkably reduced in the PLGA-CD-DEX-RVC group on day 14. PLGA-CD-DEX-RVC nanofibers can restrict drugs flow to motor nerves and of relieving pain for extended periods. We suggest that PLGA-CD-DEX-RVC nanofibers can serve as a useful treatment for neuropathic pain in clinics. ？ 2021 Elsevier B.V. English Elsevier B.V. Thiolate poly(lactic-co-glycolic acid) nanofibers loaded with dexamethasone and ropivacaine show enhanced sustained release in the treatment of neuropathic pain through a local therapy technique Article 10.1016/j.cej.2021.133356 1 Chemical Engineering Journal, v.431 Chemical Engineering Journal 431 N scie scopus 000785062000003 2-s2.0-85118701378 Engineering, Environmental Engineering, Chemical Engineering Article DRUG-DELIVERY TOPICAL DELIVERY CELLS NANOPARTICLES CYCLODEXTRIN SYSTEM PLGA Beta-cyclodextrin Chronic constriction injury Dexamethasone Neuropathic pain PLGA Ropivacaine