He Rongyan, Li Mingjuan, Li Weitao, Li Wenqi, Xiao Shuting, Cao Qiuyu, Wang Huanbai, Zhangsun Dongting, Luo Sulan
Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou 570228, China.
Mar Drugs. 2025 Apr 7;23(4):161. doi: 10.3390/md23040161.
Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. This study developed a sustained-release hydrogel microneedle patch encapsulating GeXIVA[1,2] to address these challenges. Optimized 4:3 (/) polyvinyl alcohol (PVA)-sucrose hydrogel formulation achieved 98.6% structural integrity and controlled swelling (ratio = 1.9 at 48 h). The microneedles demonstrated uniform conical morphology (height: 889 ± 49 µm, base: 381 ± 26 µm) enabling epidermal penetration. In spared nerve injury (SNI) models, a single microneedle patch application increased mechanical paw withdrawal thresholds from 0.056 g to 0.7269 g, maintaining efficacy for 3 days. Chronic constriction injury (CCI) models showed comparable pain relief. Notably, microneedle patch treatment improved locomotor function in SNI mice (total movement: 1518 cm vs. 1126 cm untreated). This hydrogel microneedle patch platform extends GeXIVA[1,2]'s analgesic duration from hours to days through sustained release, while resolving administration challenges through transdermal delivery, expanding the potential applications of GeXIVA[1,2], and demonstrating a promising strategy for the chronic neuropathic pain management.
慢性神经性疼痛严重损害生活质量，目前的治疗方法常常会产生副作用。我们的研究小组将αO-芋螺毒素GeXIVA[1,2]确定为一种源自海洋芋螺的强效镇痛候选物。然而，其临床应用受到快速清除和给药复杂的限制。本研究开发了一种包裹GeXIVA[1,2]的缓释水凝胶微针贴片来应对这些挑战。优化后的4:3（/）聚乙烯醇（PVA）-蔗糖水凝胶配方实现了98.6%的结构完整性和可控的溶胀（48小时时溶胀率 = 1.9）。微针呈现出均匀的锥形形态（高度：889 ± 49 µm，基部：381 ± 26 µm），能够穿透表皮。在 spared nerve injury（SNI）模型中，单次应用微针贴片可使机械性缩爪阈值从0.056 g提高到0.7269 g，并保持3天的疗效。慢性压迫性损伤（CCI）模型显示出类似的疼痛缓解效果。值得注意的是，微针贴片治疗改善了SNI小鼠的运动功能（总移动距离：1518 cm，未治疗组为1126 cm）。这种水凝胶微针贴片平台通过缓释将GeXIVA[1,2]的镇痛持续时间从数小时延长至数天，同时通过透皮给药解决了给药难题，扩大了GeXIVA[1,2]的潜在应用范围，并展示了一种用于慢性神经性疼痛管理的有前景的策略。
