State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Department of Pharmacy, Suzhou Science & Technology Town Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
Drug Deliv. 2022 Dec;29(1):2984-2994. doi: 10.1080/10717544.2022.2122632.
Colchicine (Col) is used to prevent and treat acute gout flare; however, its therapeutic use is strictly limited owing to severe gastrointestinal side effects after oral administration. Therefore, we developed a dissolvable Col-loaded microneedle (MN) with hyaluronic acid to deliver Col the transdermal route. We studied the preparation, mechanical properties, skin insertion, skin irritation, drug content, and transdermal release of the Col-loaded MN. The pharmacokinetics of Col after Col-loaded MN application were compared with those of Col solution gavage over 24 h. Knee joint edema evaluation and the hindfoot mechanical threshold test were conducted to determine the pharmacodynamic profile. The dissolvable Col-loaded MN possessed sufficient mechanical strength to penetrate the skin and release the loaded drug. No skin irritation was observed for 3 days after application. We found that 3.36-fold more Col contained in MNs was delivered through the skin compared with that in gel , and moderate relative bioavailability . The Col-loaded MN significantly relieved swollen knee joints and mechanical hypernociception in an acute gout model in rats. The dissolvable Col-loaded MN array reduced inflammation and pain via topical administration when acute gout occurred. Reducing the gastrointestinal side effects of Col-loaded MNs is expected to optimize the therapeutic effects of Col and improve patient compliance.
秋水仙碱（Col）用于预防和治疗急性痛风发作；然而，由于口服后会产生严重的胃肠道副作用，其治疗用途受到严格限制。因此，我们开发了一种含有透明质酸的可溶解秋水仙碱负载微针（MN），以经皮途径给药。我们研究了载 Col MN 的制备、机械性能、皮肤插入、皮肤刺激性、药物含量和经皮释放。在 24 小时内比较了 Col 负载 MN 给药后 Col 的药代动力学与 Col 溶液灌胃后的药代动力学。通过膝关节肿胀评估和后足机械阈值试验来确定药效学特征。可溶解的 Col 负载 MN 具有足够的机械强度穿透皮肤并释放负载的药物。应用后 3 天内未观察到皮肤刺激。我们发现，与凝胶相比，MN 中包含的 Col 多释放了 3.36 倍，并且具有中等的相对生物利用度。在急性痛风模型大鼠中，载 Col MN 显著缓解了肿胀的膝关节和机械性痛觉过敏。在急性痛风发作时，可溶解的 Col 负载 MN 阵列通过局部给药减轻炎症和疼痛。减少 Col 负载 MN 的胃肠道副作用有望优化 Col 的治疗效果并提高患者的依从性。
