Bahnick Alexander J, Dziewior Courtney S, Li Yize, Chou Amy, Segal Maddison, Augustine Emily K, Ji Ru-Rong, Becker Matthew L
Department of Chemistry, Duke University, Durham, NC, 27708, USA.
Center for Translational Pain Medicine, Department of Anesthesiology, Duke University, Durham, NC, 27710, USA.
Adv Healthc Mater. 2024 Dec;13(31):e2402113. doi: 10.1002/adhm.202402113. Epub 2024 Aug 12.
Microneedle array patches (MAPs) are extensively studied for transdermal drug delivery. Additive manufacturing enables precise control over MAP customization and rapid fabrication. However, the scope of 3D-printable, bioresorbable materials is limited. Dexamethasone (DXM) is widely used to manage inflammation and pain, but its application is limited by systemic side effects. Thus, it is crucial to achieve high local drug concentrations while maintaining low serum levels. Here, poly(propylene fumarate-co-propylene succinate) oligomers are fabricated into DXM-loaded, bioresorbable MAPs via continuous liquid interface production 3D printing. Thiol-ene click chemistry yields MAPs with tailorable mechanical and degradation properties. DXM-loaded MAPs exhibit controlled elution of drug in vitro. Transdermal application of DXM-loaded MAPs in a murine tibial fracture model leads to substantial relief of postoperative pain. Pharmacokinetic analysis shows that MAP administration is able to control pain at a significantly lower dose than intravenous administration. This work expands the material properties of 3D-printed poly(propylene fumarate-co-propylene succinate) copolyesters and their use in drug delivery applications.
微针阵列贴片(MAPs)在经皮给药方面得到了广泛研究。增材制造能够精确控制MAP的定制和快速制造。然而,可3D打印的生物可吸收材料的范围有限。地塞米松(DXM)被广泛用于控制炎症和疼痛,但其应用受到全身副作用的限制。因此,在维持低血清水平的同时实现高局部药物浓度至关重要。在此,通过连续液体界面生产3D打印将聚(富马酸丙酯-共-琥珀酸丙酯)低聚物制成负载DXM的生物可吸收MAPs。硫醇-烯点击化学产生具有可定制机械和降解性能的MAPs。负载DXM的MAPs在体外表现出药物的可控释放。在小鼠胫骨骨折模型中经皮应用负载DXM的MAPs可显著减轻术后疼痛。药代动力学分析表明,与静脉注射相比,MAP给药能够以显著更低的剂量控制疼痛。这项工作扩展了3D打印的聚(富马酸丙酯-共-琥珀酸丙酯)共聚酯的材料性能及其在药物递送应用中的用途。