School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Fakultas Farmasi, Universitas Megarezky, Jl. Antang Raya No. 43, Makassar 90234, Indonesia.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
Carbohydr Polym. 2023 Nov 15;320:121194. doi: 10.1016/j.carbpol.2023.121194. Epub 2023 Jul 11.
Carvedilol, a β-blocker prescribed for chronic heart failure, suffers from poor bioavailability and rapid first pass metabolism when administered orally. Herein, we present the development of tip microarray patches (MAPs) composed of ternary cyclodextrin (CD) complexes of carvedilol for transdermal delivery. The ternary complex with hydroxypropyl γ-cyclodextrin (HPγCD) and poly(vinyl pyrrolidone) (PVP) reduced the crystallinity of carvedilol, as evidenced by DSC, XRD, NMR, and SEM analysis. MAPs were fabricated using a two-step process with the ternary complex as the needle layer. The resulting MAPs were capable of breaching ex vivo neonatal porcine skin to a depth ≈600 μm with minimal impact to needle height. Upon insertion, the needle dissolved within 2 h, leading to the transdermal delivery of carvedilol. The MAPs displayed minimal toxicity and acceptable biocompatibility in cell assays. In rats, MAPs achieved significantly higher AUC levels of carvedilol than oral administration, with a delayed T and sustained plasma levels over several days. These findings suggest that the carvedilol-loaded dissolving MAPs have the potential to revolutionise the treatment of chronic heart failure.
卡维地洛是一种用于治疗慢性心力衰竭的β受体阻滞剂，但口服时生物利用度差，且首过代谢迅速。本文介绍了用三元环糊精（CD）复合物制备的用于透皮给药的卡维地洛尖端微阵列贴片（MAPs）。与羟丙基γ-环糊精（HPγCD）和聚乙烯吡咯烷酮（PVP）的三元复合物降低了卡维地洛的结晶度，这可以通过 DSC、XRD、NMR 和 SEM 分析证明。MAPs 是使用两步法制备的，其中三元复合物为针层。结果表明，所得的 MAPs 能够穿透离体新生猪皮至约 600μm 的深度，对针的高度影响最小。插入后，针在 2 小时内溶解，导致卡维地洛的透皮递送。MAPs 在细胞试验中表现出最小的毒性和可接受的生物相容性。在大鼠中，MAPs 使卡维地洛的 AUC 水平显著高于口服给药，T 延长，血浆水平持续数天。这些发现表明，载有卡维地洛的可溶解 MAPs 有可能彻底改变慢性心力衰竭的治疗方法。
