Alshaer Walhan, Alhaj Abbas Ayman, Thaher Yazan Al, Alkhatib Hatim, Jabaiti Samir, Tarawneh Ola, Al-Buqain Rula, Abdelghany Sharif
Cell Therapy Center, University of Jordan Amman 11942 Jordan.
Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Jordan Amman 11942 Jordan
RSC Adv. 2025 Jul 10;15(29):24074-24086. doi: 10.1039/d5ra03291a. eCollection 2025 Jul 4.
Considering the limited research on microneedles for potent transdermal oral hypoglycemic drugs, in this study, we formulated, glimepiride nanocrystals and incorporated them into PVA-based, sucrose-dissolving microneedles. Nanocrystals were formulated using two different aqueous surfactant solutions as antisolvents, PVP (at concentrations of 0.2% w/v or 2.5% w/v) and SLS (0.2% w/v), with or without a post-drying grinding step. Glimepiride nanocrystals using 0.2% w/v SLS with grinding showed the smallest particle size of 348 ± 27 nm with a PI of 0.29 ± 0.05, which was confirmed by SEM imaging. Therefore, the SLS-with-grinding formula was used for incorporation into a polymeric microneedle formulation composed of 23% w/w PVA and 15% w/w sucrose (GLIM_MN). GLIM_MN showed a microneedle height of 500 ± 14 μm and a sharp tip, as shown under SEM imaging. Furthermore, GLIM_MN could withstand a force of 32 N for 30 seconds at a rate of 0.5 mm per second. Moreover, GLIM_MN successfully penetrated three layers of Parafilm, which is analogous to the mechanical properties of the skin, and successfully penetrated excised BALB/c mice skin to a depth of 480 ± 15 μm, as shown by bright-field image microscopy. Moreover, GLIM_MN showed full penetration of the array into excised human skin to a depth of 276 ± 65 μm. Subsequently, we monitored the glucose level in healthy BALB/c mice for over 24 hours. The GLIM_MN treated group showed a rapid decline in the blood glucose level, reaching a minimum level at 5 hours. This was also corroborated with an increase in the level of serum insulin in the GLIM_MN treated group compared with that in the untreated group 5 hours after administration. Moreover, GLIM_MN-treated mice showed no significant change in the serum C-reactive protein level compared with that in the untreated group, indicating no inflammation upon microneedle administration. These results collectively indicate that our glimepiride dissolving microneedle formulation can enhance the delivery of glimepiride with minimal invasiveness, causing no inflammation. Therefore, it can be considered a potential treatment in the management of type 2 diabetes mellitus, avoiding the drawbacks associated with conventional oral administration.
考虑到针对强效透皮口服降糖药物的微针研究有限，在本研究中，我们制备了格列美脲纳米晶体，并将其纳入基于聚乙烯醇（PVA）的蔗糖溶解型微针中。使用两种不同的水性表面活性剂溶液作为反溶剂来制备纳米晶体，即聚乙烯吡咯烷酮（PVP，浓度为0.2% w/v或2.5% w/v）和十二烷基硫酸钠（SLS，0.2% w/v），并进行或不进行干燥后研磨步骤。使用0.2% w/v SLS并经过研磨的格列美脲纳米晶体显示出最小粒径，为348±27 nm，多分散指数（PI）为0.29±0.05，这通过扫描电子显微镜（SEM）成像得到证实。因此，采用含研磨步骤的SLS配方来制备由23% w/w PVA和15% w/w蔗糖组成的聚合物微针制剂（GLIM_MN）。如SEM成像所示，GLIM_MN的微针高度为500±14μm，针尖尖锐。此外，GLIM_MN能够以每秒0.5毫米的速度承受32 N的力达30秒。而且，GLIM_MN成功穿透了三层类似于皮肤机械性能的石蜡膜，并如明场图像显微镜所示，成功穿透切除的BALB/c小鼠皮肤至480±15μm的深度。此外，GLIM_MN显示阵列完全穿透切除的人皮肤至276±65μm的深度。随后，我们对健康的BALB/c小鼠的血糖水平进行了超过24小时的监测。GLIM_MN治疗组的血糖水平迅速下降，在5小时时达到最低水平。给药5小时后，GLIM_MN治疗组血清胰岛素水平升高，这也证实了上述结果。此外，与未治疗组相比，GLIM_MN治疗的小鼠血清C反应蛋白水平无显著变化，表明微针给药后无炎症反应。这些结果共同表明，我们的格列美脲溶解型微针制剂能够以最小的侵入性增强格列美脲的递送，且不会引起炎症。因此，它可被视为2型糖尿病管理中的一种潜在治疗方法，避免了传统口服给药的缺点。
