Naloxone, an FDA-approved opioid inhibitor, used to reverse opioid overdose complications has up till date faced challenges associated with its delivery. Limitations include the use of invasive delivery forms and the need for frequent redosing due to its short half-life. The goal of the current study was to design a transdermal rapidly dissolving polymeric microneedle (MN) patch with delivery and pharmacokinetic properties comparable to that seen with the commercially available NAL products, eliminating their delivery limitations. Patches of varying dimensions (500 µm; 100 array,800 µm; 100array, and 600 µm; 225 array) were fabricated to evaluate the effect of increasing MN length, and density (no. of needles/unit area) on drug release. Drug dose in each of these patches was 17.89 ± 0.23 mg, 17.2 ± 0.77 mg, and 17.8 ± 1.01 mg, respectively. Furthermore, the insertion efficiency of each of the MN patches was 94 ± 4.8%, 90.6 ± 1.69%, and 96 ± 1.29%, respectively. Compared to passive permeation, a reduced lag time of about 5–15 min was observed with a significant drug flux of 15.09 ± 7.68 g\(\mu\)/cm²/h seen in the first 1 h (p < 0.05) with the array of 100 needles (500 µm long). Over 24 h, a four and ten-fold increase in permeation was seen with the longer length and larger density MN patch, respectively, when compared to the 500 µm (100 array) patch. Model simulations and analyses revealed the significance of needle base diameter and needle count in improving systemic pharmacokinetics of NAL.

Graphical abstract

中文翻译：

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基于微针的皮肤贴剂的机械建模引导优化，用于快速透皮递送纳洛酮用于阿片类药物过量治疗

纳洛酮是一种经 FDA 批准的阿片类抑制剂，用于逆转阿片类药物过量并发症，迄今为止面临着与其递送相关的挑战。局限性包括使用侵入性递送形式以及由于其半衰期短而需要频繁重新给药。当前研究的目标是设计一种透皮快速溶解聚合物微针 (MN) 贴剂，其递送和药代动力学特性可与市售 NAL 产品相媲美，从而消除其递送限制。制作了不同尺寸的贴片（500 µm；100 阵列、800 µm；100 阵列和 600 µm；225 阵列）以评估增加 MN 长度和密度（针数/单位面积）对药物释放的影响。每个贴片的药物剂量分别为 17.89 ± 0.23 mg、17.2 ± 0.77 mg 和 17.8 ± 1.01 mg。此外，每个 MN 贴片的插入效率分别为 94 ± 4.8%、90.6 ± 1.69% 和 96 ± 1.29%。与被动渗透相比，观察到滞后时间减少了约 5-15 分钟，药物流量显着为 15.09 ± 7.68 g\(\mu\) /cm ² /h 在前 1 小时 ( p  < 0.05) 中看到 100 针阵列（500 µm 长）。在 24 小时内，与 500 µm（100 阵列）贴片相比，长度更长和密度更大的 MN 贴片的渗透率分别增加了四倍和十倍。模型模拟和分析揭示了针底直径和针数在改善 NAL 全身药代动力学方面的重要性。

图形概要