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<p>Huperzine A (Hup A), a reversible acetylcholinesterase inhibitor, shows protective potential against neurotoxic poisoning. Current formulations (oral tablets/capsules and injectables) face limitations: oral administration suffers from first-pass metabolism and fluctuating plasma concentrations due to frequent dosing, while injectables require sterile administration, reducing long-term compliance. The aim of this study was to prepare dissolving microneedles (MNs) patches containing Hup A for pretreatment against soman (GD) poisoning. Hyaluronic acid (HA), polyvinylpyrrolidone K30 (PVP K30) and sorbitol were selected as matrix materials in specific proportions and concentration ranges based on single-factor screening experiments and orthogonal design optimization. In order to further evaluate the potential of the Hup A MNs, optimized formulations were selected for subjected to characterization. This evaluation encompassed morphological observation, mechanical properties, skin penetration efficacy, recovery time, <i>in vitro</i> drug release study, permeability assays, pharmacokinetic study, and pharmacodynamic study. Statistical analyses were performed using Student's t-tests for pairwise comparisons and one-way ANOVA for multiple comparisons. The results demonstrated that prepared Hup A MNs had a conical shape with a smooth surface and sharp tips. Hup A MNs had sufficient mechanical strength (122.3 ± 15.3 N) to penetrate through the skin and could be quickly skin of recovery 6&#xa0;min. In permeability assays, the cumulative Hup A release was about 35.4&#xa0;μg at 2&#xa0;h and 58&#xa0;μg at 10&#xa0;h. Pharmacodynamic results demonstrated that compared to oral administration, Hup A MNs reduced the onset time (30&#xa0;min <i>vs</i>. 60&#xa0;min) and extended the effective prevention duration against GD poisoning (6&#xa0;h <i>vs</i>. 2&#xa0;h). Pharmacokinetic analysis showed that MNS administration can maintain a more lasting and stable blood concentration as compared to oral administration. MNs are a valuable drug delivery system, benefiting the patients with minimal skin invasion. Taken together, these results demonstrated that Hup A-loaded MNs are acquiring a new alternative for pretreatment of OPNAs.</p> Graphical Abstract <p></p>

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Development and Evaluation of Huperzine A-Loaded Microneedles for Transdermal Delivery and Pretreatment of GD Poisoning

  • 期刊论文

  • 发表日期：

    2025年6月6日

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  • Guixiang Yang,
  • Yi Zhang,
  • Chong Li,
  • Xingle Xia,
  • Qian Jin,
  • Liqin Li,
  • Xingxing Zong,
  • Dongxin Liu,
  • Jingchen Wei,
  • Xuejun Chen,
  • Chen Wang

摘要

Huperzine A (Hup A), a reversible acetylcholinesterase inhibitor, shows protective potential against neurotoxic poisoning. Current formulations (oral tablets/capsules and injectables) face limitations: oral administration suffers from first-pass metabolism and fluctuating plasma concentrations due to frequent dosing, while injectables require sterile administration, reducing long-term compliance. The aim of this study was to prepare dissolving microneedles (MNs) patches containing Hup A for pretreatment against soman (GD) poisoning. Hyaluronic acid (HA), polyvinylpyrrolidone K30 (PVP K30) and sorbitol were selected as matrix materials in specific proportions and concentration ranges based on single-factor screening experiments and orthogonal design optimization. In order to further evaluate the potential of the Hup A MNs, optimized formulations were selected for subjected to characterization. This evaluation encompassed morphological observation, mechanical properties, skin penetration efficacy, recovery time, in vitro drug release study, permeability assays, pharmacokinetic study, and pharmacodynamic study. Statistical analyses were performed using Student's t-tests for pairwise comparisons and one-way ANOVA for multiple comparisons. The results demonstrated that prepared Hup A MNs had a conical shape with a smooth surface and sharp tips. Hup A MNs had sufficient mechanical strength (122.3 ± 15.3 N) to penetrate through the skin and could be quickly skin of recovery 6 min. In permeability assays, the cumulative Hup A release was about 35.4 μg at 2 h and 58 μg at 10 h. Pharmacodynamic results demonstrated that compared to oral administration, Hup A MNs reduced the onset time (30 min vs. 60 min) and extended the effective prevention duration against GD poisoning (6 h vs. 2 h). Pharmacokinetic analysis showed that MNS administration can maintain a more lasting and stable blood concentration as compared to oral administration. MNs are a valuable drug delivery system, benefiting the patients with minimal skin invasion. Taken together, these results demonstrated that Hup A-loaded MNs are acquiring a new alternative for pretreatment of OPNAs.

Graphical Abstract