【摘要】 目的 构建一种可递送胰岛素的相转化微针，提供一种无痛且有效的胰岛素非注射给药途径。方法 采用实验室自制的3D打印机制备微针，并从外观形态、机械强度、溶胀性能、载药量与稳定性评价微针。利用Franz扩散池和离体大鼠皮肤考察微针的体外透皮特性，并以大鼠为模型动物进行药动学和药效学研究。结果 本研究制备的相转化胰岛素微针形态均一，机械性能良好，可快速溶胀释放药物，载药量为每根针3.78μg,室温干燥放置3个月后载药量为3.71μg,无显著性差异，说明在室温干燥环境可至少保存3个月。体外透皮实验显示，该微针的药物累计释放率在3 h时达到最大，超过40%。药动学研究表明，微针应用2 h后血浆胰岛素浓度达到峰值3.66 ng·mL^-1。药效学研究表明，微针能在1 h内迅速降低1型糖尿病大鼠的血糖，与皮下注射胰岛素效果相似，且降血糖效果可维持至6 h。结论 本研究成功制备了相转化胰岛素微针，其各项性能良好，并可有效降低1型糖尿病大鼠的血糖。更多还原

【Abstract】 OBJECTIVE To develop insulin-loaded phase-transition microneedles（MNs）, providing a painless and effective non-injection delivery system for insulin administration. METHODS MNs were fabricated using a self-developed 3D printing technique. They were evaluated in terms of morphology, mechanical strength, swelling properties, drug loading capacity, and stability. The in vitro transdermal characteristics of MNs were studied using Franz diffusion cells and rat skin. Pharmacokinetic and pharmacodynamic studies were conducted using rats as model animals. RESULTS The insulin-loaded MNs prepared in this study were conical and uniformly distributed. They exhibited excellent mechanical properties and could rapidly swell to release the drug. The drug load of each needle was 3.78 μg, after three months of storage at room temperature, the drug load was 3.71 μg, with no significant difference, and the MNs could be stored for at least 3 months in dry room temperature environment. In vitro transdermal experiments demonstrated that the cumulative drug release rate reached its maximum of over 40% at 3 h. Pharmacokinetic studies indicated that plasma insulin concentration peaked at 3.66 ng·mL^-1 2 h after MNs application. Pharmacodynamic studies showed that MNs rapidly reduced blood glucose levels in type 1 diabetic rats within 1 hour, achieving a glucose-lowering effect similar to subcutaneous insulin injection, and persisted for up to 6 hours. CONCLUSION The insulin-loaded phase-transition MNs has excellent and stable quality, and can effectively lower blood glucose in type I diabetic rats.更多还原