目的 制备不同微针长度（针长）马钱子碱（ brucnine，Bru）可溶性微针（ Bru-DMNs），探讨针长对微针刺入性能及治疗效果的影响。方法 采用两步离心法制备不同针长（ 350、450、550、650、750、850 ?m） Bru-DMNs。通过铝箔及鼠皮穿刺实验考察各针长微针穿刺性能；在体溶解实验考察各针长微针溶解性能；皮肤HE染色观察各针长微针刺入皮肤的深度；皮肤屏障恢复实验评估各针长微针对皮肤角质层的影响；采用Franz扩散池考察各针长微针体外透皮性能；体内药效学评估各针长微针对类风湿性关节炎（ rheumatoid arthritis，RA）的治疗作用。结果 350、850 μm针长微针穿刺效果较差，450、550、650、750 μm针长微针穿刺性能较佳，能成功刺入皮肤形成微孔通道成功递送药物，刺入皮肤后可快速溶解，微针越长，溶解越快；针长越长，刺入皮肤越深，皮肤角质层孔道闭合越慢（ 4～6 h）； 450 μm针长微针促渗效果较差，长度达到550 μm时即有较好促渗效果；各针长微针均可不同程度缓解和治疗RA，长度达到550 μm时即可达到理想疗效。结论 当微针长度达到550 μm时，各项性能良好，具有显著的促渗效果和治疗效果。

Objective To investigate the effect of needle length on microneedle penetration performance and therapeutic effect, brucine dissolving microneedles (Bru-DMNs) with different lengths were fabricated. Methods Bru-DMNs with different needle lengths (350, 450, 550, 650, 750, 850 μm) were prepared by two-step centrifugation. The puncture performance of each needlelength microneedle was evaluated by aluminum foil and rat skin puncture experiments. The solubility of each needle-length microneedles was investigated by in vivo dissolution test; Skin HE staining was used to observe the penetration depth of each BruDMNs into the skin. Skin barrier restoration experiment was conducted to evaluate the effect of needle length on cuticle. The transdermal properties of the microneedles with different needle lengths were investigated in vitro by Franz diffusion cell. The therapeutic effect of each needle-length microneedles on rheumatoid arthritis (RA) was evaluated by in vivo pharmacodynamics. Results Microneedle lengths of 350 and 850 μm had poor puncture effect, while microneedle lengths of 450, 550, 650 and 750 μm had better puncture performance, which could successfully penetrate into the skin to form microporous channels for successful delivery of drugs. After penetrating into the skin, the drug could be dissolved quickly. The longer the microneedles, the faster the dissolution. The longer the microneedles, the deeper the penetration of skin, the slower the closure of cuticle pores (4-6 h). Microneedles with a length of 450 μm was less effective in promoting osmosis, while a length of 550 μm was more effective in promoting osmosis. All needle lengths of microneedles could relieve and treat RA to varying degrees, and the ideal effect could be achieved when the length reached 550 μm. Conclusion When the length of microneedles reaches 550 μm, all the properties are good, and it has a significant pro-permeation effect and therapeutic effect.

R283.6

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