School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.
Shandong International Biotechnology Park Development Co., Ltd., Yantai 264670, China.
Int J Pharm. 2022 Feb 5;613:121433. doi: 10.1016/j.ijpharm.2021.121433. Epub 2021 Dec 28.
A double-layer silk fibroin microneedles (SF-MNs) was proposed for the transdermal delivery of triptorelin. Two-step pouring and centrifugation were employed to prepare SF-MNs. Triptorelin was wrapped in MNs in the form of microcrystals with a size of ∼1 μm. β-sheet nanocrystals (the secondary structure of silk fibroin) were adjusted in content by methanol-vapor treatment to manipulate the characteristics of SF-MNs prepared with two concentrations of silk fibroin. The mechanical strength of MNs was measured and analyzed in proportion to the β-sheet content. The triptorelin in MNs could be released sustainedly in phosphate-buffered saline for 168 h, and the release amount decreased with increasing β-sheet content. The Ritger-Peppas equation was employed to fit the release data. A linear decreasing relationship was observed between the diffusion coefficient and increased β-sheet content. After administration to rats, SF-MNs exhibited long-term testosterone inhibition and maintained castration levels for ≥7 d. Manipulable mechanical properties and release behavior combined with biocompatibility and biodegradability render SF-MNs as viable long-term transdermal delivery devices for triptorelin.
双层丝素纳米针（SF-MNs）被提议用于曲普瑞林的透皮递送。采用两步浇注和离心法制备 SF-MNs。曲普瑞林以尺寸约为 1μm 的微晶形式包裹在 MNs 中。β-折叠纳米晶体（丝素的二级结构）通过甲醇蒸汽处理来调整含量，以控制两种浓度丝素制备的 SF-MNs 的特性。根据β-折叠含量对 MNs 的机械强度进行了测量和分析。MNs 中的曲普瑞林在磷酸盐缓冲液中可持续释放 168 小时，释放量随β-折叠含量的增加而减少。采用 Ritger-Peppas 方程拟合释放数据。观察到扩散系数与增加的β-折叠含量之间呈线性递减关系。在大鼠给药后，SF-MNs 表现出长期的睾酮抑制作用，并保持去势水平≥7 天。可操纵的机械性能和释放行为以及生物相容性和可生物降解性使 SF-MNs 成为曲普瑞林可行的长期透皮递送装置。
