具有边缘激活器的可变形囊泡,用于通过皮肤传递非精神活性大麻素
Elisa Vettorato1, Marisa Fiordelisi1, Silvia Ferro1
1Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo, 5, Padova 35131, Italy.
Current pharmaceutical design
|March 14, 2024
概括
改进的合成和转基因组合增强了脱氧-大麻素的通过皮肤传递,这是一种强大的大麻素来缓解疼痛. 这些新型囊泡在通过皮肤输送脂性药物方面表现有前途.
科学领域:
- 药理学和制药学 药理学和制药学
- 药物输送系统 药物输送系统
- 大麻素研究 研究 大麻素研究
背景情况:
- 像大麻素这样的脂性药物通过皮肤传递受到皮肤屏障功能的阻碍.
- 脱氧大麻二醇 (DOC) 显示出抗沉醉性质,但由于合成和配方方面的挑战,缺乏市场可用性.
- 带有透增强剂的膀系统为改善通过皮肤递送药物的可行解决方案.
研究的目的:
- 开发具有边缘激活剂 (乙醇,油酸,利蒙烯) 的基于脂的新型囊泡 (晶体体),用于通过皮肤输送脂性大麻素.
- 改善脱氧大麻 (DOC) 的合成,以提高其立体选择性和产量.
- 通过使用这些新型膀系统,评估DOC和大麻 (CBD) 的皮肤透和透.
主要方法:
- 通过易斯酸介导的凝结,增强了脱氧大麻 (DOC) 的立体选择性合成.
- 优化载有CBD或DOC的转基因组,使用不同度的烯基醇 (PG),油酸 (OA) 或烯.
- 使用光素载荷的透体进行ex-vivo皮肤透和积累大麻素研究,并使用光素载荷的透体进行透深度分析.
主要成果:
- 通过对抗选择性化,提高了脱氧大麻 (DOC) 合成产量,从12%增加到48%.
- 经过优化的转基因组实现了纳米尺寸 (208-321 nm) 和高捕获效率 (>80%).
- 活体研究表明,皮肤透率提高 (可达21.32μg/cm2的CBD) 和透深度 (可达240μm的PG).
结论:
- 成功地实现了脱氧大麻 (DOC) 的高产合成.
- 优化的转基因组有效地封装并增强脂性大麻素的通过皮肤传递.
- 这些发现凸显了发达的转基因组在通过皮肤输送具有挑战性的脂友性药物的潜力.
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