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用于眼部治疗的大麻二酚纳米乳剂 - 抗炎、伤口愈合活性及其在体外人角膜替代物中的生物利用度。

Cannabidiol nanoemulsion for eye treatment - Anti-inflammatory, wound healing activity and its bioavailability using in vitro human corneal substitute.

机构信息

Department of Biochemistry and Microbiology, University of Chemistry and Technology, Technicka 3, 16628 Prague 6, Czech Republic.

Department of Mathematics, Informatics and Cybernetics, University of Chemistry and Technology, Technicka 3, 16628 Prague 6, Czech Republic.

出版信息

Int J Pharm. 2023 Aug 25;643:123202. doi: 10.1016/j.ijpharm.2023.123202. Epub 2023 Jul 3.

Abstract

Cannabidiol (CBD) is the non-psychoactive component of the plant Cannabis sativa (L.) that has great anti-inflammatory benefits and wound healing effects. However, its high lipophilicity, chemical instability, and extensive metabolism impair its bioavailability and clinical use. Here, we report on the preparation of a human cornea substitute in vitro and validate this substitute for the evaluation of drug penetration. CBD nanoemulsion was developed and evaluated for stability and biological activity. The physicochemical properties of CBD nanoemulsion were maintained during storage for 90 days under room conditions. In the scratch assay, nanoformulation showed significantly ameliorated wound closure rates compared to the control and pure CBD. Due to the lower cytotoxicity of nanoformulated CBD, a higher anti-inflammatory activity was demonstrated. Neither nanoemulsion nor pure CBD can penetrate the cornea after the four-hour apical treatment. For nanoemulsion, 94 % of the initial amount of CBD remained in the apical compartment while only 54 % of the original amount of pure CBD was detected in the apical medium, and 7 % in the cornea, the rest was most likely metabolized. In summary, the nanoemulsion developed in this study enhanced the stability and biological activity of CBD.

摘要

大麻二酚(CBD)是大麻属植物(L.)的非精神活性成分,具有很强的抗炎作用和伤口愈合作用。然而,其高亲脂性、化学不稳定性和广泛的代谢会降低其生物利用度和临床应用。在这里,我们报告了一种体外人角膜替代品的制备,并验证了该替代品用于评估药物渗透。制备了 CBD 纳米乳剂并对其稳定性和生物活性进行了评价。在室温条件下储存 90 天,CBD 纳米乳的理化性质保持稳定。在划痕实验中,纳米制剂与对照组和纯 CBD 相比,显著提高了伤口闭合率。由于纳米制剂 CBD 的细胞毒性较低,因此表现出更高的抗炎活性。在 4 小时的顶端处理后,纳米乳和纯 CBD 都不能穿透角膜。对于纳米乳,初始 CBD 量的 94%仍留在顶端隔室,而只有 54%的原始纯 CBD 量检测到在顶端培养基中,7%在角膜中,其余的很可能被代谢。综上所述,本研究中开发的纳米乳增强了 CBD 的稳定性和生物活性。

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