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大麻二酚在水包油纳米乳液和纳米乳液填充水凝胶中的包封:结构与生物学评估研究。

Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study.

作者信息

Demisli Sotiria, Galani Eleni, Goulielmaki Maria, Kyrilis Fotios L, Ilić Tanja, Hamdi Farzad, Crevar Milkica, Kastritis Panagiotis L, Pletsa Vasiliki, Nallet Frédéric, Savić Snežana, Xenakis Aristotelis, Papadimitriou Vassiliki

机构信息

Institute of Chemical Biology, National Hellenic Research Foundation, Athens, Greece; Department of Biochemistry & Biotechnology, University of Thessaly, Larissa, Greece.

Institute of Chemical Biology, National Hellenic Research Foundation, Athens, Greece; Department of Food Science & Human Nutrition, Agricultural University of Athens, Greece.

出版信息

J Colloid Interface Sci. 2023 Mar 15;634:300-313. doi: 10.1016/j.jcis.2022.12.036. Epub 2022 Dec 11.

DOI:10.1016/j.jcis.2022.12.036
PMID:36535166
Abstract

HYPOTHESIS

Lipophilic cannabidiol can be solubilized in oil-in water nanoemulsions, which can then be impregnated into chitosan hydrogels forming another colloidal system that will facilitate cannabidiol's release. The delivery from both systems was compared, alongside structural and biological studies, to clarify the effect of the two carriers' structure on the release and toxicity of the systems.

EXPERIMENTS

Oil-in-water nanoemulsions (NEs) and the respective nanoemulsion-filled chitosan hydrogels (NE/HGs) were formulated as carriers of cannabidiol (CBD). Size, polydispersity and stability of the NEs were evaluated and then membrane dynamics, shape and structure of both systems were investigated with EPR spin probing, SAXS and microscopy. Biocompatibility of the colloidal delivery systems was evaluated through cytotoxicity tests over normal human skin fibroblasts. An ex vivo permeation protocol using porcine ear skin was implemented to assess the release of CBD and its penetration through the skin.

FINDINGS

Incorporation of the NEs in chitosan hydrogels does not significantly affect their structural properties as evidenced through SAXS, EPR and confocal microscopy. These findings indicate the successful development of a novel nanocarrier that preserves the NE structure with the CBD remaining encapsulated in the oil core while providing new rheological properties advantageous over NEs. Moreover, NE/HGs proved to be more efficient as a carrier for the release of CBD. Cell viability assessment revealed high biocompatibility of the proposed colloids.

摘要

假设

亲脂性大麻二酚可溶解于水包油纳米乳液中,然后可将其浸渍到壳聚糖水凝胶中,形成另一种胶体系统,从而促进大麻二酚的释放。对这两种系统的释放情况进行了比较,并开展了结构和生物学研究,以阐明两种载体的结构对系统释放和毒性的影响。

实验

制备了水包油纳米乳液(NEs)和各自填充有纳米乳液的壳聚糖水凝胶(NE/HGs)作为大麻二酚(CBD)的载体。评估了NEs的粒径、多分散性和稳定性,然后通过电子顺磁共振自旋探针法、小角X射线散射法和显微镜技术研究了两种系统的膜动力学、形状和结构。通过对正常人皮肤成纤维细胞进行细胞毒性测试,评估了胶体递送系统的生物相容性。采用猪耳皮肤进行体外渗透实验,以评估CBD的释放及其透过皮肤的情况。

研究结果

通过小角X射线散射法、电子顺磁共振法和共聚焦显微镜观察发现,将NEs掺入壳聚糖水凝胶中不会显著影响其结构特性。这些结果表明成功开发了一种新型纳米载体,该载体保留了NE结构,CBD仍包裹在油相中,同时具有优于NEs的新流变学特性。此外,NE/HGs被证明是更有效的CBD释放载体。细胞活力评估显示所提出的胶体具有高生物相容性。

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