Department of Pharmaceutical Technology, University of Innsbruck, Institute of Pharmacy, Center for Chemistry and Biomedicine, 6020, Innsbruck, Austria; Thiomatrix Forschungs- und Beratungs GmbH, Trientlgasse 65, 6020 Innsbruck, Austria.
Vectura Fertin Pharma, Avenue de Rhodanie 50, 1007 Lausanne, Switzerland.
J Colloid Interface Sci. 2025 Jan;677(Pt A):1108-1119. doi: 10.1016/j.jcis.2024.07.233. Epub 2024 Jul 31.
To evaluate the impact of the surface decoration of cannabidiol (CBD) loaded self-emulsifying drug delivery systems (SEDDS) on the efficacy of the formulations to cross the various barriers faced by orally administered drugs.
Polyethylene glycol (PEG)-free polyglycerol (PG)-based SEDDS, mixed zwitterionic phosphatidyl choline (PC)/PEG-containing SEDDS and PEG-based SEDDS were compared regarding stability against lipid degrading enzymes, surface properties, permeation across porcine mucus, cellular uptake and cytocompatibility.
SEDDS with a size of about 200 nm with narrow size distributions were developed and loaded with 20-21 % of CBD. For PG containing PEG-free SEDDS increased degradation by lipid degrading enzymes was observed compared to PEG-containing formulations. The surface hydrophobicity of placebo SEDDS increased in the order of PG-based to mixed PC/PEG-based to PEG-based SEDDS. The influence of this surface hydrophobicity was also observed on the ability of the SEDDS to cross the mucus gel layer where highest mucus permeation was achieved for most hydrophobic PEG-based SEDDS. Highest cellular internalization was observed for PEG-based Lumogen Yellow (LY) loaded SEDDS with 92 % in Caco-2 cells compared to only 30 % for mixed PC/PEG-based SEDDS and 1 % for PG-based SEDDS, leading to a 100-fold improvement in cellular uptake for SEDDS having highest surface hydrophobicity. For cytocompatibility all developed placebo SEDDS showed similar results with a cell survival of above 75 % for concentrations below 0.05 % on Caco-2 cells.
Higher surface hydrophobicity of SEDDS to orally deliver lipophilic drugs as CBD seems to be a promising approach to increase the intracellular drug concentration by an enhanced permeation through the mucus layer and cellular internalization.
评估大麻二酚（CBD）负载自乳化给药系统（SEDDS）的表面修饰对制剂穿过口服药物面临的各种屏障的功效的影响。
比较了无聚乙二醇（PEG）的聚甘油（PG）基SEDDS、混合两性离子磷脂酰胆碱（PC）/PEG 含SEDDS 和 PEG 基 SEDDS 对脂质降解酶的稳定性、表面特性、跨猪黏液渗透、细胞摄取和细胞相容性。
开发了粒径约为 200nm 且粒径分布较窄的 SEDDS，并负载了 20-21%的 CBD。与含有 PEG 的制剂相比，含有 PG 的无 PEG 的 SEDDS 观察到降解增加。赋形剂 SEDDS 的表面疏水性按 PG 基到混合 PC/PEG 基到 PEG 基 SEDDS 的顺序增加。这种表面疏水性也影响 SEDDS 穿过黏液凝胶层的能力，最疏水的 PEG 基 SEDDS 具有最高的黏液渗透率。在用 Caco-2 细胞进行测定时，载有聚乙二醇化鲁米诺黄（LY）的 PEG 基 SEDDS 的细胞内内化最高，为 92%，而混合 PC/PEG 基 SEDDS 仅为 30%，PG 基 SEDDS 仅为 1%，导致具有最高表面疏水性的 SEDDS 的细胞摄取增加了 100 倍。对于细胞相容性，所有开发的赋形剂 SEDDS 在 Caco-2 细胞上浓度低于 0.05%时，细胞存活率均高于 75%，结果相似。
SEDDS 的更高表面疏水性似乎是通过增强穿过黏液层的渗透和细胞内化来提高细胞内药物浓度的有前途的方法，以递送至亲脂性药物如 CBD。
