a Department of Pharmacology , Guilin Medical University , Guilin , China.
b Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine , Nanjing Agricultural University , Nanjing , China.
Drug Dev Ind Pharm. 2019 Jan;45(1):124-129. doi: 10.1080/03639045.2018.1526183. Epub 2018 Oct 26.
Akebia saponin D (ASD) exhibits a variety of pharmacological activities, such as anti-osteoporosis, neuroprotection, hepatoprotection, but has poor oral bioavailability. A self-nanoemulsifying drug delivery system loaded with akebia saponin D - phospholipid complex (APC-SNEDDS) (composition: Peceol: Cremophor EL: Transcutol HP: ASD: phospholipid; ratio: 10:45:45:51:12.3, w:w:w:w:w) was first developed to improve the oral absorption of saponins and it was found to significantly enhance ASD's oral bioavailability by 4.3 - fold (p < .01). This study was conducted to elucidate the mechanism of enhanced oral absorption of ASD by the drug delivery system of APC-SNEDDS. The aggregation morphology and particle size of ASD and APC-SNEDDS prepared in aqueous solutions were determined by transmission electron microscope and particle size analyzer, respectively. Stability of ASD and APC-SNEDDS in gastrointestinal luminal contents and mucosa homogenates were also explored. The differences of in situ intestinal permeability of ASD and APC-SNEDDS were compared. APC-SNEDDS reduced the aggregation size from 389 ± 7 nm (ASD) to 148 ± 3 nm (APC-SNEDDS). APC-SNEDDS increased the remaining drug in large intestine luminal contents from 47 ± 1% (ASD) to 83 ± 1% (APC-SNEDDS) during 4 h incubation. APC-SNEDDS provided an 11-fold increase in Ka value and an 11-fold increase in P value compared to ASD. In summary, APC-SNEDDS improved ASD's oral bioavailability mainly by increasing membrane permeability, destroying self-micelles and inhibiting the intestinal metabolism.
三叶木通皂苷 D（ASD）具有多种药理活性，如抗骨质疏松、神经保护、肝保护等，但口服生物利用度差。首次开发了载三叶木通皂苷 D-磷脂复合物的自微乳给药系统（APC-SNEDDS）（组成：Peceol：Cremophor EL：Transcutol HP：ASD：磷脂；比例：10：45：45：51：12.3，w：w：w：w：w），以提高皂苷的口服吸收，发现其可使 ASD 的口服生物利用度显著提高 4.3 倍（p < 0.01）。本研究旨在阐明 APC-SNEDDS 给药系统增强 ASD 口服吸收的机制。采用透射电子显微镜和粒径分析仪分别测定 ASD 和 APC-SNEDDS 在水溶液中的聚集形态和粒径。还探讨了 ASD 和 APC-SNEDDS 在胃肠道腔内容物和黏膜匀浆中的稳定性。比较了 ASD 和 APC-SNEDDS 的原位肠通透性差异。APC-SNEDDS 将聚集尺寸从 389 ± 7 nm（ASD）减小至 148 ± 3 nm（APC-SNEDDS）。在 4 小时孵育期间，APC-SNEDDS 使大肠腔内容物中剩余药物从 47 ± 1%（ASD）增加至 83 ± 1%（APC-SNEDDS）。与 ASD 相比，APC-SNEDDS 使 Ka 值增加了 11 倍，使 P 值增加了 11 倍。综上所述，APC-SNEDDS 主要通过增加膜通透性、破坏自微乳和抑制肠道代谢来提高 ASD 的口服生物利用度。
