Onodera Risako, Hayashi Tomohiro, Motoyama Keiichi, Tahara Kohei, Takeuchi Hirofumi
Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Pharmaceutics. 2022 Feb 10;14(2):394. doi: 10.3390/pharmaceutics14020394.
The oral bioavailability of drugs is limited by factors such as poor membrane permeability, low solubility, and low dissolution rate. Silymarin (SLM) is a health-food active ingredient that is good for immunosuppression and tumor suppression. However, obtaining a good oral bioavailability is difficult owing to its poor solubility and low dissolution ability. To overcome these concerns, we previously prepared SLM nanoparticles (NPs) using the high-pressure crystallization method (PureNano) and freeze-dried them with erythritol (Ery) or hydroxypropyl-β-CyD (HP-β-CyD) as a water-soluble dispersion stabilizer. In the present study, we investigated the mechanism underlying the improved absorption of SLM/hypromellose (HPMC)/HP-β-CyD NPs after oral administration. The SLM/HPMC nano-suspension prepared using PureNano exhibited a narrow size distribution. The size of the SLM/HPMC/HP-β-CyD NPs was approximately 250 nm after hydration. The SLM/HPMC/HP-β-CyD NPs were rapidly dissolved, and demonstrated a high solubility under supersaturated conditions. Additionally, they exhibited good wettability and their membrane permeability was improved compared with that of SLM original powder. These results suggest that the formulation of SLM NPs using PureNano and freeze-drying with HP-β-CyD improves the absorption of SLM after oral administration by enhancing solubility, wettability, and membrane permeability.
药物的口服生物利用度受到诸如膜通透性差、溶解度低和溶出速率低等因素的限制。水飞蓟素（SLM）是一种对免疫抑制和肿瘤抑制有益的健康食品活性成分。然而，由于其溶解度差和溶出能力低，难以获得良好的口服生物利用度。为了克服这些问题，我们之前使用高压结晶法（PureNano）制备了水飞蓟素纳米颗粒（NPs），并以赤藓糖醇（Ery）或羟丙基-β-环糊精（HP-β-CyD）作为水溶性分散稳定剂对其进行冷冻干燥。在本研究中，我们研究了口服给药后水飞蓟素/羟丙甲纤维素（HPMC）/HP-β-CyD NPs吸收改善的潜在机制。使用PureNano制备的水飞蓟素/HPMC纳米混悬液呈现出窄粒度分布。水飞蓟素/HPMC/HP-β-CyD NPs水化后的粒径约为250 nm。水飞蓟素/HPMC/HP-β-CyD NPs迅速溶解，并在过饱和条件下表现出高溶解度。此外，它们具有良好的润湿性，与水飞蓟素原粉相比，其膜通透性得到改善。这些结果表明，使用PureNano制备水飞蓟素NPs并与HP-β-CyD一起冷冻干燥，可通过提高溶解度、润湿性和膜通透性来改善口服给药后水飞蓟素的吸收。
