School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210023, China.
Suzhou Hospital of Traditional Chinese Medicine, 18 Yangsu Avenue, Suzhou 215003, China.
Colloids Surf B Biointerfaces. 2018 Oct 1;170:187-193. doi: 10.1016/j.colsurfb.2018.06.013. Epub 2018 Jun 9.
Phenolic acids are widely distributed in the plant kingdom and possess a broad spectrum of pharmacological activity. However, low oral bioavailability restricts their application. In this study, a high dispersed phyto- phospholipid complex with mesoporous silica containing TPGS 1000 (TPC-SD) was fabricated using Tanshinol (Tan) as model drug. Phospholipid complex (PC) was employed to improve the n-octanol/water partition coefficient (log P) and apparent permeability coefficients (P) of Tan. Mesoporous silica was used to compensate for the negative effects of phospholipid on drug's dispersion and dissolution owing to its viscosity and poor water-solubility. TPGS 1000, a P-gp inhibitor, was used to block the efflux of Tan. Log P tests showed that the lipophilicity of Tan was significantly enhanced by Tanshinol phospholipid complex (TPC) formation. In vitro dissolution results showed that the cumulative dissolution percentage of Tan from TPC-SD was 4.33- fold of that from TPC in 120 min A Caco-2 permeability test confirmed that P (AP-BL) of TPC and TPC-SD increased approximately 2.22- and 3.53- fold compared to those of unformulated Tan, respectively (p < 0.01, p < 0.01). Pharmacokinetic studies demonstrated that the AUC of TPC-SD was 2.23- and 1.47- fold compared with those of unformulated Tan and TPC, respectively (p < 0.01, p < 0.01). These results indicated that the high dispersed phyto- phospholipid complex/TPGS 1000 by mesoporous silica can be a promising drug delivery system to improve the oral bioavailability of free phenolic acids.
酚酸广泛分布于植物界，具有广泛的药理活性。然而，其口服生物利用度低限制了其应用。本研究以丹参醇（Tan）为模型药物，制备了载有 TPGS1000 的高分散植物磷脂复合物/介孔硅（TPC-SD）。采用磷脂复合物（PC）提高 Tan 的正辛醇/水分配系数（log P）和表观渗透系数（P）。介孔硅用于补偿磷脂对药物分散和溶解的负面影响，因为其具有粘性和较差的水溶性。TPGS1000 是一种 P-糖蛋白抑制剂，用于阻止 Tan 的外排。log P 测试表明，Tan 的亲脂性通过丹参醇磷脂复合物（TPC）的形成得到显著增强。体外溶出结果表明，TPC-SD 中 Tan 的累积溶出百分比在 120 分钟内是 TPC 的 4.33 倍。Caco-2 通透性试验证实，TPC 和 TPC-SD 的 P（AP-BL）分别比未成型 Tan 增加了约 2.22 倍和 3.53 倍（p<0.01，p<0.01）。药代动力学研究表明，TPC-SD 的 AUC 分别是未成型 Tan 和 TPC 的 2.23 倍和 1.47 倍（p<0.01，p<0.01）。这些结果表明，介孔硅载高分散植物磷脂复合物/TPGS1000 可以成为提高游离酚酸口服生物利用度的有前途的药物传递系统。
