Tanshinone IIA (TSIIA) is a promising phytomedicine that has been extensively studied due to its numerous biological activities, especially as an anticancer drug. However, it suffers from poor oral bioavailability owing to low aqueous solubility, poor permeability and exposure to first-pass metabolism. This study endeavored to improve TSIIA oral bioavailability by encapsulation into lipid nanocapsules (LNCs) for the first time. A previously reported phase-inversion method was used to prepare Tanshinone II A loaded LNCs (TSIIA-LNCs) with slight modifications based on a constructed phase diagram. They were then in-vitro characterized and their oral pharmacokinetics were studied in rats. TSIIA-LNCs showed excellent colloidal properties (size; 70 nm, PDI < 0.2 and zeta-potential; -13.5 mV), a high percent entrapment efficiency (98%) and a good drug payload (2.6 mg/g). Furthermore, the in-vivo pharmacokinetic study revealed a significant enhancement in both the rate and extent of absorption of TSIIA-LNCs compared with TSIIA suspension with about 3.6-fold increase in AUC 0-inf value (p ≤ 0.01). Additionally, a significant increase in both half-life and mean residence time was exhibited by TSIIA-LNCs (p ≤ 0.01), confirming their long circulating properties. Therefore, the elaborated LNCs could be addressed as a promising nanoplatform permitting higher TSIIA oral bioavailability.

中文翻译：

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使用脂质纳米胶囊提高丹参酮IIA的口服生物利用度：制剂，体外评估和药代动力学

丹参酮IIA（TSIIA）是一种很有前途的植物药，由于其众多的生物活性，尤其是作为一种抗癌药，已经得到了广泛的研究。然而，由于水溶性低，通透性差和暴露于首过代谢，其口服生物利用度差。这项研究致力于通过首次封装到脂质纳米胶囊（LNC）中来提高TSIIA口服生物利用度。先前报道的相转化方法用于制备丹参酮II A负载的LNC（TSIIA-LNC），并根据所构建的相图进行了一些改动。然后对其进行体外表征，并在大鼠中研究其口服药代动力学。TSIIA-LNCs表现出优异的胶体性质（尺寸； 70 nm，PDI <0.2和ζ电势； -13.5 mV），较高的包封率（98％）和良好的药物有效载荷（2.6 mg / g）。此外，体内药代动力学研究表明，与TSIIA悬浮液相比，TSIIA-LNCs的吸收速率和吸收程度均有显着提高，AUC 0-inf值提高了约3.6倍（p≤0.01）。另外，TSIIA-LNCs的半衰期和平均停留时间均显着增加（p≤0.01），证实了它们的长循环特性。因此，精心设计的LNC可以作为一种有前途的纳米平台解决，从而可以实现更高的TSIIA口服生物利用度。TSIIA-LNC的半衰期和平均停留时间均显着增加（p≤0.01），证实了它们的长循环特性。因此，精心设计的LNC可以作为一种有前途的纳米平台解决，从而可以实现更高的TSIIA口服生物利用度。TSIIA-LNC的半衰期和平均停留时间均显着增加（p≤0.01），证实了它们的长循环特性。因此，精心设计的LNC可以作为一种有前途的纳米平台解决，从而可以实现更高的TSIIA口服生物利用度。