Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt.
Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt; Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Int J Pharm. 2020 Aug 30;586:119598. doi: 10.1016/j.ijpharm.2020.119598. Epub 2020 Jul 3.
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 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.
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，特别是作为一种抗癌药物，已经进行了广泛的研究。然而，由于其低水溶性、低渗透性和易受首过代谢的影响，其口服生物利用度较差。本研究首次尝试将其包封于脂质纳米胶囊（LNCs）中以提高其口服生物利用度。采用改进的相转化法，根据构建的相图，对载丹参酮 IIA 的 LNCs（TSIIA-LNCs）进行了初步研究。然后对其进行了体外表征，并在大鼠体内研究了其口服药代动力学。TSIIA-LNCs 表现出良好的胶体性质（粒径：70nm，PDI<0.2，Zeta 电位：-13.5mV）、高包封效率（98%）和良好的载药量（2.6mg/g）。此外，体内药代动力学研究表明，与 TSIIA 混悬液相比，TSIIA-LNCs 能显著提高 TSIIA 的吸收速度和程度，AUC 值增加了约 3.6 倍（p≤0.01）。此外，TSIIA-LNCs 还表现出半衰期和平均停留时间的显著延长（p≤0.01），证实了其长循环特性。因此，精心设计的 LNCs 可以作为一种有前途的纳米平台，提高 TSIIA 的口服生物利用度。
