Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Polymer and Pigments Department, National Research Center, Cairo, Egypt.
Drug Deliv. 2020 Dec;27(1):996-1009. doi: 10.1080/10717544.2020.1787557.
The work aimed to improve both absorption and hepatic availability of sofosbuvir. Bilosomes and galactose-anchored bilosomes were investigated as potential nanocarriers for this purpose. Sofosbuvir is a class III drug with high solubility and low permeability. Thus, the drug entrapment into lipid-based galactose-anchored carriers would enhance drug permeability and improve its liver availability. The galactosylated taurocholate was designed and synthesized based on molecular docking studies, where both galactose and taurocholate molecules were connected in a way to avoid affecting crucial interactions and avoid steric clashes with their cellular uptake receptors. The suggested nano-carriers were prepared using a thin-film hydration technique with sodium taurocholate and span 60 as stabilizers. The prepared formulae were statistically optimized using a central composite design. The optimized plain and galactosylated formulae, composed of SAA to drug ratio of 1:1 w/w and sodium taurocholate to span ratio of 10:1 w/w, have a vesicular size, zeta potential and entrapment efficiency in the range of 140-150 nm, -50 mV and 85%, respectively. The optimized formulae were lyophilized to increase their physical stability and facilitate accurate drug dosing. In vivo results showed that Sofosbuvir availability in the liver was significantly increased after oral administration of the plain and the galactosylated bilosomal formulae when compared to the oral drug solution with relative targeting efficiencies (RTIs) of 1.51 and 3.66, respectively. These findings confirmed the hypothesis of considering the galactosylated bilosomes a promising nanocarrier to efficiently target sofosbuvir to the liver.
这项工作旨在提高索非布韦的吸收度和肝脏可用性。双分子层囊泡和半乳糖锚定的双分子层囊泡被研究为潜在的纳米载体。索非布韦是一种 III 类药物，具有高溶解度和低通透性。因此，将药物包封在基于脂质的半乳糖锚定载体中会增强药物通透性并提高其肝脏可用性。基于分子对接研究设计和合成了半乳糖化牛磺胆酸钠，其中半乳糖和牛磺胆酸钠分子以一种避免影响关键相互作用并避免与细胞摄取受体发生空间冲突的方式连接。所提出的纳米载体是使用薄膜水化技术用牛磺胆酸钠和司盘 60 作为稳定剂制备的。使用中心复合设计对制备的配方进行了统计学优化。优化的普通和半乳糖化配方，由 SAA 与药物的比例为 1:1(w/w)和牛磺胆酸钠与司盘的比例为 10:1(w/w)组成，具有 140-150nm、-50mV 和 85%的囊泡大小、Zeta 电位和包封效率。优化的配方被冻干以增加其物理稳定性并便于准确给药。体内结果表明，与口服索非布韦溶液相比，口服普通和半乳糖化双分子层囊泡配方后，肝脏中索非布韦的可用性显著增加，相对靶向效率(RTIs)分别为 1.51 和 3.66。这些发现证实了将半乳糖化双分子层囊泡视为将索非布韦有效靶向肝脏的有前途的纳米载体的假设。
