Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Drug Delivery & Tissue Regeneration and Jiangsu Provincial, Jiangsu University, Zhenjiang 212013, PR China.
Research Center for Medicinal Function Development of New Food Resources, Zhenjiang 212001, PR China; Jiangsu Tian Sheng Pharmaceutical Co., Ltd., No. 10 Baohua Development Zone, Jurong, Zhenjiang, Jiangsu, PR China.
Int J Pharm. 2019 May 30;563:53-62. doi: 10.1016/j.ijpharm.2019.03.034. Epub 2019 Mar 16.
Isoliquiritigenin (ISL) has a great variety of pharmacological effects especially liver cancer therapy, but its poor solubility, bioavailability and liver targeting have limited its clinical use. In order to solve the aforementioned shortcomings, the TPGS-modified proliposomes loaded with ISL (ISL-TPGS-PLP) was prepared in this study. ISL-TPGS-PLP was fabricated via thin-film dispersion method and was characterized by the appearance, particle size, zeta potential and morphology. HPLC was used to evaluate entrapment efficiency (EE), in vitro release and stability of ISL-TPGS-PLP single or combined while appropriate physicochemical parameters were measured with DLS. Meanwhile, the pharmacokinetics and tissue distribution were also studied after oral administration. The results demonstrated that ISL-TPGS-PLP had a mean size of 23.8 ± 0.9 nm, high EE of 97.33 ± 0.40%. More importantly, nearly 90% ISL was released from ISL-TPGS-PLP within 24 h while only 50% was released from ISL suspension. In the pharmacokinetics study, the area under the curve (AUC of ISL-TPGS-PLP was 1.53 times higher than that of ISL suspension. The Tissue distribution study showed that the ISL released from ISL-TPGS-PLP was higher in the liver than the free ISL suspension. Altogether, ISL-TPGS-PLP could ameliorate the ISL solubility, bioavailability and liver targeting ability, suggesting that ISL-TPGS-PLP could serve as a promising nanocarrier for liver cancer therapy.
异甘草素（ISL）具有多种药理作用，尤其对肝癌治疗效果显著，但由于其溶解度低、生物利用度差和肝靶向性有限，限制了其临床应用。为了解决上述缺点，本研究制备了 TPGS 修饰的载有异甘草素的前体脂质体（ISL-TPGS-PLP）。ISL-TPGS-PLP 通过薄膜分散法制备，并通过外观、粒径、Zeta 电位和形态进行了表征。采用 HPLC 评估 ISL-TPGS-PLP 单药或联合用药的包封率（EE）、体外释放和稳定性，并通过 DLS 测量适当的物理化学参数。同时，还研究了口服给药后的药代动力学和组织分布。结果表明，ISL-TPGS-PLP 的平均粒径为 23.8±0.9nm，包封率高达 97.33±0.40%。更重要的是，ISL-TPGS-PLP 在 24h 内几乎有 90%的 ISL 释放，而 ISL 混悬液只有 50%的 ISL 释放。在药代动力学研究中，ISL-TPGS-PLP 的 AUC 是 ISL 混悬液的 1.53 倍。组织分布研究表明，ISL-TPGS-PLP 释放的 ISL 在肝脏中的含量高于游离 ISL 混悬液。总之，ISL-TPGS-PLP 可以改善 ISL 的溶解度、生物利用度和肝靶向能力，表明 ISL-TPGS-PLP 可以作为一种有前途的肝癌治疗纳米载体。
