文献类型：期刊文献

英文题名：Formulation, characterization, and In vitro evaluation of lenvatinib-loaded solid lipid nanoparticles functionalized with Twenty-Polyglycerol vitamin E succinate for liver cancer treatment

作者：Zhou, Yanyan[1];Luo, Shengnan[1];Jiang, Zhe[2];Luo, Xiang[1,2];Yu, Zhangsen[1];Wang, Zhixin[1];Zhu, Kewu[1]

机构：[1]Shaoxing Univ, Ctr Drug Delivery Syst Res, Sch Med, Shaoxing 312000, Zhejiang, Peoples R China;[2]Shaoxing Univ, Coll Chem & Chem Engn, Zhejiang Engn Res Ctr Fat Soluble Vitamin, Shaoxing, Zhejiang, Peoples R China

年份：2025

外文期刊名：DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY

收录：SCI-EXPANDED(收录号：WOS:001545227100001)、、Scopus(收录号：2-s2.0-105012610496)、WOS

基金：This research was supported by the General Scientific Research Projects of Zhejiang Provincial Department of Education (No. Y202145959).

语种：英文

外文关键词：Lenvatinib; solid lipid nanoparticles; Twenty-Polyglycerol vitamin E succinate; tween 80; hepatocellular carcinoma; drug delivery

外文摘要：ObjectiveLenvatinib (LEN), a first-line treatment for advanced hepatocellular carcinoma (HCC), faces limitations due to adverse effects and drug resistance. This study aimed to develop LEN-loaded solid lipid nanoparticles (SLNs) modified with Twenty-polyglycerol vitamin E succinate (PG20-VES@LEN-SLNs) to enhance therapeutic efficacy and compare them with Tween80-modified SLNs (Tween80@LEN-SLNs).MethodsThe formulation of LEN-SLNs was optimized based on particle size and polydispersity index (PDI) by screening lipid matrices (GMS, GMP, SA, CP, GB, GMD), surfactant types (Tween80, PG20-VES, TPGS1000, F68), and GMS:SPC ratios. Physicochemical properties were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR). Encapsulation efficiency (EE), drug loading (DL), and in vitro drug release profiles were evaluated. Cytotoxicity against HepG2, Huh-7, and L02 cells was assessed via MTT assay, while cellular uptake in HepG2 was visualized using Nile Red-labeled SLNs.ResultsOptimized PG20-VES@LEN-SLNs exhibited a smaller particle size (294.6 +/- 10.4 nm vs. 308.6 +/- 29.5 nm for Tween80@LEN-SLNs) and higher EE (80.7 +/- 5.1% vs. 72.7 +/- 4.0%). Both formulations showed sustained drug release over 48 h, significantly slower than free LEN (97.4% released in 24 h). PG20-VES@LEN-SLNs demonstrated superior cytotoxicity against HepG2 cells (IC50 = 36.47 mu M) compared to Tween80@LEN-SLNs (IC50 = 42.49 mu M) and free LEN (IC50 = 116.8 mu M), with enhanced cellular uptake observed via confocal microscopy. In Huh-7 cells, PG20-VES@LEN-SLNs and Tween80@LEN-SLNs reduced the IC50 of lenvatinib from 189.21 mu M (free LEN) to 18.04 mu M and 18.41 mu M, respectively.ConclusionPG20-VES@LEN-SLNs effectively improved LEN's therapeutic index through sustained release, enhanced tumor cell targeting, and synergistic cytotoxicity. This study highlights PG20-VES as a multifunctional surfactant for advanced HCC nanotherapy, offering a promising strategy to overcome clinical limitations of LEN.