文献类型：期刊文献

英文题名：Coupling simulation and experimental study of drug loading and releasing behaviors in phytol-based micelles

作者：Shen, Hong[1,2] Zhang, Changwei[1] Zhou, Hao[1] Li, Wenjun[1] Tong, Zhenkai[1] Wang, Chengzhang[1] Jiang, Jianxin[2]

第一作者：Shen, Hong

机构：[1] Chemical Engineering of Forest Products, Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing, 210042, China; [2] Department of Chemistry and Chemical Engineering, Beijing Forestry University, Beijing, 100083, China

年份：2024

卷号：416

外文期刊名：Journal of Molecular Liquids

收录：EI(收录号：20244617359595);Scopus(收录号：2-s2.0-85208660463)

语种：英文

外文关键词：Controlled drug delivery - Cytotoxicity - Dissipative particle dynamics - Drug dosage - Targeted drug delivery

摘要：Phytol, as a potential drug-carrier, can regulate the cellular reactive oxygen species (ROS) levels in a dose-dependent manner, decreasing them at lower doses and increasing them at higher doses. In this study, we developed phytol-based micelles composed of phytol, PEG, and OE, which can clearly enhance drug delivery efficacy and simultaneously protect normal cells. Drug-loading and -releasing mechanisms of phytol-based micelles were investigated combined with dissipative particle dynamics (DPD) simulations and experimental. The simulation results indicate that Ph4EO22Ph4 exhibits the most desirable properties for forming phytol-based micelles compared with other phytol-based polymers we designed. We found that co-loading (purpurin 18 a) P18 and paclitaxel (PTX) within the Ph4EO22Ph4 micelle not only enhances the encapsulation efficiency (EE) of P18 (P18's EE rised from 85.16 % to 91.17 %) but also optimizes the overall micellar structure, exhibiting excellent DL capability along with sustained release (75.2 % PTX releasing after 72 h) performance under acidic conditions. The release mechanism varies with the loaded drugs, in which PTX is released in its molecular form while P18 is released through P18/Ph4 particles. In the latter case, Ph4 within the particles significantly facilitates cellular uptake of P18 drugs by 4T1 cells, thereby enhancing therapeutic efficacy. Interestingly, Ph4EO22Ph4 exhibited significantly higher cytotoxicity towards 4T1 cells compared to HC11. Therefore, the phytol-based micelles incorporating a concentration-dependent hydrophobic block and a steric effect-driven hydrophilic block composed of PEG demonstrated enhanced efficacy and reduced toxicity. The present study presents a novel phytol-based micelle system incorporating DPD simulation and experimental validation, which effectively addresses the challenges encountered by P18 and PTX. Moreover, it comprehensively investigates drug loading and releasing behaviors in phytol-based micelles from various perspectives, thereby offering valuable insights for the design of alternative drug delivery systems. ? 2024