Preparation, in vitro and in vivo evaluation of phloretin-loaded TPGS/Pluronic F68 modified mixed micelles with enhanced bioavailability and anti-ageing activity

作者：Jiaying Li, Tingyuan Li, Mingjie Gong, Xiaowen Wang, Qinyang Hua, Xia Jiang, Qilong Wang, Elmurat Toreniyazov, Jiangnan Yu, Xia Cao, Michael Adu‐Frimpong, Ximing Xu · 发表于：Journal of drug targeting · 年份：2025 · DOI：10.1080/1061186x.2025.2469753 · 被引用次数：6 · 研究领域：Nanoparticle-Based Drug Delivery、Hydrogels: synthesis, properties, applications、Seaweed-derived Bioactive Compounds

Phloretin exhibits strong antioxidant and anti-ageing properties by inhibiting mitochondrial oxidation of glutamate, succinic acid, and ascorbic acid. However, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To enhance its bioavailability and efficacy, we incorporated phloretin into nano-micelles (phloretin-MM) using the thin film dispersion method. Characterisation revealed that the optimal formulation had TPGS and Pluronic F68 in a 4:1 ratio as the excipients, which resulted in spherical micelles with an average particle size of 33.28 nm and an encapsulation efficiency of 71.2 ± 0.48%. The in vitro release profile showed that the phloretin-MM showed significantly higher cumulative release rates than free phloretin across various pH conditions, while the pharmaceutical analysis in rats indicated that phloretin-MM significantly improved the oral bioavailability of phloretin (about 5 folds) in circulation. Additionally, through the analysis of the staining of zebrafish under light microscopy and the average gray value, it can be concluded that phloretin has anti-ageing drug effect, and phloretin-MM is better than free phloretin. These findings suggest that TPGS/Pluronic F68-modified phloretin-MM could serve as an excellent nano-drug carrier system, potentially enhancing the solubility, bioavailability, and anti-ageing effects of phloretin for broader clinical applications.