Zhang Wei, Zhang Qian, Yang Yuhan, Chen Yangyi, Wei Jinbin, Lu Fenglai, Li Dianpeng
Guangxi Institute of Botany, Chinese Academy of Sciences, No. 85 Yanshan Town, Yanshan District, Guilin, 541006, People's Republic of China.
Department of Pharmacy, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, People's Republic of China.
Drug Deliv Transl Res. 2025 Jan;15(1):312-324. doi: 10.1007/s13346-024-01597-8. Epub 2024 Apr 20.
A novel multi-functional micelle delivery system was developed for enhancing the oral absorption of paclitaxel (PTX). The delivery carriers were constructed by modifying chitosan-stearic acid (CS-SA) micelles with L-carnitine (LC) and co-encapsulating quercetin (Que), and the PTX-loaded micelles were prepared by film-sonication dispersing technique. The as-prepared micelles showed homogeneous spherical shapes with a small particle size of 148.3 ± 1.7 nm, high drug loading of 7.05% and low critical micelle concentration (CMC) of 16.89 µg/ml. Compared to the in-house PTX formulation similar to the commercial injection Taxol™, the target PTX-loaded micelles had obvious sustained-release effects and exhibited an oral relative bioavailability of 168.08%. The cellular uptake studies of Caco-2 cells confirmed the micellar modification of LC and the co-loading of Que played important roles in promoting the absorption of drug loaded in micelles. The CYP3A4 enzyme test demonstrated the micelles had an inhibitory effect on the metabolic enzyme due to the presence of Que. These findings confirmed the potential of the multi-functional chitosan polymeric micelles based on synergistic effect as an effective oral delivery system.
开发了一种新型多功能胶束递送系统，以提高紫杉醇（PTX）的口服吸收。通过用左旋肉碱（LC）修饰壳聚糖-硬脂酸（CS-SA）胶束并共包封槲皮素（Que）来构建递送载体，并采用薄膜超声分散技术制备载PTX的胶束。所制备的胶束呈现均匀的球形，粒径小，为148.3±1.7nm，载药量高，为7.05%，临界胶束浓度（CMC）低，为16.89μg/ml。与内部类似市售注射剂紫杉醇™的PTX制剂相比，目标载PTX胶束具有明显的缓释效果，口服相对生物利用度为168.08%。Caco-2细胞的细胞摄取研究证实，LC的胶束修饰和Que的共负载在促进胶束中所载药物的吸收方面发挥了重要作用。CYP3A4酶试验表明胶束由于Que的存在对代谢酶有抑制作用。这些发现证实了基于协同效应的多功能壳聚糖聚合物胶束作为一种有效的口服递送系统的潜力。
