Chen Xiaolan, Zhou Han, Chua An Wen Asly, Wang Shengyi, Zhang Lei, Yang Haifeng, Mao Yujuan, Jia Jiping, Wang Dada, Wang Jing, Cao Zhaoli, Xu Bohui, Xu Ying, Shen Yan, Zhang Wenli, Zheng Yi
Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, Jiangsu, People's Republic of China.
Department of Pharmaceutics, China Pharmaceutical University, Jiangsu, 210009, People's Republic of China.
Int J Nanomedicine. 2025 Apr 25;20:5377-5391. doi: 10.2147/IJN.S514455. eCollection 2025.
Mulberry leaf polysaccharide (MLP) has gained attention as a potential anti-diabetic agent for lowering blood glucose and improving insulin sensitivity. However, the low gastrointestinal stability and oral bioavailability limit its clinical application. To address this issue, a novel drug-caged liposomes (MLP-CL) was developed to enhance oral delivery efficiency of MLP compared to conventional drug-encapsulated liposomes (MLP-L).
MLP-L and MLP-CL were prepared by the thin-film hydration method. Subsequently, the structural integrity of these liposomes was assessed via in vitro release test and confocal laser microscopy (CLSM) analysis. Madin-Darby canine kidney (MDCK) cells were employed to investigate the cellular uptake mechanisms and transcellular transport efficiency. Finally, the biodistribution profiles and transport mechanisms of liposomes were evaluated through in vivo fluorescence imaging and pharmacokinetic studies in Sprague Dawley rats.
Compared to MLP-L, which released 80% of MLP within 4 hours, MLP-CL showed sustained release with only 40% released in the same period. MLP-CL also enabled more effective co-delivery of MLP and liposomes to MDCK cells, indicating improved structural integrity and cellular uptake. Transcellular transport assay confirmed that MLP-CL was transported across cells more efficiently. In vivo, MLP-CL increased intestinal accumulation and raised plasma MLP concentration by 50%. Additionally, by comparing the discrepancy between the lymphatic-suppression model and the normal model, it was found that 63.56% of MLP-CL was absorbed through the lymphatic pathway compared to 18.05% for MLP-L.
Compared to conventional MLP-L, conjugation of polysaccharide improves the structural integrity of MLP-CL in the gastrointestinal tract, which in turn improves lymphatic uptake and bioavailability. This provides an effective strategy for the design of polysaccharide delivery systems.
桑叶多糖（MLP）作为一种潜在的降血糖和改善胰岛素敏感性的抗糖尿病药物受到关注。然而，其低胃肠道稳定性和口服生物利用度限制了其临床应用。为解决这一问题，开发了一种新型药物包封脂质体（MLP-CL），与传统的药物包封脂质体（MLP-L）相比，可提高MLP的口服递送效率。
采用薄膜水化法制备MLP-L和MLP-CL。随后，通过体外释放试验和共聚焦激光显微镜（CLSM）分析评估这些脂质体的结构完整性。使用Madin-Darby犬肾（MDCK）细胞研究细胞摄取机制和跨细胞转运效率。最后，通过体内荧光成像和Sprague Dawley大鼠的药代动力学研究评估脂质体的生物分布概况和转运机制。
与在4小时内释放80% MLP的MLP-L相比，MLP-CL显示出缓释特性，同期仅释放40%。MLP-CL还能更有效地将MLP和脂质体共同递送至MDCK细胞，表明其结构完整性和细胞摄取得到改善。跨细胞转运试验证实MLP-CL能更有效地跨细胞转运。在体内，MLP-CL增加了肠道蓄积，并使血浆MLP浓度提高了50%。此外，通过比较淋巴抑制模型和正常模型之间的差异，发现63.56%的MLP-CL通过淋巴途径吸收，而MLP-L为18.05%。
与传统的MLP-L相比，多糖的缀合改善了MLP-CL在胃肠道中的结构完整性，进而提高了淋巴摄取和生物利用度。这为多糖递送系统的设计提供了一种有效策略。
