Combined Mulberry Leaf Polysaccharide-Caged Liposomes for Effective Oral Drug Delivery in Rat Model

Xiaolan Chen,1,* Han Zhou,2,* Asly Chua An Wen,2 Shengyi Wang,2 Lei Zhang,2 Haifeng Yang,1 Yujuan Mao,1 Jiping Jia,1 Dada Wang,1 Jing Wang,1 Zhaoli Cao,1 Bohui Xu,3 Ying Xu,4 Yan Shen,2 Wenli Zhang,2 Yi Zheng1 1Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, Jiangsu, Peopl...

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Main Authors: Chen X, Zhou H, Chua An Wen A, Wang S, Zhang L, Yang H, Mao Y, Jia J, Wang D, Wang J, Cao Z, Xu B, Xu Y, Shen Y, Zhang W, Zheng Y
Format: Article
Language:English
Published: Dove Medical Press 2025-04-01
Series:International Journal of Nanomedicine
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Online Access:https://www.dovepress.com/combined-mulberry-leaf-polysaccharide-caged-liposomes-for-effective-or-peer-reviewed-fulltext-article-IJN
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author Chen X
Zhou H
Chua An Wen A
Wang S
Zhang L
Yang H
Mao Y
Jia J
Wang D
Wang J
Cao Z
Xu B
Xu Y
Shen Y
Zhang W
Zheng Y
author_facet Chen X
Zhou H
Chua An Wen A
Wang S
Zhang L
Yang H
Mao Y
Jia J
Wang D
Wang J
Cao Z
Xu B
Xu Y
Shen Y
Zhang W
Zheng Y
author_sort Chen X
collection DOAJ
description Xiaolan Chen,1,* Han Zhou,2,* Asly Chua An Wen,2 Shengyi Wang,2 Lei Zhang,2 Haifeng Yang,1 Yujuan Mao,1 Jiping Jia,1 Dada Wang,1 Jing Wang,1 Zhaoli Cao,1 Bohui Xu,3 Ying Xu,4 Yan Shen,2 Wenli Zhang,2 Yi Zheng1 1Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, Jiangsu, People’s Republic of China; 2Department of Pharmaceutics, China Pharmaceutical University, Jiangsu, 210009, People’s Republic of China; 3School of Pharmacy, Nantong University, Jiangsu, Nantong, People’s Republic of China; 4College of Pharmacy, Jiangsu University, Zhenjiang, 212013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenli Zhang, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu, 211198, People’s Republic of China, Email zwllz@163.com Yi Zheng, Jiangsu Agri-Animal Husbandry Vocational College, 8 Fenghuang East Road, Taizhou, Jiangsu, 225300, People’s Republic of China, Email 1997010030@jsahvc.edu.cnIntroduction: 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).Methods: 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.Results: 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.Conclusion: 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. Keywords: bioavailability, diabetes management, liposome, mulberry leaf polysaccharides, oral drug delivery
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spelling doaj-art-ad48eac27349449ea19b6877cf6b47da2025-08-20T02:30:19ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-04-01Volume 2053775391102417Combined Mulberry Leaf Polysaccharide-Caged Liposomes for Effective Oral Drug Delivery in Rat ModelChen XZhou HChua An Wen AWang SZhang LYang HMao YJia JWang DWang JCao ZXu BXu YShen YZhang WZheng YXiaolan Chen,1,* Han Zhou,2,* Asly Chua An Wen,2 Shengyi Wang,2 Lei Zhang,2 Haifeng Yang,1 Yujuan Mao,1 Jiping Jia,1 Dada Wang,1 Jing Wang,1 Zhaoli Cao,1 Bohui Xu,3 Ying Xu,4 Yan Shen,2 Wenli Zhang,2 Yi Zheng1 1Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, Jiangsu, People’s Republic of China; 2Department of Pharmaceutics, China Pharmaceutical University, Jiangsu, 210009, People’s Republic of China; 3School of Pharmacy, Nantong University, Jiangsu, Nantong, People’s Republic of China; 4College of Pharmacy, Jiangsu University, Zhenjiang, 212013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenli Zhang, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu, 211198, People’s Republic of China, Email zwllz@163.com Yi Zheng, Jiangsu Agri-Animal Husbandry Vocational College, 8 Fenghuang East Road, Taizhou, Jiangsu, 225300, People’s Republic of China, Email 1997010030@jsahvc.edu.cnIntroduction: 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).Methods: 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.Results: 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.Conclusion: 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. Keywords: bioavailability, diabetes management, liposome, mulberry leaf polysaccharides, oral drug deliveryhttps://www.dovepress.com/combined-mulberry-leaf-polysaccharide-caged-liposomes-for-effective-or-peer-reviewed-fulltext-article-IJNbioavailabilitydiabetes managementliposomemulberry leaf polysaccharidesoral drug delivery.
spellingShingle Chen X
Zhou H
Chua An Wen A
Wang S
Zhang L
Yang H
Mao Y
Jia J
Wang D
Wang J
Cao Z
Xu B
Xu Y
Shen Y
Zhang W
Zheng Y
Combined Mulberry Leaf Polysaccharide-Caged Liposomes for Effective Oral Drug Delivery in Rat Model
International Journal of Nanomedicine
bioavailability
diabetes management
liposome
mulberry leaf polysaccharides
oral drug delivery.
title Combined Mulberry Leaf Polysaccharide-Caged Liposomes for Effective Oral Drug Delivery in Rat Model
title_full Combined Mulberry Leaf Polysaccharide-Caged Liposomes for Effective Oral Drug Delivery in Rat Model
title_fullStr Combined Mulberry Leaf Polysaccharide-Caged Liposomes for Effective Oral Drug Delivery in Rat Model
title_full_unstemmed Combined Mulberry Leaf Polysaccharide-Caged Liposomes for Effective Oral Drug Delivery in Rat Model
title_short Combined Mulberry Leaf Polysaccharide-Caged Liposomes for Effective Oral Drug Delivery in Rat Model
title_sort combined mulberry leaf polysaccharide caged liposomes for effective oral drug delivery in rat model
topic bioavailability
diabetes management
liposome
mulberry leaf polysaccharides
oral drug delivery.
url https://www.dovepress.com/combined-mulberry-leaf-polysaccharide-caged-liposomes-for-effective-or-peer-reviewed-fulltext-article-IJN
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