Yolk-shell cationic liposomes overcome mucus and epithelial barriers for enhanced oral drug delivery
Yu Qiu,
Yan Zhuo,
Yangyuan Ye,
Xiang Li,
Zhu Zhu,
Bingqi Wang,
Cong Guo,
Yuan Liu,
Miaorong Yu
Affiliations
Yu Qiu
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Yan Zhuo
Nanchang University College of Pharmacy, Nanchang 330006, China
Yangyuan Ye
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China
Xiang Li
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
Zhu Zhu
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Bingqi Wang
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
Cong Guo
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
Yuan Liu
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Miaorong Yu
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China; Corresponding author at: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Liposomes have garnered attention for their potential in oral drug delivery. However, they encounter obstacles when traversing the mucus and epithelial barriers of the gastrointestinal tract. Recent studies indicate that the very characteristics enabling liposomes to penetrate mucus may adversely affect their cellular uptake. In this study, we introduce a novel strategy focused on liposome biomechanical properties, specifically stiffness. Inspired by the stiffness-mediated transformation behaviour of entities like cancer cells in biological environments, we developed yolk-shell structured cationic liposomes (YS-CLip) by incorporating mesoporous silica nanoparticles. Compared to their single-membrane structured counterparts, the YS-CLip demonstrated higher stiffness, adopting an ellipsoidal shape after stress, facilitating rotation-enhanced mucus penetration. This facilitated simultaneous circumvention of mucus diffusion and epithelial absorption barriers. In rats, orally administered YS-CLip adeptly bypassed both mucus and intestinal impediments, leading to an amplified bioavailability of doxorubicin, outperforming both their single-membrane counterparts and certain mucus-penetrating liposomes. Collectively, our findings illuminate the pivotal role of biomechanical stiffness in liposomal formulation, endorsing YS-CLip as a prospective strategy to navigate oral drug delivery challenges.
