Glu‐derived Zwitterionic Micelles Conquering the Intestinal Mucosal Barrier toward Oral Delivery

Liu, Kedong; Chen, Yun; Yang, Dutao; Cai, Yanfei; Yang, Zhaoqi; Jin, Jian

doi:10.1002/cnma.202300324

Cited by 2 publications

(1 citation statement)

References 40 publications

(59 reference statements)

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“…First,the macroinitiator poly(lactic acid)-EBiB (PLA-Br) was synthesized according to our reported procedure . Then three zwitterionic polymers with different polymerization degrees of betaine (CB15/30/45) and guanidine-based cationic copolymer (Gua15) were all synthesized by a similar synthesis pathway.…”

Section: Methodsmentioning

confidence: 99%

Betaine-Based and Polyguanidine-Inserted Zwitterionic Micelle as a Promising Platform to Conquer the Intestinal Mucosal Barrier

Liu,

Chen,

Yang

et al. 2023

ACS Appl. Mater. Interfaces

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Developing nanocarriers for oral drug delivery is often hampered by the dilemma of balancing mucus permeation and epithelium absorption, since huge differences in surface properties are required for sequentially overcoming these two processes. Inspired by mucus-penetrating viruses that universally possess a dense charge distribution with equal opposite charges on their surfaces, we rationally designed and constructed a poly(carboxybetaine)-based and polyguanidine-inserted cationic micelle platform (hybrid micelle) for oral drug delivery. The optimized hybrid micelle exhibited a great capacity for sequentially overcoming the mucus and villi barriers. It was demonstrated that a longer zwitterionic chain was favorable for mucus diffusion for hybrid micelles but not conducive to cellular uptake. In addition, the significantly enhanced internalization absorption of hybrid micelles was attributed to the synergistic effect of polyguanidine and proton-assisted amine acid transporter 1 (PAT1). Moreover, the retrograde pathway was mainly involved in the intracellular transport of hybrid micelles and transcytosis delivery. Furthermore, the prominent intestinal mucosa absorption in situ and in vivo liver distribution of the oral hybrid micelle were both detected. The results of this study indicated that the hybrid micelles were capable of conquering the intestinal mucosal barrier, having a great potential for oral application of drugs with poor oral bioavailability.

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Section: Methodsmentioning

confidence: 99%