In recent years, zwitterionic materials have drawn great attention in oral drug delivery system due to their capacity for rapid mucus diffusion and enhanced cellular internalization. However, zwitterionic materials tend to show strong polarity that was hard to directly coat hydrophobic nanoparticles (NPs). Inspired by Pluronic coating, a simple and convenient strategy to coat NPs with zwitterionic materials using zwitterionic Pluronic analogs was developed in this investigation. Poly(carboxybetaine)-poly(propylene oxide)-Poly(carboxybetaine) (PCB-PPO-PCB, PPP), containing PPO segments with MW > 2.0 kDa, can effectively adsorb on the surface of PLGA NPs with typical core-shell spherical in shape. The PLGA@PPP4K NPs were stable in gastrointestinal physiological environment and sequentially conquered mucus and epithelium barriers. Proton-assisted amine acid transporter 1 (PAT1) was verified to contribute to the enhanced internalization of PLGA@PPP4K NPs, and the NPs could partially evade lysosomal degradation pathway and utilize retrograde pathway for intracellular transport. In addition, the enhanced villi absorption in situ and oral liver distribution in vivo were also observed compared to PLGA@F127 NPs. Moreover, insulin-loaded PLGA@PPP4K NPs as an oral delivery application for diabetes induce a fine hypoglycemic response in diabetic rats after oral administration. The results of this study demonstrated that zwitterionic Pluronic analogs-coated NPs might provide a new perspective for zwitterionic materials application as well as oral delivery of biotherapeutics.
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| http://dx.doi.org/10.1016/j.ijbiomac.2023.123870 | DOI Listing |
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