Hydrophilic and Electroneutral Nanoparticles to Overcome Mucus Trapping and Enhance Oral Delivery of Insulin.

Molecular Pharmaceutics
Xinyi TanXing Tang

Abstract

The oral delivery of macromolecules using nanoparticles is limited by secreted mucus, resulting in low contact or internalization via intestinal cells and, thus, both mucus trapping and further low cellular uptake need to be overcome. Here, hydrophilic and electroneutral nanoparticles were developed to overcome mucus trapping and enhance the oral delivery of macromolecules. Mesoporous silica nanoparticles (MSNs) were synthesized and modified with a hydrophilic block polymer (poly(lactic acid)-methoxy poly(ethylene glycol), PLA-PEG), and then an overall electroneutrality and promoted cellular uptake were achieved by sequential modification with cell-penetrating peptides (CPPs). Reduced hydrophobic and electrostatic interactions of MSN@PLA-PEG-CPP with mucus decreased mucus trapping by 36.0%, increased the cellular uptake of MSN@PLA-PEG-CPP by 2.3-folds in mucous conditions via active heparan sulfate proteoglycan receptor (HSPG)-mediated and caveolae-mediated endocytosis and electrostatic interactions. Furthermore, insulin, a model macromolecular drug, was successfully loaded into the nanoparticles (INS@MSN@PLA-PEG-CPP). Compared with insulin solution, in vitro cellular uptake in mucous conditions and in vivo pharmacodynamic effe...Continue Reading

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Citations

May 18, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Wen FuHuixia Lv
Jun 30, 2021·Nanomedicine : Nanotechnology, Biology, and Medicine·Natalia N PorfiryevaVitaliy V Khutoryanskiy

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