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In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions

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Acta Pharmaceutica Sinica B 2021年第4期11卷 989-1002页

作者： Ana LMartínez-López Carlos JGonzález-Navarro Paula Aranaz JoséLVizmanos Juan MIrache NANO-VAC Research Group Department of Chemistry and Pharmaceutical TechnologySchool of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Center for Nutrition Research School of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Department of Biochemistry&Genetics School of ScienceUniversity of NavarraPamplona 31080Spain Navarra Institute for Health Research(IdiSNA) Pamplona 31080Spain

The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of insulin.These nanocarriers,based on the coating of zein nanoparticles with a polymer conjugate containing PEG,displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 mg/mg.In intestinal pig mucus,the diffusivity of these nanoparticles(PPA-NPs)was found to be 20-fold higher than bare nanoparticles(NPs).These results were in line with the biodistribution study in rats,in which NPs remained trapped in the mucus,whereas PPA-NPs were able to cross this layer and reach the epithelium surface.The therapeutic effcacy was evaluated in Caenorhabditis elegans grown under high glucose conditions.In this model,worms treated with insulin-loaded in PPA-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in NPs.This finding was associated with a signifcant reduction in the formation of reactive oxygen species(ROS)as well as an important decrease in the glucose and fat content in worms.These effects would be related with the mucus-permeating ability of PPA-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms(similar to mucus)and,thus,the absorption of insulin.

关键词： Nanoparticles Oral delivery Mucus-permeating Biodistribution Insulin Caenorhabditis elegans ROS

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