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

作　　者：Ana LMartínez-López Carlos JGonzález-Navarro Paula Aranaz JoséLVizmanos Juan MIrache 

机构地区：[1]NANO-VAC Research Group,Department of Chemistry and Pharmaceutical Technology,School of Pharmacy and Nutrition,University of Navarra,Pamplona 31080,Spain [2]Center for Nutrition Research,School of Pharmacy and Nutrition,University of Navarra,Pamplona 31080,Spain [3]Department of Biochemistry&Genetics,School of Science,University of Navarra,Pamplona 31080,Spain [4]Navarra Institute for Health Research(IdiSNA),Pamplona 31080,Spain

出　　处：《Acta Pharmaceutica Sinica B》2021年第4期989-1002,共14页药学学报（英文版）

基　　金：supported by Postdoctoral Fellowship from the National Council for Science and Technology of Mexico(CONACyT,Grant No.291231,Mexico)。

摘　　要：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 

分 类 号：R965[医药卫生—药理学]