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 Ana L.Martínez-López;Carlos J.González-Navarro;Paula Aranaz;José L.Vizmanos;Juan M.Irache

作者机构：NANO-VAC Research GroupDepartment of Chemistry and Pharmaceutical TechnologySchool of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Center for Nutrition ResearchSchool of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Department of Biochemistry&GeneticsSchool of ScienceUniversity of NavarraPamplona 31080Spain Navarra Institute for Health Research(IdiSNA)Pamplona 31080Spain 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第4期

页      面：989-1002页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 100602[医学-中西医结合临床] 

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

主　　题：Nanoparticles Oral delivery Mucus-permeating Biodistribution Insulin Caenorhabditis elegans ROS 

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.