Original articles
Ana L. Martínez-López, Carlos J. González-Navarro, Paula Aranaz, José L. Vizmanos, Juan M. Irache. In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions[J]. Acta Pharmaceutica Sinica B, 2021, 11(4): 989-1002

In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions
Ana L. Martínez-Lópeza, Carlos J. González-Navarrob, Paula Aranazb, José L. Vizmanosc,d, Juan M. Irachea
a NANO-VAC Research Group, Department of Chemistry and Pharmaceutical Technology, School of Pharmacy and Nutrition, University of Navarra, Pamplona 31080, Spain;
b Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, Pamplona 31080, Spain;
c Department of Biochemistry & Genetics, School of Science, University of Navarra, Pamplona 31080, Spain;
d Navarra Institute for Health Research(IdiSNA), Pamplona 31080, Spain
Abstract:
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 μg/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 efficacy 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 significant 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.
Key words:    Nanoparticles    Oral delivery    Mucus-permeating    Biodistribution    Insulin    Caenorhabditis elegans    ROS    Lifespan    Zein    Epithelium   
Received: 2020-11-08     Revised: 2020-12-18
DOI: 10.1016/j.apsb.2021.02.020
Funds: The first author was supported by Postdoctoral Fellowship from the National Council for Science and Technology of Mexico (CONACyT, Grant No. 291231, Mexico).
Corresponding author: Juan M.Irache, jmirache@unav.es     Email:jmirache@unav.es
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Authors
Ana L. Martínez-López
Carlos J. González-Navarro
Paula Aranaz
José L. Vizmanos
Juan M. Irache

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