Journal
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
Volume 11, Issue 2, Pages 647-658Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s13346-021-00919-4
Keywords
Nanoparticles; Oral delivery; Mucus-permeating; Zein; PEG; C. elegans
Funding
- Mexican National Council for Science and Technology (CONACyT) [291231]
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The study evaluated the potential of nanocarriers for oral insulin delivery, specifically using zein nanoparticles coated with a Gantrez (R) AN-PEG conjugate. Results showed that ZNP-GP had higher diffusion coefficient in pig intestinal mucus compared to ZNP, and both types of nanoparticles displayed similar behavior under simulated intestinal conditions. Furthermore, nanoencapsulated insulin in ZNP-GP showed significantly greater effects on reducing glucose and fat accumulation in Caenorhabditis elegans N2 compared to ZNP or insulin in solution.
The aim was to evaluate the potential of nanocarriers, based on the coating of zein nanoparticles (ZNP) with a Gantrez (R) AN-PEG conjugate (GP), for the oral delivery of insulin. ZNP-GP displayed less negative surface charge and a 14-fold higher diffusion coefficient in pig intestinal mucus than ZNP. Both nanoparticles showed a spherical shape and an insulin load of 77.5 mu g/ mg. Under simulated gastric conditions, ZNP-GP released significantly lower amount of insulin than ZNP, while under simulated intestinal conditions, both types of nanoparticles displayed similar behaviour. In Caenorhabditis elegans wild-type N2, grown under high glucose conditions, insulin treatments reduced glucose and fat accumulation without altering the growth rate, the worm length, or the pumping rate. The effect was significantly greater (p < 0.001) when insulin was nanoencapsulated in ZNP-GP compared with that encapsulated in ZNP or formulated in solution. This would be related to the highest capability of ZNP-GP to diffuse in the dense peritrophic-like layer covering intestinal cells in worms. In daf-2 mutants, the effect on fat and glucose reduction by insulin treatment was suppressed, indicating a DAF-2 dependent mechanism. In summary, ZNP- GP is a promising platform that may offer new opportunities for the oral delivery of insulin and other therapeutic proteins.
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