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  • Title: Design and Investigation of Penetrating Mechanism of Octaarginine-Modified Alginate Nanoparticles for Improving Intestinal Insulin Delivery.
    Author: Li M, Sun Y, Ma C, Hua Y, Zhang L, Shen J.
    Journal: J Pharm Sci; 2021 Jan; 110(1):268-279. PubMed ID: 32663595.
    Abstract:
    The aim of the study is to design octaarginine (R8)-modified insulin-alginate nanoparticles (INS-SA/R8 NPs) as the oral insulin delivery system, and further investigate its penetrating mechanism. The characterization results indicated that the surface of INS-SA/R8 NPs was smooth and the average diameter was about 300 nm. INS-SA/R8 NPs exhibited a stronger stability in the simulated gastrointestinal fluids and had a better controlled release than unmodified alginate nanoparticles (INS-SA NPs). Moreover, INS-SA/R8 NPs group had the strongest insulin transport capacity and the largest amount of insulin uptake in all experimental groups. Most importantly, the improvement of insulin intestinal uptake was further confirmed in rat intestine in vivo, and its penetrating mechanism might be involved in the production of endogenous nitric oxide (NO) signal molecule. In addition, in vivo hypoglycemic studies showed that orally administrated INS-SA/R8 NPs produced a better hypoglycemic effect as compared with INS-SA NPs in diabetic rats. Meanwhile, from the cytotoxicity analysis, INS-SA/R8 NPs were safe for oral administration. Taken together, INS-SA/R8 NPs was a good oral insulin delivery system, which might also be suitable for other protein drugs.
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