期刊
JOURNAL OF CONTROLLED RELEASE
卷 313, 期 -, 页码 1-13出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2019.10.006
关键词
Oral delivery; Paracellular transport; Caco-2; Tight junctions; Hypoglycemic effect
资金
- National Natural Science Foundation of China [31571794, 31560437, JUFSTR20180204]
- Six talent peaks project in Jiangsu Province [NY-128]
- Guangxi science and Technology Major Project [guikeAA17202029]
Non-invasive means of insulin administration circumvent some of the inconveniences of injections. Oral administration in particular is convenient, pain-free, and allows favorable glucose homeostasis, but is subject to chemical instability, enzymatic degradation, and poor gastrointestinal absorption. Natural polymeric nanoparticles have emerged as a promising oral delivery system for peptide therapeutics due their safety, biocompatibility, and stability. In this study, self-assembled nanocomposites from chitosan (CS) and insulin-loaded, zein-carboxymethylated short-chain amylose (IN-Z-CSA) nanocomposites were synthesized to improve oral bioavailability of insulin. The optimized IN-Z-CSA/CS0.2% nanocomposites exhibited an average size of 311.32 +/- 6.98 nm, a low polydispersity index (0.227 +/- 0.01), a negative zeta potential (43.77 +/- 1.36 mV), an encapsulation efficiency of 89.6 +/- 0.9%, and a loading capacity of 6.8 +/- 0.4%. The IN-Z-CSA/CS0.2% nanocomposites were stable in storage conditions. The transepithelial permeability of the N-Z-CSA/CS0.2% nanocomposites was 12-fold higher than that of insulin. Cellular uptake studies revealed that the IN-Z-CSA/CS0.2% nanocomposites were internalized into Caco-2 cells by both endocytosis and a paracellular route. Additionally, in pharmacological studies, orally administered IN-Z-CSA/CS0.2% nanocomposites had a stronger hypoglycemic effect with a relative bioavailability of 15.19% compared with that of IN-Z-CSA(1.0%) nanocomposites. Furthermore, cell toxicity and in vivo tests revealed that the IN-Z-CSA/CS0.2% nanocomposites were biocompatible. Overall, these results indicate that the IN-Z-CSA/CS0.2% nanocomposites can improve oral bioavailability of insulin and are a promising delivery system for insulin or other peptide/protein drugs.
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