Construction of Oral Insulin-Loaded Solid Lipid Nanoparticles and Their Intestinal Epithelial Cell Transcytosis Study].

Ya-Xian Zheng, Qin He, Min Xu, Yuan Huang

Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 2021 Jul

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To construct solid lipid nanoparticle (SNPs) drug delivery system loaded with peptide and protein drugs by using mixedsolvents, to study the transcytosis mechanisms of SNPs across intestinal epithelial cells, and to improve the endocytosis and transcytosis efficiency of peptide and protein drugs. The formulation of insulin-loaded water-in-oil-in-water solid lipid nanoparticles (INS-SNPs) was prepared by using a methanol-chloroform mixed solvent. The formulation was optimized with the single factor screening method. The optimized INS-SNPs were then characterized in terms of their morphology, stability and drug release properties. The cytotoxicity, cellular uptake and endocytosis mechanisms of INS-SNPs were then assessed on Caco-2 cells. The transcytosis efficiency of INS-SNPs was finally evaluated by using cellular monolayer in Transwell ® insert. The size, zeta potentials and drug loading efficiency of the optimized INS-SNPs were observed to be (145.4±0.5) nm, (-12.9±0.2) mV and (7.93±0.02)%, respectively. INS-SNPs were then shown to maintain desirable colloidal stability and sustained release of insulin in the simulated intestinal fluid. It was revealed that the cellular uptake of INS-SNPs reached its maximum after cellular incubation for 2 hours and was 1.53-fold higher than that of free insulin. Investigation of the endocytic mechanism revealed that INS-SNPs enter intestinal epithelial cells mainly through the clathrin-mediated and caveolae-mediated endocytosis pathways. Further investigation revealed that the amount of INS-SNPs permeating the cell monolayers was 1.54-fold higher than that of free insulin, which was comparable to the increase in their cellular uptake efficiency, indicating that INS-SNPs displayed enhanced absorption across the intestinal epithelium. The INS-SNPs prepared with mixed solvents in this study could significantly enhance the transcytosis efficiency of peptide and protein drugs, displaying great potentials in the application of oral drug delivery. This study may provide information and reference for the designing of efficient oral nano-drug delivery system in the future. Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).

Citation

Ya-Xian Zheng, Qin He, Min Xu, Yuan Huang. Construction of Oral Insulin-Loaded Solid Lipid Nanoparticles and Their Intestinal Epithelial Cell Transcytosis Study]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 2021 Jul;52(4):570-576