SEDDS for intestinal absorption of insulin: Application of Caco-2 and Caco-2/HT29 co-culture monolayers and intra-jejunal instillation in rats

International Journal of Pharmaceutics
Jingying LiuAnette Müllertz

Abstract

To face the challenges of oral delivery of peptide and protein (P/P) drugs, self-emulsifying drug delivery systems (SEDDSs) containing monoacyl phosphatidylcholine (MAPC), Labrasol (LAB) and medium-chain (MC) monoglycerides as permeation enhancers (PEs) were evaluated for their effect on intestinal absorption of insulin. In this study, insulin was complexed with phosphatidylcholine (SPC) to form an insulin-SPC complex (ins-SPC) with increased lipophilicity. The following three SEDDSs: MCT(MAPC) (MC triglycerides and MAPC included), MCT(RH40) (MC triglycerides and Kolliphor® RH40 included) and LCT(MAPC) (long-chain triglycerides and MAPC included) were loading with ins-SPC (4% or 8% w/w of SPC). Three SEDDSs generated emulsions with droplet sizes between 50 and 470 nm and with zeta potentials between -5 to -25 mV in a simulated intestinal medium. Mucus-secreting Caco-2/HT29-MTX-E12 co-culture and Caco-2 monolayers were used as in vitro cell transport models to investigate insulin permeability. In comparison to insulin HBSS solution, MCT(MAPC) significantly increased the insulin permeability across co-culture and Caco-2 monolayers (2.0-2.5 × 10-7 cm/s). In an intra-jejunal (i.j.) instillation model in rats, MCT(RH40) significantl...Continue Reading

Citations

Mar 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sarah L Perry, David Julian McClements
Jun 2, 2020·Advanced Drug Delivery Reviews·D J BraydenR J Mrsny
Oct 9, 2020·International Journal of Pharmaceutics·Haniyeh EtezadiAndreas Bernkop-Schnürch
May 18, 2021·Acta Pharmaceutica Sinica. B·Fei XiaYi Lu

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