Enhanced oral bioavailability of insulin using PLGA nanoparticles co modified with cell penetrating peptides and Engrailed secretion peptide (Sec)
Abstract Biodegradable polymer nanoparticle drug carriers are an attractive strategy for oral delivery of peptide and protein drugs. However, their ability to cross the intestinal epithelium membrane is largely limited. Therefore, in the present study, cell penetrating peptides (R8, Tat, penetratin) and a secretion peptide (Sec) with N terminal stearylation were introduced to modify nanoparticles (NPs) on the surface to improve oral bioavailability of peptide and protein drugs. In vitro studies conducted in Caco 2 cells showed the value of the apparent permeability coefficient (Papp) of the nanoparticles co modified with Sec and penetratin (Sec Pen NPs) was about two times greater than that of the nanoparticles modified with only penetratin (Pen NPs) while the increase of transcellular transport of nanoparticles modified together with Sec and R8 (Sec R8 NPs) or Sec and Tat (Sec Tat NPs) was not significant compared with nanoparticles modified with only R8 (R8 NPs) or Tat (Tat NPs) Using insulin as the model drug, in vivo studies performed on rats indicated that compared to Pen NPs, the relative bioavailability of insulin for Sec Pen NPs was 1.71 times increased after ileal segments administration, and stronger hypoglycemic effects was also observed. Therefore, the nanoparticles co modified with penetratin and Sec could act as attractive carriers for oral delivery of insulin.
Drug delivery