Modified nanoparticles with cell penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation
Abstract Colon is an ideal absorptive site for oral protein and peptide drug (insulin) and yet it poses multiple barriers against the drug absorption, such as the barriers against the drug diffusion from colon lumen toward the absorptive mucosa and permeation across colon epithelium. In this study, modified nanoparticles (Tat CS NPs) with cell penetrating peptide (Tat) and amphipathic chitosan derivative (a CS) were used as carriers to improve colonic absorption of the drug. With a CS as emulsifier and poly(lactic co glycolic acid) as matrix material, Tat CS NPs were prepared and evaluated in vitro/vivo. Using Caco 2 cell monolayers to imitate the colonic epithelial cells, it was found that the cellular uptake amount and transcellular transportation performance of Tat CS NPs were much enhanced compared with those of CS NPs and PVA NPs. The efficacy evaluation on diabetic rat models demonstrated that the hypoglycemic effect of Tat CS NPs loaded with insulin was 6.89 times higher than that of PVA NPs, and 1.79 times higher than that of CS NPs. By gavage of [99mTc] isotope labeled Tat CS NPs in mini pigs and single photon emission computed tomography (SPECT) on pigs' gastrointestinal tract, it was further proved that the nanoparticles could reach colon and produce pharmacological effect. In conclusion, Tat CS NPs as vehicles for colon specific drug delivery may be an efficient approach to improve oral bioavailability of protein and peptide drugs.
Drug delivery