Enhanced oral insulin delivery via surface hydrophilic modification of chitosan copolymer based self-assembly polyelectrolyte nanocomplex

[Display omitted] It is desirable to design nanoparticles for oral insulin delivery that can cross mucus layer and epithelial membrane in the intestine in the meantime. Thus, using chitosan (CS) as the nanocarrier, the objective of this study is to elucidate the contribution of surface hydrophilic and hydrophobic modification on the oral absorption of insulin and the essential for these two strategies combination. First of all, the polyelectronic nanocomplexes (PEC) based on synthesized CS-g-polyethylene glycol monomethyl ether (mPEG) copolymers with different mPEG graft ratios were prepared by self-assembly method and their physicochemical properties were characterized, and surface hydrophilicity and interaction with mucus were estimated. The hypoglycemic effect and pharmacological availability of the PECs following oral administration were evaluated in rats. It was found that the best absorption was achieved at mPEG graft ratio 10%. Thereafter, with newly synthesized mPEG10%-CS-glyceryl monocaprylate (GMC)10% copolymers, the added hydrophobic modification on the in vitro and in vivo properties of the mPEG10%-CS based PECs were explored. Further modification of CS-mPEG10% with GMC led to prolonged therapeutic effect but without statistical difference in pharmacological availability. In summary, this study indicated that the in vivo absorption of nanocarrier was surface property dependent, with appropriate hydrophilicity preferred over hydrophobic modification.