Peroral insulin delivery : new concepts and excipients

A number of chitosan derivatives were synthesized and compared to the previously synthesized derivatives for their permeation enhancing activity. Using these derivatives insulin nanoparticles were prepared and their effect was compared to the free polymer and insulin in Caco-2 cells. The results suggested that the paracellular transport of insulin across the intestinal cells was more pronounced with the free soluble polymer due to the availability of more positive charge in free soluble polymer. A novel Gas Empowered Drug Delivery (GEDD) system was then designed using CO2 force to transport insulin, Polyethylene Oxide (PEO) as well as trimethyl chitosan (TMC) to the surface of the small intestine. PEO and TMC act as mucoadhesive polymer and permeation enhancer in the system, respectively. The GEDD system is enterically coated to protect the protein against the acidic environment of the stomach. The insulin transport across the intestinal membrane has been increased up to 9 times in the ex-vivo studies in sheep__s intestine using the GEDD system. Moreover, the in-vivo results showed a 5.5 fold enhancement in comparison to free insulin in rabbits as well as a relative bioavailability of 1.1 _0.4% in compare to the s.c. injection. The GEDD system is easy to manufacture and shows promising future for peroral delivery of peptide drugs.