Development and in-vivo evaluation of insulin-loaded chitosan phthalate microspheres for oral delivery

Novel chitosan phthalate microspheres containing insulin were prepared by emulsion cross‐linking technique. The feasibility of these microspheres as oral insulin delivery carriers was evaluated. The pH‐responsive release behaviour of insulin from microspheres was analysed. The ability of chitosan phthalate‐insulin microspheres to enhance intestinal absorption and improve the relative pharmacological availability of insulin was investigated by monitoring the plasma glucose and insulin level of streptozotocin‐induced diabetic rats after oral administration of microspheres at insulin dose of 20 IU kg−1. In simulated gastric fluid (pH 2.0), insulin release from the microspheres was very slow. However, as the pH of the medium was changed to simulated intestinal fluid (pH 7.4), a rapid release of insulin occurred. The relative pharmacological efficacy for chitosan phthalate microspheres (18.66 ± 3.84%) was almost four‐fold higher than the efficacy of the chitosan phthalate‐insulin solution administration (4.08 ± 1.52%). Chitosan phthalate microspheres sustained the plasma glucose at pre‐diabetic level for at least 16 h. These findings suggest that the microsphere is a promising carrier as oral insulin delivery system.