Bioadhesive interaction and hypoglycemic effect of insulin-loaded lectin-microparticle conjugates in oral insulin...

Biodegradable microparticles were prepared with alginate by the piezoelectric ejection process, and lectin (wheat germ agglutinin, WGA) was conjugated to alginate microparticles to take advantage of the protective effects of alginate microparticles and the mucoadhesive properties of WGA for improved oral delivery of insulin. Their specific interaction with model mucin was determined by pig mucin (PM) immobilized surface plasmon resonance (SPR) biosensor and in vitro adsorption studies. The hypoglycemic effects of alginate and WGA-conjugated alginate microparticles were examined after oral administration in streptozotocin-induced diabetic rats. The alginate microparticles were fabricated by ejecting alginate/insulin solution into 0.1 M CaCl2 solution through a nozzle actuated by the piezoelectric transducer. The WGA was conjugated to alginate microparticles by activating hydroxyl groups with carbonyldiimidazole (CDI). The affinity constant (K(A)) of alginate-WGA microparticles from the SPR data (K(A)=5.455 g(-1) L) was about nine times greater than alginate microparticles (K(A)=0.628 g(-1) L). In vitro experiments in the mucin solution showed that the conjugated WGA enhanced the interaction about three times. In vivo studies with diabetic rats showed that the blood glucose level of SPF rats was lowest when alginate-WGA microparticles were orally administered. Larger K(A) of alginate-WGA microparticles resulted in larger glucose change (%) from base level. Still, it is not clear whether the transport of insulin through the intestinal mucous membrane was influenced by the increase of residence time at intestinal membrane through the specific adsorption of WGA-conjugated microparticles. However, it is concluded that alginate-WGA microparticles enhance the intestinal absorption of insulin sufficient to drop the glucose level of blood.