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Microspheres As A Nasal Delivery System For Peptide Drugs
Published 1992 · Chemistry
Abstract Microspheres of starch and dextran, cross-linked with epichlorohydrine, function as an enhancer system for the absorption of insulin in rats. The effect on the glucose level is rapid and maximal reduction of plasma glucose is seen within 30–40 min. Starch microspheres are more effective than dextran spheres in inducing a decrease in blood sugar. The starch microspheres have been evaluated from a toxicological point of view in rabbits. The spheres were administered 2 times per day for 8 weeks and in two dosages, 10 and 20 mg. Scanning electron microscopy of the nasal mucosa showed no alterations. The only finding observed in light microscopy was a small hyperplasia in the septum wall. A preliminary test on healthy volunteers with starch microspheres given nasally for 1 week shows good acceptability. A temporary widening of the tight junctions in a monolayer of human epithelial (Caco2) cells was seen in the presence of dry starch microspheres. The widening of the tight junctions coincided with the increased absorption rate of insulin. A conceivable hypothesis with regard to the mechanism of action of DSM can be that the epithelial mucosa is dehydrated, with a reversible “shrinkage” of the cells, thus giving a physical separation of the intercellular junctions.