Nasal drug delivery insulin

Pereswetoff-Morath,L.,and Edman, P. (1995),Dextran microspheres as a potential nasal drug delivery system for insulin—in vitro and in vivo properties, Int. J. Pharm., 124, 37 14. 

Inhalable drug delivery At present, there are many drugs that are applied through the nasal pathway (inhalable drug delivery [IDD]). Besides small molecules (such as hormones), even much larger molecules (such as insulin and other proteins) have been reported as useful IDD systems. However, they need to meet certain critical demands ... 

Parenteral administration is not perceived as a problem in the context of drugs which are administered infrequently, or as a once-off dose to a patient. However, in the case of products administered frequently/daily (e.g. insulin to diabetics), non-parenteral delivery routes would be preferred. Such routes would be more convenient, less invasive, less painful and generally would achieve better patient compliance. Alternative potential delivery routes include oral, nasal, transmucosal, transdermal or pulmonary routes. Although such routes have proven possible in the context of many drugs, routine administration of biopharmaceuticals by such means has proven to be technically challenging. Obstacles encountered include their high molecular mass, their susceptibility to enzymatic inactivation and their potential to aggregate. 

J. Wang, Y. Tabata, and K. Morimoto. Aminated gelatin microspheres as a nasal delivery system for peptide drugs Evaluation of in vitro release and in vivo insulin absorption in rats. J Control Release 113 31-37 (2006). 

The nasal application of drugs is an area of growing interest (21) and a number of publications has shown that simple molecules as well as more complex species (eg calcitonin, insulin etc) can be well absorbed by this route, either directly or in the presence of so-called absorption enhancers. One problem with such materials could be too rapid clearance of the delivery system from the nasal cavity through the efficient action of the mucociliary system. For this reason Ilium has considered the use of microsphere systems. 

With the advent of new biotechnological techniques endogenous compounds like insulin, buserelin or octreotide have become available at affordable prices. All of these substances still have to undergo needle application. Until today the development of alternative delivery systems for the nasal, buccal, peroral, rectal and pulmonary routes for the administration of those class III drugs according to the biopharmaceutics classification system (BCS) (Amidon et al. 1995) could not keep pace with this development of endogenous compounds or is not economic enough for the health care payers (e.g. insulin application via the pulmonary route). 

Chitosan is a linear cationic polysaccharide made up of copolymers of glucosamine and A-acetylglucosaminc. It is commercially obtained by alkaline deacetylation of chitin [53, 68] and has been used for the nasal delivery of a number of drugs. The usefulness of chitosan in the enhancement of nasal absorption was reported first by Ilium [69]. Later, Ilium and his group also published experimental results indicating that solution formulations with 0.5% chitosan promoted the absorption of nasally administered insulin in rat and sheep [70]. 

Varshosaz, J., Sadrai, H., and Heidari, A. (2006), Nasal delivery of insulin using bioadhesive chitosan gels, Drug Deliv., 13, 31-38. 

Among the cyclodextrins, the use of DMpCD was shown to have the highest effect on the transnasal bioavailability of insulin in rats. Several studies reported on their concentration-dependent effect. Besides for peptides, the methylated p-cyclodextrins have shown to be useful in nasal delivery of lipophilic drugs. The toxicological profile of dimethyl p-cyclo-dextrins and of randomly methylated p-cyclodextrins appeared excellent. Attention should be paid, if possible, onbioavailability differences between animal and human models. 

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