Nasal delivery insulin

Mitra R, Pezron I, Chu WA, Mitra AK (2000) Lipid emulsions as vehicles for enhanced nasal delivery of insulin. Int J Pharm 205 127-134. 

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). 

Varshosaz, J., H. Sasrai, and R. Alinagari. 2004. Nasal delivery of insulin using chitosan microspheres. J Microencapsul 21 761. 

Aspden, T.J., L. Ilium, and O. Skaugrud. 1996. Chitosan as a nasal delivery system Evaluation of insulin absorption enhancement and effect on nasal membrane integrity using rat models. Eur J Pharm Sci 4 23. 

Dyer, A.M., et al. 2002. Nasal delivery of insulin using novel chitosan based formulations A comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles. Pharm Res 19 998. 

The nasal delivery of insulin was demonstrated as early as 1922 by Woodyatt [59]. Since then, numerous studies have focused on this methodology. Some of the early studies included absorption of insulin from the nasal mucosa in human diabetics, the use of an insulin sprayer that contained saponin, and insulin in ethylene glycol or trimethylene glycol applied to the nose in the form of drops or sprays the last... 

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]. 

Dyer, A. M., Hinchcliffe, M., Watts, P., Castile, J., Jabbal-Gill, I., Nankervis, R., Smith, A., and Ilium, L. (2002), Nasal delivery of insulin using novel chitosan based formulations A comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles, Pharm. Res., 19, 998-1008. 

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

Crystalline cellulose, hydroxypropyl cellulose, and Carbopol 934 have been studied in combination with lyophilized insulin as bioadhesive powder dosage forms for nasal delivery. Each formulation tested resulted in an decrease in plasma glucose level after nasal administration in dog and rabbit models. The most effective formulation, crystalline cellulose blended with insulin, decreased the plasma glucose level to 49% of the control value. In ternary systems the lyophilized Carbopol 934 and insulin blend with crystalline cellulose powder has been the most effective, leading to a hypoglycemia on the order of one-third of the effect obtained after intravenous injection of the same dose of insulin. The plasma glucose levels obtained in the volunteers after administration of the insulin-Carbopol-crystalline cellulose powder formulation were quite variable [38],... 

The nasal absorption of insulin after administration in chitosan powder was the most effective formulation for nasal delivery of insulin in sheep compared to chitosan nanoparticles and chitosan solution [11], Similarly, chitosan powder formulations have been shown to enable an efficient nasal absorption of goserelin in a sheep model where bioavailabilities of 20-40% were obtained depending on the nature of the formulation [9],... 

Callens, C., and Remon, J. P. (2000), Evaluation of starch-maltodextrin-Carbopol 974 P mixtures for the nasal delivery of insulin in rabbits, J. Controlled Release, 66, 215-220. 

Bjork, E., and Edman, P. (1988), Degradable starch microspheres as a nasal delivery system for insulin, Int. I. Pharm., 47,233-238. 

Ilium, L., Farraj, N. F., Fisher, A. N., Gill, I., Miglietta, M., and Benedetti, L. M. (1994), Hyaluronic acid ester microspheres as a nasal delivery system for insulin, J. Controlled Release, 29,133-141. 

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. 

Microspheres prepared from hyaluronan esters have been evaluated for the vaginal administration of calcitonin in the treatment of postmenopausal osteoporosis. Microspheres prepared from hyaluronan esters have also been used experimentally as delivery devices for nerve growth factors, and as a nasal delivery system for insulin. ... 

Therefore, several efforts on developing the nasal delivery system of insulin with nontoxic and nonirritant properties have been done. 

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