Insulin chitosan

Since the concentrations of insulin to be administered in the sheep model would have been large, the insulin-loaded chitosan nanoparticles were not investigated in that model. However, the pharmacodynamics and pharmacokinetics of various insulin-chitosan preparations were compared with postloaded insulin-chitosan nanoparticles. It was found that chitosan solution and chitosan powder formulations were far better, with the chitosan powder formulation showing a bioavailability of 17% as against 1.3 and 3.6% for the chitosan nanoparticles and chitosan solution [72], The effects of the concentration and osmolarity of chitosan and the presence of absorption enhancers in the chitosan solution on the permeation of insulin across the rabbit nasal mucosa in vitro and in vivo were investigated, and the same... 

Microparticles W/O emulsification solvent evaporation Insulin Chitosan-TBA In rats Improved bioavailability 93... 

Degim Z, Degim T, Acarturk F, et al. (2005). Rectal and vaginal administration of insulin-chitosan formulations An experimental study in rabbits. J. Drug. Target. 13 563-572. 

For the preparation of nanoparticles based on two aqueous phases at room temperature one phase contains chitosan and poly(ethylene oxide) and the other contains sodium tripolyphosphate. The particle size (200-1000 nm) and zeta potential (between -i- 20 mV and -l- 60 mV) could be modulated by varying the ratio chitosan/PEO-PPO. These nanoparticles have great proteinloading capacity and provide continuous release of the entrapped protein (particularly insulin) for up to one week [100,101]. 

Ohya et al. reported poly(ethyleneglycol)-grafted chitosan nanoparticles as peptide drug carriers. The incorporation and release of insulin was dependent on the extent of the reaction of poly(ethyleneglycol) with chitosan [190]. 

Surini S, Akiyama H, Morishita M, Nagai T, Takayama K. Release phenomena of insulin from an implantable device composed of a polyion complex of chitosan and sodium hyaluronate. J Controlled Release 2003 90 291-301. 

A. H. Krauland, V. M. Leitner, V. Grabovac, and A. Bernkop-Schnurch. In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. J Pharm Sci 95 2463-2472 (2006). 

Ilium et al. [49] evaluated chitosan solutions as delivery platforms for nasal administration of insulin to rats and sheep. They reported a concentration-dependent absorption-enhancing effect with minimal histological changes of the nasal mucosa in all concentrations applied. 

Another trend observed during the past decade was the coating of liposomes with mucoadhesive polymers. Liposomes are coated with chitosan, long-ehain polyvinyl alcohol, and polyacrylates bearing a cholesteryl group [90]. Chitosan-eoated liposomes showed superior adhesion properties to rat intestine in vitro than the other polymer-eoated liposomes. In vivo, chitosan-coated liposomes containing insulin substantially reduced blood glueose levels after oral administration in rats, whieh were sustained up to 12 hr after administration [90]. 

Takeuchi, H., Yamamoto, H., Niwa, T., Hino, T., and Kawashima, Y., Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes, Pharm. Res., 13 896-901 (1996). 

Femandez-Urrusuno et al. (1999) investigated the potential of chitosan (MW <50,000-130,000 DD 70-87%) nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. Nanoparticles prepared by ionotropic gelation with tripolyphosphate... 

Fernandez-Urrusuno, R., Calvo, P., Remunan-Lopez, C., Vila-Jato, J. L., and Alonso, M. J. (1999). Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm. Res. 16,1576-1581. 

FIGURE 3.2 Blood glucose concentration-time profiles in normal rats after oral administration of insulin-containing chitosan-coated liposomes, insulin-containing plain liposomes and insulin solution, and subcutaneous administration of insulin solution. Sol, solution Lip, liposomes Ch, chitosan s.c., subcutaneous. The results are expressed as the mean values. 

Wu, Z.H., et al. 2004. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice. Acta Pharmacol Sin 25 966. 

Pan, Y., et al. 2002. Bioadhesive polysaccharide in protein delivery system chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int J Pharm 249 139. 

Tozaki, H., et al. 1997. Chitosan capsules for colon-specific drug delivery improvement of insulin absorption from the rat colon. J Pharm Sci 86 1016. 

Krauland, A.H., D. Guggi, and A. Bernkop-Schnurch. 2004. Oral insulin delivery The potential of thiolated chitosan-insulin tablets on non-diabetic rats. J Control Release 95 547. 

Chitosan is a cationic polysaccharide produced from the deacetylation of chitin, a component of crab and shrimp shells [7,57,58], Chitin is composed of units of 2-deoxy-2-(acetylamino) glucose joined by glycosidic bonds that form a linear polymer. Ilium et al. [7,57,58] demonstrated the ability of chitosan to increase the bioavailability of insulin and other small peptides and polar macromolecules in different animal models. In both the sheep and rat models, the addition of chitosan at concentrations of 0.2%-0.5% to nasal formulations of insulin resulted in significant increases in plasma insulin and reductions in blood glucose. Reversibility studies indicated that the effect of chitosan on the nasal absorption of insulin... 

Chitosans 0.1%-1% Rat, sheep Calcitonin, insulin, goserelin growth hormone C, F 57-68... 

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. 

Femandez-Urrasuno, R., et al. 1999. Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm Res 16 1576. 

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. 

H. Tozaki, T. Fujita, A. Yamamoto, S. Muranishi, T. Sugiyama, A. Terabe, T. Mat-sumoto, and T. Suzuki, Chitosan capsules for colon-specific drug delivery Improvement of insulin absorption from the rate colon, Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 23 551-552 (1996). 

K. Aiedeh, E. Gianas, I. Orienti, V. Zecchi, Chitosan microcapsules as controlled release systems for insulin, J. Microencapsulation 14 567-576 (1997). 

---