Insulin cyclodextrin effects

Shao, Z., et al. 1994. Cyclodextrins as mucosal absorption promoters of insulin. II. Effects of beta-cyclodextrin derivatives on alpha-chymotryptic degradation and enteral absorption of insulin in rats. Pharm Res 11 1174. 

Shao, Z., Li, Y., Chermak, T., and Mitra, A. K., 1994a, Cyclodextrins as mucosal absorption promotors of insulin, n. Effects of P-cyclodextrin derivatives on a-chymotryptic degradation and enteral absorption ofinsulin in rats, Pharm. Res. 11 1174—1179. 

Another type of absorption enhancer, which has been shown to have a better safety profile, is cyclodextrin (CD) [39]. CDs have been shown to form inclusion complexes with lipophilic drugs, thereby improving their aqueous solubility and stability. A powdered insulin formulation containing dimethyl-(3-cyclodextrin improved the absolute bioavailability of insulin by 13% in rabbits compared to a control liquid formulation (1%) of insulin with dimethyl-(3-cyclodextrin [40]. Recently, hydroxypropyl (3-cyclodextrin has been shown to be more effective for enhancing the nasal absorption of acyclovir than a range of other absorption enhancers in vivo [41]. 

Schipper, N.G.M., et al. 1993. Nasal insulin delivery with dimethyl- 3-cyclodextrin as an absorption enhancer in rabbits-powder more effective than liquid formulations. Pharm Res 10 682. 

Merkus, F.W., et al. 1991. Absorption enhancing effect of cyclodextrins on intranasally administered insulin in rats. Pharm Res 8 588. 

Ahsan, F., et al. 2003. Effects of permeability enhancers, tetradecylmaltoside and dimethyl-beta-cyclodextrin, on insulin movement across human bronchial epithelial cells (16HBE14o ). Eur J Pharm Sci 20 27. 

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. 

Tokihiro, K. Irie, T. Uekama, K. Varying effects of cyclodextrin derivatives on aggregation and thermal behavior of insulin in aqueous solution. Chem. Pharm. Bull. 

Irie, T., Wakamatsu, K., Arima, H., Aritomi, H., and Uekama, K., 1992, Enhancing effects of cyclodextrins on nasal absorption of insulin in rats, Int J. Pharm. 84 129-139. 

Zhang N, Li J, Jiang W, Ren C, li J, Xin J, Li K. Effective protection and controlled release of insulin by cationic p-cyclodextrin polymers from alginate/chitosan nanoparticles. Int J Pharm. 2010 393(l-2) 213-9. 

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