Insulin in rabbits

Maitani, Y., et al. 1995. The effect of soybean-derived sterol and its glucoside as an enhancer of nasal absorption of insulin in rabbits in vitro and in vivo. Int J Pharm 117 129. 

In addition, the buccal delivery of insulin in rabbits has been shown to be increased from approximately 3-5% by co-administration of edetate (least effective), sodium dextransulfate, sodium methoxysalicylate, sodium deoxycholate, sodium lauryl sulfate, sodium taurocholate and Brij 35 (most effective) with Brij 35 increasing the bioavailability of insulin to 12% by this route. 

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. 

PEGylated chitosan nanoparticles were shown to enhance insulin absorption to a greater extent compared with non-nanoparticulate forms of chitosan and insulin alone. Chitosan nanoparticles were also found to enhance nasal absorption of insulin in rabbit, regardless of chitosan molecular weight. Recently, Al-Qadi and co-workers reported that intratracheal administration of diy insulin powder microencapsulated in chitosan nanoparticles increased its distribution to the deep lungs, and facilitated release of a biologically active form of insulin to rat blood. Moreover, they observed a more pronounced and prolonged effect compared to non-formulated insulin. ... 

Nidiihata, T., Kim, S., Morishita, S., Kamada, A., Yata, N., and Higuchi, T., 1983b Adjuvant effects of glyceryl esters of acetoacetic acid on rectal absorption of insulin and insulin in rabbits, J. Pharm. Sci. 72 280-285. 

Normal Rabbits. Six male, white rabbits (2.5 - 3.0 kg) were housed individually. Animals were fasted overnight for 16 hours (with access to water) prior to each experiment to reduce the gastrointestinal content and absorption variability. After treatment with either a control dose or experimental insulin in poly(acrylic acid) resin dose, a one week washout period was required before the next experiment. The protocol called for blood samples to be taken from an indwelling ear catheter at -1, -.5, -.25, +.5, +1, +1.5, +2, +3, +4, +5 and +6 hours. Serum glucose levels were determined by an oxidase colorimetric method using the Sigma 510 Glucose Kit. 

Conjunctival insulin absorption in rabbits estimated as plasma insulin levels after punctal occlusion was also shown to be increased by bile salts (sodium deoxycholate, glycocholate, and taurocholate) and a surfactant (polyoxyethylene-9-lauryl ether) [200], Their rank order of effectiveness at 1% was sodium deoxycholate > polyoxyethylene-9-lauryl ether > sodium glycocholate = sodium taurocholate. There was an 18-, 29-, 3-, and 3-fold increase, respectively, in conjunctival absorption. Sodium deoxycholate, a dihydroxy bile salt, was more effec-... 

Hayakawa E, Yamamoto A, Shoji Y, Lee VH (1989) Effect of sodium glyco-cholate and polyoxyethylene-9-lauryl ether on the hydrolysis of varying concentrations of insulin in the nasal homogenates of the albino rabbit. Life Sci 45 167— 174. 

Hosny, E.A., et al. 1997. Hypoglycemic effect of oral insulin in diabetic rabbits using pH-dependent coated capsules containing sodium salicylate without and with sodium cholate. Pharm Acta Helv 72 203. 

Watanabe, Y., et al. 1992. Absorption enhancement of polypeptide drugs by cyclodextrins. I. Enhanced rectal absorption of insulin from hollow-type suppositories containing insulin and cyclodextrins in rabbits. Chem Pharm Bull 40 3042. 

Ichikawa, K., et al. 1980. Rectal absorption of insulin suppositories in rabbits. J Pharm Pharmacol 32 314. 

Yamamoto, A., et al. 1992. A mechanistic study on enhancement of rectal permeability to insulin in the albino rabbit. J Pharmacol Exp Ther 263 25. 

Kim, S., et al. 1983. Effect of enamine derivatives on the rectal absorption of insulin in dogs and rabbits. J Pharm Pharmacol 35 100. 

Lee, S. 2004. Noninvasive ultrasonic transdermal insulin delivery in rabbits using the light-weight cymbal array, Diabetes Technol Ther 6 808. 

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. 

Soybean-derived sterol mixture (SS), soybean-derived steryl glucosides (SG), and their individual components have been extensively studied for their ability to promote the nasal absorption of drugs, particularly insulin [79,80], Maitani et al. [79] demonstrated that the nasal administration of SG plus insulin to rabbits resulted in significant reductions in blood glucose. The effect of SG was dose dependent to 1%, with a plateau being reached thereafter. Muramatsu et al. [81] have demonstrated that SG perturbs the phospholipids in artificial membranes (i.e., liposomes). Furthermore, circular dichroism studies with insulin in the presence or absence of SG have indicated that the enhancer had little effect on the dissociation of insulin hexamers to monomers. These results suggest that the action of SS and SG involves interaction with the nasal membrane rather than interaction with insulin molecules. 

Deurloo, M.J., et al. 1989. Absorption enhancement of intranasally administered insulin by sodium taurodihydrofusidate (STDHF) in rabbits and rats. Pharm Res 6 853. 

Ando, T., et al. 1998. Nasal insulin delivery in rabbits using soybean-derived sterylglucoside and sterol mixtures as novel enhancers in suspension dosage forms. Biol Pharm Bull 21 862. 

Carstens, S., et al. 1993. Transport of insulin across rabbit nasal mucosa in vitro induced by didecanoyl-L-alpha-phosphatidylcholine. Diabetes 42 1032. 

Morimoto, K., et al. 1982. Effective vaginal absorption of insulin in diabetic rats and rabbits using polyacrylic acid aqueous gel bases. Int J Pharm 12 107. 

Sasaki, H. 1994. Effect of preservatives on systemic delivery of insulin by ocular instillation in rabbits. J Pharm Pharmacol 46 871. 

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