Intranasal insulin

Intranasal insulin Intranasal insulin has been studied in 25 patients with Alzheimer s disease 12 received placebo and 13 received Novolin R 20 imits using a Via-nase Electronic Atomizer [29. Fasting glucose and insulin concentrations did not change, but there was a reduction in postprandial insulin concentrations in those who used insulin. At 21 days those who used insulin appeared to have improved attention compared with controls. 

F. W. Merkus, N. G. Schipper, and J. C. Verhoef. The influence of absorption enhancers on intranasal insulin absorption in normal and diabetic subjects. J Control Release 41 69-75 (1996). 

M. Hinchcliffe and L. Ilium. Intranasal insulin delivery and therapy. Adv Drug Deliv Rev 35 199-234 (1999). 

II.f.1.3. Insulin delivery. Traditionally insulin was given intramuscularly and later subcutaneously. New technology has provided devices for insulin administrations including pen-devices, air powered injectors, external insulin infusion pumps (or continuous subcutaneous insulin infusion, CSII), and implantable insulin infusion pumps. Some novel forms of insulin delivery have been introduced, for example intranasal insulin gives peak insulin concentrations at 10-20 minutes after administration, but most insulin is still administered subcutaneously. 

Receptor-mediated endocytosis may be possible because receptors have a high affinity for BDNF (Deckner et al. 1993). A linear relation between intranasal administration of -labeled NGF and brain concentrations of the compound suggest that this transportation is not mediated by receptors and that this releasing method of agents to the brain via olfactory nerves may be effective for many therapies (Frey et al. 1995). BDNF and the insulin-type growth factor (IGF-1) are currently used in clinical studies (Appel 1997). 

STDHF has also been shown to enhance intranasal delivery of insulin. The bioavailability of insulin (51 aa) formulated as a nasal drop or spray containing STDHF was 16% to 47% in healthy volunteers [22].The... 

Ixe, W.A., B.A. Narog, T.W. Patapofl) and Y.J. Wang, Intranasal bioavailability of insulin powder formulations effect of permeation enhancer-to-protein ratio. J Pharm Sci, 1991. 80(8) 725-9. 

Gizurarson S, Bechgaard E. Intranasal administration of insulin to humans. Diabetes Res Clin Pract 1991 12(2) 71-84. 

Hilsted J, Madsbad S, Hvidberg A, Rasmussen MH, Krarup T, Ipsen H, Hansen B, Pedersen M, Djurup R, Oxenboll B. Intranasal insulin therapy the clinical realities. Diabetologia 1995 38(6) 680 1. 

Lalej-Bennis D, Boillot J, Bardin C, Zirinis P, Coste A, Escudier E, Chast F, Peynegre R, Selam JL, Slama G. Efficacy and tolerance of intranasal insulin administered during 4 months in severely hyperglycaemic Type 2 diabetic patients with oral drug failure a cross-over study. Diabet Med 2001 18(8) 614-8. 

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

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

Jacobs, M.A., et al. 1993. The pharmacodynamics and activity of intranasally administered insulin in healthy male volunteers. Diabetes 42 1649. 

Thorne, R.G., et al. 2004. Delivery of insulin-like growth factor-1 to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 127 481. 

Martinez, J. A., Francis, G., Liu, W., Pradzin-sky, N., Fine, J., et al. (2008) Intranasal delivery of insulin and a nitric oxide synthase inhibitor in an experimental model of amyotrophic lateral sclerosis. Neuroscience. 

Intranasal administration of insulin-like growth factor-I bypasses the blood-brain barrier and protects against focal cerebral ischemic damage./. Neurol. Sci. 187 91-97. 

Our observation that CMC lacked the ability to increase the systemic activity of desmopressin is consistent with the findings of Morimoto et al. (13), who reported that 1% CMC failed to enhance intranasal absorption of insulin, whereas, another bioadhesive agent, polyacrylic acid gel, effectively promoted insulin absorption. As the mechanism by which bioadhesives such as polyacrylic acid gel and carboxypolymethylene promote intranasal peptide absorption remains unclear, it is not possible to explain the demonstrated lack of similar activity by CMC. 

Chitosan and its derivatives have been applied to enhance the absorption of proteins (e.g., insulin) and polypeptides (e.g., buserelin). /V-Trimethyl chitosan chloride exhibits opening of the tight junctions of the intranasal and intestinal epithelial cells so that the transport of hydrophilic compounds is increased through the para-cellular transport pathway. The absorption-enhancing effect was concentration dependent and reversible and dependent on the integrity of the intercellular cell contact zone. 

G5. Garnero, P., Tsouderos, Y., Marton, I., Pelissier, C., Varin, C., and Delmas, P. D., Effects of intranasal 17beta-estradiol on bone turnover and serum insulin-like growth factor I in postmenopausal women. J. Clin. Endocrinol. Metab. 84, 2390-2397 (1999). 

Morimoto et al. [64] studied the nasal absorption of insulin using polyacrylic acid gel. When insulin was formulated with 0.1% w/v polyacrylic acid gel base (pH 6.5), the maximum hypoglycemic effect was seen 30 min following intranasal administration in 1% w/v gel base, however, it took lh to reach the maximum effect. There was no effect of the pH (4.5, 6.5, and 7.5) of 0.1% w/v polyacrylic acid gel on the extent of nasal absorption. 

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