Intranasal Absorption

There are no data that could be used to estimate Al bioavailibility following intranasal exposure to indicate whether this represents a significant route of exposure [4], but toxicity through this route has not been reported. 

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Hussain, M.A., et al. 1989. The use of alpha-aminoboronic acid derivatives to stabilize peptide drugs during their intranasal absorption. Pharm Res 6 186. 

Hinchcliffe, M., I. Jabbal-Gill, and A. Smith. 2005. Effect of chitosan on the intranasal absorption of salmon calcitonin in sheep. J Pharm Pharmacol 57 681. 

Additional factors influencing nasal peptide absorption include particle residence time and formulation pH and osmolarity. Ohwaki et al (10) measured the effect of solution pH and osmolarity on the intranasal absorption of secretin, a 27 amino acid peptide, in rats. Nasal secretin absorption, as measured by pancreatic secretion rates, was maximal at a formulation pH of 3.0 almost eight times greater than at neutral pH. Solution osmolarity had less effect overall on secretin absorption, maximal absorption occurring in a hyperosmolar saline solution of 0.462 M. 

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. 

Bioadhesive agents, use to enhance intranasal absorption of peptides and proteins, 304... 

Aluminum enters the human organism via the gastrointestinal (water, beverages, drugs, cosmetics, foods) or respiratory apparatus (inhaled dust), by intranasal absorption to the brain, and by transdermal absorption [15]. Most of the metal is excluded by intervention of the gastrointestinal barrier and by renal function. Also, some accumulation occurs in the entire body, including brain, heart muscle, bones, and lungs (Fig. 1). 

Pontiroli et al. [76] looked at the intranasal absorption of calcitonin in normal subjects. Their study included six healthy volunteers who had no family history of endocrine or metabolic diseases. Human calcitonin (Cibacalcin Ciba-Geigy) was administered intravenously or mixed with sodium glycocholate, a surfactant, in distilled water and instilled as nose drops. Plasma concentrations of calcitonin were found to be consistently higher when compared with intranasal administration of... 

There has been a report on chitosan utility in improving the intranasal absorption of high-molecular-weight (>10-kDa) therapeutic protein. Chitosan glutamate powder blend or granules with recombinant hGH have been evaluated for intranasal administration in sheep. Relative to subcutaneous injection the nasal formulations produced bioavailabilities of 14 and 15%, respectively [77],... 

Notwithstanding these factors, the physical characteristics of compounds for optimal intranasal absorption are the same as for other absorption routes. The drug must dissolve in the fluids of the nasal mucosa and must be sufficiently lipophilic to cross the membranes of the nasal epithelium. Nasal absorption is facilitated by the high permeability of small venules and capillaries associated with the nasal mucusa. 

The thin, porous and highly vascularised nasal epithelium has a high total blood flow, which facilitates fast absorption of substances. Direct transport to the systemic circulation or the central nervous system makes it possible to obtain a rapid therapeutic effect. The intranasal absorption depends on the mucociliary clearance, pathological conditions such as infections, allergy and obstruction, mucus secretion, moisture content, enzymatic degradation, and blood flow. It should be remembered that the blood flow can be affected by either locally or systemically active substances. These phenomena can determine the nasal absorption of substances. Oxymetazoline and clonidine reduce the blood flow, while phenylephrine and salbutamol raise it. 

The mucociliary clearance rate may influence the intranasal absorption of systemically active substances. Pathological conditions and an accelerated rate of mucociliary clearance shorten the contact time between active substance and the absorbing mucosa. A delayed mucociliary clearance will have the opposite effect. Nasal hypersecretion dilutes the medicine solution and delays passive absorption. In addition it may lead to a local loss of some of the medicine due to a washout effect. A change in pH of the mucus layer may have consequences oti the ionisation of some substances, and thus on their absorption [11]. 

The quest for acceptable insulin delivery via the nasal route has not been very successful as the problems of low bioavailabilily, local irritation, and probable toxicity in long-term use are unresolved despite the huge efforts that have been made. The major problem, which seems very hard to solve, is to reach an adequate biological availability. A common concern is also that local disease, such as the common cold or chronic rhinitis, might impede the efficiency of intranasal absorption and alter the systemic availability. 

Yoshimoto J, Yagi S, Ono J, Sugita K, Hattori N, Fujioka T, Fujiwara T, Sugimoto H, Hashimoto N. Development of anti-influenza drugs H. Improvement of oral and intranasal absorption and the anti-influenza activity of stachyflin derivatives. J. Pharm. Pharmacol. 2000 52(10) 1247-1255. 

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