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Bile Salt–Fatty Acid Mixed Micelles As Nasal Absorption Promoters Of Peptides. II. In Vivo Nasal Absorption Of Insulin In Rats And Effects Of Mixed Micelles On The Morphological Integrity Of The Nasal Mucosa

P. Tengamnuay, A. Mitra
Published 2004 · Chemistry, Medicine

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The effectiveness of mixed micelles in promoting nasal absorption of peptides has been demonstrated in vivo by employing insulin as a model compound. Insulin in the absence of adjuvants was not absorbed following intranasal administration. The results confirmed previous findings by others that absorption of insulin via alternative routes required absorption enhancers. Mixed micelles between NaGC and linoleic acid were found to rapidly deliver insulin into systemic circulation, with a concomitant decrease in plasma glucose. The extent of the hypoglycemic response was significantly greater than that produced by NaGC alone (55 vs 47%, P < 0.05). Emulsion of linoleic acid, on the other hand, did not produce any significant insulin absorption. The findings thus supported previous in situ data that mixed micelles were more effective than NaGC or linoleic acid in promoting nasal absorption of peptides. Histopathologic examination of the rat nasal mucosa revealed that the extent of morphological alterations caused by mixed micelles was of mild to moderate severity even after 5 hr of exposure. However, studies involving more frequent and prolonged exposures are necessary to assess the practicality of these adjuvants before any clinical application can be attempted.



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