Insulin absorption from emulsions

The subcutaneous route for administration of insulin has many serious drawbacks, and alternative routes continue to attract considerable research interest. Nearly all available orifices of the human body seem to have gained attention as presenting possible noninvasive sites for insulin absorption. However, even by using modem enhancer techniques, only a small or minor fraction of the hormone becomes bioavailable when provided by most of these routes, except perhaps the pulmonary route. Key barriers to insulin absorption via the alternative routes are the resistance of those membranes to insulin penetration, the tendency of insulin to exist in associated form, and insulin proteolysis. Protection from proteolysis through some sort of encapsulation, the use of complex emulsion systems, and/or the use of protease inhibitors—association of the hormone with polymeric particles, and addition of permeation enhancers have been utilized to overcome those barriers. The absorption and enzymatic barriers to nonparenterally administered protein dmgs and the use of enhancers to modify absorption have been discussed in recent reviews (Lee, 1986 Lee e/a/., 1991a Zhou, 1994). The present review of alternative administration of insulin mainly covers investigations published since 1970. 

Permeation enhancers are used to improve absorption through the gastric mucosa. Eor example, oral dehvery of insulin (mol wt = 6000) has been reported from a water-in-oH- emulsion containing lecithin, nonesterified fatty acids, cholesterol [57-88-5], and the protease inhibitor aprotinin [9087-70-1] (23). 

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