Approximately 350 million people worldwide suffer from diabetes mellitus (DM) and this
number increases yearly. Since the discovery and clinical application of insulin in 1921,
subcutaneous injections have been the standard treatment for DM. Because insulin is hydrophilic
and has a high molecular weight and low bioavailability, this molecule is poorly absorbed if
administered orally.
The aim of this study is to evaluate nasal delivery systems for insulin, using Sprague Dawley rats
as the nasal absorption model. Pheroid technology and N-trimethyl chitosan chloride (TMC)
with different dosages of insulin (4, 8 and 12 IU/kg bodyweight insulin) was administered in the
left nostril of the rat by using a micropipette. Pheroid technology is a patented (North-West
University) carrier system consisting of a unique oil/water emulsion that actively transports drug
actives through various physiological barriers. These formulations were administered nasally to
rats in a volume of 100 p/kg bodyweight in different types of Pheroids (vesicles, with a size of
1.7 1 - 1.94 pm and microsponges, with a size of 5.7 1 - 8.25 pm).
The systemic absorption of insulin was monitored by measuring arterial blood glucose levels
over a period of 3 hours. The TMC formulation with 4 IU/kg insulin produced clinically relevant
levels of insulin in the blood and as a result also the maximal hypoglycaemic effect. TMC is a
quaternary derivative of chitosan and is able to enhance the absorption of various peptide drugs
by opening tight junctions between epithelial cells. Pheroid formulations were also effective in
lowering blood glucose levels but only at higher doses (8 and 12 IU/kg) of insulin. This study
indicated that Pheroid rnicrosponges had a faster onset of action and a slightly better absorption
of insulin when compared to Pheroid vesicles, but many more studies are needed in this field.
Although the results of this study with absorption enhancers are encouraging, nasal insulin
bioavailability is still very low, and the Pheroid formulations and long-term safety of nasal
insulin therapy have yet to be investigated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/730 |
| Date | January 2006 |
| Creators | De Bruyn, Tanile |
| Publisher | North-West University |
| Source Sets | North-West University |
| Detected Language | English |
| Type | Thesis |
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