## 3 Results and Discussion
### Insulin Permeation across Excised Respiratory Sheep Nasal Epithelial Tissues  
The Papp values for insulin permeation across excised respiratory sheep nasal epithelial tissues after the application of the different microparticle formulations is shown in Figure 4.  
The relatively low Papp value for insulin alone in the control group of 0.23 \(\times\) 10\({}^{-6}\) cm/s across excised respiratory sheep nasal epithelial tissues was expected because insulin is a large (5.8 kDa) hydrophilic peptide molecule with poor membrane permeation properties [41,42].  
The E + AVP emulsion microparticles exhibited a Papp value of 4.95 \(\times\) 10\({}^{-6}\) cm/s for insulin, while the AVP emulsion microparticles exhibited a Papp value of 7.91 \(\times\) 10\({}^{-6}\) cm/s for insulin. The AVP ionic gelation microparticles showed a Papp value of 6.03 \(\times\) 10\({}^{-6}\) cm/s for insulin. All 3 of the microparticle formulations showed a statistically significantly (\(p<0.05\)) higher Papp value for insulin across the excised respiratory sheep nasal epithelial tissues in comparison to that of the control group.  
As explained before, the _A. vera_ polysaccharides were previously shown to increase drug permeation across epithelial tissues by means of tight junction modulation and thereby allow for increased paracellular diffusion [21,43]. The ex vivo permeation results across the excised respiratory sheep nasal epithelial tissues showed that the microparticle formulations containing _A. vera_ polysaccharides advanced insulin delivery significantly compared to the control group. The results obtained from this ex vivo permeation study across excised  
Figure 4: Apparent permeability coefficient (Papp) values for insulin across excised respiratory sheep nasal epithelial tissues after application of the microparticle formulations and insulin alone (control group). AVP emulsion = insulin microparticle formulation prepared by emulsion-solvent evaporation consisting of _A. vera_ polysaccharides only, E + AVP emulsion = emulsion-solvent evaporation with Eudragit® L100 and _A. vera_ polysaccharide, and AVP ionic gelation = ionic gelation with _A. vera_ polysaccharide only. * Statically significantly different from the control group (\(n=6\); \(p<0.05\)). ** Statistically significant difference between AVP emulsion group and E + AVP emulsion group.  
respiratory epithelial tissues indicated that the microparticle formulations can potentially deliver insulin effectively into systemic circulation after intranasal administration. This may potentially be used for blood glucose control in diabetic patients. However, follow-up in vivo studies is needed to confirm if clinically significant plasma levels can be achieved after intranasal administration.  
Furthermore, the nasal insulin delivery results obtained from this current study on _A. vera_ polysaccharide microparticle formulations are in line with a previous study where chitosan-TBA microparticles enhanced insulin delivery [18]; however, further in vivo studies are needed to compare the absolute bioavailability of insulin from the _A. vera_ polysaccharide microparticles with that of previous microparticle formulations.