## 3 Results and Discussion
It was stated that the mucoadhesive properties of the nanoparticle and the cohesiveness of the particle polymers could be affected by the swelling index [19]. Mucoadhesive nanoparticles are expected to absorb liquid from the stomach mucosal tissue. Furthermore, swelling of the nanoparticles and the capillary effects of the mucosal tissue lead to a stronger mucoadhesion. The percent swelling of the MNS formulation is 168 \(\pm\) 15% (Figure 6). Figure 4: SEM image of nanoparticles used in this study. Figure 5: Particle size distribution of sitagliptin nanoparticles. Bioadhesion studies were then performed to investigate the mucoadhesive properties of the nanoparticles. Our data indicate that the mucoadhesion of sitagliptin nanoparticles (6.1 \(\pm\) 0.5 h) is excellent (ex vivo). The adhesion between nanoparticles and mucin (the glycoprotein predominant in the mucosal tissue) is primarily due to electrostatic forces, the functional carboxyl groups on the sitagliptin nanoparticles, and the hydrogen bonds in the mucus molecules, creating adhesive forces between the nanoparticle polymers. This characterized mucoadhesive property of the sitagliptin nanoparticles then lead to the study of sitagliptin release at the gastrointestinal tract (GIT) from the nanoparticles. However, in the control group (sitagliptin in drug solution), sitagliptin was splashed out straight away from the rat intestinal mucosa, indicating a lack of mucoadhesive property. Sitagliptin nanoparticles were then assessed for in vitro release (Figure 7). Approximately 41.5% of the total sitagliptin in mucoadhesive nanoparticles was released within the first hour of delivery, suggesting that sitagliptin was adsorbed or fused from the surface of the nanoparticles significantly at the beginning of the delivery. This could be explained by a prime \"burst effect\" in the clinical setting that facilitates the optimized nanoparticle formulation to be released, and has a fast effect in patients. Nevertheless, the sitagliptin discharged from the albumin nanoparticles was retained up to 12 h (99.1%), indicating the mucoadhesive nanoparticles have the potential for controlled drug release. On the contrary, sitagliptin was rapidly released--up to 91.5% in the first half hour from the control group. These results indicate a controlled and efficient release of the sitagliptin nanoparticles. The data obtained from this in vitro sitagliptin release from nanoparticles studies are then compared using different kinetic models, including first-order, Higuchi, [PERSON], Baker and Lonsdale, Hixson and Crowell, and Korsmeyer-Peppas [17]. A macro written graphing tool (SigmaPlot version 9.01) was used to study the mechanism of the nanoparticle drug release and the release rate. The correlation coefficient value (\(R^{2}\)) was also considered when selecting a significant model or curve fit that would best to investigate the extent of the sitagliptin release. Data suggest that Korsmeyer-Peppas model is an ideal fit, with \(R^{2}\) = 0.994 (Figure 7). According to the Korsmeyer-Peppas fit, the release of the drug, sitagliptin, from the nanoparticles, is through the polymeric matrix, and follows [PERSON]'s law of diffusion. The release pattern of mucoadhesive sitagliptin nanoparticles according to the classical [PERSON]'s diffusion, together with the initial swelling of the nanoparticles and the early drug adsorption on the surface of the nanoparticle, possibly contribute to the \"burst\" release [20]. After this \"burst\" effect, the sitagliptin release from the nanoparticle pattern is better controlled, and maintained for longer period of time. Figure 6: Swelling measurement of nanoparticle formulation. To assess the percentage drug concentration, sitagliptin suspension and MNS nanoparticles were orally ingested into Sprague-Dawley rats, as previously described. The mucoadhesiveness of the nanoparticles were examined at 30 min, 1 h, 4 h, 6 h, 8 h, and 12 h in vivo.