# Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery
## 3 Results
### Characterization of Nanocapsules  
SVT nanocapsules appeared macroscopically as an opalescent white homogeneous dispersion. The total SVT content in the formulations was found to be 0.94 \(\pm\) 0.04 mg\(\cdot\)mL\({}^{-1}\) for LNC\({}_{\text{SVT-LMWchit}}\) and 0.96 \(\pm\) 0.02 mg\(\cdot\)mL\({}^{-1}\) for LNC\({}_{\text{SVT-HMWchit}}\). Regarding the encapsulation efficiency (EE), SVT was not detected in the ultrafiltrate for both formulations, indicating almost complete encapsulation. The high EE achieved is probably linked to the high SVT distribution coefficient (log D) of 4.72, which confirms its great affinity for the lipophilic phase, and its concentration in the core of the nanocapsules [55]. Laser diffraction (LD) analysis showed D[4,3] of 150 \(\pm\) 7 nm (LNC\({}_{\text{LMWchit}}\)), 157 \(\pm\) 6 nm (LNC\({}_{\text{HMWchit}}\)), 163 \(\pm\) 2 nm (LNC\({}_{\text{SVT-LMWchit}}\)), and 161 \(\pm\) 3 nm (LNC\({}_{\text{SVT-HMWchit}}\)), with Span values of 1.3 \(\pm\) 0.1, 1.3 \(\pm\) 0.1, 1.4 \(\pm\) 0.03, and 1.2 \(\pm\) 0.2, respectively. According to the results obtained with this technique, there were no significant differences in terms of the particle diameter and polydispersity, between the formulations with and without SVT (\(p>0.05\)). The shapes of the curves in the radar chart presented in Figure 1 are fingerprints of the formulations, which demonstrate the narrow size distributions and confirm their low polydispersities [56]. All of the formulations showed similar behaviors and they had \(d_{0.9}\) calculated both for the cumulative distribution by number, and by a volume lower than 300 nm (Figure 1). Figure 1: Radar chart presenting the volume-weighted mean diameters (D[4,3]) and the diameters at percentiles 10, 50, and 90 under the size distribution curves by volume and by the number of particles. Chitosan-coated simvastatin-loaded lipid-core nanocapsules developed with **(A)** low-MW chitosan and **(B)** high-MW chitosan. The mean particle size was further confirmed by DLS and NTA analysis, as shown in Table 1. The DLS analysis showed a narrow particle size distribution for all of the formulations (PDI \(<\) 0.2). In particular, the encapsulation of SVT did not affect the particle size of the nanocapsules coated with low-MW chitosan. In fact, the diameters of LNC\({}_{\text{LMWchit}}\) and LNC\({}_{\text{SVT-LMWchit}}\) were not significantly different (\(p>\) 0.05). On the other hand, the presence of SVT led to a significant size increase (\(p\leq\) 0.05) in the case of LNC\({}_{\text{SVT-HMWchit}}\) (210 \(\pm\) 10 nm) when compared with the blank nanocapsules (LNC\({}_{\text{HMWchit}}\), 188 \(\pm\) 7 nm) according to the NTA analysis, but not according to the DLS data. This difference may be explained by the formation of a small number of particle agglomerates, compared to the formulation prepared without the drug. In addition, these agglomerates appeared to be detected more efficiently by the NTA technique compared to DLS. This is supported by the particle number density (PND) also measured by NTA, which evidenced, upon SVT encapsulation, almost a halving of the particle number density (PND), which was 1.1 \(\pm\) 0.4 \(\times\) 10\({}^{12}\) particles/mL for LNC\({}_{\text{HMWchit}}\) and 6.6 \(\pm\) 0.2 \(\times\) 10\({}^{11}\) particles/mL for LNC\({}_{\text{SVT-HMWchit}}\) (Table 1). Furthermore, in general, the nanocapsules coated with HMW chitosan showed a slightly higher mean diameter than those coated with LMW chitosan (\(p>\) 0.05), probably as a consequence of the higher molecular weight and higher viscosity of the chitosan in the water phase. In general, it has been reported that the higher the viscosity of the dispersion medium, the higher the mean diameter of the nanoparticles produced [57]. The zeta potentials of LNC\({}_{\text{LMWchit}}\) and LNC\({}_{\text{HMWchit}}\) were similar to those determined for the SVT-loaded nanocapsules. Therefore, the encapsulation of SVT did not significantly affect this parameter (\(p>\) 0.05).