# Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery
## 4 Discussion  
Over the past couple of decades, pharmaceutical nanotechnology has received considerable attention and demonstrated significant potential for the development of innovative medicinal products, both for the therapy and the diagnosis of severe diseases [59]. In this work, we report a new preparation method of lipid-core PCL nanocapsules, optimizing a two-step process (self-assembly step followed by a coating step) into a one-pot technique to develop chitosan-coated nanoparticles. Moreover, we compared the pharmaceutically relevant properties in terms of physicochemical characterization, mucoadhesive properties, drug release, and permeability studies of \(\mathrm{LNC}_{\mathrm{SVT-LMWchit}}\) and \(\mathrm{LNC}_{\mathrm{SVT-HMWchit}}\) coated by chitosan with low MW and high MW, in view of a nose-to-brain administration. Polymeric nanocapsules containing poly(\(\epsilon\)-caprolactone), capric/caprylic triglyceride, and sorbitan monostearate, and coated with chitosan, were developed. This formulation has the advantage of efficiently encapsulating lipophilic drugs such as simvastatin [34; 35]. The production of positively-coated lipid-core nanocapsules in one step, avoiding the use of non-ionic surfactants in the aqueous phase, is the main novelty of this approach. Previously, we developed mucoadhesive amphiphilic nanocapsules based on a blend of PCL and poly(methyl methacrylate-b-2-(dimethylamino)ethyl methacrylate) for the nose-to-brain delivery of olanzapine. Nevertheless, the self-assembly of the nanocapsules by using this block copolymer (positive surface) avoids the use of sorbitan monostearate in the formulation. Indeed, the cores of those nanocapsules are composed exclusively of medium-chain triglycerides [29]. Sorbitan monostearate dispersed in core of the lipid-core nanocapsules has been demonstrated to provide  
Figure 7: Histopathological sections of rabbit nasal mucosa after 4 h of permeation test in Franz-type diffusion cells treated with (**A**) PBS pH 6.4 (negative control), (**B**) SVT, (**C**) \(\mathrm{LNC}_{\mathrm{SVT-LMWchit}}\), and (**D**) \(\mathrm{LNC}_{\mathrm{SVT-HMWchit}}\). Sections are stained with hematoxylin and eosin. an addition diffusional barrier to control the drug release, and an increase of the rigidity of the nanocapsules polymer wall [34; 36]. Furthermore, a comparative study conducted with polymeric nanocapsules demonstrated that the presence of sorbitan monostearate instead of sorbitan monooleate in the core improved the anti-apoptotic and antioxidant effects of melatonin during bovine embryo development [60]. In the present development, it was possible to obtain in a one-step process, lipid-core nanocapsules incorporating sorbitan monostearate in the oily core, and decorated on the surface with chitosan, providing mucoadhesion and penetration-enhancing properties that appear to be fundamental for nose-to-brain delivery [21]. The combination between the composition and the interfacial deposition of the pre-formed polymer method produced nanocapsules with adequate particle sizes and narrow size distributions, as was confirmed by complementary techniques such as laser diffraction, DLS, and NTA. Besides that, coating the nanocapsules with chitosan with different molecular weights (21 kDa and 152 kDa) influenced their pharmaceutical properties. For example, chitosan molecular weight and viscosity in water affected the sizes of the nanoparticles. In fact, particle size could be reduced by using lower molecular weight chitosan [61; 62]. Actually, for LNC\({}_{\text{SVT-HMWchit}}\), the higher mean particle hydrodynamic diameter could be attributed to the lengths of the chains of chitosan present on the particle surface, possibly expanding the water hydration shell of the nanoparticle. In addition, low-MW chitosan has been reported to have a higher aqueous solubility, and this, together with shorter polymer chains, contributes to forming smaller particles compared to high-MW chitosan [63].