## 5 Chitosan Nanocarriers in Brain Targeting
### Emulsions
Values for DTE (Drug Targeting Efficiency) % indicate that the drug loaded microemulsion increased the brain drug targeting by a 7-fold after intranasal administration when compared to the intranasal drug solution in vivo. The high viscosity of the formulation and the addition of chitosan aspartate induced the opening of tight junction resulting by a 7.6-fold and the use of cyclodextrin further increased the DTE by 8.6-fold. The size of the microemulsion droplets was less than the size of the axons in the _filia olfactoria_ and hence, their uptake into the neurons was by endocytic mechanisms through the intra-axonal route [107]. The addition of cyclodextrin to chitosan carriers has the potential to enhance the pharmacokinetics, pharmacodynamics, stability, and brain uptake of the formulation. Similar research reports indicated the aforementioned properties when cyclodextrin are employed in drug delivery systems [108; 109]. Zolmitriptan is used to treat migraine but it suffers from low bioavailability after administration either by oral or nasal route. In order to enhance its bioavailability, it was incorporated into nanoemulsion formulation for targeted delivery from the nose to the brain [110]. The formulation exhibited a high permeation coefficient on the nasal mucosa than the drug solution. The high transport of the drug from the formulation to the brain was influenced by the small globule size of the formulation resulting in the drug uptake transcellularly via olfactory neurons through the endocytic pathway. The presence of chitosan enhanced the interaction between the formulation and the nasal mucosa. The interaction resulted in an extended nasal clearance time and contact time. Chitosan capability to form a hydrogen bond with the negative-charged nasal mucosa induced the opening of tight junctions with an improved drug permeation effect through the nasal mucosa [110]. Nanoemulsions loaded with kaempfer and chitosan was evaluated for their capability to induce antitumor activity against glioma cells, a deadly type of brain tumor [111]. The formulations exhibited low polydispersity index and were characterized by nanoscale droplets. The high free energy and large surface area of the nanosized droplets are attributed to the high drug permeation via the mucosal surfaces. The use of chitosan in the formulation influenced the globule size of the formulation and the positive zeta potential. The high viscosity of the formulation extended the residence time in the nasal cavity with a delay in the drug release to the mucosal surface. Ex vivo permeation studies performed on porcine nasal mucosa revealed that the permeation of the drug from the formulation was significant and higher than the permeation of the drug solution. The interaction of the formulation with the epithelial cells increased the drug absorption via the nasal mucosa. The drug permeability was influenced significantly by the coating of the nanoparticles. The formulation induced a significant decrease in cell viability. The increased cytotoxic effect of the formulation indicated a good uptake of the drug into the glioma cells resulting from the positive charge of the carrier. Nanoparticles with a positive charge exhibit better interaction with the cell membrane with a negative charge, leading to a high drug uptake and a good cytotoxic effect. The small size of the nanoparticles also facilitated the drug uptake by the cells. Chitosan facilitated the transportation of nanoparticles via absorptive mediated transcytosis. The results indicate that the formulation is a potential therapeutic for the nose to brain delivery [111]. [PERSON] et al. investigated various mucoadhesive agents such as Pluronic F127, Carbopol 934 P, Pluronic F68, chitosan, sodium alginate, and sodium CMC in emulsions containing nimodipine.