## 5 Chitosan Nanocarriers in Brain Targeting
### Liposomes  
Liposomes are vesicles that can be nano- or microsize and are composed of aqueous compartment surrounded by lipid bilayers [113]. Their distinct physicochemical properties make them suitable for the loading of therapeutic agents which are either hydrophilic, lipophilic, or hydrophobic in nature [113; 114]. Hydrophilic therapeutic agents are loaded in the aqueous apartment of the liposomes and are also loaded between the external water phase and the lipid bilayer. Lipophilic or hydrophobic therapeutic agents are loaded into the lipid bilayers hydrophobic core of the liposomes [113; 114]. Furthermore, the use of cationic lipids is important for the incorporation of DNA and RNA. Liposomes offer several unique properties such as good biocompatibility, low toxicity, targeted drug delivery, and good biodegradability, etc. [114; 115]. Due to the aforementioned properties, macromolecules such as antibodies, peptides, and polymers are used to modify their surfaces in order to enhance the blood circulation and for brain-specific delivery [114; 115]. Liposomes have been developed for brain targeting (Table 4). [PERSON] et al. developed ghrelin-containing liposomes formulation coated with chitosan for administration via nasal route for the treatment of cachexia [116]. Ghre \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Drug** & **Composition** & **Physicochemical Properties** & **Biological Outcome** & **References** \\ \hline Rosmarinic acid & 0.1\% chitosan final concentration (w/v), 8.5\% oil phase (w/v), and 3:10 leithin to oil phase ratio (w/w) & High mucoadhesive property. & The extended permeation time was also significant with a high drug penetration via the porcine nasal mucosa. The nanoemulsion did not induce a cytotoxic effect on the MRC-5 cell lines, human lung fibroblast cells. & [105] \\ \hline Ropinirole & Chitosan & Globule size of 58.61, polydispersity (0.201), and viscosity (31.42 MPa). & Ex vivo study revealed drug transportation in the different parts of the Wister rat brain. & [106] \\ \hline Buspirone & Chitosan aspartate and hydroxylpropyl-\(\beta\)-cyclodextrin & The high viscosity. The size of the microorganism droplets was less than the size of the axons in the _filia olratoria_ & Increased brain drug targeting by a 7-fold after intranasal administration when compared to the intranasal drug solution in vivo. & [107] \\ \hline Zolmitriptan & Chitosan & A high permeation coefficient on the nasal mucosa and small globule size & Extended nasal clearance time and contact time. & [110] \\ \hline Kaempfer & Chitosan & Low polydispersity index. High free energy and large surface area of the nanosized droplets. Low viscosity & Extended residence time in the nasal cavity with a delay in the drug release to the mucosal surface. High permeation of the drug from the formulation. Increased cytotoxic effect of the formulation against glioma cells. & [111] \\ \hline Nimodipine & Pluronic F 127, Carbopol 934 P, Pluronic F 68, chitosan, sodium alginate and sodium CMC, Capuml MCM, Labrasol and Transcutol P & Nasal uptake of nimodipine from the microemulsion formulation followed a sustained release with maximal plasma concentration achieved over a period of 6 h. In vivo pharmacokinetic studies in rats showed a high drug uptake in the brain & [112] \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Chitosan-based emulsions for intranasal drug administration. hormone. In the body, it undergoes a rapid degradation resulting from several factors such as hepatic first-pass, plasmatic enzyme digestion, rapid renal elimination, and pH-sensitive degradation. The abovementioned factors result in its short plasmatic half-life in human plasma which is 9-13 min [117]. The coating of anionic liposomes with chitosan resulted in a significant increase in Z-average with a resultant charge of positive (6 mV).