## 5 Chitosan Nanocarriers in Brain Targeting
### Liposomes
The electrostatic interactions of the formulation with the negative sialic acid of mucins increased the mucoadhesion and extended the residence of the formulation in the nasal cavity, and hence enhanced the brain uptake [116]. In a similar report by [PERSON] et al., chitosan-coated anionic liposomes were prepared as liquid and powder formulations for nose-to-brain delivery of phrelin. The coated liposomes powder formulation adhesion to mucins was significant with a high drug-entrapment efficiency and enzymatic protection against trypsin. The in vitro study of the formulation from a UDS (unit-dose system) aerosol on artificial nasal cavity indicated that the total recovered drug was 23% in the nasal valves section, 25% in the turbinates section, 0% in the rhinpharynx and filter sections, and 52% in the olfactory region. The high drug recovery in the olfactory region, a site for the transportation of drug to the central nervous system, suggests that chitosan-coated liposomes are suitable for a nose-to-brain delivery. However, it is important to indicate that the nasal cast is not suitable for the evaluation of mucociliary clearance mechanism [118]. [PERSON] et al. developed intranasal liposomes loaded with fexofenadine, a drug used to treat allergic rhinitis. The liposomes and the drug loaded liposomes exhibited small lipid vesicles of 359 nm. They exhibited a narrow size distribution. Coating the surface of the liposomes with chitosan enhanced their stability at storage of 4 \({}^{\circ}\)C. A 3-fold higher adsorption of mucin was significant in the liposomes  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Drug** & **Composition** & \begin{tabular}{c} **Physicochemical** \\ **Properties** \\ \end{tabular}  & **Biological Outcome** & **References** \\ \hline \multirow{6}{*}{Ghrelin} & \multirow{6}{*}{Chitosan} & \begin{tabular}{c} Particle size range of \\ 146.9 \(\pm\) 2.7 to \\ 194 \(\pm\) 6.1 nm, for \\ uncoated and coated \\ liposomes, respectively. \\ The potential in the \\ range of 0.3 \(\pm\) 1.2 mV \\ to 6 \(\pm\) 0.4 mV \\ \end{tabular}  & \begin{tabular}{c} Increased mucoadhesion and \\ extended residence time of the \\ formulation in the nasal cavity, \\ and hence enhanced \\ brain uptake \\ \end{tabular}  & \multirow{6}{*}{[116]} \\  & \multirow{6}{*}{Chitosan} & \begin{tabular}{c} Particles size of \\ 195–263 nm, zeta \\ potential range of \\ +5–9 MV, \\ \end{tabular}  & \begin{tabular}{c} In vitro study of the formulation \\ from a USB aerosol on artificial \\ nasal cavity indicated that the \\ total recovered drug was 23% in \\ the nasal valves section, 25% in \\ the turbinates section, 0% in the \\ rhinpharynx and filter sections, \\ and 52% in the olfactory region \\ \end{tabular}  & \ \begin{tabular}{c} In vitro study of the formulation \\ from a USB aerosol on artificial \\ nasal cavity indicated that the \\ total recovered drug was 23% in \\ the nasal valves section, 25% in \\ the turbinates section, 0% in the \\ rhinpharynx and filter sections, \\ and 52% in the olfactory region \\ \end{tabular}  & \begin{tabular}{c} 3-fold higher adsorption of mucin \\ in the liposomes coated with \\ chitosan. Extended time in the \\ nasal cavity when compared to the \\ uncoated liposomes. Improved \\ bioavailability of fexofenadine. \\ Reduced mucociliary clearance \\ and increased drug retention in \\ the nasal cavity. \\ \end{tabular}  & \multirow{6}{*}{[119]} \\  & \multirow{6}{*}{[120]} \\  & \multirow{6}{*}{[121]} \\  & \multirow{6}{*}{[122]} \\  & \multirow{6}{*}{[123]} \\  & \multirow{6}{*}{[124]} \\  & \multirow{6}{*}{[125]} \\  & \multirow{6}{*}{[126]} \\  & \multirow{6}{*}{[127]} \\  & \multirow{6}{*}{[128]} \\  & \multirow{6}{*}{[129]} \\  & \multirow{6}{*}{[128]} \\  &  
coated with chitosan, indicating their capability to be retained for an extended time in the nasal cavity when compared to the uncoated liposomes. The bioavailability of fxofenadine increased by 34% after the administration of the chitosan coated formulation via the nasal route.