# Nanocarriers-Assisted Nose-to-Brain Delivery of Levodopa: Current Progress and Prospects
## 6 Nose-to-Brain Delivery of L-DOPA
### Polymeric Nanoparticles for Nose-to-Brain Delivery of L-DOPA
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Nano-Carrier System** & **Size/Zeta Potential** & **Active Targeting** & **Scientific Result** & **Reference** \\ \hline N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N-trimethyl-6-O-glycol chitosan nanoparticles & 72.0 \(\pm\) 5.0 nm/ +40.5 \(\pm\) 2.1 mV & n.a. & \begin{tabular}{c} 17-fold higher maximum \\ plasma concentration \\ of dopamine \\ \end{tabular} & [22] \\ \hline Chitosan nanoparticles & 553 \(\pm\) 52 nm/ +46.2 \(\pm\) 2.3 mV & n.a. & \begin{tabular}{c} Twice increased \\ bioavailability \\ of L-DOPA \\ \end{tabular} & [70] \\ \hline Chitosan nanoparticles & 164.5 \(\pm\) 3.4 nm/ +28.3 mV & n.a. & \begin{tabular}{c} Improved recovery of \\ dopamine in the brain \\ \end{tabular} & [171] \\ (in in situ gelling Poloxamer 407 base & +28.3 mV & n.a. & \begin{tabular}{c} Improved recovery \\ dopamine in the brain \\ \end{tabular} & [174] \\ or simple aqueous suspension) & 187.3–210.4 nm/ +2.90 to \(-\)38.1 mV & n.a. & \begin{tabular}{c} Improved \\ mucoadhesive properties \\ \end{tabular} & [174] \\ \hline Chitosan-thioglycolic acid conjugated nanoparticles into in situ gelling Poloxamer 407 base & 222.6 nm/ +27.91 mV & n.a. & \begin{tabular}{c} Enhanced \\ brain bioavailability \\ \end{tabular} & [175] \\ \hline Chitosan nanoparticles into in situ & 109.9 \(\pm\) 1.30 nm/ +26.36 \(\pm\) 2.58 mV & n.a. & \begin{tabular}{c} Simultaneous delivery \\ of L-DOPA and selegiline \\ to the brain; \\ improved effects on the \\ motor functions \\ \end{tabular} & [176] \\ \hline Sodium hyaluronate and chitosan microparticles (nasal powder) & 10–40 \(\upmu\)m/n.a. & n.a. & \begin{tabular}{c} Controlled in vitro drug \\ release; higher in vitro \\ permeation rate \\ \end{tabular} & [177] \\ \hline Chitosan nanoparticles & 62.18 nm/n.a. & n.a. & \begin{tabular}{c} Simultaneous delivery of \\ L-DOPA and selegiline to \\ the brain \\ \end{tabular} & [178] \\ \hline Polylactic acid/ + & Average pore sizes +100–200 \(\upmu\)m/n.a. & n.a. & \
\begin{tabular}{c} Controlled drug release \\ for 14 days \\ \end{tabular} & [179] \\ \hline Gelatin microspheres & 16.2 \(\pm\) 4.2 \(\upmu\)m/n.a. & n.a. &
\begin{tabular}{c} Extended in vitro \\ drug release \\ \end{tabular} & [170] \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Polymeric nanocarriers for nose-to-brain delivery of L-DOPA. Among all nanotechnological attempts for nose-to-brain delivery of L-DOPA, the ones based on polymeric carriers are prevalent. Indeed, polymeric nanoparticles offer the most advantages with respect to nasal drug delivery, including drug stabilization, mucoadhesion, optional in situ gelling properties, permeation enhancement, and vast opportunities for functionalization. Still, polymeric nanomaterials are considered challenging for clinical translation mostly for two reasons as follows: (1) the low reproducibility and difficulty achieving consistency in the particles' parameters between batches, and (2) the purification from toxic intermediates. Therefore, we would like to emphasize the fact that the reported in vitro and pre-clinical results are only one of the aspects to be considered for stepping toward a clinical trial. No less important are the simplicity of the production methodology and the eco-friendly initiative [184; 185].