# 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  
[PERSON] et al. used an emulsification-solvent extraction technique to microencapsulate L-DOPA into gelatin microspheres. The resulting particles were of the size 16.2 \(\pm\) 4.2 \(\upmu\)m and were shown to prolong the drug release in comparison to non-formulated L-DOPA. The authors related the smaller diameter of the microspheres to a higher drug liberation extent. Although the study reports only preliminary in vitro results, it still stands out as the first successful attempt to achieve control over L-DOPA's liberation from a microparticulate system intended for intranasal delivery of the drug [170]. [PERSON] et al. conducted a study on Wistar rats and reported a notably higher dopamine concentration in the brain tissue when L-DOPA-loaded chitosan nanoparticles were used as drug carriers instead of a standard saline solution. The authors devoted this result to the polymer's mucoadhesive and permeation-enhancing abilities. Additionally, the nanoparticles were incorporated into a thermo-gelling system of Poloxamer 407, by which the researchers observed a lower drug release rate in vitro and an evident decrease in dopamine concentration in vivo. The latter finding was attributed to the high viscosity of the hydrogel, which limits the particles' migration and drug absorption [171]. [PERSON] et al. tested poly(lactic-co-glycolic acid) (PLGA) nanoparticles (250 \(\pm\) 50 nm) as a nose-to-brain drug delivery system of L-DOPA on Wistar rats with 6-hydroxydopamine-induced PD. The authors established the prolonged effect of the nano-formulated L-DOPA and the significantly improved motor functions in the test group in comparison to the control group receiving the L-DOPA standard solution [172]. [PERSON] et al. performed an in vivo investigation of wheat germ agglutinin (WGA)-grafted L-DOPA-loaded PLGA nanoparticles (329.0 \(\pm\) 188.3 nm; \(\zeta\) \(-\)4.47 \(\pm\) 0.576 mV) on male mice with methyl-phenyl-tetrahydrofuranyropyridine (MPTP)-induced parkinsonism by intranasal application. The authors reported an extended drug release pattern achieved by the polymeric nanocarriers and improved tissue deposition of L-DOPA, better tolerability, lower cytotoxicity, and higher clinical efficiency of the WGA-functionalized samples as compared to the non-grafted PLGA nanoparticles [173]. [PERSON] et al. formulated L-DOPA into PLGA and chitosan nanoparticles and compared the physicochemical and morphological characteristics of both types of delivery systems with respect to their potential use as nose-to-brain drug carriers. Most desirable properties were achieved by a model of chitosan nanoparticles with a droplet size of 553 \(\pm\) 52 nm, polydispersity index (PDI) of 0.522, and encapsulation efficiency of 82.38% \(\pm\) 1.63. The authors emphasized the zeta potential value of the optimal chitosan nano-formulation; the latter, being +46.2 \(\pm\) 2.3 mV, falls within the most favorable range for colloidal stability and also sets a prerequisite for electrostatic attraction of the nanocarriers to the sialic residues on the mucosal proteins and thus enhanced residence time and transnasal absorption. The in vivo experiments on Wistar rats demonstrated twice as high bioavailability of L-DOPA (measured as the area under the curve, or AUC) achieved by the chitosan nanoparticles, as compared to the standard L-DOPA solution [70]. [PERSON] et al. encapsulated L-DOPA into positively charged (+40.5 mV) N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycol chitosan (GCPQ) nanoparticles of 300 nm and obtained with them in situ disintegrable micro aggregates (7.2 \(\upmu\)m) [22]. The researchers compared the dopamine levels in the brains of rats treated intranasally with aqueous dispersions of the GCPQ microparticles and crystalline L-DOPA as a reference.