# Nanocarriers-Assisted Nose-to-Brain Delivery of Levodopa: Current Progress and Prospects
## 7 Conclusions  
This review aimed to discover and summarize the scientific attempts and results of the nanocarrier-mediated L-DOPA intranasal administration for alternative PD therapy. The nose-to-brain drug delivery is widely recognized as a highly preferable and efficient approach in the treatment of neurological conditions. In 2018, a clinical trial in Australia focused on a nose-to-brain POD device with L-DOPA recognized the need for further research and development in order to achieve a better understanding of the pharmacokinetics following the intranasal administration of the drug and faster onset of action. Solid improvements have been achieved ever since by the use of various nano-scaled drug carriers, among which are prolonged release, improved permeability, enhanced brain uptake and bioavailability, and decreased toxicity. To date, 19 reports were found particularly on L-DOPA's implementation in intranasal formulations, above 60% of which are from the past 5 years (2020-2024). Ten of nineteen research groups have performed in vivo studies and reported positive outcomes, whereas the rest are focused on revealing the developments' potential for intranasal application based on in vitro characterization and drug stabilization. The investigations leaning on polymeric nanocarriers prevail, which is to be expected considering the low chemical stability of L-DOPA, the transmucosal transportation particularities in the nasal cavity, and the highly recommended adhesive properties of the drug-delivering units. The majority of L-DOPA-loaded polymeric nanoparticles for nose-to-brain delivery rely on poly(lactic-co-glycolic acid), chitosan, or chitosan derivatives. Only three reports of lipid-based or hybrid nanotechnologies for the intranasal delivery of L-DOPA were found, and none of the inorganic nanocarriers-assisted nose-to-brain administration of the drug. Crucial characteristics of the nano-formulations that stand out are the particles' charge (zeta potential), size, and the hydrophobicity/hydrophilicity of the vesicles; positively charged colloids have demonstrated better results and generally have gained more interest. Two attempts were found for active targeting of L-DOPA to the olfactory neurons, and those were based on functionalization with wheat germ agglutin (a lectin representative) and glutathione. Mainly two types of dosage forms are being tested for the intranasal application of L-DOPA-loaded nanocarriers--intranasal powders and in situ gelling nasal sprays. A very important and challenging aspect, beyond the nanotechnology achievable, is the development of precise devices eligible for nose-to-brain delivery of drugs, which may also be a turning point for the successful clinical implementation of intranasal L-DOPA.  
Conceptualization, M.D. and N.I.; methodology, M.D. and N.I.; investigation, M.D. and N.I.; writing--original draft preparation M.D. and N.I.; writing--review and editing, V.A.; visualization, N.I.; supervision, V.A.; project administration, V.A.; funding acquisition, V.A. All authors have read and agreed to the published version of the manuscript.  
This research received no external funding.  
Not applicable.  
No new data were created or analyzed in this study. Data sharing is not applicable to this article.  
We would like to express our gratefulness to the National program \"Young scientists and post-doctoral researchers-2\", Bulgaria.  
The authors declare no conflicts of interest.