title: Chitosan coated nanostructured lipid carriers for brain delivery of proteins by intranasal administration.
abstract: The remarkable increase in the prevalence of neurodegenerative diseases has become a serious public health problem. Considering the lack of effective treatments to address these diseases and the difficulties in accessing the brain due to the blood-brain barrier (BBB), to attain a successful strategy to improve drug delivery to the brain, the administration route becomes a point of interest. The intranasal route provides a non-invasive method to bypass the BBB. Moreover, the development of new technologies for the protection and delivery of peptides is an interesting approach to consider. Thus, in this work, a suitable chitosan coated nanostructured lipid carrier (CS-NLC) formulation with the capacity to reach the brain after being intranasally administered was successfully developed and optimized. The optimal formulation displayed a particle size of 114 nm with a positive surface charge of +28 mV. The in vitro assays demonstrated the biocompatibility of the nanocarrier and its cellular uptake by 16HBE14o- cells. Furthermore, no haemagglutination or haemolysis processes were observed when the particles were incubated with erythrocytes, and no toxicity signals appeared in the nasal mucosa of mice after the administration of CS-NLCs. Finally, the biodistribution study of CS-NLC-DiR demonstrated an efficient brain delivery of the particles after intranasal administration. In conclusion, CS-NLC can be considered to be a safe and effective nanocarrier for nose-to-brain drug delivery; however, to obtain a higher concentration of the drug in the brain following intranasal administration, further modifications are warranted in the CS-NLC formulation.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain.
authors.forename: Oihane
authors.initials: O
authors.lastname: Gartziandia
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain.
authors.forename: Enara
authors.initials: E
authors.lastname: Herran
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Pedraz
authors.affiliation: Neuroscience Laboratory, Research Institute, Hospital 12 de Octubre, Madrid, Spain; Neurodegenerative Diseases Biomedical Research Centre (CIBERNED), Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain.
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz 01006, Spain. Electronic address: rosa.hernandez@ehu.es.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Hernandez
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D006461:Hemolysis; D006801:Humans; D008055:Lipids / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures; D011506:Proteins / Q000008:administration & dosage*
chemical_list: D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D008055:Lipids; D011506:Proteins; D048271:Chitosan
keywords: Biodistribution; Blood–brain barrier (BBB); Intranasal administration; Nanostructured lipid carrier (NLC); Neurodegenerative disorders (ND)