Journal of Alzheimer’s Disease 59 (2017) 961–974 DOI 10.3233/JAD-160355 IOS Press 961 Development of Nasal Lipid Nanocarriers Containing Curcumin for Brain Targeting Gustavo Richter Vaz a , Gabriela H¨ adrich a , Juliana Bidone b , Jamile Lima Rodrigues a , Mariana Corrˆ ea Falkembach a , Jean-Luc Putaux c,d , Mariana Appel Hort a , Jos´ e Maria Monserrat e , Antˆ onio Sergio Varela Junior g , Helder Ferreira Teixeira b , Ana Luiza Muccillo-Baisch a , Ana Paula Horn f and Cristiana Lima Dora a,∗ a Laborat´ orio de Nanotecnologia Aplicada ` a Sa ´ ude, Programa de P´ os-Gradua¸ c˜ ao em Ciˆ encias da Sa ´ ude, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil b Laborat´ orio de Desenvolvimento Galˆ enico, Programa de P´ os-gradua¸ c˜ ao em Ciˆ encias Farmacˆ euticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil c Universit´ e Grenoble Alpes, Centre de Recherches sur les Macromol´ ecules V´ eg´ etales, Grenoble, France d CNRS, Centre de Recherches sur les Macromol´ ecules V´ eg´ etales, Grenoble, France e Instituto de Ciˆ encias Biol ´ ogicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil f Laborat´ orio de Neurociˆ encias – Instituto de Ciˆ encias Biol ´ ogicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil g Laborat´ orio de Reprodu¸ c˜ ao Animal Comparada – Instituto de Ciˆ encias Biol ´ ogicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil Accepted 1 June 2017 Abstract. Background: Curcumin (CUR) has properties that can be useful for the treatment of Alzheimer’s disease. Such properties are the inhibition of amyloid--protein (A) aggregation, A-induced inflammation, and activities of -secretase and acetyl- cholinesterase. However, previous studies have revealed that CUR exhibited low bioavailability and difficulties in reaching the brain. Objective: To overcome such drawbacks, this study aims at developing nasal lipid nanocarriers loaded with CUR to effectively target the brain. Methods: The lipid nanocarriers (NE) were prepared using the hot solvent diffusion associated with the phase inversion temperature methods. Physico-chemical and morphological characterizations and in vitro drug release of the nanocarriers were carried out. The CUR permeation/retention was analyzed in Franz-type diffusion cell using porcine nasal mucosa. Confocal laser scan and histopathological studies were also performed. Results: The results showed that the NE sizes ranged between 18 nm and 44 nm with negative zeta potential. The CUR content ranged from 0.24 to 1.50 mg/mL with an encapsulation efficiency of 99%. The profiles of CUR release indicated a biphasic kinetics. CUR-NE permeation across the porcine nasal mucosa was higher when compared to free CUR. These results have also been validated through an analysis on a confocal microscopy. In addition, no toxicity on the nasal mucosa has been observed in a histopathological analysis. Conclusion: These results suggest that it is possible to develop NEs with a high content of CUR and small particle size. Such an encapsulation increases the potential of CUR permeation across the porcine nasal mucosa. Keywords: Antioxidant, brain targeting, curcumin, degenerative diseases, diffusion cell Franz-type, intranasal route, lipid nanocarrier ∗ Correspondence to: Cristiana Lima Dora, Laborat´ orio de Nanotecnologia Aplicada ` a Sa´ ude, Programa de P´ os-Graduac ¸˜ ao em Ciˆ encias da Sa´ ude, Universidade Federal do Rio Grande (FURG), Av. It´ alia, km 8, Campus Carreiros, Rio Grande, RS 96210-900, Brazil. Tel.: +55 53 32935313; E-mail: cristianadora@ gmail.com. ISSN 1387-2877/17/$35.00 © 2017 – IOS Press and the authors. All rights reserved