Development of Nasal Lipid Nanocarriers Containing Curcumin for Brain Targeting

Article type: Research Article

Authors: Vaz, Gustavo Richter^a | Hädrich, Gabriela^a | Bidone, Juliana^b | Rodrigues, Jamile Lima^a | Falkembach, Mariana Corrêa^a | Putaux, Jean-Luc^{c; d} | Hort, Mariana Appel^a | Monserrat, José Maria^e | Varela Junior, Antônio Sergio^g | Teixeira, Helder Ferreira^b | Muccillo-Baisch, Ana Luiza^a | Horn, Ana Paula^f | Dora, Cristiana Lima^{a; *}

Affiliations: [a] Laboratório de Nanotecnologia Aplicada à Saúde, Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil | [b] Laboratório de Desenvolvimento Galênico, Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil | [c] Université Grenoble Alpes, Centre de Recherches sur les Macromolécules Végétales, Grenoble, France | [d] CNRS, Centre de Recherches sur les Macromolécules Végétales, Grenoble, France | [e] Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil | [f] Laboratório de Neurociências –Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil | [g] Laboratório de Reprodução Animal Comparada –Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, Rio Grande, RS, Brazil

Correspondence: [*] Correspondence to: Cristiana Lima Dora, Laboratório de Nanotecnologia Aplicada à Saúde, Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Rio Grande (FURG), Av. Itália, km 8, Campus Carreiros, Rio Grande, RS 96210-900, Brazil. Tel.: +55 53 32935313; E-mail: [email protected].

Abstract: Background:Curcumin (CUR) has properties that can be useful for the treatment of Alzheimer’s disease. Such properties are the inhibition of amyloid-β-protein (Aβ) aggregation, Aβ-induced inflammation, and activities of β-secretase and acetylcholinesterase. 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

DOI: 10.3233/JAD-160355

Journal: Journal of Alzheimer's Disease, vol. 59, no. 3, pp. 961-974, 2017