An innovative nanocarrier for neuroprotection

Abstract

In the last decades, the incidence of age-related neurodegenerative diseases (ARND) has gained relevance due to the progressive increase of average life expectancy and the limited therapeutic solutions available. The multifactorial etiology of ARND suggests the benefit of investing in the study of multi-target active compounds, such as polyphenols. Within polyphenols sources, the plants of Curcuma genus have acquired great importance mainly due to properties presented by Curcumin, a bioactive known for its anti-inflammatory and antioxidant properties recognised as valuable for the treatment/prophylaxis of ARND. However, in a first step of our research, by a multi-technique biophysical study, curcumin revealed a weak pharmacokinetic profile with low bioavailability and solubility, bioaccumulation, high affinity to human serum albumin as well as a tendency to induce membrane biophysical changes. Based on these results and to improve the benefits of curcumin in the treatment of ARND, this research aimed the encapsulation of curcumin in stealth nanocarriers (NC) of dioctadecyldimethyl-ammonium bromide (DODAB) and 1-oleoyl-rac-glycerol (MO) (1:2). The NC present high encapsulation efficiency. Also, by dynamic/electrophoretic light scattering and nanoparticle tracking analysis, the NC developed exhibited sizes lower than 200 nm, high stability when stored up to 4 months and a positive superficial charge, allowing the permeation of the blood-brain barrier by absorption-mediated transcytosis which increases their interest for biomedical purposes. An in vitro biphasic controlled release, of 94,5% of curcumin (R2=0,998) after 50 h was also observed. Furthermore, after successful PEGylation, the ability to prevent interactions with plasma proteins, was also confirmed. Moreover, by fluorescence decay of a lipophilic probe (DPH-PA) under the action of a peroxyl radical generator (AAPH) the antioxidant activity was confirmed. In undergoing assays, the effects of curcumin, empty NC and curcumin loaded NC are analysed in human dopaminergic SH-SY5Y cells using two cytotoxicity assays, dimethylthiazol diphenyltetrazolium (MTT) reduction and neutral red uptake (NR).