Development and evaluation of curcumin delivery systems for oral administration to improved brain health

Abstract

Curcumin is a multitherapeutic agent with great therapeutic potential in central nervous system (CNS) diseases. However, its hydrophobicity and low bioavailability hinder its application. To circumvent these drawbacks, we developed polymer-based and lipid-based curcumin nano-formulations.

This study aimed to compare the physicochemical properties, in vitro release studies, permeation studies in Caco-2 cells and antidepressant activity of polymer-based and lipid-based of curcumin nano-formulations (CNF). The curcumin solid dispersions, as a polymer-based, were developed using melting solvent method. Two formulations of curcumin solid dispersion were prepared with polyvinylpyrrolidone (PVP) as a carrier without (CSD) and with surfactant as a co-carrier (CSD-S). While curcumin loaded solid self- emulsifying drug delivery systems (C-SSEDDS), as a lipid-based, were developed using Neusilin®UFL2 as a solid carrier. All developed CNF significantly showed improvement in curcumin water solubility, > 100-folds as compared to the free curcumin. Spherical droplets of < 200 nm were obtained when CNF were diluted with water. Within 5 min, 100% of the curcumin could be released from CSD and CSD-S, whereas only 60–70% of the curcumin from C-SSEDDS could be released. Moreover, permeation studies in Caco-2 cell monolayer revealed that all formulations provided significantly greater cellular accumulation and absorption compared with the free curcumin. In addition, the physical and chemical stability of CNF was stable for at least 6-month storage at 4 ºC and room temperature.

Then, the antidepressant activities of CNF were investigated using a dexamethasone (Dex)-induced depression rat model. Results showed that Dex administration conduct to a range of depression-related behavioral traits, including anhedonia, despair, weight loss and anxiety-like behavior. All CNF given orally for 3 weeks showed an antidepressant-like effect on depressive rat model, as confirmed by the significantly higher rat body weight and sucrose consumption. Both of CSD and C-SSEDDS significantly reduced the immobility duration (p