Synthesis of New Water Soluble β-Cyclodextrin@Curcumin Conjugates and In Vitro Safety Evaluation in Primary Cultures of Rat Cortical Neurons

Abstract

Self-aggregation of Curcumin (Cur) in aqueous biological environment decreases its bioavailability and in vivo therapeutic efficacy, which hampers its clinical use as candidate for reducing risk of neurodegenerative diseases. Here, we focused on the design of new Cur- β-Cyclodextrin nanoconjugates to improve the solubility and reduce cell toxicity of Cur. In this study, we described the synthesis, structural characterization, photophysical properties and neuron cell toxicity of two new water soluble β-CD/Cur nanoconjugates as new strategy for reducing risks of neurodegenerative diseases. Cur was coupled to one or two β-CD molecules via triazole rings using CuAAC click chemistry strategy to yield β-CD@Cur and (β-CD)2@Cur nanoconjugates, respectively. The synthesized nanoconjugates were found to be able to self-assemble in aqueous condition and form nano-aggregates of an average diameter size of around 35 and 120 nm for β-CD@Cur and (β-CD)2@Cur, respectively. The photophysical properties, water solubility and cell toxicity on rat embryonic cortical neurons of the designed nanoconjugates were investigated and compared to that of Cur alone. The findings revealed that both new nanoconjugates displayed better water solubility and in vitro biocompatibility than Cur alone, thus making it possible to envisage their use as future nano-systems for the prevention or risk reduction of neurodegenerative diseases.

A Review of the Role of Curcumin in Metal Induced Toxicity

“…These approaches propose various methods: the use of enhancers, compounds that promote the delivery of biologically active substances, such as the alkaloid piperine [65]; CUR incorporation into liposomes [66]; phospholipids loaded with CUR [67]; the use of analogs that have structural and pharmacological similarities of CUR [68]; and CUR incorporation into nanoparticles [69,70] (Figure 4). Moreover, remarkable results have been achieved by combining CUR in complexes with cyclodextrins [71] or phosphatidylcholine [10,72]. Integrating CUR into various nanosystems is the most promising and producti technique to improve the biological activity of poorly water-soluble CUR.…”