In-vitro studies of curcumin encapsulated mesoporous Fe-Phenanthroline nanocluster for reduction of amyloid β plaque

Abstract

The etiology of Alzheimer's disease (AD) is attributed to the overproduction and accumulation of misfolded amyloid-β (Aβ) protein. Presently accessible drugs for AD only suppress the symptoms for a limited period of time, thereby limiting the efficacy of current therapies. Therefore, nanoformulation of potential therapeutics in AD, that can be more efficacious and that have limited off target effects and that are less toxic are warranted. In the current study, we engineered Curcumin (Cur) encapsulated NIP (within pores of average size 2.443 nm) which forms NCIP having size 48.86 ± 2.275 nm, spherical morphology and partially crystalline in nature. The novelty in this formulation is that for the first time we are reporting its nanoformulation and its use in the reduction of Aβ Plaque. Also it has the ability to cross the Blood Brain Barrier. We assessed the potentiality of a fluorescent NCIP in reducing Aβ plaques using an in-vitro AD model. We evaluated the anti-inflammatory effects of these Cur based nanoformulations by assessing the pro-inflammatory cytokines levels in the culture milieu. We noticed, NCIP is able to reduce Aβ plaque formation by 51.4% accompanied by significant percentage decline in Tumor Necrosis Factor- α (TNF-α; 93.4%), Apolipoprotein E (APOE; 90.4%) and Interleukin 8 (IL-8; 90.7%) expression respectively as compared to the untreated control. Our novel nanoformulation possesses significant anti-inflammatory properties and has potential therapeutic utility in AD. Additionally, the NCIP nanoformulation enables the utilization of the nutraceutical “Curcumin” as an effective therapeutic and circumvents the limitations of its utility due its poor solubility in water.