Collation of fullerenes and carbon nanotubes with genistein for synergistic anti-Alzheimer's activity by amyloid-β deaggregation

Abstract

This research study aimed to compare the therapeutic potential of two pharmacologically-active carbon-based nanocarriers, Fullerene (C60) and Multi-wall carbon nanotubes (MWCNTs), both loaded with genistein (GEN), for their synergistic action on amyloid-β (Aβ) plaques in Alzheimer's disease. Utilizing a 32 Factorial design with Design Expert® software, the researchers optimized the formulations. The optimized batch OPC60 and OP-MWCNT displayed particle sizes of 444.02 ± 1.23 nm and 236.91 ± 1.22 nm, respectively, with excellent encapsulation efficiencies of 86.13 ± 2.68 % and 85.13 ± 2.89 %. Both formulations exhibited favourable in-vitro release profiles in brain pH (7.2), with OPC60 and OP-MWCNTs releasing 83.25 ± 0.36 % and 87.38 ± 0.49 %, respectively. Ex-vivo and in-vivo brain distribution studies on male Wistar rats demonstrated successful controlled release of GEN in the brain through intranasal administration. The formulations permeated the nasal membrane mainly via receptor-mediated endocytosis, involving scavenger receptor class B type 1 (SR-B1). Pharmacokinetic analysis yielded parameters for OPC60, including AUC0-24 of 6688 μgh/L, Cmax of 321 ± 4.67 μg, Tmax of 24 h, and T1/2 of 6.7 h. For OP-MWCNTs, the parameters were AUC0-24 of 5942 μgh/L, Cmax of 339.41 ± 2.84 μg, Tmax of 24 h, and T1/2 of 9.4 h. Both formulations showed promising potential for reversing Alzheimer's disease and could serve as viable alternatives soon. Further research is warranted to understand the mechanisms underlying their therapeutic effects and address safety and clinical translation challenges for large-scale production and medical applications.