Lactoferrin-conjugated quercetin-loaded organically modified silica nanocargoes ameliorate cognitive impairment in a rat model of amnesia

Abstract

Quercetin, a naturally occurring flavonoid, exerts potential pharmacological and therapeutic effects, primarily due to its antioxidant properties and ability to mitigate cognitive impairment. However, its inadequate bioavailability, poor absorption, and rapid clearance limit its therapeutic efficacy. To overcome these limitations, we developed organically modified silica (ORMOSIL) nanoparticles conjugated with lactoferrin (LF), a glycoprotein renowned for its ability to cross the blood–brain barrier and exert neuroprotective effects. This scaffold aims to enhance quercetin delivery to the brain, ultimately improving therapeutic outcomes. This study employed a multi-faceted approach, involving the detailed characterization of nanoparticles, and in vivo assessment using a rat model to evaluate cognitive functions after scopolamine-induced amnesia. Behavioral tests, biochemical assessment, potential to inhibit the acetylcholinesterase enzyme, and histological findings collectively indicate improved efficacy of LF-Q-ORMOSIL compared to quercetin and ORMOSIL alone in an acute study. Furthermore, in vivo and ex vivo biodistribution patterns suggest better retention and increased brain targeting of the LF-conjugated formulation in the brain. Our findings demonstrate that LF-Q-ORMOSIL holds promise for enhanced delivery and therapeutic efficacy in mitigating cognitive deficits associated with neurodegenerative processes.