Exploring the potential of intranasally administered naturally occurring quercetin loaded into polymeric nanocapsules as a novel platform for the treatment of anxiety

Abstract

Anxiety is one of the most prevalent forms of psychopathology that affects millions worldwide. It gained more importance under the pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/benefit ratio resulting in a shift toward active ingredients with better safety profile such as the naturally occurring quercetin (QRC). The delivery of QRC is hampered by its low water solubility and low bioavailability. The potential to enhance QRC delivery to the brain utilizing polymeric nanocapsules administered intranasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best formula displayed a particle size of 227.8 ± 11.9 nm, polydispersity index of 0.466 ± 0.023, zeta potential of − 17.5 ± 0.01 mV, and encapsulation efficiency % of 92.5 ± 1.9%. In vitro release of QRC loaded polymeric nanocapsules exhibited a biphasic release with an initial burst release followed by a sustained release pattern. Behavioral testing demonstrated the superiority of QRC loaded polymeric nanocapsules administered intranasally compared to QRC dispersion administered both orally and intranasally. The prepared QRC loaded polymeric nanocapsules also demonstrated good safety profile with high tolerability.

Natural Flavonoids and Ferroptosis: Potential Therapeutic Opportunities for Human Diseases

“…As an excellent natural product, flavonoids are beneficial to human health and have few adverse side effects. , It is important to recognize that the bioavailability of most dietary flavonoids is low, which is related to factors such as structure, glycosylation, and colonic microbial metabolism . Structural modification and novel delivery systems are common methods to improve the bioavailability and efficacy of flavonoids. − For example, phospholipon 90H complex of genistein not only improved the water solubility, dissolution rate, membrane permeation rate, and oral bioavailability of genistein but also significantly enhanced its anti-inflammatory activity . Notably, Fe 2 O 3 /Fe 3 O 4 @mSiO 2 nanoparticles of apigenin had good magnetic targeting and showed stronger antitumor activity by promoting ferroptosis in A549 cells .…”

Comparative Serum and Brain Pharmacokinetics of Quercetin after Oral and Nasal Administration to Rats as Lyophilized Complexes with β-Cyclodextrin Derivatives and Their Blends with Mannitol/Lecithin Microparticles

“…Moreover, superparamagnetic iron oxide nanoparticles have successfully enhanced Que brain exposure in healthy rats [ 25 ]. Furthermore, nanoformulations have been developed as candidates for the nose-to-brain (NTB) administration of Que [ 26 , 27 ] and more extensively evaluated in the context of in vivo studies [ 28 , 29 ]. However, despite the advantages of powders compared to nanoformulations, in terms of stability, simplicity of production, cost and ease of administration, the technology of nasal powders has not been applied in Que NTB delivery.…”

“…This approach aims to overcome these limitations and improve Que’s access to the central nervous system (CNS). In this context, we have analyzed and characterized the nasal powders of Que used in previous studies [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. More specifically, to increase Que’s aqueous solubility, lyophilized products were produced using the well-known host molecules hydroxypropyl-β-cyclodextrin (HP-β-CD) and methyl-β-cyclodextrin (Me-β-CD) as solubility enhancers [ 30 , 31 ].…”