Enhanced antidepressant effects of BDNF-quercetin alginate nanogels for depression therapy

Abstract

Background Brain-derived neurotrophic factor (BDNF) with neuronic development and function is a promising therapeutic agent for treating depressive disorder, according to the neurotrophin hypothesis. However, the delivery of BDNF into the brain is not easy as these large protein molecules cannot efficiently cross the blood-brain barrier (BBB) and easily suffer oxidative damage in vivo. Therefore, the quercetin-based alginate nanogels (quercetin nanogels) loaded with BDNF have been developed, which could efficiently bypass the BBB via the nose-to-brain pathway and protect BDNF from oxidative damage, providing an effective route for the therapy of depressive disorders by intranasal delivery. Results Quercetin nanogels exhibited uniform size distribution, excellent biocompatibility, and potent antioxidant and anti-inflammatory activities. Quercetin nanogels in the thermosensitive gel achieved sustained and controlled release of BDNF with non-Fick’s diffusion, exhibited rapid brain distribution, and achieved nearly 50-fold enhanced bioavailability compared to oral quercetin. Quercetin nanogels as a therapeutic drug delivery carrier exerted antidepressant effects on reserpine-induced rats, effectively delivered BDNF to reverse despair behavior in stress-induced mice, and exhibited antidepressant effects on chronic mild unpredictable stimulation (CUMS) rats. These antidepressant effects of BDNF-Quercetin nanogels for CUMS rats are associated with the regulation of the glutamatergic system, PI3K-Akt, and BDNF-TrkB signaling pathway. Conclusions In this study, we provide a promising strategy for brain delivery of BDNF for treating depressive disorders, effectively achieved through combining quercetin nanogels and intranasal administration.

Quercetin in Drug Carriers: Polymer Composite, Physical Characteristics, and In vitro Study

“…Moreover, these materials effectively reversed depressive behavior, reduced anhedonia and weight loss, as well as improved inflammatory cytokine levels and dramatic pyramidal cell damage in the hippocampal CA1 and CA3 subregions of a rat model. Quercetin nanogels also improved CUMS-induced cell apoptosis and proliferation in the hippocampal region (Xu et al, 2023) .…”

“…Increased sodium alginate concentrations reduce (Kalalo et al, 2022) ; drug loading; great promise for the combined (Xu et al, 2023) ; therapy of depressive disorder when quercetin (Szulc Musioł et al, 2023) nanogels were administered intranasally; showed favorable physico-mechanical characteristics and durability.…”

“…Hot-melt extrusion (Khor et al, 2017) Chitosan-Fluorescein Oxidative degradation and ionic (Zhou et al, 2022) ; Isothiocyanate-Zein cross-linking; coacervation (Al-Musawi et al, 2023) ; (Elmowafy et al, 2023) Sodium Alginate Aerosolization ionic gelation (Kalalo et al, 2022) ; (Xu et al, 2023) ; (Szulc Musioł et al, 2023) Inulin-Chitosan-Emulsion-assisted gelation, ionic gelation (Nalini et al, 2019) ; Sodium Alginate (Liu et al, 2022) ; (Liu et al, 2023) Glyceryl Behenate Emulsification (Chakraborty et al, 2017) ; (Rosita et al, 2022) ; (Hariyadi et al, 2022) Chitosan-Polycaprolactone Ultra-homogenization (Zhou et al, 2021) ; (Azeem et al, 2022) ; (Viscusi et al, 2023) Chitosan Ionic cross-linking (Helmy et al, 2020) ; (Wiggers et al, 2022) ; (Azeem et al, 2023) Chitosan-Alumina-Double oil in water emulsification; (Liu et al, 2017) ; PLGA-Oleic Acid gelation ionic and spray drying (Lee et al, 2018) ; (Nematollahi et al, 2021) Alginate-Hydroxyapatite Gelation method; electrostatic (Malvano et al, 2021) ; microencapsulation (Kim et al, 2022) ; (Montone et al, 2023) Eudragit S100…”

“…In vitro inflammatory cytokine levels were elevated by quercetin nanogels, which also showed protective properties against protein degradation and antioxidant activity without impairing cell viability, proliferation, or immune response. Quercetin nanogels ingested quickly spread throughout the brain in less than 30 minutes and increased the drug bioavailability by almost 50 times at a lower dosage (Xu et al, 2023) . The chemical structure of sodium alginate is shown in Figure 32, while the SEM images are presented in Figure 33.…”

Black Chokeberry (Aronia melanocarpa) Juice Supplementation Improves Oxidative Stress and Aging Markers in Testis of Aged Rats

“…There is a paucity of data in the literature on the effects of dietary polyphenols on neurotrophic factors in testes. Reports on the influence of functional foods on these factors have mainly focused on brain structure and function [55][56][57][58][59][60][61][62][63].…”