Journal Article

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

Song, Xu-Jiao, Gao, Li-Na, Chen, Yi-Bing, Wang, Qiangsong, Cui, Yuan-Lu, Dong, Qin-Wei, Xu, Dong

2023

Overview

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. Highlights Natural antioxidant quercetin-based alginate nanogels protect BDNF from oxidative damage and have a quick brain distribution. Intranasal quercetin nanogels exhibit significantly higher bioavailability compared to oral quercetin. BDNF-Quercetin nanogels in thermosensitive gel release BDNF and quercetin in a sustained and controlled manner. BDNF-Quercetin nanogels in thermosensitive gel have significant antidepressant effects on stress-induced mice and rats.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 1-Phosphatidylinositol 3-kinase / Advanced local therapies from nano-engineered implants and biomaterials / AKT protein / Alginates / Alginic acid / Analysis / Antidepressants / Antioxidants / BDNF / Bioavailability / Biocompatibility / Biotechnology / Blood-brain barrier / Brain damage / Brain-derived neurotrophic factor / Care and treatment / Chemistry / Chemistry and Materials Science / Controlled release / Corticosteroids / Depression, Mental / Depressive disorder / Drug delivery / Drug delivery systems / Drugs / Glutamatergic transmission / Health aspects / Hydrogels / Inflammation / Intranasal administration / Intranasal delivery / Kinases / Mental depression / Mental disorders / Molecular Medicine / Nanogels / Nanotechnology / Oxidative stress / Particle size / Pharmacology / Proteins / Quercetin / Rats / Reserpine / Signal transduction / Size distribution / Spectrum analysis / TrkB receptors / Vehicles