Alginate nanogels-based thermosensitive hydrogel to improve antidepressant-like effects of albiflorin via intranasal delivery

• Published in: Drug delivery Vol. 28; no. 1; pp. 2137 - 2149
• Main Authors: Xu, Dong, Qiao, Tao, Wang, Yue, Wang, Qiang-Song, Cui, Yuan-Lu
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2021; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Administration, Intranasal; Albiflorin nanogels; alginate; Alginates - chemistry; Animals; Antidepressants; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacokinetics; Antidepressive Agents - pharmacology; Brain - drug effects; Bridged-Ring Compounds - administration & dosage; Bridged-Ring Compounds - pharmacokinetics; Bridged-Ring Compounds - pharmacology; Chemistry, Pharmaceutical; Cytokines - drug effects; depression; Depression - drug therapy; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Carriers - chemistry; Drug Liberation; Hydrogels; intranasal delivery; Male; Mental depression; Mice; Mice, Inbred ICR; Nanogels - chemistry; Particle Size; Rats; Rats, Sprague-Dawley; Surface Properties; thermosensitive hydrogel; alginate; intranasal delivery; Albiflorin nanogels; depression; thermosensitive hydrogel
• ISSN: 1071-7544; 1521-0464
• DOI: 10.1080/10717544.2021.1986604

Depression is a primary public health problem. However, current antidepressants work slowly, and together with side effects. Herein, the alginate nanogels were constructed to load albiflorin (albiflorin nanogels), which further formed albiflorin nanogel loaded self-assembled thermosensitive hydrogel system (albiflorin-NGSTH) and were used to improve its antidepressant effects. The nanogel showed a nano-scaled particle size and stronger antioxidant activity. Rheological studies showed that albiflorin-NGSTH had a sol-gel transition at approximately 28 °C. Albiflorin-NGSTH quickly entered the brain by intranasal delivery, and had a continuously release for albiflorin. Preliminary results of mice behavioral despair tests found that albiflorin-NGSTH had no effects on independent exploratory behavior and anxiety of the mice, and significantly decreased immobility duration of the mice in tail suspension test (TST). Moreover, the intranasally administrated albiflorin-NGSTH at a low dose improved depressive behavior, decreased levels of proinflammatory cytokines, and repaired neuronal damage of chronic unpredictable mild stress (CUMS) rats, which indicated an excellent potential for depression therapy. The treatment of albiflorin-NGSTH on depressive disorder was achieved by regulating signal pathway related to depression. Therefore, albiflorin-NGSTH has an excellent potential for clinical application in intranasal drug delivery systems.