A Multifunctional Nanocarrier System for Highly Efficient and Targeted Delivery of Ketamine to NMDAR Sites for Improved Treatment of Depression
Jing Ge, Ronghua Tan, Qian Gao, Rui Li, Pengxin Xu, Hang Song, Shenqi Wang, Ying Wan, Lei Zhou
Advanced Healthcare Materials April 8, 2023 DOI: 10.1002/adhm.202300154 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Depressed mice |
| Topics | Depression Esketamine Ketamine |
| Key points | The AC-RM@HA-MS-KA nanoparticle system crossed the blood-brain barrier, accumulated in target brain areas, and alleviated depressive symptoms and improved cognitive function in depressed mice, which nearly returned to normal without obvious addiction symptoms. |
Abstract
Ketamine (KA), commonly used as an anesthetic, is now widely studied as an antidepressant for the treatment of depression. However, due to its side effects, such as addiction and cognitive impairment, the dosage and frequency of (S)‐ketamine approved by the FDA for the treatment of refractory depression is very low, which limits its efficacy. Here, a new multifunctional nanocarrier system (AC‐RM@HA‐MS) with specific targeting capabilities is developed to improve the efficacy of KA treatment. KA‐loaded NPs (AC‐RM@HA‐MS‐KA) are constructed with a multilayer core–shell structure. KA‐loaded mesoporous silica NPs are prepared, conjugated with hyaluronic acid (HA) as pore gatekeepers, and sheathed with an RBC‐membrane (RM) for camouflage. Finally, the surface is tagged with bifunctional peptides (Ang‐2‐Con‐G, AC) to achieve specific targeting. One peptide (Ang‐2) is acted as a guide to facilitate the crossing of the blood–brain barrier (BBB), while the other (Con‐G) is functioned as a ligand for the targeted delivery of KA to the N‐methyl‐D‐aspartate receptor sites. Animal experiments reveal that AC‐RM@HA‐MS‐KA NPs effectively cross the BBB and directionally accumulate in the curing areas, thereby alleviating the depressive symptoms and improving the cognitive functions of depressed mice. After treatment, the depressed mice almost completely return to normal without obvious symptoms of addiction.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.