Nanoformulation of Brain‐Derived Neurotrophic Factor with Target Receptor‐Triggered‐Release in the Central Nervous System

Abstract

Brain-derived neurotrophic factor (BDNF) is identified as a potent neuroprotective and neuroregenerative agent for many neurological diseases. Regrettably, its delivery to the brain is hampered by poor serum stability and rapid brain clearance. Here, a novel nanoformulation is reported composed of a bio-compatible polymer, poly(ethylene glycol)--poly(L-glutamic acid) (PEG-PLE), that hosts the BDNF molecule in a nanoscale complex, termed here Nano-BDNF. Upon simple mixture, Nano-BDNF spontaneously forms uniform spherical particles with a core-shell structure. Molecular dynamics simulations suggest that binding between BDNF and PEG-PLE is mediated through electrostatic coupling as well as transient hydrogen bonding. The formation of Nano-BDNF complex stabilizes BDNF and protects it from nonspecific binding with common proteins in the body fluid, while allowing it to associate with its receptors. Following intranasal administration, the nanoformulation improves BDNF delivery throughout the brain and displays a more preferable regional distribution pattern than the native protein. Furthermore, intranasally delivered Nano-BDNF results in superior neuroprotective effects in the mouse brain with lipopolysaccharides-induced inflammation, indicating promise for further evaluation of this agent for the therapy of neurologic diseases.

Smart Supramolecular “Trojan Horse”‐Inspired Nanogels for Realizing Light‐Triggered Nuclear Drug Influx in Drug‐Resistant Cancer Cells

“…The flow cytometric results indicated that the internalization of SiPINGs was significantly inhibited by genistein, CPZ, amiloride, sodium azide, and 4 °C treatment (Figure S9, Supporting Information), revealing the caveolin‐, clathrin‐, and macropinocytosis‐mediated endocytosis. Meanwhile, SiPINGs presented favorable biocompatibility with low dark‐ and photo‐toxicities detected by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐ H ‐tetrazolium bromide (MTT) and flow cytometry‐based apoptosis assays (Figure c,d; Figure S8c,d and Table S1, Supporting Information), which can be credited to the biocompatible components (including PEG–PLE, silicon‐containing nanomaterials, and United States Food and Drug Administration (FDA)‐approved ICG) and the very low content of ICG (which could not cause a significant temperature increase in the cells). The results also suggested that the high intracellular local concentration of ICG had negligible influence on the cell viability.…”

Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury

“…Evacuated tubes were used to collect venous blood samples and ethylenediaminetetraacetic acid dipotassium was used as an anticoagulant. All plasma samples were processed as previously described (22)(23)(24). The plasma samples were processed in a centrifuge at 3,000 x g for 10 min at 4˚C and separated into a RNase-free tube.…”

Nanosized Delivery Systems for Therapeutic Proteins: Clinically Validated Technologies and Advanced Development Strategies

“…Recently, uniform core-shell self-assembled particles, based on poly(ethylene glycol)-b-poly(l-glutamic acid) (PEG-PLE), were proposed to stabilize and to improve BDNF delivery throughout the brain (Jiang et al, 2018).…”