Neurophilic Biomimetic Lipoprotein-Mediated Targeted Nerve Growth Factor Delivery for Traumatic Brain Injury Therapy

Area of Science:

• Neuroscience
• Biomaterials Science
• Drug Delivery Systems

Background:

• Traumatic brain injury (TBI) causes neuronal death and dysfunction.
• Nerve growth factor (NGF) shows neuroprotective potential but faces delivery challenges.
• Poor blood-brain barrier (BBB) permeability and targeting limit NGF's clinical application.

Purpose of the Study:

• To develop a brain-targeted drug delivery system for NGF.
• To overcome BBB penetration and neural targeting limitations for TBI treatment.
• To create a neurophilic biomimetic lipoprotein for enhanced NGF delivery.

Main Methods:

• Engineered a biomimetic lipoprotein with a core preserving NGF bioactivity (Nc).
• Created an ApoE3-reconstituted high-density lipoprotein shell (Nc-rHDL) for BBB penetration.
• Modified with αRDP peptide for neural targeting (Nc-rHDL@P).
• Evaluated in vitro BBB models and controlled cortical impact (CCI) mice.

Main Results:

• Nc-rHDL@P efficiently crossed the BBB and localized to injured brain regions.
• Demonstrated enhanced neuronal survival, neurite outgrowth, and neural stem cell differentiation in vitro.
• Significantly reduced inflammation and glial scar formation in vivo.
• Improved motor function, spatial learning, and memory in CCI mice.

Conclusions:

• The developed neurophilic biomimetic lipoprotein platform enables effective brain-targeted NGF delivery.
• This approach shows promise for treating TBI and other neurological disorders.
• The platform has broad potential for delivering other neurotrophins beyond NGF.