Dual Functionalized Liposomes for Selective Delivery of Poorly Soluble Drugs to Inflamed Brain Regions

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Neuroscience

Background:

• The blood-brain barrier (BBB) presents a significant challenge for delivering therapeutics to the brain.
• Matrix metalloproteinases (MMPs) are enzymes often upregulated in pathological brain conditions.

Purpose of the Study:

• To develop dual-functionalized liposomes capable of crossing the BBB and releasing cargo in an MMP-rich environment.
• To evaluate the efficacy and safety of these liposomes for targeted drug delivery.

Main Methods:

• Liposomes were surface-functionalized with a modified apolipoprotein E peptide (mApoE) for BBB penetration and an MMP-sensitive moiety for triggered release.
• MMP-sensitive lipopeptides (MSLPs) were synthesized and incorporated into mApoE liposomes.
• Liposome characteristics, in vitro BBB crossing, MMP-triggered release, biocompatibility, and therapeutic effect were assessed.

Main Results:

• The dual-functionalized liposomes exhibited a size < 180 nm and negative ζ-potential.
• They successfully crossed an in vitro BBB model with high endothelial permeability.
• Efficient release of encapsulated dye was observed upon exposure to MMP2 or MMP9.
• The liposomes demonstrated high biocompatibility in neuronal cultures.
• Glibenclamide-loaded liposomes reduced proinflammatory cytokine release from activated microglial cells.

Conclusions:

• Dual-functionalized liposomes represent a promising strategy for targeted drug delivery across the BBB.
• The mApoE functionalization facilitates brain entry, while MMP-sensitivity enables localized drug release.
• This approach holds potential for treating neurological disorders characterized by MMP activity and inflammation.