Dual-Responsive Methotrexate-Human Serum Albumin Complex-Encapsulated Liposomes for Targeted and Enhanced...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Atherosclerosis (AS) plaque barriers impede drug delivery to macrophages.
• Targeted drug delivery and on-demand release are crucial for effective AS treatment.

Purpose of the Study:

• To develop a smart nanoplatform for precise drug delivery and release in AS plaques.
• To overcome the challenge of thick fibrous caps in plaque sites.

Main Methods:

• Encapsulation of methotrexate-human serum albumin (MTX-HSA) complex into pH-sensitive liposomes.
• Modification with ROS-responsive PEG2000-TK-DSPE (PTD) to create PTD/Lipo/MTX-HSA.
• Evaluation of penetration, targeting, and anti-inflammatory efficacy in vitro and in AS mouse models.

Main Results:

• PTD/Lipo/MTX-HSA demonstrated enhanced penetration through macrophage spheroids.
• The formulation achieved precise targeting in an AS mouse model.
• On-demand drug release was triggered by ROS and acidic pH, inhibiting inflammatory factors.

Conclusions:

• The developed dual-responsive nanoplatform shows potential for penetrating deep atherosclerotic plaques.
• This strategy offers a promising therapeutic approach for effective AS treatment.
• The formulation exhibits safety and highlights the potential of smart nanoplatforms.