Construction of EGFR-Targeted Triptolide Liposomes Using Uniform Design Optimization and Therapeutic Evaluation in...

Area of Science:

• Nanotechnology
• Oncology
• Pharmacology

Background:

• Triptolide (TP) shows anti-glioma potential but suffers from poor solubility, systemic toxicity, and inadequate tumor targeting.
• Existing challenges hinder the clinical translation of TP for glioma treatment.

Purpose of the Study:

• To develop and characterize a novel epidermal growth factor receptor (EGFR)-targeted liposomal formulation of TP (TP-CTX-Lip) to enhance its delivery efficiency and therapeutic window.
• To evaluate the in vitro and in vivo efficacy and safety of TP-CTX-Lip for targeted glioma therapy.

Main Methods:

• Formulation optimization using a uniform design approach and preparation via thin-film hydration-ultrasonication.
• Characterization of physicochemical properties, in vitro release kinetics, and cytotoxicity in high-EGFR and low-EGFR glioma cells.
• In vivo efficacy and developmental toxicity assessment using zebrafish models.

Main Results:

• Optimized TP-CTX-Lip exhibited favorable characteristics (size: 131.3 nm, PDI: 0.24, EE: 85.83%, DL: 13%).
• TP-CTX-Lip showed significantly enhanced cytotoxicity in high-EGFR U87-MG cells (IC50 = 10.4 nM) compared to low-EGFR cells and non-targeted liposomes.
• In vivo studies demonstrated reduced developmental toxicity in zebrafish and suppressed orthotopic U87-MG xenograft growth, indicating an improved therapeutic window.

Conclusions:

• The EGFR-targeted TP-CTX-Lip formulation significantly enhances the tumor selectivity and safety profile of TP.
• This novel targeted liposomal strategy presents a promising approach for effective and safer glioma therapy.