Methotrexate-Lactoferrin Targeted Exemestane Cubosomes for Synergistic Breast Cancer Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Breast cancer treatment often combines hormonal therapy and chemotherapy, but limited outcomes arise from challenges in simultaneous and selective drug delivery.
• Existing treatments face pharmacokinetic differences between agents, hindering effective co-administration to cancer cells.

Purpose of the Study:

• To develop a hybrid carrier system for simultaneous and targeted delivery of exemestane (EXE) and methotrexate (MTX) for breast cancer treatment.
• To create a dual drug delivery system that overcomes pharmacokinetic limitations and enhances therapeutic synergy.

Main Methods:

• Exemestane (EXE) was loaded into liquid crystalline nanoparticles (LCNPs), and methotrexate (MTX) was conjugated to lactoferrin (Lf).
• Anionic EXE-loaded LCNPs were coated with cationic MTX-Lf conjugate via electrostatic interactions, forming Lf-targeted dual drug-loaded LCNPs.
• Characterization included particle size, polydispersity index, drug loading efficiency, and in vitro cytotoxicity assays against MCF-7 cells.

Main Results:

• The Lf-targeted dual drug-loaded LCNPs showed a particle size of 143.6 ± 3.24 nm and a PDI of 0.180.
• High drug loading was achieved: 95% EXE encapsulation efficiency and 33.33% MTX conjugation efficiency.
• Synergistic effects were observed, with combination indices (CI) of 0.342 (in vitro) and 0.242 (in vivo), alongside significant dose reduction indices.

Conclusions:

• The Lf-targeted dual drug-loaded LCNPs demonstrate superior synergistic cytotoxic activity against breast cancer cells.
• Enhanced cellular uptake of targeted LCNPs into MCF-7 cells was observed compared to non-targeted carriers.
• This novel system shows promise for combined hormonal and chemotherapeutic approaches in breast cancer treatment.