Surface modified methotrexate loaded erythrocytes for enhanced macrophage uptake

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Immunology

Background:

• Macrophages play a crucial role in identifying and clearing senescent cells.
• Targeting macrophages can enhance drug delivery for diseases like cancer.
• Erythrocytes offer a biocompatible platform for drug encapsulation.

Purpose of the Study:

• To develop novel erythrocyte-based drug carriers with enhanced macrophage uptake.
• To investigate surface modification techniques for improving drug delivery efficacy.
• To evaluate the potential of modified erythrocytes for treating Reticuloendothelial System (RES) tumors.

Main Methods:

• Methotrexate-loaded erythrocytes were prepared using the preswell dilution technique.
• Erythrocyte surfaces were modified by desialation (trypsin treatment) and hemichrome induction (phenylhydrazine treatment).
• In vitro macrophage uptake and in vivo organ localization of modified erythrocytes were assessed.

Main Results:

• Surface modification significantly enhanced erythrocyte uptake by macrophages.
• Trypsin-treated (Tt) erythrocytes showed 3-5 times increased macrophage uptake.
• Phenylhydrazine-treated (PhT) erythrocytes demonstrated 5-6 times increased macrophage uptake.
• Modified erythrocytes showed promising in vivo organ distribution patterns.

Conclusions:

• Surface-modified erythrocytes are effective carriers for enhanced macrophage targeting.
• Desialation and hemichrome induction are viable strategies for improving erythrocyte drug delivery.
• These modified erythrocytes hold potential for targeted therapy of RES tumors.