Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Polymeric vesicles offer potential for targeted drug delivery.
• Glycol chitosan-based nanoparticles are explored for enhanced therapeutic applications.
• Doxorubicin (Dox) is a widely used chemotherapeutic agent with limitations in targeted delivery.

Purpose of the Study:

• To evaluate targeted polymeric glycol chitosan vesicles as carrier systems for doxorubicin (Dox).
• To assess the biological properties and efficacy of transferrin (Tf)-targeted and glucose-targeted vesicles.
• To compare the performance of targeted vesicles with non-targeted vesicles and free doxorubicin.

Main Methods:

• Covalent attachment of transferrin (Tf) to doxorubicin (Dox)-loaded palmitoylated glycol chitosan (GCP) vesicles.
• Preparation of glucose-targeted niosomes for comparative analysis.
• Biological evaluation using confocal microscopy, flow cytometry, cytotoxicity assays, and a mouse xenograft model.

Main Results:

• Transferrin (Tf) vesicles demonstrated rapid uptake, with doxorubicin (Dox) reaching the nucleus within 60-90 minutes.
• Tf-targeted vesicles showed higher uptake and increased cytotoxicity compared to non-targeted GCP Dox vesicles.
• While in vitro results indicated an advantage for Tf-GCP vesicles, particularly in drug-resistant cells, in vivo studies showed reduced activity compared to free doxorubicin, despite a superior safety profile.

Conclusions:

• Targeted transferrin (Tf) vesicles exhibited promising in vitro characteristics for doxorubicin (Dox) delivery.
• The in vitro therapeutic advantage of Tf-targeted vesicles did not translate to improved in vivo efficacy.
• All tested vesicle formulations demonstrated a better safety profile in vivo than free doxorubicin, but were less active in reducing tumor size.