Advances in Doxorubicin Chemotherapy: Emerging Polymeric Nanocarriers for Drug Loading and Delivery

Effective and targeted delivery of doxorubicin (DOX) remains a significant challenge due to its dose-limiting cardiotoxicity and systemic side effects. Liposomal formulations like Doxil^® have improved tumor targeting and reduced toxicity, but issues such as limited stability, poor release control, and insufficient site-specific delivery persist. As a result, there is a growing interest in advanced drug delivery systems, particularly polymeric nanocarriers, which offer biocompatibility, tunable properties, and ease of fabrication.

This review is organized into two key sections. The first section provides a comprehensive overview of DOX, including its mechanism of action, clinical challenges, and the limitations of current chemotherapy approaches. The second section highlights recent advances in polymeric nanocarriers for DOX delivery, focusing on polymeric micelles as well as other promising systems like hydrogels, dendrimers, polymersomes, and polymer-drug conjugates.

Initial discussions explore current strategies enhancing DOX's clinical translation, including methods to address cardiotoxicity and multidrug resistance. The latter part presents recent studies that report improved drug loading efficiency in polymeric nanocarriers through techniques such as core/shell modifications, enhanced hydrophobic interactions, and polymer-drug conjugation.

Despite notable progress in polymeric nanocarrier-based DOX delivery, challenges like limited circulation time, immunogenicity, and manufacturing scalability continue to hinder clinical application. Continued innovation in this field is crucial for the development of safe, effective, and clinically translatable polymeric nanocarriers for cancer therapy.