From Liposomes to Leapfrogs: The New Era of Anthracycline Nanocarriers.

Anthracyclines are potent therapeutic agents widely used in cancer treatment and other medical applications, including infectious diseases and inflammatory disorders. However, their clinical utility is often restricted by severe systemic toxicity, poor biodistribution, and the emergence of multidrug resistance (MDR). To address these limitations, nanocarrier-based drug delivery systems have been developed to improve therapeutic selectivity and safety. Among them, liposomal formulations have achieved the highest level of clinical translation. FDA-approved liposomal anthracyclines such as Doxil® (doxorubicin), DaunoXome® (daunorubicin), and Vyxeos® (daunorubicin-cytarabine) have demonstrated enhanced pharmacokinetics, reduced cardiotoxicity, and improved therapeutic outcomes compared with conventional formulations. Beyond liposomes, alternative and emerging nanocarriers, including polymeric nanoparticles, micellar systems, dendrimeric carriers, and hybrid lipid-polymer constructs, are being explored to achieve higher drug loading, controlled release, and targeted tissue penetration. These formulations also show promise for antimicrobial and immunomodulatory therapies. Nevertheless, key challenges such as safety concerns, large-scale production, and regulatory barriers continue to impede broad clinical adoption. This review provides a comprehensive overview of liposomal and alternative nanoformulations for anthracyclines, discussing their advantages, limitations, and clinical potential while addressing the key challenges that must be overcome for their successful translation into widespread medical use, while also highlighting emerging biohybrid, extracellular vesicle-based, and stimuli-responsive systems that represent leapfrogging innovations in anthracycline delivery.