• Nanocarrier-Based Delivery of Doxorubicin in Breast Cancer: Liposomal Formulations and Cardiotoxicity Reduction
  • Reyhaneh Amiri,1 Majid Alipour,2,* Saloome Beikzade,3 Kimia Dehghanpour Nasrabadi,4
    1. Department of cell and molecular Biology, Babol Branch Islamic Azad University, Babol, Iran
    2. Comprehensive Health Research Centre, Babol Branch, Islamic Azad University, Babol, Iran
    3. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
    4. Department of Cell and Molecular Biology, Faculty of Medical Sciences, Islamic Azad University, Gholhak Branch, Tehran, Iran


  • Introduction: Introduction: Breast cancer remains one of the most prevalent and lethal malignancies among women worldwide, with an increasing global incidence projected to surpass 2.5 million new cases by 2025. Doxorubicin (DOX), a cornerstone chemotherapeutic agent, has demonstrated broad-spectrum antitumor activity and significant efficacy in breast cancer treatment. However, its clinical utility is limited by dose-dependent cardiotoxicity, systemic toxicity, and tumor resistance. To address these challenges, liposomal formulations, particularly PEGylated liposomal doxorubicin (PLD), have been developed to enhance drug stability, modify pharmacokinetics, and reduce off-target toxicity while maintaining therapeutic potency. This review evaluates the comparative efficacy, cardioprotective benefits, limitations, and future perspectives of liposomal DOX in breast cancer therapy.
  • Methods: Methods: A comprehensive literature review was conducted, examining preclinical and clinical studies that investigated conventional DOX and liposomal DOX formulations in breast cancer treatment. Sources included peer-reviewed experimental data, clinical trial outcomes, and pharmacokinetic studies. Key focus areas included drug delivery mechanisms, tumor selectivity, therapeutic efficacy, cardiotoxicity profiles, and adverse effects. Comparative analyses were performed to assess differences between conventional DOX and liposomal counterparts, with emphasis on PEGylated and sphingomyelin-based formulations.
  • Results: Findings indicate that liposomal DOX retains the potent anticancer activity of conventional DOX while demonstrating improved tolerability. Preclinical studies showed enhanced tumor inhibition, reduced cardiac uptake, and the ability to overcome multidrug resistance mechanisms. Clinical trials confirmed that PLD achieved comparable or superior efficacy in both monotherapy and combination regimens, with improved progression-free survival and reduced cardiotoxicity. Importantly, liposomal encapsulation altered biodistribution, leading to preferential accumulation in tumor tissues and reduced exposure to cardiac tissue. Sphingomyelin-based liposomes further improved formulation stability and circulation time compared with phosphatidylcholine-based vesicles. Despite these benefits, challenges remain, including formulation instability, adverse effects such as hand–foot syndrome, and higher treatment costs. Emerging research highlights advanced strategies such as ligand-targeted, triggerable, and multifunctional liposomes, integrating chemotherapy with gene and immunotherapy approaches to further optimize efficacy and safety.
  • Conclusion: Liposomal doxorubicin represents a significant advancement in breast cancer therapy, providing an effective solution to the limitations of conventional DOX by reducing systemic and cardiac toxicities without compromising antitumor efficacy. PEGylation, sphingomyelin incorporation, and surface modifications have enhanced stability, pharmacokinetics, and tumor selectivity, establishing liposomal DOX as a safer anthracycline alternative. Continued innovation in nanocarrier design, including stimuli-responsive and actively targeted formulations, holds promise for expanding its clinical utility. Collectively, experimental and clinical evidence supports liposomal DOX as a validated and evolving therapeutic strategy that improves treatment outcomes and patient quality of life in breast cancer management.
  • Keywords: Breast Cancer, Liposomal Doxorubicin, Targeted Drug Delivery, Nanocarriers