TLD: An optimized liposomal doxorubicin formulation with small vesicle size for improved anti-tumor efficacy

• TLD is a clinical phase liposomal formulation of doxorubicin with a low drug-to-lipid ratio and a small diameter of only 35.6 nm (cryo-TEM) and 65.2 nm (DLS). • In vitro, TLD had lower IC 50 value compared to Caelyx (13.1 vs 21.3 µg/mL, respectively) in the human breast cancer cell line MCF7. • In vivo, both in a mouse breast cancer model 4T1 and in a fibrosarcoma model WEHI-164, TLD performed equally well to Caelyx. Talidox (TLD) is an innovative liposomal doxorubicin formulation designed to enhance drug delivery efficiency and reduce systemic toxicity over existing liposomal doxorubicin formulations. This publication consolidates 10 years of preclinical research on TLD, integrating physicochemical characterization, and in vitro and in vivo efficacy. TLD has a reduced particle size and optimized drug-to-lipid ratio compared to Caelyx, aiming to improve tumor penetration and uptake and therefore therapeutic efficacy. The preclinical studies in breast cancer and soft tissue sarcoma models highlight the improved efficacy of TLD over free doxorubicin combined with a very good safety profile. This is complemented by the already published favorable risk-benefit ratio of TLD found in clinical trials.