Engineering Next-Generation Taxane Nanomedicines for Clinical Translation

Background: Taxanes have been a cornerstone in the management of a wide range of cancers, including ovarian, breast, and lung cancer, owing to their microtubule-stabilizing mechanism. Despite their clinical success, their therapeutic utility remains constrained by poor aqueous solubility, a need for toxic solubilizing vehicles, unpredictable pharmacokinetics, and systemic toxicity. Nanomedicine has redefined chemotherapeutic delivery paradigms, with liposomal systems emerging as leading platforms due to their safety and scalability. Purpose: This review aims to critically evaluate the physicochemical and formulation barriers that have limited the successful development of taxane-loaded nanoformulations and to highlight how model-informed principles can be leveraged to improve drug retention, stability, and translational potential. Review Scope: Early liposomal systems faced challenges, including premature drug release and rapid carrier opsonization, limitations that are particularly relevant for compounds with unfavorable biopharmaceutical properties. For taxanes such as paclitaxel, strong partitioning into the lipid bilayer can result in membrane destabilization and premature leakage. Conventional passive loading approaches have shown limited success for these molecules, prompting exploration of active loading strategies. Remote loading utilizes transmembrane gradients to improve drug retention and loading efficiency by concentrating therapeutics within the liposomal core; however, the non-ionizable nature of taxanes restricts the applicability of this approach. Conclusions: These limitations highlight the need for a rational nanocarrier design focused on drug–lipid interactions, physicochemical optimization, surface engineering, controlled release, manufacturing feasibility, and regulatory considerations. Integrating these principles may facilitate the development of robust, scalable, and clinically relevant taxane liposomal formulations, supporting the effective translation of these natural-product-derived therapeutics into improved cancer treatment strategies.