Cubosomes in Anticancer Drug Delivery: Structural Insights, Formulation Strategies, and Translational Perspectives

ABSTRACT

Cancer chemotherapy remains plagued by poor drug solubility, non‐specific biodistribution, dose‐limiting toxicity, and multidrug resistance. Lipid‐based nanocarriers have emerged as promising solutions, and cubosomes nanoscale dispersions of bicontinuous cubic liquid crystalline phases offer unique advantages for anticancer drug delivery. This review comprehensively examines cubosomes as advanced platforms for cancer therapy, focusing on their structural characteristics, formulation strategies, and translational potential. The bicontinuous cubic architecture provides distinct hydrophilic, hydrophobic, and amphiphilic domains within a single nanoparticle, enabling unprecedented versatility in drug loading and combination therapy. We discuss composition of cubosomes (stabilizers), preparation methods (top‐down vs. bottom‐up), and characterization techniques (DLS, cryo‐TEM, SAXS). Mechanisms governing drug localization, encapsulation, and diffusion‐controlled release are elucidated, followed by a critical evaluation of applications including conventional chemotherapeutics, targeted delivery, nucleic acid therapeutics, and emerging theranostic platforms. Despite encouraging preclinical evidence, significant challenges remain formulation stability, scalable manufacturing under cGMP, comprehensive safety evaluation, and navigation of evolving regulatory pathways for nanomedicines. No cubosome‐based anticancer therapy has yet received clinical approval. Addressing these hurdles through improved formulation strategies, quality‐by‐design approaches, and interdisciplinary collaboration will be essential for translation. Cubosomes represent a versatile, promising platform whose future success depends on sustained research efforts bridging laboratory innovation and clinical reality.