Liposomal and liposome-based formulations of pentacyclic triterpenoids in cancer nanomedicine: A critical appraisal of preclinical progress and future perspectives

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Pentacyclic triterpenoids (PTs) comprise a broad range of multifunctional plant-derived compound that serve as attractive scaffolds for the development of anticancer drugs. Their modes of action range from triggering apoptosis to modulating oncogenic signaling pathways and the tumor microenvironment. Despite these therapeutic benefits, their clinical formulation has been limited by features such as poor bioavailability, hydrophobicity, high metabolism rates, and off-target toxicity. To overcome these limitations, liposomal nanocarriers provide a convenient delivery platform to improve pharmacokinetic profiles and enhance tumor-specific accumulation of PTs. This review provides a critical assessment of studies published between 2020 and 2026 on liposomal and liposome-based formulations of PTs for cancer therapy, focusing on the four PTs with the most extensive liposomal literature, namely betulinic acid (BA), ursolic acid (UA), glycyrrhizic acid (GA) and celastrol; studies of structurally related triterpenoids (e.g., betulin, oleanolic acid, lupeol, raddeanin A, platycodin D2) and of triterpenoid-containing extracts are considered as ancillary evidence. Approaches including liposome pegylation, ligand-mediated drug delivery, biotherapeutic surface modification, and co-delivery liposomal systems are reviewed. The main focus is on integrating formulation design with the physicochemical and pharmacokinetic properties of PTs. Moreover, the reviewed evidence indicates that liposomal encapsulation can improve cellular uptake and, in selected preclinical models, enhance antitumor activity and target-specific effects.