Breast cancer continues to pose a significant therapeutic challenge due to issues such as drug resistance, systemic toxicity, and limited selectivity of current treatments. This has led to growing interest in natural compounds with multitarget activity. Betulin, a pentacyclic triterpene obtained from the bark of Betula species, has attracted attention because of its diverse biological effects and relative abundance. In breast cancer models, betulin has been reported to influence key cellular processes, including mitochondrial-mediated apoptosis, generation of reactive oxygen species (ROS), and modulation of signaling pathways such as nuclear factor kappa B (NF-κB) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR). Despite these promising observations, the practical use of betulin remains limited by its poor aqueous solubility and low bioavailability. These limitations reduce its effective concentration at target sites and restrict its therapeutic potential. Phytosome-based delivery systems have been explored as a way to improve these properties by forming molecular complexes between betulin and phospholipids, thereby enhancing membrane interaction and absorption. Relevant literature for this review was collected from major scientific databases using keywords related to betulin, breast cancer, phytosomes, apoptosis, nanocarriers, and drug delivery systems. This article critically examines the relationship between the physicochemical properties of betulin, its mechanistic role in breast cancer, and the potential application of phytosome-based delivery systems in improving therapeutic performance. The review highlights the ability of betulin to modulate apoptosis, oxidative stress, inflammatory signaling, and proliferation-associated pathways relevant to breast cancer progression. In addition, the available evidence suggests that phytosome-mediated delivery may represent a promising strategy for overcoming the physicochemical limitations associated with betulin. However, direct experimental studies specifically evaluating betulin-loaded phytosomes in breast cancer remain limited, emphasizing the need for further in vivo validation, pharmacokinetic characterization, and translational investigation.
Yuvraj et al. (2026) studied this question.