Recent advancements of betulinic acid-based drug delivery systems for cancer therapy (2002–2023)

Betulinic acid, a compound classified as a pentacyclic triterpenoid, is found in abundance in a variety of medicinal plants and natural substances. Its broad spectrum of biological and medicinal properties, particularly its potent antitumor activity, has gained significant attention in recent years. The anticancer properties of betulinic acid are governed by mitochondrial signalling pathways and it exhibit selectivity for cancerous tissue, leaving non-cancerous cells and normal tissue unharmed. This characteristic is particularly valuable in chemo-resistant cases. Nevertheless, the medicinal potential of betulinic acid is hindered by its poor water solubility and short half-life, leading to sub-optimal effectiveness. This issue is being tackled by a variety of nano-sized drug delivery systems, such as polymeric nanoparticles, magnetic nanoparticles, polymeric conjugates, nanoemulsions, liposomes, nanosuspensions, carbon nanotubes, and cyclodextrin complexes. This article focuses on recent advances in nanoformulations that are tailored to the delivery of betulinic acid with enhanced effectiveness.