Abstract
Neglected parasitic diseases such as Chagas disease and malaria continue to pose major public health challenges, particularly in low-resource settings. Current therapies are often limited by high toxicity, poor efficacy, drug resistance, and limited accessibility. Phytochemicals, naturally occurring compounds in plants, have played a crucial role in medicine since ancient times and have gained renewed attention for their demonstrated antiparasitic activity. However, many products of natural origin (PNOs) face significant barriers to clinical use, including poor solubility, low bioavailability, and chemical instability. These limitations have driven researchers to explore alternative and innovative approaches based on the use of PNOs to tackle these parasitic infections more effectively. This review provides a comprehensive overview of key PNOs with proven activity against Trypanosoma cruzi and Plasmodium spp., the causative agents of Chagas disease and malaria, respectively. Recent advances in the design of phytonanoformulations are analyzed and discussed, emphasizing the potential of nanocarrier-based systems incorporating PNOs as a strategy to improve the pharmacokinetic and therapeutic properties of these natural products. By critically examining the integration of phytochemicals into nanotechnology-based drug delivery platforms, this review highlights the promise of phytonanotechnology to overcome current limitations in antiparasitic therapy and support the development of more effective and accessible treatments for neglected parasitic diseases.