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Nanoparticles (NPs) have been extensively used as smart vehicles for the target delivery of therapeutic, immunotherapeutic, and diagnostic agents. The versatility of NPs applications partly arises from the possibility of manufacturing various NPs types depending on the nature of starting materials. In most cases, amphiphilic materials such as phospholipids, solid lipids, fatty acid derivatives, and blends of oils/surfactants, are used to make distinct NPs, namely liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), micelles, and nanoemulsions, respectively. In the pipeline of raw materials, saponins have emerged as a promising alternative for NPs formulation. Saponins are plant-derived secondary metabolites (phytochemicals) with excellent amphiphilic properties, which allow them to play crucial roles in nanotechnology, including their usage as reagents for micellar preparation as well as stabilizing agents for several NPs. Saponin-based NPs have been used to improve the solubility, and pharmacological profile of various active ingredients, encompassing vaccines, owing to inherent immunostimulant/adjuvant properties of saponins. In this review, we mainly discuss the state of the art in biomedical and pharmaceutical applications of saponin-containing NPs, focusing on using saponins as raw materials to make original NPs or as adjuvants for improving already established NPs. The physicochemical properties of saponins have been highlighted, before describing putative nano-formulations with huge promise for drug delivery and vaccine development. The opportunities and challenges pertaining to saponins-containing NPs have been pointed out to set the stage for establishing saponins as an intriguing raw material for the effective translational development of revolutionary nanomedicines.

Nanoparticles (NPs) have significantly advanced medical applications, including drug delivery, immunotherapy, vaccines, and diagnostics. This versatility is partly due to the potential of tailoring NPs from multiple sources. Notably, saponins, amphiphilic plant metabolites, have shown great promise in NP formulation. This study explored the development of micellar NPs using saponin crude fractions (SCFs) extracted from five Congolese plant species: Millettia laurentii, Penthaclethra eetveldeana, Schwenckia americana, Musa paradisiaca, and Musa sapientum. Plant materials were subjected to histological examination through optical microscopy, while phytochemical analyses by thin-layer chromatography confirmed the presence and predominance of saponins in the SCFs. We used a phthalocyanine-isoniazid hybrid (Pc-INH) as a hydrophobic probe to determine the critical micellar concentrations of SCFs and explore the feasibility of developing cost-effective saponin-based micelles (SBMs). Phytochemical screenings indicated saponins in the extracted SCF and other metabolites like flavonoids, phenolic acids, and anthocyanins. Dynamic light scattering and transmission electron microscopy analyses revealed the formation of nano-sized particles, particularly noting SBMs from P. eetveldeana with notable dimensions (157 ​nm, PDI of 0.27, and ZP of −4.01 ​mV) and spherical shape. The micelles from M. laurentii exhibited superior encapsulation efficiency for Pc-INH (55%) compared to control micelles formulated from pure saponin (33%). In vitro tests showed that M. paradisiaca SBMs have the best safety profile for red blood cells, with a 10% hemolysis rate compared to a 150% rate for bulk SCFs. However, there is a significant difference between SCFs and SBMs (p ​

Malaria is one of the most devastating diseases across the globe, particularly in low-income countries in Sub-Saharan Africa. The increasing incidence of malaria morbidity is mainly due to the shortcomings of preventative measures such as the lack of vaccines and inappropriate control over the parasite vector. Additionally, high mortality rates arise from therapeutic failures due to poor patient adherence and drug resistance development. Although the causative pathogen (Plasmodium spp.) is an intracellular parasite, the recommended antimalarial drugs show large volumes of distribution and low-to no-specificity towards the host cell. This leads to severe side effects that hamper patient compliance and promote the emergence of drug-resistant strains. Recent research efforts are promising to enable the discovery of new antimalarial agents; however, the lack of efficient means to achieve targeted delivery remains a concern, given the risk of further resistance development. New strategies based on green nanotechnologies are a promising avenue for malaria management due to their potential to eliminate malaria vectors (Anopheles sp.) and to encapsulate existing and emerging antimalarial agents and deliver them to different target sites. In this review we summarized studies on the use of plant-derived nanoparticles as cost-effective preventative measures against malaria parasites, starting from the vector stage. We also reviewed plant-based nanoengineering strategies to target malaria parasites, and further discussed the site-specific delivery of natural products using ligand-decorated nanoparticles that act through receptors on the host cells or malaria parasites. The exploration of traditionally established plant medicines, surface-engineered nanoparticles and the molecular targets of parasite/host cells may provide valuable insights for future discovery of antimalarial drugs and open new avenues for advancing science toward the goal of malaria eradication.