Title: Magic bullets: What they are, and how they are made

Human infectious diseases are mainly caused by invading pathogens (bacteria, viruses, fungi, parasites), most of which are too small in size to be seen with the naked eye. Generally, infections arise when these pathogens start to grow and multiply within human cells and tissues. To efficiently and effectively eliminate these invading pathogens without negatively affecting the surrounding human cells, nor overall human health, is a magical process that can only be achieved using a rationally constructed agent (medicine) rather than relying on trial and error (chance). Effective medicines are built rationally through an iterative process that involves systematic and subtle structural alterations. These structural alterations are made repeatedly until the desired pharmacological activity (in vitro and in vivo) and drug-like properties are attained.

Combating the BTIDs using innovative self-emulsification drug delivery systems

Self-emulsifying drug delivery systems (SEDDSs) represent a groundbreaking approach to improving the treatment of diseases (for example, tuberculosis, malaria and HIV/AIDS), which are often managed with poorly water-soluble, lipophilic drugs. These drugs exhibit low bioavailability, particularly in malnourished patients who cannot consume the fatty meals necessary for effective absorption. SEDDSs address this issue by forming fine oil-in-water or water-in-oil emulsions upon contact with gastrointestinal or dermal fluids, requiring only mild agitation, in other words, gastric peristalsis – no specialised equipment or external energy input is needed. SEDDSs are pre-concentrates consisting of lipophilic drugs dissolved in oil, mixed with surfactants and co-surfactants. Upon administration, they spontaneously emulsify, creating micro- or nano-emulsions that enhance lipophilic drug solubility and facilitate lymphatic transport, bypassing first-pass metabolism. For dermal application, the formulation must navigate limited water availability by carefully balancing hydrophilic and lipophilic components. Natural and essential oils, selected for their penetration-enhancing and therapeutic properties, are central to the performance of SEDDSs. Development challenges include precise excipient selection, formulation stability, and achieving the desired droplet size to control drug release. Tools such as pseudoternary phase diagrams aid formulation design, particularly for fixed-dose combinations with varying solubility profiles. SEDDSs offer scalable, stable and cost-effective solutions, holding immense potential to revolutionise infectious disease therapy, especially in resource-limited settings.

*(BTIDs = big three infectious diseases, namely tuberculosis, malaria and HIV/AIDS)