Tailoring the multi-functional properties of phospholipids for simple to complex self-assemblies

The unique interfacial properties, huge diversity, and biocompatible nature of phospholipids make them an attractive pharmaceutical excipient. The amphiphilic nature of these molecules offers them the property to self-assemble into distinct structures. The solubility, chemical and structural properties, surface charge, and critical packing parameters of phospholipids play an essential role during formulation design. This review focuses on the relationship between the structural features of a phospholipid molecule and the formation of different lipid-based nanocarrier drug delivery systems. This provides a rationale and guideline for the selection of appropriate phospholipids while designing a drug delivery system. Finally, we refer to relevant recent case studies covering different types of phospholipid-based systems including simple to complex assemblies. Different carriers in the size range of 50 nm to a few microns can be prepared using phospholipids. The carriers can be delivered through oral, intravenous, nasal, dermal, transmucosal, and subcutaneous routes. A wide range of applicability can be achieved by incorporating various hydrophilic and lipophilic additives in the phospholipid bilayer. Advanced research has led to the discovery of phospholipid complexes and cell membrane mimicking lipids. Overall, phospholipids remain a versatile pharmaceutical excipient for drug delivery. They play multiple roles as solubilizer, emulsifier, surfactant, permeation enhancer, coating agent, release modifier, and liposome former.