Recently, several nano-vesicular delivery systems are developed to resolve the problems associated with many drugs such as liposomes, nanoparticles, and niosomes. Unfortunately, their use is limited by the oral route due to the obstacles that face them in the gastrointestinal tract (GIT) such as pH, bile salts, and metabolic enzymes. Due to these difficulties, bilosomes which are non-ionic surfactant nano-vesicular delivery systems encompassing bile salts in their membrane have represented a recent approach to entrap the drug, protect it from gastric degradation, and increase its bioavailability. The presence of the non-ionic surfactants and bile salts in their compositions affect their properties as they make them more stable chemically and impart elasticity to the vesicle that enables them to squeeze through smaller pores than their diameters and penetrate deeply through the tissue layers, respectively. With the aim to deliver the oral vaccine, biological therapeutics, and traditional small-molecule drugs, bilosomes showed their high ability to protect the entrapped peptides and proteins after oral administration.

In this review, we will clarify the unique properties of bilosomes that make them the best choice as nano-vesicular drug delivery systems, compositions, preparation techniques, and methods of characterizations representing the factors that affect their parameters. Furthermore, this review represents the therapeutic applications of bilosomes by various routes of administration and the effect of changing bilosomal components into their therapeutic efficacy. Finally, information on the future prospections of bilosomes through different routes and their marketing approaches is addressed.