C.J. Drummond, X. Mulet, C.E. Conn, C. Fong, M. Moghaddam, S.M. Sagnella, X.J. Gong, J. Zhai
Keywords: drug delivery, medical imaging, lipid self-assembly nanoparticles, theranostic agents, lyotropic liquid crystals
Summary:The creation of high dimension (2D and 3D) ordered amphiphile self-assembly materials, or lyotropic liquid crystalline mesophase materials, has been amply demonstrated, but their integration into clinical drug delivery and medical imaging platforms has been over-shadowed by the ubiquitous liposome, which is based on a 1D lamellar lyotropic liquid crystalline structure. Particles generated from stabilised amphiphilic materials, are created through the dispersion of self-assembled small amphiphilic (including lipid) molecules. Amphiphiles, which contain a hydrophilic headgroup and a hydrophobic hydrocarbon chain region, may self-assemble upon addition of water to form structures with long range order, termed lyotropic liquid crystalline mesophases. Some of these structures, when prepared from amphiphiles with very low aqueous solubility, can be dispersed to form nanoparticles which retain the internal order of the bulk ‘parent’ mesophase. Typical internal structures include inverse bicontinuous cubic mesophases (which when dispersed form ‘cubosomes’), inverse hexagonal (hexosomes) or lamellar mesophase (liposomes). The materials and their application to drug delivery and medical imaging are very much in their infancy relative to liposomes. Consequently, whilst the mesophases have been successfully dispersed into nanoparticles, their translation to advanced theranostic agents remains immature. This presentation will outline the properties that have driven these versatile amphiphile self-assembly materials to be part of the development of the next generation of advanced nanoparticles, and will focus, through providing specific recent examples from our research, on five aspects of the nanoparticle. The first aspect is the relationship between matrix composition and structure and the effect on the therapeutic potential of the nanoparticle. Second, the effects of drug loading on the particle internal structure and the relationship between internal nanostructure and their drug release profiles will be discussed. The loading capacity of the nanoparticles with respect to medical imaging agents, such as MRI contrast agents, will be addressed, as this is essential to the development of multifunctional theranostic vehicles. The fourth important element is the interface between the nanoparticle and its surrounding environment, which plays a crucial role in both the stabilisation of the nanoparticle and the resulting in vivo interactions. Finally, the potential to functionalise the outer layer of these nanoparticles and how this can be used to impart targeting capability will be described. Transformation and innovation in the field of drug delivery can be achieved by using rationally designed matrices that incorporate a range of properties including sustained drug release targeted to specific sites in the body, simultaneous imaging-based diagnostic tools, and a reduction in adverse side effects from therapeutic compounds. As such, one of the fundamental driving forces for nanomedical materials research is the belief that tailored multifunctional nanostructured particles have the potential to become a complete framework solution to provide the next generation of advanced drug delivery agents.