Progress and challenges of lyotropic liquid crystalline nanoparticles for innovative therapies

Since the late 20th century, we have witnessed a growing and substantial advance in nanomedicine, in part due to the development of multifunctional and multimodal nanoplatforms that have enabled improved efficacy, biocompatibility, and novel therapeutic applications. Non-lamellar liquid-crystalline nanoparticles, especially, reverse hexagonal and cubic bicontinuous mesophases, have gained the attention of the scientific-academic community due to their intriguing and functional characteristics, such as self-organization into two- and three-dimensional supramolecular structures, high symmetry, and ability to accommodate hydrophobic and hydrophilic small molecules, peptides, proteins, nucleic acids, and imaging agents. Furthermore, these particles can be easily modified with specific and/or bioresponsive molecules allowing targeting and improved therapeutic performance. In this contribution we provide an overview of advances in the design and architecture of LCNPs, strategies to overcome biological barriers and main findings about interactions with different types of interfaces. We highlight recent applications in topical, oral, pulmonary and intravenous drug delivery in preclinical in vivo studies. We discussed the current scenario and translational obstacles faced for clinical translation, as well as our perspectives.