Tailoring lyotropic liquid crystals for skin barrier penetration: Exploring composition and structure–function relationships

Lyotropic liquid crystals (LLCs) have garnered attention as a promising nanocarrier delivery system for enhancing skin permeation owing to their unique structural properties, such as improved drug loading and controlled drug release and versatility. LLCs are greatly explored for topical drug delivery owing to their strong bio-adhesive nature and structural similarity to the biological membranes when applied topically, which improves skin retention and permeation of the drugs. This review explores the functionality of structural design, especially the optimization of micellar systems, hexagonal and lamellar phases, and bicontinuous cubic and sponge phases, to achieve efficient skin permeation of therapeutic loaded LLCs. Furthermore, customization of surfactant to achieve skin compatibility and permeation is explored along with incorporating molecular modifications, functionalization, and the influence of surfactant hydrophilic–lipophilic balance. Additionally, the review illuminates the impact of LLCs curvature and the engineering of ordered and disordered phases for optimal drug release. Emerging advanced techniques such as surface modification with various ligands, stimuli-responsive LLCs for on-demand drug release, and combination therapies with multifunctional LLCs for synergistic effects that can promote targeted and site-specific drug delivery have also been discussed. The detailed findings have been discussed in this review with appropriate case studies. Challenges and future perspectives in designing and formulating LLCs for skin permeation are addressed to ignite future research. The knowledge and advancements presented in this review pave the way for developing next-generation LLCs-based systems, enabling enhanced permeation through the skin and opening new possibilities in the treatment of various dermatological conditions.