Lipid nanoparticles in topical dermal drug delivery: Does chemistry of lipid persuade skin penetration?

Lipid nanostructures such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) significantly fetched the attention of scientific fraternity owing to lucrative advantages like easy scale-up, low cost, and remarkable stability. In addition, SLNs and NLCs are usually incorporated into the topical dermal drug delivery cargo to augment drug delivery. However, a number of factors determine the penetration of lipid nanoparticles in the stratum corneum layer like particle size ≤ 100 nm illustrated high penetration efficiency mainly via trans-follicular route, positive surface charge demonstrated enhanced penetration capacity and chemistry of lipids where a parabolic relationship exhibited with the lipid chain length in fatty acids, fatty acid esters and fatty alcohols and penetration efficiency. Admixture of dissimilar lipids augments the drug loading capacity owing to the creation of imperfections in the lipid matrix. Therefore, in present review, we have highlighted the hot melt extrusion which is a green technology based scale-up technique for manufacturing the lipid nanoparticles in addition to industry pertinent characterization parameters. This review also decodes the role of geometry of lipid molecules in the penetration of lipid nanostructures into the skin with special emphasis on molecular interactions between lipid core and ceramides (sphingolipids) of stratum corneum layer that play an important role in skin barrier function, cell adhesion and epidermal differentiation.