Chemical modification of sialylated oligosaccharides to functionalize nanostructured lipid carriers: exploring two different strategies†

Abstract

Nanostructured lipid carriers (NLCs) are innovative lipid-based formulations made up of a carefully balanced mixture of solid and liquid lipids in their core. This unique architecture offers several advantages over traditional lipid nanoparticles, including enhanced stability and improved drug loading capacity. NLC nanoparticles hold great promise across various sectors, including pharmaceuticals, healthcare, dietary supplements, functional foods and beverages, as well as cosmetics and personal care products. To enhance the targeting capabilities of these nanoparticles, their surface must be functionalized with biomolecules to support specific interactions with biological receptors. Here, we compared two synthesis strategies for functionalizing the surface of NLCs with N-acetyl-neuraminic acid (Neu5Ac), a major carbohydrate involved in many cellular functions. 6′- and 3′-Sialyllactose were enzymatically produced and directly functionalized on their reducing ends using either oxime ligation or reductive amination. In the first strategy, thiol-modified oligosaccharides were grafted onto maleimide-decorated NLCs, and the second strategy focused on incorporating sialylated glycolipids into the formulation. Both methods successfully produced stable and monodisperse nanoparticles with sizes ranging from 60 to 100 nm. The functionalization efficiency (46 to 86%) was assessed by quantifying Neu5Ac present at the particle surface. The grafting approach yielded safe nanoparticles that show potential for use in anti-adhesive therapies against pathogens, such as the influenza viruses. However, their effectiveness needs to be optimized by further increasing carbohydrate density on the nanoparticle surface.