Tuneable Glycosylated Polypeptide Nanoparticles by N-Carboxyanhydride Emulsion Polymerisation

Biodegradeable nanoparticles produced by emulsion polymerisation find applications in many fields such as nutraceutical, agriculture, and medicine. Crucial aspects of tuneabaility have recently focused on the shape, size and core composition as a way to control the drug loading, biodistribution and targeting capabilities within medicinal drug delivery applications. Consequently, glycosylated nanoparticles have received increased interest in the field as the tuneable nature of the emulsion process combined with the well documented targeting ability of glycans has the potential to create libraries of well-designed delivery vehicles.<br/>Our interests lie in a new class of nanoparticles fully based on synthetic polypeptides which allow for a premeditated surface through the utilisation of a high molecular weight surfactant remaining adsorbed onto the surface. Therefore we have recently developed a novel route for the synthesis of glycosylated degradable nanoparticles composed of a polypeptide core and a glycopeptide shell. Herein, the synthesis and analysis of a series of degradable glycosylated polypeptide nanoparticles (GlycoPep NPs) is described. GlycoPep NPs were synthesised by miniemulsion ring-opening polymerisation (ROP) of <i>N</i>-carboxyanhydrides (NCA) in aqueous conditions; during which varying glycopolypeptides were utilised as surfactants. The size of the GlycoPep NP’s could be tailored based on the core and surfactant polypeptide composition and the concentration ratio. Dynamic light scattering (DLS), Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM) and Asymmetric Field Flow Fractionation (AF4) confirmed the highly stable and reproducible nature of the particles produced. The nanoparticles could be lyophilised and resuspended in water and buffer solutions, enhancing their bio-applicability. We will look to elucidate their binding interactions by utilising the pendant sugar within the surfactant as the system is only composed of bio-relevant materials. This methodology therefore opens up a library of bio-inspired glycosylated polypeptide nanoparticles which can be highly tuned giving them significant potential for the delivery of therapeutic agents.