Beyond PEGylation: Alternative surface-modification of nanoparticles with mucus-inert biomaterials

Mucus is a highly hydrated viscoelastic gel present on various moist surfaces in our body including the eyes, nasal cavity, mouth, gastrointestinal, respiratory and reproductive tracts. It serves as a very efficient barrier that prevents harmful particles, viruses and bacteria from entering the human body. However, the protective function of the mucus also hampers the diffusion of drugs and nanomedicines, which dramatically reduces their efficiency. Functionalisation of nanoparticles with low molecular weight poly(ethylene glycol) (PEGylation) is one of the strategies to enhance their penetration through mucus. Recently a number of other polymers were explored as alternatives to PEGylation. These alternatives include poly(2-alkyl-2-oxazolines), polysarcosine, poly(vinyl alcohol), other hydroxyl-containing non-ionic water-soluble polymers, zwitterionic polymers (polybetaines) and mucolytic enzymes. This review discusses the studies reporting the use of these polymers or potential application to facilitate mucus permeation of nanoparticles.