Table 2.

Particle coatings to promote stealth characteristics

Stealth coating	Mechanism of action	Clinical applications	Advantages	Disadvantages
Polyethylene glycol (PEG)	Hydrophilic polymer generates steric repulsion, reducing protein adsorption202	Chronic inflammatory diseases (multiple sclerosis, arthritis, Crohn’s disease), gout, haemophilia, chronic kidney disease, prostate cancer, leukaemia, acromegaly, and hepatitis B and C203	Biocompatible202 FDA approval for human use123 Tuneability: effective PEGylation depends on chain length, PEG chain architecture, grafting density202	Does not completely eliminate protein adsorption202 Does not protect polymer particle from phagocytosis by neutrophils in human blood175
Chitosan	Polysaccharide primary amino groups yield cationic properties204	No FDA-approved particle-based formats, but has been evaluated in a clinical study in a nasal spray formulation of fentanyl chitosan205: chitosan nanoparticles enhanced bioavailability and systemic exposure205	Biocompatible, biodegradable, non-toxic, stable206 Fine tuning of properties by tuning molecular weight206 Mucoadhesive204,206 Antimicrobial206 Controlled drug release204,206	Weak non-fouling properties204
Cell membrane	Natural cell membranes are collected and coated onto synthetic particles207	Polymeric nanoparticles coated with prostate-specific membrane antigens enhanced particle accumulation within prostate tumours207	Prolonged circulation207 Enhanced targeting capabilities207 Ability to directly modulate immunity207 Biomimetic	Batch-to-batch variation207
Zwitterion	Contains both positive and negative moieties, creating overall neutral charge202; both moieties interact with water molecules so that the hydration layer prevents opsonization202; the anti-fouling properties increase as the distance between oppositely charged moieties decreases202	No FDA-approved product	Non-haemolytic202 Reduced nonspecific protien adhesion202	Cannot be used for active targeting202 Difficult to tune surface properties202 Cellular uptake is not inhibited202
Ionic liquids	Particles can be suspended in ionic liquid emulsions or covalently bonded with ionic liquids208; intramolecular and intermolecular interactions between the ionic liquid and particle/loaded drug determine the particle properties208	No FDA-approved product	Tuneable208 Stealth208 Antimicrobial208 Stable208	Mechanism of degradation is unknown208,209