Engineering polymer surfaces reduces nanoparticles (NPs) aggregation and phagocytosis due to effective shielding, hindering recognition by the reticuloendothelial system (RES). The shielding of NPs is complex and affected by the type of groups used in terms of charge and hydrophilicity. This will, in turn, affect NPs biodistribution which will determine the length of activity of the drug. Polysaccharides are nowadays recognized for decreasing the uptake of particulate carriers by the mononuclear phagocytic system (MPS). Chitosan is considered as an attractive candidate due to its biocompatibility, biodegradability, non-toxicity and low cost. In this study clozapine (CZP)-loaded NPs were coated with chitosan, pluronic F-68, polyethylene glycol (PEG) 4000 and polysorbate 80. The factors affecting drug encapsulation efficiency, particle size, surface charge, surface hydrophilicity, pharmacokinetics and biodistribution were studied. The results proved that although a similarity in surface hydrophilicity, chitosan-stealth NPs showed different pharmacokinetic profile and biodistribution behavior compared to polysorbate-stealth NPs.
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