Table 1.

General overview of chitosan NP preparation methods [134].

Method	Main Principle(s)	Advantage(s)	Drawback(s)
Emulsification and crosslinking	Covalent crosslinking	Simple process steps	Use of harmful chemicals
Reversed micelles	Covalent crosslinking	Ultrafine NPs below 100 nm	Time-consuming process Complex application Use of harmful chemicals
Phase inversion precipitation	Precipitation	High encapsulation capacity for specific compounds	Requires high shear force Use of harmful chemicals
Emulsion-droplet coalescence	Precipitation		Requires high shear force Use of harmful chemicals
Ionic gelation	Ionic crosslinking	Use of mild chemicals. Simple process. Ease of adjusting NP size
Ionic gelation with radical polymerization	Polymerization and crosslinking		Time-consuming process Complex application
Self-assembly	Electrostatic and/or hydrophobic interaction	Highly stable NPs. Use of mild chemicals Adjustable procedure	Hard to control when carried out on a large scale
Top-down	Acid hydrolysis and deacetylation		Time-consuming process Complex application Need an extra step for drug loading
Spray drying	Atomization	Simple and fast process. Does not require another separation or drying steps	Large particle size Not suitable for use with temperature-sensitive substances
SCASA	Atomization	Acid- or harmful solvent-free method. Does not require another separation or drying steps	Time-consuming process Requires a specially designed system Large particle size