Table 2.

Major methods used in the fabrication of PLGA NPs.

Method	Procedure	Size Range (nm)	Advantages	Disadvantages	Examples
Emulsion evaporation	A non-water miscible solvent containing PLGA is emulsified with an aqueous solution containing a surfactant using high shear force	≈50 to 700	Relatively non-toxic, small particle size, easy to scale up, and can be used to encapsulate both water-soluble and water-insoluble drugs	Drug stability may be affected during high energy mixing, and long solvent removal step	[27,28,29,30]
Nanoprecipitation	A water-miscible solvent containing PLGA is dispersed into an aqueous phase using low energy mixing	≈80 to 700	Simple, rapid, narrow size distribution, and non-toxic solvents and low energy are used	Low entrapment efficiency of polar drugs, long solvent removal step, and particle size is considerably affected by polymer concentration	[31,32,33]
Solvent diffusion	A partially water miscible solvent containing PLGA is emulsified with an aqueous solution of a suitable surfactant	≈50 to 400	Toxic solvents and high stress shear are avoided	Large quantities of water and long agitation time are required, polymer concentration notably affect the particle size, and low entrapment efficiency of polar drugs	[34,35,36]
Salting out	A water-miscible solvent containing PLGA is emulsified with an aqueous phase containing a high concentration of salts under high shear stress agitation. The resulting o/w emulsion is diluted with water	≈100 to 500	Rapid, high concentrations of PLGA can be used, no high stress shear is required, and suitable for heat-sensitive drugs	Purification step is needed, solvents used may be explosive, and not suitable for lipophilic drugs	[37,38,39,40]