Table 2.

Advantages and disadvantages of each protein nanoparticle generation methods.

Method	Advantage	Disadvantage
Emulsion/solvent extraction	High stability The shape and size of nanoparticles can be controlled by reaction conditions High encapsulation efficiency	Generating particles larger than those obtained by desolvation Thermodynamic instability → Need surfactants and stabilizers
Polyelectrolyte complexation/complex coacervation method	High stability Small nanoparticles Can be mixed with sensitive drugs (protein or peptide) The shape and size of nanoparticles can be controlled by reaction conditions	Difficulty of scale-up
Electrospray technique	High stability Small nanoparticles Scalable at industry-level and already in use	Low flow This technique may induce some macromolecule degradation due to the stress involved in the operation parameters (e.g. Thermal stress in drying, shear stress in the nozzle).
Nano spray drying	Control of particle size, shape, and morphology One-step semi-continuous process Processing of heat-sensitive substances with low risk of degradation Cost-effective	Limited to small-scale production Challenging to incorporate hydrophobic drugs
Desolvation method	High stability Simple to manufacture Small nanoparticles High encapsulation efficiency The shape and size of nanoparticles can be controlled by reaction conditions.	Only possible for proteins that can be minimally affected by the de-soluble process itself or diluted by transporter proteins
Self-assembly	High encapsulation efficiency Small nanoparticles High stability	Difficult to control the size and shape of nanoparticles. Protein strain potential exists