Processing and Scale-up of Polymeric Nanoparticles - Intracellular Delivery: Fundamentals and Applications - page 439

insulin while others are considering these nanoparticles for the delivery of antigens
entering the formulation of vaccines (Mao et al. 2006 ; Weber et al. 2010 ; Woitiski
et al. 2009b ).

2.2 Methods Based on the Formation of an Emulsion

The second class of methods requires the preparation of an emulsion prior to the
formation of nanoparticles. This part of the chapter will present methods for the
preparation of the required emulsion and then the different methods used to convert
the emulsion into dispersion of polymer nanoparticles.

2.2.1 Preparation of Emulsions Suitable for Nanoparticle Preparation

The preparation of the emulsion is critical in the sense that it will influence the size
of the polymer particles at the end of the preparation. It consists in mixing two
immiscible phases together, the polymer solution being the dispersed phase of the
emulsion. The sense of the emulsion, i.e. water in oil (W/O) or oil in water (O/W),
depends on the nature of the polymer and solubility properties. Oil in oil (O/O)
emulsions were introduced to improve drug incorporation performance in nanopar-
ticles (Nah et al. 2008 ). In general, simple emulsions are used to prepare nano-
spheres. Preparation of nanocapsules can be achieved from multiple emulsions
water in oil in water (W/O/W) (Lu et al. 1999 ; Bilati et al. 2003 ). In this latter case,
the polymer is dissolved in the intermediate oily phase while the drug is dissolved
in the aqueous inner phase. More complex emulsions were recently proposed to
produce double walled particles (Zheng 2009 ). Although the technique is presently
applied to produce microparticles which are larger particles than that of the nano-
meter range but it can be expected that such methods of emulsification will soon be
applied to produce nanoparticles as well.
Several methods are suitable to prepare the required simple emulsions straight
from the two separate phases. This includes ultrasounds, extrusion through microp-
orous and nanoporous materials, microfluidic systems and co-solvent assisted
emulsification (Ouzo effect) (Table 1 ).
For all other methods, the two phases are premixed before being submitted to
specific treatments providing the emulsion of the desired characteristics. For
instance, very small size emulsions, i.e. nano-emulsion can be generated from a
bi-continuous system prepared with poly(ethylene glycol) (PEG) containing
surfactants through a phase inversion method (Anton et al. 2008 ). The conver-
sion of the bi-continuous system into an oil-in-water nano-emulsion is induced
by simultaneous dilution and temperature drop. This method requires a very low
energy to achieve the formation of the desired emulsion. Depending on the char-
acteristics of the PEG surfactant, it can be applied at temperature ranging from
40°C to 90°C.