(Scheme 1). After evaporation of solvent, the settled solidified nanoparticles are
collected by ultracentrifugation and washed with distilled water to remove additives
and remaining solvent. PLGA nanoparticles were prepared with a diameter of
130 nm using this method [53]. Nanoparticles based on poly(organophosphazene)
derivatives were developed with a particle size of around 200 nm using acetone and
poloxamine 908 as the solvent and stabilizing agent, respectively [54]. PLGA
nanoparticles have been prepared with a typical particle size of 60–200 nm by
employing dichloromethane and acetone (8:2 v/v) as the solvent and PVA as the
stabilizing agent [55]. PLGA nanoparticles of about 200 nm were developed by
using dichloromethane 1% (w/v) as the solvent and PVA or Span 40 as the
stabilizing agent [56]. Both the single-emulsion and double-emulsion methods
have been applied for preparation of the nanoparticles and the effect of the emulsion
method and the experimental parameters on the particle size have been studied. In
the case of the single-emulsion method, an increase in the PVA (stabilizer) concentration results in a significant decrease in the nanoparticle size, while the homogenizer speed, the evaporation rate and freeze-drying only slightly influence the
particle size. In the case of the double-emulsion method, PVA concentration in
the internal aqueous phase decreases the nanoparticle size as compared to the PVA
concentration in the external aqueous phase. The homogenizer speed and freezedrying only slightly influence the nanoparticle size. The influence of experimental
parameters such as temperature, solvent evaporation method, surfactant concentration and internal aqueous phase volume and the influence of the molecular mass of
the polymer on the particle size, zeta potential, residual surfactant percentage, and
the polydispersity index of the PLA nanoparticles have been reported using the
double-emulsion method [57]. Poly(ethylene glycol) (PEG)-coated nanoparticles
have been also prepared with a mean diameter of about 200 nm [58]. The influence
of the sonication process has been studied on the characteristics of PLGA
nanoparticles prepared using a water-in-oil/water solvent evaporation method
[59]. The effect of solvent was investigated using two organic solvents (methylene
chloride and ethyl acetate) as the dispersed phase to prepare nanoparticles of PLGA
and the nanoparticles were found to be larger in methylene chloride than in ethyl
acetate [60].
5.2 Salting-Out
This process is based on the separation of a water-soluble solvent from aqueous
solution through the salting-out effect. Initially, polymer and drug are dissolved in a
solvent such as acetone and then the polymer solution is emulsified into an aqueous
solution containing electrolytes (such as magnesium chloride, calcium chloride and
magnesium acetate), non-electrolytes (such as sucrose), and a colloidal stabilizer
such as poly(vinyl pyrrolidone) or hydroxyethylcellulose. Finally, the oil/water
emulsion is diluted with a sufficient volume of water to enhance the diffusion of
acetone into the aqueous phase by inducing the formation of nanospheres. Both the
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S.K. Pandey et al.
collected by ultracentrifugation and washed with distilled water to remove additives
and remaining solvent. PLGA nanoparticles were prepared with a diameter of
130 nm using this method [53]. Nanoparticles based on poly(organophosphazene)
derivatives were developed with a particle size of around 200 nm using acetone and
poloxamine 908 as the solvent and stabilizing agent, respectively [54]. PLGA
nanoparticles have been prepared with a typical particle size of 60–200 nm by
employing dichloromethane and acetone (8:2 v/v) as the solvent and PVA as the
stabilizing agent [55]. PLGA nanoparticles of about 200 nm were developed by
using dichloromethane 1% (w/v) as the solvent and PVA or Span 40 as the
stabilizing agent [56]. Both the single-emulsion and double-emulsion methods
have been applied for preparation of the nanoparticles and the effect of the emulsion
method and the experimental parameters on the particle size have been studied. In
the case of the single-emulsion method, an increase in the PVA (stabilizer) concentration results in a significant decrease in the nanoparticle size, while the homogenizer speed, the evaporation rate and freeze-drying only slightly influence the
particle size. In the case of the double-emulsion method, PVA concentration in
the internal aqueous phase decreases the nanoparticle size as compared to the PVA
concentration in the external aqueous phase. The homogenizer speed and freezedrying only slightly influence the nanoparticle size. The influence of experimental
parameters such as temperature, solvent evaporation method, surfactant concentration and internal aqueous phase volume and the influence of the molecular mass of
the polymer on the particle size, zeta potential, residual surfactant percentage, and
the polydispersity index of the PLA nanoparticles have been reported using the
double-emulsion method [57]. Poly(ethylene glycol) (PEG)-coated nanoparticles
have been also prepared with a mean diameter of about 200 nm [58]. The influence
of the sonication process has been studied on the characteristics of PLGA
nanoparticles prepared using a water-in-oil/water solvent evaporation method
[59]. The effect of solvent was investigated using two organic solvents (methylene
chloride and ethyl acetate) as the dispersed phase to prepare nanoparticles of PLGA
and the nanoparticles were found to be larger in methylene chloride than in ethyl
acetate [60].
5.2 Salting-Out
This process is based on the separation of a water-soluble solvent from aqueous
solution through the salting-out effect. Initially, polymer and drug are dissolved in a
solvent such as acetone and then the polymer solution is emulsified into an aqueous
solution containing electrolytes (such as magnesium chloride, calcium chloride and
magnesium acetate), non-electrolytes (such as sucrose), and a colloidal stabilizer
such as poly(vinyl pyrrolidone) or hydroxyethylcellulose. Finally, the oil/water
emulsion is diluted with a sufficient volume of water to enhance the diffusion of
acetone into the aqueous phase by inducing the formation of nanospheres. Both the
182
S.K. Pandey et al.