Biomedical Engineering Reference
In-Depth Information
pilot plant for the production of nanoparticles by nanoprecipitation includes one
reservoir (can be several litres) for the polymer solution, one reservoir (can be sev-
eral litres as well) with the polymer non-solvent, a receiver of large capacity (can be
several litres), the mixing device and pumps used to feed the mixing device with the
polymer solution on the one hands and the non-solvent on the other hands with per-
fectly controlled flow rates. A pilot plan built with reservoirs of 3 L each and a
T-shape mixing device can convert 5 g of polymer into nanoparticles in 2 h with a
very good reproducibility (Galindo-Rodriguez et al. 2005 ; Tewa-Tagne et al. 2007 )
4
Treatment of Nanoparticles and Preparation for Storage
After synthesis, several types of treatments may be necessary to apply on nanopar-
ticle dispersions including purification, sterilization and preparation for storage.
Purification is often required to remove traces of impurities such as residual
organic solvent, excess of surfactants, salts and large polymer aggregates (Vauthier
and Bouchemal 2009 ). Volatile organic solvents can be removed by evaporation
under reduced pressure. Although this method can easily be applied on small
amounts of nanoparticle dispersions, ultrafiltration (Allemann et al. 1993 ), diafil-
tration (Tishchenko et al. 2003 ) and cross-flow microfiltration (Allemann et al.
1993 ; Limayem et al. 2004 ; Quintanar-Guerrero et al. 1998 ) are suitable methods
to treat large volumes of nanoparticle dispersions. Filtration can be used to remove
aggregates (Govender et al. 1999 ; Murakami et al. 1999 ). Centrifugations and ultra-
centrifugations can be used to separate nanoparticles from the dispersing medium
which retains all excess of reagent not included in the nanoparticles during prepara-
tion (Bouchemal et al. 2004, 2006 ; Govender et al. 1999 ; Calvo et al. 1997 ; Sahoo
et al. 2002 ; Nguyen et al. 2003 ; Lambert et al. 2000 ). Dialysis (Chauvierre et al.
2003 ) and gel filtration (Beck et al. 1990 ) are alternative methods when difficulties
of dispersion of nanoparticles arise after centrifugation.
In general, the solid content of nanoparticle dispersions as prepared by the
previously described methods is rather low (Desgouilles et al. 2003 ; Legrand et al.
2007 ). In some case, it is so low that it compromises the application as drug deliv-
ery system as the volume to administer to reach a therapeutic concentration in drug
in vivo is much above the maximal volume tolerated for the administration.
Therefore, nanoparticle dispersions may need to be concentrated prior to their
in vivo administration. Straightforward methods to increase nanoparticle concen-
tration are freeze drying, spray drying, ultracentrifugation and solvent evapora-
tion. Although these methods are suitable for several types of nanoparticles, the
main problem resides in the formation of aggregates which form when nanopar-
ticles come in contact with each other (Abdelwahed et al. 2006 ; Avgoustakis
2004 ; Bozdag et al. 2005 ; Vauthier et al. 2008 ). Methods given the more satisfactory
results without any risk of causing nanoparticle aggregation are based on dialysis
and ultrafiltration. Difficulties which might be encountered with simple ultrafiltra-
tion (i.e. clogged membranes with nanoparticles) can be resolved using diafiltration
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