Biomedical Engineering Reference
In-Depth Information
2004 ; Barbosa et al. 2008 ). At the end of the preparation, the polymer solvent is
removed by evaporation or ultrafiltration. Nanoparticles produced by nanoprecipi-
tation are generally characterized by a diameter ranging from 200 to 300 nm. This
size range is rather narrow and was found to result from the precipitation of poly-
mer chains with well define molecular weight (Legrand et al. 2007 ).
Several theoretical works have been developed to explain the formation of the
nanoparticles from the nucleation of supersaturated zones in the solution which
form during mixing the polymer solution with the non solvent (Johnson and
Prud'homme 2003 ; Ganachaud and Katz 2005 ; Lince et al. 2008 ; Aubry et al.
2009 ). Optimized conditions for the production of nanoparticles with the highest
yield of nanoparticle production are fulfilled when the polymer is dissolved in a teta
solvent at a concentration comprised in the dilute regimen which means that the
polymer chains are surrounded by enough solvent so that they remain separated in
the solution (Legrand et al. 2007 ). In other words, in the optimal conditions poly-
mer molecules do not overlap with each other and remain independent in the solu-
tion. By increasing polymer concentration in the solution above the critical
interpenetrating concentration C*, polymer molecules overlap each others promot-
ing the formation of aggregates instead of individual nanoparticles. To adjust sol-
vency properties some authors have suggested to use binary blends of solvents such
as acetone with small amount of added water (Thioune et al. 1997 ), or blends of
ethanol and acetone (Murakami et al. 1999 ). Another optimization parameter
includes the molecular weight of the polymer. Indeed, nanoparticles were found to
be formed by polymer chains with define molecular weight. It was shown that all
polymer chains with a mean molecular weight outside the optimal molecular
weight precipitate as aggregates. Thus, by choosing polymers with optimal molecu-
lar weight, i.e. molecular weight of polymer chains found in nanoparticles, yield of
nanoparticle production can be optimized while formation of aggregates can be
avoided. Nanoprecipitation methods suit well to prepare drug carriers incorporating
lipophilic drugs. Indeed, in general, the drug to be encapsulated in the nanospheres
produced by this technique is simply added in the polymer solution (Niwa et al.
1993 ; Murakami et al. 2000 ; Chorny et al. 2002 ; Peltonen et al. 2004 ).
Although the main type of nanoparticles prepared by nanoprecipitation is nano-
spheres, the method can easily be adapted to produce nanocapsules by adding a
small amount of oil in the polymer solution (Fessi et al. 1989 ). During mixing of
the polymer solution with the non solvent of the polymer, the oil splits as tiny drop-
lets around which the polymer precipitates to form the nanocapsule shell. The dis-
persion phenomenon of the oil was explained by the “Ouzo or Pastis effect”
elucidated by Vitale and Katz ( 2003 ).
It is noteworthy that polymer micelles can be prepared by nanoprecipitation of
amphiphilic copolymers (Trivedi and Kompella 2010 ). In general, polymer micelles
are formed spontaneously in a solution just because the concentration of the
amphiphilic molecule is above the Critical Micellar Concentration (CMC).
Although polymer micelles form spontaneously, artefacts can be used to promote
their formation from amphiphilic polymers with low CMC in water and to favour
drug entrapment with a high payload (Fournier et al. 2004 ; Gaucher et al. 2010a, b ;
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