Biomedical Engineering Reference
In-Depth Information
with tripolyphosphate in presence of PEG to achieve stability of the nanoparticles
(Calvo et al. 1997 ). Chitosan nanoparticles were designed as delivery systems for
macromolecules (Janes et al. 2001 ; Brunel et al. 2010 ).
2.1.3
Formation of Nanoparticles from Polyelectrolyte Complexes
Another method for the production of nanoparticles is based on formation of
polyelectrolyte complexes (PEC). In this method, two polymers of opposite charges
are brought together to interact and form aggregates in the nanosize range (Berger
et al. 2004 ; Schatz et al. 2004 ; Goycoolea et al. 2009 ; Oyarzun-Ampuero et al. 2009 ;
Woitiski et al. 2009a, b ). Originally, this approach was suggested to develop drug
carriers for nucleic acid delivery. Complexes were prepared by mixing polycations
like poly(lysine) (PLL) or poly(ethylenimine) (PEI) and nucleic acids which are
negatively charged macromolecules (Boussif et al. 1995 ; Coll et al. 1999 ; Jeong
et al. 2007 ; Sun and Zhang 2010 ). The main difficulty with this method was to
produce nanoparticles which remained stable over time. Stability of nanoparticles
can be improved by using block copolymers including a poly(ethylene glycol)
(PEG) moiety combined with either the polycation or the nucleic acid. The nano-
particles obtained with these copolymers are sterically stabilized. The PEG chains
form a corona at the surface of the core of the nanoparticles formed by the
poly(electrolyte) complex between the nucleic acid and the polycation (Kabanov
et al. 2005 ; Jeong et al. 2007 ; Joralemon et al. 2010 ).
Recent studies provide relevant methodologies to prepare stable and well define
nanoparticles by mixing polyelectrolytes of opposite charges. A pioneer work was
given by the group of Delair who drawn a concept in which one polyelectrolyte is
a guest for the second polyelectrolyte of opposite charge which is the host. They
clearly demonstrated that the host and guest balance control the formation of well
define nanoparticles with either positive or negative charges (Schatz et al. 2004 ;
Drogoz et al. 2007 ). This approach is now successfully applied by many authors
using various polymers (Berger et al. 2004 ; Schatz et al. 2004 ; Oyarzun-Ampuero
et al. 2009 ; Goycoolea et al. 2009 ; Woitiski et al. 2009a, b ; Mao et al. 2006; Sun
et al. 2008 ). Briefly, the polyelectrolyte with the larger molecular weight is consid-
ered as the host while the polyelectrolyte of opposite charge with a much lower
molecular weight is consider as the guest. To obtain nanoparticles, the guest poly-
electrolyte is added into a solution containing the host polyelectrolyte. Parameters
such as the respective concentration of the two polyelectrolytes, and the ratio of
their molecular weight are affecting the characteristics of the produced nanoparti-
cles (Drogoz et al. 2007 ).
Nanoparticles made of polyelectrolyte complexes are largely developed for
hydrophilic macromolecular drugs. These nanoparticles are suitable for all types of
nucleic acids (Brunel et al. 2010 ; Sun and Zhang 2010 ). Peptides and proteins
which are ampholyte molecules are a second category of drug molecules which are
associated with such nanoparticles (Mao et al. 2006 ; Woitiski et al. 2009b ). Several
works are considering their use for the development of an oral formulation of
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