Biomedical Engineering Reference
In-Depth Information
partially penetrating (or diffusing) into a PSS terminating PEM upon adsorption. This
penetration is preferred when the positive charge of the protein is high.
Release of bioactive molecules or of film components can be triggered by a wide variety
of stimuli, such as ionic strength, light, temperature, and sensitivity to hydrolysis. The
various methods developed for controlling each of these parameters have been reviewed
in detail by De Geest et al. (2007) in their recent review on polyelectrolyte capsules and by
Tang et al. (2006). It appears that film porosity, a certain level of hydration, and diffusion
are important to allow for molecule mobility.
Surface Mediated Transfection
The controlled delivery of DNA complexes from PEMs offers the potential to enhance gene
transfer by maintaining an elevated concentration of DNA within the cellular microenvi-
ronment with an appropriate polyelectrolyte film carrier that will facilitate DNA introduc-
tion. There are already several very interesting reviews about gene delivery through LbL
method (Jewell and Lynn 2008; Lynn 2007). In this chapter, we will highlight recent studies
that present new advances in this field.
Jessel et al. (2006) reported the fabrication of substrates containing
β
-cyclodextrin-DNA
(CD-DNA) complexes embedded in a PEM film in which specific expression of nuclear or
cytoplasmic proteins is selectively and sequentially produced. These CD-DNA complexes
adsorbed on PEM films acted as an efficient gene delivery tool to transfect cells. Synthesis
of new cationic polymers is one of the important developments in the field of PEMs for
gene delivery. Lu et al. (2008) reported a biodegradable polycation poly(2-aminoethyl pro-
pylene phosphate), which could form multilayers with plasmid DNA (pDNA) and lead to
prolonged pDNA delivery up to 2 months. Reducible polycations such as those contain-
ing disulfide bonds are also of interest for triggering gene release from PEM films under
reductive conditions in the presence of DTT for instance (Blacklock et al. 2007; Blacklock
et al. 2009; Chen et al. 2007). Cai et al. (2008) reported multilayers of galactosylated CHI
and pDNA. Because the galactose group is a specific ligand for the asialoglycoprotein
receptor (ASGP-R) of hepatocytes, these films have a specific higher transfection rate on
hepatoma G2 cells. An elegant strategy for bifunctionalization of PEM films was devel-
oped by Meyer et al. (2008). These authors show that it is possible to functionalize PEM
films both for cell transfection and for activation via a peptide signaling pathway. Toward
this end, they prepared films containing pDNA precomplexed with PEI and a peptide
molecule NBPMSH. This peptide, grafted to PGA was used as a signal molecule for mela-
noma cells B16-F1 and for its ability to enhance gene delivery in a receptor-independent
manner.
Another development relies on the incorporation and functionality of other gene mate-
rials, such as viral vectors and silencing (Dimitrova et al. 2007; Dimitrova et al. 2008; Jia
et al. 2007). Recently, Dimitrova et al. (2008) demonstrated, using hepatitis C virus infec-
demonstrated, using hepatitis C virus infec-
tion (HCV) as a model, that siRNAs targeting the viral genome were efficiently deliv-
ered by PEM films. This delivery method resulted in a marked, dose-dependent, specific,
and sustained inhibition of HCV replication and infection in hepatocyte-derived cells.
Comparative analysis demonstrated that delivery of siRNAs by the films was more sus-
tained and durable than siRNAs delivery by standard methods, including electroporation
or liposomes. The antiviral effect of siRNAs films was reversed by a hyaluronidase inhibi-
tor, suggesting that active degradation of films by cellular enzymes is required for siRNA
delivery.
Recently, Dimitrova et al. (2008) demonstrated, using hepatitis C virus infec-
Search WWH ::
Custom Search