Non-viral Gene Therapy - Intracellular Delivery: Fundamentals and Applications - page 669

The diameter and zeta-potential of the MEND were around 300 nm and −40 mV,
respectively. The encapsulation efficiency of the DNA could be greater than 70%.
This MEND based nano-system can serve as effective vectors for the intranuclear
or cytosolic delivery of a variety of therapeutics including pDNA, ODN and siRNA
as well as other molecules.

6.6 Polymer Nanoparticles for Simultaneous

Drug/Gene Delivery

Considerable recent studies have been focusing on the development of polymer
nanoparticles, especially assembled nanostructures for dual-release of drugs and
nucleic acids. The first nano-vehicle designed for the co-delivery of drugs and DNA
was developed by Yang and colleagues (Wang et al. 2006 ). For creating the
nanoparticles for dual-release by self-assembly, they synthesized a biodegradable
cationic amphiphilic copolymer, consisting of cholesterol side chains and a cationic
main chain. This copolymer (PMDS-Chol) was synthesized by grafting N-(2-
bromoethyl) carbarmoyl onto the hydrophilic poly(N-methyldietheneamine seba-
cate) (PMDS) that was produced by condensation polymerization between
N-methyldiethanolamine and sebacoyl chloride. Core-shell structured nanoparticles
with a hydrophobic cholesterol core and a cationic shell could be spontaneously
formed the self-assembly of PMDS-Chol in an aqueous solution. Hydrophobic
drugs such as paclitaxel and indomethacin could be effectively incorporated into
the core, while the cationic shell of the resulting drug-loaded nanoparticles could
be used to bind pDNA. In vitro release study indicated that the DNA binding did
not affect the release profiles of payload indomethacin, whereas paclitaxel release
from the nanoparticles was slightly faster than that from the nanoparticle/DNA
complexes. More importantly, these nanoparticles could achieve high transfection
efficiency and the possibility of simultaneously delivering drugs and genes to the
same cells. Enhanced transfection of pDNA or siRNA with the simultaneous deliv-
ery of paclitaxel has been demonstrated by in vitro and in vivo studies. In particular,
the co-delivery of paclitaxel with an IL-12-encoded plasmid using these nano-
assemblies suppressed cancer growth more efficiently than the delivery of either
paclitaxel or the plasmid in a 4T1 mouse breast cancer model. Moreover, the
co-delivery of paclitaxel with Bcl-2-targeted siRNA increased cytotoxicity in
MDA-MB-231 human breast cancer cells. These results clearly demonstrated the
synergistic/combined effect of co-delivery of a therapeutic drug and gene. Other
assemblies constructed using cationic amphiphilic copolymers of various architec-
tures have also been developed for the simultaneous delivery of various drug/gene
combinations (Wang et al. 2007 ; Qiu and Bae 2007 ; Zhu et al. 2008, 2010 ; Cheng
et al. 2009 ; Wiradharma et al. 2009 ).
To develop a multifunctional polymer nanocarrier via host-guest interactions
for simultaneous drug and gene delivery, b-CDs were conjugated onto branched
polyethylenimine (PEI-CD) to synthesize a host polymer (Zhang et al. 2010 ).