Biomedical Engineering Reference
In-Depth Information
are PLL and copolymers, PEI and copolymers, poly(-amino esters), and poly[2-
(dimethyalamino)ethyl methacrylate] and polyesters. The fundamental function of
the cationic vector is binding of the DNA and its compaction into particles. General
factors influencing DNA-binding affinity, which are innate to the chemical structure
of the polymer, are as follows:
l
number of charge groups per polymer,
l
type of charge group (e.g., primary, secondary, or quaternary amino groups),
l
spacing of charge groups within the polymer,
l
degree of branching in the polymer backbone, and
l
hydrophobicity of the cationic vector.
In addition, the external parameters affecting conditions of the microenvironment
are concentration, ionic strength of polyplex solution, positive / negative charge ratios
of polymer and DNA, and method of polyplex formation.
4.2.1.1 PLL and Copolymers
PLL and its copolymer ( Fig. 4.2 ) were the first cationic polymers widely explored
for in vivo gene delivery. Polylysine is a biodegradable linear polypeptide of varying
length consisting of 20-1000 amino acids. Due to its positive charge, PLL is able
to condense DNA. PLL also protects DNA from cellular degradation by nucleases.
Any ligand can be easily attached to PLL for PLL chemical coupling. PLL has
shown better transfection efficiency compared to naked DNA. However, it is unstable
H 2 N
H 2 N
O
N
H
x
z
O
O
N
H
x
z
O
HN
O
HN
O
: Sugars (lactose, galactose)
AWBP
Antibody
Folate
O
N
O
n
O
y
O
y
H 2 N
PLL
PLL- g -PLG
PLL- g -PLG-Ligand
Figure 4.2 Chemical structures of PLL-based gene vectors. AWBP, arterial wall binding
protein.
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