Cationic Polymers for the Delivery of Therapeutic Nucleotides - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 46

high transfection efficiency were designed and synthesized as non-
viral gene delivery vectors by Chen

The density of disulfide
linkages in the synthesized hyperbranched polymers was tuned
by varying the feed molar ratio of the bisacrylamide monomers.
The results demonstrate that disulfide content in PAA controls the
MW of the polycation degradation products, ease of polyplexes
disassembly, polycation cytotoxicity, and polyplexes transfection
activity. Significantly increased transfection activity was achieved
with optimized formulations of reducible polyplexes compared
with non-reducible controls.

et al.

97

reported PAA with minor
fractions of protonatable fragments in the main chain are promising
carriers for delivery of siRNA.

Vader et al.

98

2.4 Factors Influencing Cationic Polymer

Mediated Nucleotides Delivery

For a successful gene delivery, a vector competent of

performing multiple functions at a suitable timing throughout the
delivery process is required. There are several factors like surface
charge density, MW of polymer, size of polyplexes, etc., that affect
the cationic polymer mediated delivery of nucleotides.

in vivo

99

For cellular
internalization, the negatively charged cell membranes are being
facilitated by the cationic polymers due to the positive charge. One
way to achieve improved uptake into cells is by increasing the positive
surface charge of complexes. This modification is expected to result
in higher affinity to negatively charged cell membrane constituents,
and thus higher rate of uptake can be achieved.
The disproportionate size of uncondensed pDNA makes it more
difficult for the cellular uptake. The charge of the carrier can also
influence the size of the polyplexes that plays a significant role in the
endosomal uptake, the cytoplasmatic transport, and the migration
through the nucleoporecomplexes that mediate the bidirectional
transport between cytoplasm and nucleus. Bishop reported the
accepted size limit for cellular uptake is around 150 nm.

100, 101

Further, MW of cationic polymers often hinders while delivering
the therapeutic nucleotides. It has been seen that the high MW
cationic polymers have proficient gene transfection and also induce
cytotoxicity, while low MW cationic polymers possibly will reduce
cytotoxicity and have also reduced gene transfection. Some of the low