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The formation of polyion complex micelles (PIC micelles) was first verified by
our group for the pair of oppositely charged block copolymers PEG-poly(L -lysine)
and PEG-poly(a , b -aspartic acid) [
28
] . These fi rst PIC micelles presented size
around 30 nm and polydispersity of <0.1. Obviously, the core of the PIC micelle can
serve as a reservoir for molecules, once it forms a separated phase from the outer
space. In a similar association fashion, supramolecular assembly is easily obtained
when using opposite charges of oligonucleotides and polycations: the negatively
charged oligonucleotides bind the positively charged polycation to form a polyion
complex through electrostatic interactions [
3-
5
]. In addition, negatively charged
oligonucleotides such as double-stranded DNA and siRNA share many common
characteristics; thus, siRNA micelle design can benefit from the ideas and knowl-
edge previously developed for DNA delivery [
59
] .
8.5
Polymeric Micelles for siRNA Delivery
A new in vivo vector for oligonucleotides formed through the self-association of
block copolymers, and antisense DNA was reported soon after the concept of PIC
micelles [
6
]. As a result of the use of PEG-poly(L-lysine) (PEG-PLL) as the oligo-
nucleotide counterpart, spherical PIC micelles were formed entrapping the anti-
sense DNA in the core (Fig.
8.3
). Similarly, plasmid DNA (pDNA) was loaded into
Fig. 8.3
Formation of PIC micelles between PEG-PLL and antisense DNA. Adapted with permis-
sion from [
6
] . Copyright 1996 American Chemical Society
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