Biomedical Engineering Reference
In-Depth Information
d
n
4
y
3
n
g
|
7
Figure
9.16
PIC
micelle
formation
from
a
pair
of
oppositely
charged
block
copolymers.
25
induced the condensation of pDNA to be incorporated into PIC micelles
having approximately 90-100 nm diameter. The PEG segments of the block
copolymer are likely to surround the condensed pDNA to ensure the colloidal
stability of the PIC micelles. The pDNA in the PIC micelles was adequately
protected from DNase I attack. An excess of the counter polyanion potassium
poly(vinyl sulfate) (PVSK) solution in 100 mM AcONa/AcOH buffer (pH 5)
could dissociate the PIC micelles and thus induced the release of the loaded
pDNA. An appreciably higher gene expression was achieved with these
PIC micelles. Lactose was also conjugated onto the PIC micelles to enhance
the transfection efficiency of the pDNA.
28
a-Lactosyl-poly(ethylene glycol)-
poly[2-(dimethylamino)ethyl methacrylate] block copolymer (lactose-PEG-
PAMA) was synthesized to construct a PIC micellar-type gene vector
potentially useful for selective transfection of hepatic cells. Lactose-PEG-
PAMA spontaneously formed a PIC micelle with pDNA encoding luciferase
(pGL3-Luc) in aqueous solution without any precipitate formation. The
lactosylated PIC micelle thus prepared achieved substantially higher transfec-
tion efficiency compared to the control PIC micelle without lactose moieties
against HepG2 cells possessing asialoglycoprotein (ASGP) receptors recog-
nizing the h-
D
-galactose residue. This pronounced transfection efficacy of the
lactosylated PIC micelle was inhibited by the addition of excess asialofetuin
(ASF), a natural ligand against the ASGP receptor, indicating ASGP receptor-
mediated endocytosis to be a major route of the cellular uptake of the
lactosylated micelles. Notably, the lactosylated PIC micelle revealed enhanced
transfection compared to the control PIC micelle at a lower dose of pDNA,
demonstrating the feasibility of using the ligand-conjugated PIC micellar
vector for gene delivery to targeted cells.
Mao et al.
29
have developed a new block copolymer gene carrier that
comprises a PEG segment and a degradable cationic polyphosphoramidate
