Biomedical Engineering Reference
In-Depth Information
environment. For example, the negatively charged group (COO
2
or SO
3
2
)ina
zwitterionic polymer could form pH-responsive hydrolysable esters as
positively charged zwitterionic polymer precursors, which can be utilized for
a highly efficient degradable zwitterionic polymer-based gene delivery system
for DNA delivery,
31
as well as other hydrophobic drugs. The advantage of this
method is to enhance DNA unpackaging and lower the toxicity of polymers
residing in infected cells upon hydrolysis of the positively charged pCBMA
ester to the zwitterionic pCBMA. Moreover, such a charge change could also
facilitate a sticky to nonsticky surface change, which might also benefit local
drug delivery.
32
To utilize zwitterionic polymers in drug delivery, various copolymers are
synthesized through conventional free radical copolymerization or living
radical polymerization. All these copolymers with zwitterionic groups are
mainly synthesized in alcoholic solution, usually methanol or ethanol, since
the zwitterionic groups are highly hydrophilic. Sometimes, a little water is
necessary for these alcoholic solutions in order to ensure the solubility of the
final products with a large segment of zwitterionic groups. Also, some less
polar solvents, such as THF or DMSO, could be mixed with the alcohol to
dissolve hydrophobic monomers. Another route is to prepare copolymers with
precursors of zwitterionic groups and convert them to zwitterionic copolymers.
Lowe et al.
33
prepared a random copolymer of n-butyl methacrylate (BMA)
with either 10 or 30 mol% 2-(dimethylamino)ethyl methacrylate (DMAEMA)
and treated these precursor polymers with propane-1,3-sultone under mild
conditions to obtain a zwitterionic copolymer with a narrow molecular weight
distribution. Cao et al.
18
have developed PLGA-PCB block copolymers
through hydrolysis of the ester of PCB. In such a way, a block copolymer with
a sharp hydrophilicity/hydrophobicity difference could be prepared, which
could be a very useful method to prepare stable nano drug carriers with a very
low critical micelle concentration (CMC). On the other hand, Samanta et al.
developed end-functionalized polyMPC through atom-transfer radical poly-
merization (ATRP) which could conjugate to amino groups.
34
d
n
4
y
3
n
g
|
7
This MPC
polymer
provides
an
alternative
to
end-functionalized
PEG
for
forming
resistance to nonspecific protein adsorption.
10.3 Phosphorylcholine-Based Polymers for Drug
Delivery
Phosphorylcholine (PC) is a zwitterionic head group of the major polar groups
of phospholipids on cell membranes. 2-Methacryloyloxyethyl phosphorylcho-
line (MPC), a methacrylate monomer composed of PC, has a cell membrane-
like structure and has demonstrated strong non-thrombogenicity.
35
Owing
to its excellent biocompatibility, MPC is an ideal candidate for hydrophilic
shell-forming blocks and has been widely used for biomedical applications,
including drug delivery to solubilize hydrophobic drugs.
36,37
