Biomedical Engineering Reference
In-Depth Information
Another class of temperature-responsive polymers is that of poly(ethylene
oxide)- poly(propylene oxide) - poly(ethylene oxide) ( PEO - PPO - PEO ; Pluronic) block
copolymer, which consists of hydrophilic PEO segments and hydrophobic PPO
segments [54]. A temperature change at the critical micellization temperature
(CMT) would trigger a change in the polymer conformation, and this property was
subsequently utilized to control the loading and delivery of drugs. Chen
et al.
modifi ed Pluronic P123 copolymers with PEI to obtain Pluronic-
g
- PEI (2 kDa) [54] ,
where the terminal hydroxyl groups of P123 were covalently grafted to the amino
groups of the PEI polymer. The MNPs were synthesized by the coprecipitation
method, and hydroxyl groups of their surfaces exchanged with citrate ligands so
as to provide excess carboxylate groups and render the surface anionic. The
PEI- modifi ed P123 polymers were conjugated to the anionic surface of magnetite
nanoparticles through strong ionic interactions. The excess amino groups of
PEI provided the functional groups for further interactions with guest molecules
such as drugs. As these groups were confi ned at the layer between the magnetite
surface and the P123, the therapeutic molecules would be entrapped and protected
by the outer layer of the Pluronic copolymer. The schematic representation of
the fabrication strategy of the drug-loaded MNPs is shown in Figure 10.4. The
loading and release of drugs utilized the temperature- responsive micellization
feature of the Pluronic block. At low temperature, the copolymer chains are fully
extended upon interaction with water, and thus the polymer shell is open for
the entry of drug molecules. An increase in temperature above the CMT induces
copolymer dehydration and contraction of the polymer shell, forming compact
barriers that would inhibit the diffusion of the loaded molecules out of the polymer
matrix. At 20 °C, the Pluronic-coated nanoparticle has a magnetite core of
∼
20 nm
and a hydrodynamic diameter of
40 nm. The hydrodynamic diameter decreased
to 25 nm when the temperature increased from 20 to 35 °C. The nanoparticles
showed good aqueous stability and monodispersity even after 3 months of storage.
The
M
s
was
∼
51 emu g
− 1
at room temperature, and not signifi cantly different
from that of uncoated magnetite. Drug-release experiments were conducted with
ibuprofen and eosin Y as hydrophobic and hydrophilic model molecules, respec-
tively. For both ibuprofen and eosin Y, at 0 or 20 °C, almost all adsorbed molecules
were dissociated within 6 h. In contrast, at 37 ° C, only
∼
∼
20% of the drug molecules
were released in 6 h, and
95% were released in 3 days. When Pluronic-coated
nanoparticles loaded with monosialotetrahexosylganglioside (GM- 1) were
tested for the treatment of spinal cord damage in a mouse model, the particles
exhibited good biocompatibility and good recovery of spinal cord injury, despite
the amount of GM-1 administered (
>
6 mg kg
− 1
) being much lower than the
traditional dose. As PEI is known to exhibit varying degrees of toxicity, depending
on the M
w
and degree of branching [57], this issue of toxicity must be further
investigated.
∼
10.3.2.2.2
“ Grafting from ” Method
Although use of the “ grafting to ” technique
for MNPs has resulted in the successful synthesis of magnetic core- polymer shell
nanoparticles for biomedical applications (as discussed above), the technique
