Biomedical Engineering Reference
In-Depth Information
(A)
Polymer in
organic phase
Protein in
aqueous phase
Core
Shell
Evaporation
Emulsion
(B)
Polymer
Protein
Temperature
change
Anionic chain
Cationic chain
Co-solvent
(C)
Protein
Hydrophilic
chain
Hydrophobic
chain
Self
assembly
Grafting
protein
(D)
Functional
group
Figure 9.3
Techniques for immobilization of growth factors in/on nanoparticles (NPs).
(A) Encapsulation of the protein in polymeric NPs by double emulsion solvent evaporation.
(B) Encapsulation of the protein in NPs self-assembled from amphiphilic temperature-sensitive
copolymer with a critical solution temperature in aqueous solution. (C) Encapsulation of the
growth factor in ionic polymer NPs by complex coacervation. (D) Immobilization of the protein
on the surface of self-assembled NPs in aqueous solution under mild condition.
GDNF in PLGA with a fluorescent agent in the organic phase was re-emulsified in water to
form a water-oil-water emulsion. Next, the organic methylene chloride phase was evaporated
to form GDNF-encapsulated PLGA NPs. Intraspinal injection of the fluorescently labeled
GDNF-PLGA NPs demonstrated that their transport in the spinal cord was size dependent;
that is, the 20 nm NPs were transported more efficiently through the spinal cord than the
100 nm NPs. Furthermore, hind-limb locomotor function of rats treated with GDNF-
PLGA NPs was significantly higher than the PLGA or bolus GDNF rats [173].
Nanoparticles that self-assemble in aqueous solution to trap the protein, or techniques
utilizing complexation and complex coacervation of oppositely charged polyelectrolytes, are
especially suited for encapsulation of growth factors [174, 175]. Our laboratory has devel-
oped amphiphilic poly(lactide ethylene oxide fumarate) (PLEOF) macromers that are sol-
uble in aqueous solution at a physiological temperature of 37 °C [175-177] (Figure 9.3B).
Upon reducing temperature to ambient conditions, the macromers self-assemble to form
degradable NPs. Encapsulation efficiency of BMP-2 protein in PLEOF NPs was > 90%
but > 70% of the protein was released from the NPs in enzymatically active conformation in
the first week after encapsulation [175]. In another aqueous phase encapsulation, Li
et al
.
