Biomedical Engineering Reference
In-Depth Information
as the model molecule, but the loading procedure can be applied to other macromolecules, includ-
ing proteins. In that study, shells were built on 5.5 µm diameter MnCO
3
particle templates, and the
fi nal structure was (PSS/PAH)
4
(PSS/Co@Au)
1-2
(PSS/PAH)
2-10
. To test shell “open” under external
magnetic fi eld, (PSS/PAH)
4
(PSS/Co@Au)
1
(PSS/PAH)
6
shells were coincubated with FITC-labeled
dextran (MW: 2,000,000, 1 mg/mL) at pH 7.5. Under CLSM observation, the interior of capsules
was dark even after 1 h of mixing, indicating little permeability to dextran. In comparison, after
applying an alternating electromagnetic fi eld (1200 Oe, 150 Hz) to the capsule/FITC-dextran mix-
ture for 30 min, the capsules became permeable and the fl uorescence intensity inside the capsules
was similar to bulk solution. It was noticed that the sample temperature increased about 10°C-20°C
during the application of an alternating magnetic fi eld. Further thermal tests showed that the tem-
perature's infl uence on the permeability of capsules was negligible, so it was the external magnetic
fi eld contributing to the capsule permeability change.
The infl uence of frequencies (100-1000 Hz) of electromagnetic fi elds on the permeability of cap-
sule walls was investigated at a fi xed magnetic fi eld of 1200 Oe. For lower frequencies (
<
300 Hz),
there is a tendency for faster diffusion of FITC-dextran. While higher frequencies (
300 Hz) have
only negligible effects on the diffusion of FITC-dextran into capsules, even after keeping the mix-
ture for 1 h in the magnetic fi eld. It was possible that the increase of frequency reduced agitation
effects of the magnetic fi eld on the Co@Au nanoparticles embedded in the capsule walls and could
not infl uence the permeability of the magnetic capsules. It was suggested that magnetostatic interac-
tions inside the magnetic nanoparticle aggregations would lead to the appearance of a fairly large
demagnetizing fi eld [119]. In such a fi eld, they will try to align their easy axis along the direction
of the external magnetic fi eld, and this may result in the formation of rather large stresses inside
the capsule walls. Such stresses can lead to an increase of pore size in the capsule walls and the
release of encapsulated macromolecules. Under a resonant frequency, the stress may be drastically
enhanced and even rupture the shell walls.
>
10.3.2.3
Porous Particles for Protein Encapsulation
Porous polymer microparticles with optimal aerodynamics (lower particle density and larger par-
ticle size) were ideal candidates for pulmonary drug delivery [138,139]. In addition, inorganic
particles with porous structures provide a unique way of loading and delivering macromolecules.
Recently, the Sukhorukov group reported using porous CaCO
3
microparticles, with the help of
LbL self-assembly, for the encapsulation of biomacromolecules [126,127]. Inorganic porous par-
ticles were used as sacrifi cial templates for protein loading, and there were two general strategies
involved. In the fi rst strategy, the CaCO
3
microparticle was consecutively coated with oppositely
charged polymer layers, resulting in adsorption of the polyelectrolytes not only on the surface of the
template but also inside pores. Afterwards, the core material could be dissolved in the presence of
0.1 M EDTA and polyelectrolyte complexes were left inside capsules. Finally, biomacromolecules
could be spontaneously loaded into capsules through binding to those polyelectrolyte complexes.
In the second strategy, proteins were fi rst entrapped inside porous particles because of the high-
surface area (8.8
0.3 m
2
/g) and reasonably large pore size (20-60 nm). Then, alternate coating
of polyelectrolyte was used to form protein-polyelectrolyte complexes before core dissolution. One
obvious advantage of using CaCO
3
porous particles is that particle dissolution in EDTA, which
is relatively friendly to proteins than the acids used in the capsule “open” and “close” process
aforementioned.
Upon core dissolution, either gel-like matrix or clusters of polyelectrolyte complex were
observed inside shells [126,127]. The shell-loading capacity was impressive; an 11 pg (PSS/PAH)
3
shell can encapsulate about 12 pg BSA. For a capsule with 8 bilayers, the weight was 24 pg and the
amount of BSA adsorbed was found to be 63% of the total mass. Taking into account that 15 pg
of BSA was adsorbed into a microcapsule with an average diameter of 4.5-5.0 µm, the protein
concentration per capsule was approximately 250 mg/mL, which is much higher than the protein
±
