Biomedical Engineering Reference
In-Depth Information
10.4.3.1
PLGA Loaded with Taxol
PLGA nanospheres loaded with biocompatible MNPs and the anticancer drug
taxol (this is used to treat various solid tumors, such as breast and ovarian) is one
of many examples of such systems [96]. The MNPs were prepared by the copre-
cipitation method, and sodium oleate (C
17
H
33
COONa) was added as the fi rst sur-
factant to prevent their agglomeration; the result was a stable colloidal suspension.
PEG was then added as a second surfactant to the MNP-oleate system, such that
the resultant composition was 37.3 wt% magnetite, 50.6 wt% sodium oleate, and
12.1 wt% PEG. A modifi ed nanoprecipitation method was used to entrap the
MNPs and taxol into the PLGA nanospheres. An organic phase comprising PLGA
(with
D
,
L
- lactide to glycolide ratio of 85 : 15; average M
w
50 000 - 75 000 Da) and taxol
in acetone was added dropwise to an aqueous solution of Pluronic F66 (as a sta-
bilizing agent) and the PEG-coated MNPs. The mixture was then stirred vigorously
for several hours to allow complete evaporation of the organic solvent at room
temperature. The nanospheres formed were near-spherical with a mean diameter
of 250 nm, and magnetite and taxol contents of 21.5 wt% and 0.5 wt%,
respectively.
10.4.3.2
PLLA and PCL Loaded with Tamoxifen
A similar polymer, PLLA (a biodegradable polyester), has also been used for encap-
sulating MNPs and tamoxifen, a drug used widely to treat estrogen receptor-pos-
itive breast cancer [97]. The composite nanospheres with an average size of 200 nm
were synthesized via a solvent evaporation/extraction technique in an oil/water
emulsion. The superparamagnetic property (
M
s
∼
7 emu g
− 1
) of the nanospheres
was provided by
6 nm Fe
3
O
4
nanoparticles (synthesized via a high-temperature
decomposition method) encapsulated in the PLLA matrix. In the preparation
process, PLLA, tamoxifen and oleic acid-coated MNPs were dissolved in DCM and
vortexed to create the organic phase; this was then poured into a stirred aqueous
solution containing 1% PVA as emulsifi er. The mixture was sonicated and the
formed oil/water emulsion stirred at room temperature overnight to evaporate the
organic solvent. The nanospheres were then collected by centrifugation. The
encapsulation effi ciency for tamoxifen and Fe
3
O
4
MNPs was approximately 60%
and 80%, respectively, when less than 7.5 mg tamoxifen and 20 mg Fe
3
O
4
MNPs
were formulated in 100 mg PLLA in DCM. Approximately 57% of the entrapped
drug was released into PBS containing sodium lauryl sulfate as surfactant during
the fi rst 24 h, and 88% was released in 6 days. Release of the drug from these
nanospheres was very much delayed compared to that from poly(
∼
- caprolactone)
(PCL) nanospheres (prepared from an acetone/water system), where 68% of the
entrapped tamoxifen was released during the fi rst hour with almost total release
within 24 h [98]. The PLLA nanospheres with encapsulated drug and MNPs were
readily taken in by MCF-7 cells, with 182 pg of nanospheres (estimated from
intracellular iron levels) being internalized into each cell over a 4 h incubation
period, with 500 mg nanospheres per ml culture medium. At this nanosphere
concentration, the MCF-7 cancer cells exhibited morphological changes within 4 h,
such that approximately 80% were no longer viable after 4 days. In contrast, when
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