Biomedical Engineering Reference
In-Depth Information
at pH 2.5. The polymerizations were performed by mixing the water and oil phases
at a 2 : 1 weight ratio under stirring (1000 rpm) for 3 h at room temperature. The
free magnetite and surfactant were removed by several rounds of centrifugation,
after which an external magnetic fi eld was introduced for complete separation of
the magnetic PECA nanospheres. Based on results of particle morphology and
size, and the amount of drug encapsulated, the optimal monomer/magnetite ratio
was determined as 4 : 3. At this ratio, the magnetite loading capacity was 14.26%
(w/w) and the mean particle size approximately 250 nm. The
M
s
of the PECA
nanospheres was 6.5 emu g
− 1
. The drug loadings of cisplatin and gemcitabine were
38.09% (w/w) and 9.37% (w/w), respectively, this difference being attributed to
differences in drug solubility. The drug-release behavior was monitored in PBS at
37.5
0.5 °C. Gemcitabine was seen to be released more rapidly, with a plateau
being reached before 3 days. In contrast, the release behavior of cisplatin (hydro-
phobic) was slower (a plateau was reached after 7 days) than that of gemcitabine
(hydrophilic), as the affi nity of cisplatin to the oil phase was higher than that of
gemcitabine.
The same group also tested the use of PCL to prepare drug- and magnetite-
loaded nanospheres [102]. PCL (M
w
42 500 Da), magnetite (prepared via coprecipi-
tation and treated with oleic acid at 80 °C), and cisplatin or gemcitabine were
dissolved in DCM and added into the aqueous phase containing PVA as stabilizer.
After emulsifi cation of the oil-water mixture, solvent evaporation and sample
cleaning and separation, nanospheres of approximately 160 nm (as measured
by laser scattering) were obtained. The maximum amount of magnetite encapsu-
lated was determined by TGA as 25 wt%, and the
M
s
of the nanospheres
was 17.6 emu g
− 1
. The drug loading of cisplatin and gemcitabine were 24.6 and
7.6 wt%, respectively. Similar to the results obtained with the PECA nanospheres,
gemcitabine was released more rapidly and a plateau reached within 5 days,
whereas for cisplatin the plateau was reached after 27 days. The mechanism of
drug release from the magnetic PCL nanospheres was inferred to be mainly a
diffusion process from the oil core through the polymeric network constituting
the nanosphere. Magnetic PCL nanospheres containing gemcitabine, and pre-
pared by a slightly different method from above, were tested using nude mice
bearing subcutaneous human pancreatic adenocarcinoma cells
in vivo
[103] . The
encapsulation effi ciency of the nanospheres was rather low, with maximum mag-
netite and gemcitabine encapsulation effi ciencies of
±
18.6%, respec-
tively, of the theoretical loading. The effi cacy of the injected gemcitabine-containing
magnetic nanospheres in shrinking the tumor was investigated using an external
0.25 T magnet positioned cutaneously over the tumor mass for 2 h. In the absence
of a magnetic fi eld, the concentration of gemcitabine was too low for any thera-
peutic effect to occur. However, in the presence of a magnetic fi eld a signifi cant
growth suppression was observed by day 15, and after 19 days the tumor was
36.4% smaller than in the control case. The magnetic fi eld - mediated targeted drug
delivery effects were comparable to those observed with systemic drug administra-
tion at 10- to 15-fold higher levels. No other signifi cant toxic side effects were
reported.
∼
7.8% and
∼
