Preparation of magnetic drug-loaded PLGA nanospheres as biodegradable magneto-responsive drug carriers

1
Preparation of magnetic drug-loaded PLGA
nanospheres as biodegradable magneto-responsive
drug carriers
Mohsen Ashjari1, Sepideh Khoee ,2, Ali Reza
Mahdavian ,1 1 Polymer Science Department, Iran
Polymer and Petrochemical Institute, Tehran, Iran
2 Polymer Chemistry Department, School of
Science, University of Tehran, Tehran,
Iran E-Mail A.Mahdavian_at_ippi.ac.ir
Abstract
Experimental part (continued)
Results (continued)
The aim of this study is preparation of
drug-loaded biodegradable magnetic PLGA
nanospheres made by emulsification - evaporation
method. The encapsulation procedure involves the
formation of oil-in-water emulsion in which
consists of an oil phase containing magnetite
nanoparticles in an aqueous solution of drug,
emulsification in an oil phase containing PLGA
and a stabilizer and lastly emulsification double
emulsion in an aqueous PVA solution lead to
formation final multiple emulsion. The mean
diameters of the magnetic PLGA nanospheres in
this study were smaller than the critical size
required for the recognition by the
reticuloendothelial system (RES). The morphology
and size distributions of the prepared magnetic
PLGA nanospheres were investigated by SEM. The
micrographs showed that the magnetic nanospheres
were almost spherical in shape and the mean
diameter within the range of 100-300 nm with
broad size distributions. The VSM results showed
magnetite content 35 wt and good magnetic
responsivity. The VSM measurements showed
superparamagnetism of prepared magnetic
nanospheres. This study suggests that the
emulsification - evaporation process is a
prospective technique to prepare biodegradable
magnetic nanospheres containing water-soluble
sensitive agents.
Then, this double emulsion was poured into an
aqueous PVA solution and the mixture was
ultrasonicated. The resulting emulsions were
diluted in PVA solution under mechanical stirring
and the DCM was eliminated by solvent
evaporation. The resulting magnetic PLGA
nanospheres were cleaned by repeating procedure
of centrifuging and resuspending in distilled
water for three times and then were collected by
a magnet. Finally, the obtained nanospheres were
dried by lyophilization (freeze-drying) and
stored at 4C.
The presence of PLGA causes such a decrease in Ms
of the magnetic PLGA nanospheres relative to the
pristine magnetite nanoparticles. On the other
hand, it is well known that magnetic particles
less than 30nm will demonstrate the
characteristic of superparamagnetism, which can
be verified by the magnetization curve. The
remanence (Mr) and coercivity (Hc) for magnetic
PLGA nanospheres in Figure 2 were close to zero,
illustrating the superparamagnetic characteristic
of the resulting nanospheres. As shown in Figure
2, it could be observed that both types of
materials exhibit similar overall
superparamagnetic behavior.
Results
The FTIR spectrum of freeze-dried magnetic PLGA
nanosphere was obtained by the KBr pellet method.
The FTIR spectrum shows the presence of all bands
of the PLGA (ester carbonyl CO stretch band at
1756 cm-1, strong), 1171 1090 (C-O-C in ester
group, strong), 28503010, 13601460 (saturated
C-H, including CH3, CH2, and CH), 3500 (terminal
OH, weak), a peak at 1660 cm-1 that is attributed
to 5-FU and a peak at 580 cm-1 that represents
the existence of magnetite nanoparticles. Scanning
electron microscopy (SEM) is powerful tools to
characterize size, morphology and structure of
magnetic PLGA nanospheres. The prepared samples
were observed by SEM to obtain information about
the morphology and surface characterization
(shape, distribution, aggregation) of the
magnetite PLGA nanospheres. The SEM micrographs
clearly show that magnetic PLGA nanospheres are
spherical in shape (Figure 1). The surface was
primarily smooth, although some roughness could
be identified in certain areas of some
nanospheres.
Introduction
In order to avoid the inconvenient surgical
insertion of large implants, injectable
biodegradable and biocompatible polymeric
particles (microspheres, microcapsules,
nanocapsules and nanospheres) could be employed
for controlled-release dosage forms 1.
Intravenous (i.v.) administration of drugs leads
to systemic distribution throughout the body
resulting in undesirable side effects and as a
consequence only a suboptimal dosage of drugs
reaches the desired target site. Magnetic
nanodevice for targeted delivery approach
involves administration of a therapeutic agent
bound or encapsulated in a magnetic carrier 2.
These magnetic nanodevices that have unique
surface properties permitting maximum
biocompatibility and biodegradability could be
suitable for drug delivery vehicles. Such systems
can be driven and held in the specific area for a
desired period of time by applying external
localized magnetic fields. Additional advantages
of this drug delivery by magnetic targeting
include the maintenance of drug levels within a
desired range by reducing their systemic
distribution and the possibility of administering
lower but more accurately targeted doses of the
cytotoxic compounds used in these treatments 3,
4. PLGA is an FDA approved polymer for certain
clinical uses which have been utilized widely in
drug delivering system as an effective
encapsulating material. The existence of a
separate encapsulated aqueous phase allows the
possibility of protecting biologically active
agent and possibly also of controlling their
release.
Figure 2 Magnetization vs. applied magnetic
field for magnetite nanoparticles and magnetic
PLGA nanospheres.
Conclusion
Magnetic drug targeting employing nanospheres as
carriers is a promising cancer treatment avoiding
side effects of conventional chemotherapy. This
study suggests that the modified multiple
emulsion - solvent evaporation process is a
prospective technique to prepare biodegradable
magnetic nanospheres containing water-soluble
sensitive agents. As a drug-release carrier,
PLGA is expected to provide a good release of
drugs. The control of the structure of such
copolymers would allow the proper selection in
the rates of both the drug release and the
biodegradation of microspheres or nanospheres.
Acknowledgements
The financial support of Iran National Science
Foundation is greatly acknowledged.
Figure 1 F SEM micrograph of the magnetic PLGA
nanospheres.
References
To investigate the magnetic properties of
magnetite nanoparticles and drug-loaded magnetic
PLGA nanospheres, VSM measurement was used.
Figure 2 shows the magnetization curve of the
prepared magnetite nanoparticles and drug-loaded
magnetic PLGA nanospheres. The saturation
magnetization (Ms) of the pristine magnetite
nanoparticles was found to be 38.2 emu/g and
magnetic PLGA nanospheres approximately was 13.7
emu/g, revealing an approximate magnetite content
36 wt.
Experimental part
1 R. Jalil, J.R. Nixon J. Microencapsulation,
7 (1990) 297. 2 S.H. Hu, K.T. Kuo, W.L. Tung,
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3396. 3 S. Goodwin, C. Peterson, C. Hoh, C.
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In brief, magnetite nanoparticles were dispersed
in DCM. Next, the inner aqueous solution was
prepared by dissolving 5-flourouracil as a
hydrophilic drug in water. The dispersion of
magnetite was emulsified in an organic solution
of the PLGA by ultrasonication in an ice bath to
obtain an oil-in-water-in-oil double emulsion.