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The Key Laboratory of Molecular Engineering of Polymers, Ministry of Education and Department of Macromolecular
Science, Fudan University, Shanghai 200433, China
2
Keywords:
INTRODUCTION
There is growing scientific interest in developing
innovative biomaterials for biomedical applications. Among a wide range of polymeric materials,
poly (methyl methacrylate) (PMMA) has been
extensively studied in the past decades. It is
biocompatible and biostable materials, and has
already been used in bone-defect restoration.
For instance, Kelmn and other researchers have
utilized PMMA for approximately 20 years in
Europe for the management of open fractures,
chronic osteomyelitis, total joint arthroplasty, and
Correspondence to: Wei Zhong and Qiangguo Du (Telephone:
86-21-65642392; Fax: 86-21-65640293;
E-mail: weizhong@fudan.edu.cn; qgdu@fudan.edu.cn)
Journal of Pharmaceutical Sciences, Vol. 96, 15181526 (2007)
2006 Wiley-Liss, Inc. and the American Pharmacists Association
1518
succeeded in attaining an effective drug concentration at the inflammatory site without implanting extra materials, also, the effect of the inorganic
fillers on the drug release property of these
composites has been reported.69
It has been well documented that the interface
between polymer and inorganic fillers plays an
important role in the performance of polymerinorganic composite materials, such as gas permeability, selectivity, mechanical properties, and so
on.1012 It is often requested the interface between
the two materials in the composites should be well
adhesive. Organo-functional silanes, represented
as RSiX3, are often used as coupling agents to
enhance the adhesion between polymer and silica
filler.13 The methoxy or ethoxy groups, represented by X, can be hydrolyzed with water. The
silanol groups of hydrolyzed coupling agents can
be condensed with other silanol groups on a glass
or ceramic surface. The organo-functional group,
R, can be bonded chemically to a polymer matrix.
Thus, the adhesion between polymer and inorganic fillers was improved due to the chemical
bonds that formed at the interface.14 To our best
knowledge, how the interface inside organic
inorganic composite materials as well as the
coupling agents affect the drug release property
has not been studied. Understanding the interfacial interactions and structure is important to
better design and application of organicinorganic
composite drug delivery systems.
In present work, Aspirin was used as a model
drug and the drug release properties of PMMA/
silica composites were studied. Contrary to those
reported, composite drug delivery systems normally made by mixing of the polymer solution with
inorganic particles, the composites were prepared
via a solgel process by solvent mixing of PMMA
copolymers with silicic acid oligomer (SAO), a
novel silica precursor. The structure of the composite materials was characterized in order to study
the impact of the phase structure and interface
adhesion in the composite on their drug release
properties. In addition, models of mass transfer
employing Fickian diffusion law at constant
temperature and pressure were employed to
elucidate the experimental results.
1519
Mw 104
Mn 104
Polydispersity
PMMA
PMMA-3.5%
MSMA
PMMA-5%
MSMA
7.0
4.3
1.64
7.9
4.6
1.71
7.4
4.2
1.75
1520
LIN ET AL.
FT-IR Spectra
Wwet W0
100
W0
1521
SEM Images
Figure 2AC shows the scanning electron microscope (SEM) photographs of the fracture surface
of the PMMA/silica composite samples with
20 wt% silica but different amounts of MSMA.
The silica particle size of sample PMMA0/20
(Fig. 2A with 0% MSMA) is about 12 mm,
Table 2.
Sample Name
Residue (%)
DOI 10.1002/jps
PMMA0/20
PMMA3.5/20
PMMA5/20
92.6
96.8
1522
LIN ET AL.
1523
1524
LIN ET AL.
PMMA0/0
PMMA0/5
PMMA0/10
PMMA0/20
PMMA3.5/0
PMMA3.5/5
PMMA3.5/10
PMMA3.5/20
PMMA5/0
PMMA5/5
PMMA5/10
PMMA5/20
k (day1)
R2
0.0442
0.0572
0.0692
0.0950
0.0299
0.0351
0.0495
0.0496
0.0266
0.0234
0.0444
0.0450
0.998
0.993
0.990
0.992
0.997
0.998
0.991
0.972
0.997
0.998
0.994
0.991
DOI 10.1002/jps
CONCLUSION
In this study, PMMA/silica composite materials
with various MSMA proportion and silica content
have been prepared via solgel process. The
influence of MSMA proportion and silica content
on their drug release properties has been evaluated using aspirin as a model drug. The swelling
test and SEM results supported the hypothesis
that the interface between the polymer matrix
and silica particles played a key role in drug
release property of the composite system in PBS.
The drug release behaviors of the composite
samples fitted well with the Fickian diffusion
model. The drug release rate increased with the
increasing content of silica while decreased with
the amount of coupling agent in the composite
samples. The drug release rate of this composite
system can be modulated by adjusting the content
of both inorganic fillers and the coupling agent.
REFERENCES
1. Sivakumar M, Panduranga RK. 2000. Synthesis
and characterization of poly(methyl methacrylate)
functional microspheres. React Function Polym
46:2937.
2. Rhee SH. 2002. Preparation of a bioactive poly
(methyl methacrylate)/silica nanocomposite. J Am
Ceram Soc 85:13181320.
3. Ohtsuki C, Miyazaki T, Kyomoto M, Tanihara M,
Osaka A. 2001. Development of bioactive PMMAbased cement by modification with alkoxysilane
and calcium salt. J Mat Sci-Mat Med 12:895
899.
4. Ohtsuki C, Miyazaki T, Tanihara M. 2002. Development of bioactive organic-inorganic hybrid for
bone substitutes. Mat Sci Eng C 22:2734.
DOI 10.1002/jps
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LIN ET AL.
DOI 10.1002/jps