The H

1
NMR data for metronidazole acrylation resulted in the
expected peak spectrum.
The absence of a metronidazole hydroxyl hydrogen peak
at ~5 ppm suggests successful acrylation.
Multiplet vinyl peaks at ~6 ppm
Hydrogen peak d shifted downfield

The H
1
NMR data for metronidazole acrylate purification
resulted in the expected peak spectrum
The absence of characteristic TEA peaks at 2.5 and 1ppm
demonstrate the removal of TEA from the precipitate

The release study for metronidazole from PMMA scaffolds is
in progress
The release of MTZ from PMMA scaffolds matches
known literature values within a reasonable range
2
Approximately 17% of drug release occurred within the
first week
Variation from published sources is probably due to a
differing geometry

The release study for metronidazole acrylate release from
PMMA scaffolds is in progress
UV Spectroscopy methods of determining release of MTZ
were not able to distinguish between MTZ and TEA
New trial with purified MTZA is needed





Carissa Livingston
1
, Alexander M. Tatara
1
, Antonios G. Mikos
1
, F. Kurtis Kasper
1
1
Department of Bioengineering, Rice University, Houston, TX

Background
Materials and Methods
Discussion
Conclusions
Metronidazole Acrylation
200 mg of MTZ was added to 8 mL chloroform under constant
stirring to create a suspension
Suspension was purged with N
2
for 5min at 0
o
C
0.65 mL of triethylamine was added to the suspension and purged
for 5 min
0.1 mL acryloyl chloride was added to the suspension and purged
for 5 min
Mixture was gradually brought to room temperature while stirring
overnight
Chloroform was removed by rotary evaporation
Analyzed product using proton nuclear magnetic resonance
spectroscopy (H
1
NMR): deuterated dimethyl sulfoxide solvent
Polymer Synthesis
1 g of PMMA polymer was mixed with MTZ or MTZA at 5 wt%
0.5 mL liquid methyl methacrylate monomer was added and
stirred for 30-40 s until onset of doughing
Mixture was pressed into polytetrafluorethylene cylindrical molds
(6 mm in diameter and 2 mm in height) and allowed to set for 24
48 hr
Release Testing
Constructs were stored in a warm room in 2 mL of Phosphate
Buffered Saline (PBS)
At weekly time points the concentration of MTZ in PBS was
measured using a UV Spectrometer
Traditional methods of antibiotic delivery, such as intravenous or oral
delivery release a low concentration of antibiotic distributed non-
specifically throughout the body. Smart biomaterials allow for the
controlled delivery of antibiotic to the area of concern only when
bacterial agents are present. Our goal is to create a polymer that can
be used to deliver metronidazole (MTZ), an antibiotic commonly
used to treat anaerobic bacterial infections such as periodontitis or
osteomyelitis.
1
Last semester, we developed a one-pot reaction to
create an acrylated antibiotic, metronidazole acrylate (MTZA). After
synthesis of the product, the results were confirmed via H
1
NMR.
Subsequently, we copolymerized the MTZA with poly(methyl
methacrylate) (PMMA) bone cement. Further studies are needed to
purify the MTZA monomer and to ensure that MTZA is being
adequately copolymerized. Additionally, the ability of esterases to
cleave the functional group from the PMMA and antibiotic construct
will be determined. Ultimately, this research will contribute to the
creation of a smart biomaterial for use in orthopedic applications.

Objectives:
Purification of Metronidazole Acrylate
Determination of the release kinetics of Metronidazole from
Poly(Methyl Methacrylate) scaffolds
Determination of the release kinetics of Metronidazole in the
presence of bacterial esterases
References
Acknowledgements
Results

Figure 1b - The H
1
NMR data for 17.5mg metronidazole acrylate in
0.7mL of deuterated DMSO
Successful Metronidazole Acrylate Synthesis
Confirmed by H
1
NMR

Successful TEA Purification
Confirmed by H
1
NMR
Potential to allow for clean UV spectroscopy results in
PMMA/MTZA scaffolds

Release Study in Progress
Control release studies have been completed
There continues to be a need to examine release in
presence of bacterial esterase

Thanks to Brendan Watson for assistance with product synthesis
and H
1
NMR analysis.

Synthesis of Metronidazole Acrylate
For Use in a Smart Biomaterial
a
b
c d
f g,h
f g h
b
d c
a
e
a
b
c d e
a
c
d b

Figure 1a - The H
1
NMR data for 10.58 grams of metronidazole
dissolved in 10 mL of deuterated DMSO

1. THAT BACKGROUND MTZ OVERIVIEWPAPER THING
2. THAT VET PAPER RELEASE THING





Figure 2b - The H
1
NMR data of purified MTZA

Figure 2a - The H
1
NMR spectrum for TEA


Figure 3a Metronidazole Release from PMMA constructs