12 In-vivo In-vitroold.polyacs.org/uploaded/files/2016FL_POSTER_Mitra.pdf · Mitzi Nagarkatti,§...
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Converting Natural Biomass to Amphiphilic Antimicrobial Polymers in Solution and on Surfaces Tang Polymer Research Group @ USC, Columbia, SC. URL: http://www.tangpolymer.org Motivation Antimicrobial Surfaces Bacterial infectious diseases have become a widespread health care crisis. Most antibiotics used today are prone to bacterial resistance. There is a great need for a resilient platform to develop antimicrobial agents to face the evolving microbial resistance. Antimicrobial peptides are a class of natural molecules acting to defend animals from emerging pathogens. They typically target bacterial cell membranes. Antimicrobial polymers are synthetic counterparts of them. An economical method was developed to prepare cationic resin acid compounds at kilograms scale without any chromatography purification. Strong antimicrobial activities against MRSA strains and minimum toxicities towards mammalian cells. Molecular dynamics simulations and dye-leakage assays indicated a membrane-disruptive mechanism of action. Medically relevant antimicrobial and anti-biofilm coatings were developed by grafting resin acid derived compounds and polymers on surfaces. The surfaces showed antimicrobial and antibiofilm properties against Gram (-) E. Coli and Gram (+) S. aureus bacteria. Quaternary ammonium containing cationic materials can be conveniently synthesized from biomass derived resin acids and itaconic acid and can be applied as antimicrobial agents in solution and on surfaces. Strong antimicrobial and anti-biofilm properties with minimum toxicities indicate that these materials are promising for biomedical applications. Dr. Kristen P. Miller Dr. Juhua Zhou Dr. Jerry Ebalunode Dr. Jifu Wang Dr. Kejian Yao Dr. Perry Wilbon S. Parker Singleton Mitra S. Ganewatta, † Pegah Mehrpouya-Bahrami, § Md Anisur Rahman, † Louis N. Mercado, † Yung P. Chen, ‡ Mitzi Nagarkatti, § Prakash Nagarkatti, § Alan W. Decho, ‡ and Chuanbing Tang † * † Department of Chemistry and Biochemistry, ‡ Department of Environmental Health Sciences, § Department of Pathology, Microbiology and Immunology (School of Medicine), University of South Carolina, Columbia, SC 29208 Antimicrobial Polymers Natural biomass derived chemicals show the potential to be modified into amphiphilic molecules with antimicrobial properties. Objectives Hydrophobic Cationic Convert natural resin acids and itaconic acid into cationic compounds and polymers that are soluble in water. Modify solid substrate surfaces using the biomass derived cationic polymers. Introduction Itaconic acid derived cationic and hydrophobic random polymers were synthesized via RAFT polymerization and post-polymerization modifications. Conclusions Acknowledgements 22 24 26 28 30 Elution Time (min) Đ = 1.26 M n = 3200 g/mol 0 100 200 300 400 500 0 20 40 60 80 100 % Hemolysis Polymer Concentration (μg/mL) S. aureus strain Compound 1 Polymer 2 MIC (μg/mL) CA-MRSA ATCC BAA-1717 5.0 9.9 HA-MRSA ATCC BAA-29213 6.0 14.0 CA-MSSA ATCC BAA-1718 7.3 8.8 MRSA-252 ATCC BAA-1720 4.8 19.0 HC 50 (μg/mL) > 500 > 492 Selectivity index (HC 50 /MIC) > 68 > 26 0 10 20 30 40 50 60 70 B cells CD8 T cells polymer 2 compound 1 Percent of cell population in splenocytes In-vitro In-vivo control polymer 2 compound 1 control polymer 2 compound 1 control CD4 T cells • Hydrophobic ring structure • Bulkiness - steric effects • Carboxylic acid • Conjugated diene • Anhydride Key Features: • Polymerizable acrylate group • Carboxylic acid • Anhydride Ganewatta M. S.; Tang C. Polymer, 2015, 63, A1-A29. The cationic surfaces promoted human dermal fibroblast growth. Ganewatta M. S.; Miller K. P.; Singleton S. P.; Mehrpouya-Bahrami P.; Chen Y. P.; Yan Y.; Nagarkatti M.; Nagarkatti P.; Decho A. W.; Tang C. Biomacromolecules, 2015, 16, 3336–3344. 10 20 30 0 2 4 6 8 10 12 Diameter of Inhibition Zone (mm) Polymer Concentration (μg/disk) S. aureus E. coli Ganewatta M. S.; Chen Y. P.; Wang J.; Zhou J.; Ebalunde J.; Nagarkatti M.; Decho A. W.; Tang C. Chem. Sci., 2014, 5, 2011-2016.
Transcript of 12 In-vivo In-vitroold.polyacs.org/uploaded/files/2016FL_POSTER_Mitra.pdf · Mitzi Nagarkatti,§...
Converting Natural Biomass to Amphiphilic Antimicrobial
Polymers in Solution and on Surfaces
Tang Polymer Research Group @ USC, Columbia, SC. URL: http://www.tangpolymer.org
Motivation
Antimicrobial Surfaces Bacterial infectious diseases have
become a widespread health care crisis.
Most antibiotics used today are prone to
bacterial resistance.
There is a great need for a resilient
platform to develop antimicrobial agents
to face the evolving microbial resistance.
Antimicrobial peptides are a
class of natural molecules
acting to defend animals from
emerging pathogens.
They typically target bacterial
cell membranes.
Antimicrobial polymers are
synthetic counterparts of
them.
An economical method was developed to prepare cationic resin acid
compounds at kilograms scale without any chromatography purification.
Strong antimicrobial activities against MRSA strains and minimum
toxicities towards mammalian cells.
Molecular dynamics simulations and dye-leakage assays indicated a
membrane-disruptive mechanism of action.
Medically relevant antimicrobial and anti-biofilm coatings were
developed by grafting resin acid derived compounds and
polymers on surfaces.
The surfaces showed antimicrobial
and antibiofilm properties against
Gram (-) E. Coli and Gram (+) S.
aureus bacteria.
Quaternary ammonium containing cationic materials can be conveniently
synthesized from biomass derived resin acids and itaconic acid and can
be applied as antimicrobial agents in solution and on surfaces.
Strong antimicrobial and anti-biofilm properties with minimum toxicities
indicate that these materials are promising for biomedical applications.
Dr. Kristen P. Miller
Dr. Juhua Zhou
Dr. Jerry Ebalunode
Dr. Jifu Wang
Dr. Kejian Yao
Dr. Perry Wilbon
S. Parker Singleton
Mitra S. Ganewatta,† Pegah Mehrpouya-Bahrami,§ Md Anisur Rahman,† Louis N. Mercado,† Yung P. Chen,‡
Mitzi Nagarkatti,§ Prakash Nagarkatti,§ Alan W. Decho,‡ and Chuanbing Tang†*
†Department of Chemistry and Biochemistry, ‡Department of Environmental Health Sciences, §Department of Pathology, Microbiology and Immunology (School of Medicine), University of South Carolina, Columbia, SC 29208
Antimicrobial Polymers
Natural biomass derived chemicals show the potential to be modified into
amphiphilic molecules with antimicrobial properties.
Objectives
Hydrophobic Cationic
Convert natural resin acids and itaconic acid into cationic compounds
and polymers that are soluble in water.
Modify solid substrate surfaces using the biomass derived cationic
polymers.
Introduction
Itaconic acid derived cationic and hydrophobic random polymers were
synthesized via RAFT polymerization and post-polymerization
modifications. Conclusions
Acknowledgements
22 24 26 28 30
Elution Time (min)
Đ = 1.26
Mn= 3200 g/mol
0 100 200 300 400 5000
20
40
60
80
100
% H
em
oly
sis
Polymer Concentration (µg/mL)
S. aureus strain Compound 1 Polymer 2
MIC (µg/mL)
CA-MRSA ATCC BAA-1717 5.0 9.9
HA-MRSA ATCC BAA-29213 6.0 14.0
CA-MSSA ATCC BAA-1718 7.3 8.8
MRSA-252 ATCC BAA-1720 4.8 19.0
HC50 (µg/mL) > 500 > 492 Selectivity index (HC50/MIC) > 68 > 26
0
10
20
30
40
50
60
70 B cells
CD8 T cells
poly
mer
2
com
pound 1Pe
rce
nt
of
ce
ll p
op
ula
tio
n
in s
ple
no
cy
tes
In-vitro
In-vivo
contr
ol
poly
mer
2
com
pound 1
contr
ol
poly
mer
2
com
pound 1
contr
ol
CD4 T cells
• Hydrophobic ring structure
• Bulkiness - steric effects
• Carboxylic acid
• Conjugated diene
• Anhydride
Key Features: • Polymerizable acrylate group
• Carboxylic acid
• Anhydride
Ganewatta M. S.; Tang C. Polymer, 2015, 63, A1-A29.
The cationic surfaces promoted
human dermal fibroblast growth.
Ganewatta M. S.; Miller K. P.; Singleton S. P.; Mehrpouya-Bahrami P.; Chen Y. P.; Yan Y.; Nagarkatti M.; Nagarkatti P.; Decho A. W.;
Tang C. Biomacromolecules, 2015, 16, 3336–3344.
10 20 300
2
4
6
8
10
12
Dia
mete
r o
f In
hib
itio
n Z
on
e (
mm
)
Polymer Concentration (µg/disk)
S. aureus
E. coli
Ganewatta M. S.; Chen Y. P.; Wang J.; Zhou J.; Ebalunde J.; Nagarkatti M.; Decho A. W.; Tang C. Chem. Sci., 2014, 5, 2011-2016.
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