3472
E. Turos et al. / Bioorg. Med. Chem. Lett. 17 (2007) 3468–3472
dermal fibroblast cells using a CyQUANT DNA bind-
ing assay. These experiments showed that all three nano-
particle formulations are non-toxic to the fibroblast cells
at 1 mg/mL drug concentrations, which are more than
10 times the bacterial MIC levels.
Department of Homeland Security for graduate fellow-
ships to K.G.
References and notes
In summary, these studies have established that penicil-
lin-containing polyacrylate nanoparticles can be easily
prepared by free radical emulsion polymerization in
water and are effective at helping to rejuvenate the
in vitro antibacterial activity of penicillin drugs against
beta-lactamase-producing MRSA. The favorable
features of this methodology include simple, one-step
preparation of penicillin-containing nanoparticles in
aqueous media, rigid control of nanoparticle size
in the 25–40 nm range, absence of cytotoxic effects in
healthy human cell culture, and ability to incorporate
drugs covalently onto the polymer framework or non-
covalently (encapsulated) without the need for post-syn-
thetic modification of the nanoparticle. Ongoing studies
in our laboratory are attempting to elucidate the mech-
anism of bioactivity and drug release of the nanoparti-
cles, and examining their in vivo properties in animal
infection models to determine their efficacy and poten-
tial for therapeutic applications.
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Acknowledgments
We thank Dr. Thomas Koob (Shriners Hospital, Tam-
pa) for assistance with performing the cytotoxicity
experiments, Gil Brubaker (University of Florida Parti-
cle Engineering Research Center) for helping with parti-
cle analyses, and August Heim (University of South
Florida) for assistance with AFM imaging experiments.
Financial support from the National Institutes of Health
(R01 AI051351) and National Science Foundation
(0620572) is gratefully acknowledged. We sincerely
thank the NSF-IGERT (DGE 0221681) and U.S.
17. Turos, E.; Coates, C.; Shim, J.-Y.; Wang, Y.; Leslie, J. M.;
Long, T. E.; Reddy, G. S. K.; Ortiz, A.; Culbreath, M.;
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