Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 7, Issue 3, Pages 284-294Publisher
ELSEVIER
DOI: 10.1016/j.nano.2010.10.008
Keywords
PAMAM dendrimer; Erythromycin; Drug delivery; Periprosthetic inflammation; Macrophages
Funding
- Ralph Wilson Foundation for Biomedical Engineering
- Wayne State Nanotechnology Initiative
- Rumble Fellowship
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Erythromycin (EM), an antibiotic that has been used for infectious diseases, is now gaining attention because of its novel anti-inflammatory effects. We explore a dendrimer-EM nanodevice for sustained treatment of orthopedic inflammation. To sustain pharmacological activity, EM was conjugated to poly(amidoamine) dendrimer (PAMAM) through an ester bond. A bifunctional PAMAM dendrimer was prepared having neutral hydroxy and reactive amine groups on the surface and was reacted with EM prodrug (EM-2'-glutarate). The cytotoxicity, efficacy and antibacterial properties were evaluated on macrophages (RAW 264.7 cells) associated with periprosthetic inflammation. The conjugate is noncytotoxic and showed significant reduction of nitrite level (by 42% as compared with untreated cells and free EM). The zone of inhibition of the conjugate on bacterial growth at different concentrations showed similar activity compared to free EM. The anti-inflammatory properties of EM combined with the targeting potential of the dendrimer can lead to sustained and targeted intracellular delivery. From the Clinical Editor: In this study, a specific dendrimer-erythromycin conjugate nanodevice is investigated for the treatment of periprosthetic inflammation. The anti-inflammatory properties of erythromycin combined with the targeting potential of the dendrimer can lead to sustained and targeted intracellular delivery. (C) 2011 Elsevier Inc. All rights reserved.
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