Poly(amidoamine) dendrimer-erythromycin conjugates for drug delivery to macrophages involved in periprosthetic inflammation

Admira Bosnjakovic, Manoj K. Mishra, Weiping Ren, Yunus E. Kurtoglu, Tong Shi, Dianna Fan, Rangaramanujam M. Kannan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)284-294
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume7
Issue number3
DOIs
StatePublished - Jun 2011
Externally publishedYes

Keywords

  • Drug delivery
  • Erythromycin
  • Macrophages
  • PAMAM dendrimer
  • Periprosthetic inflammation

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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