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

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 EditorIn 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.

Graphical AbstractDendrimer-erythromycin (dendrimer-EM) conjugate nanodevice is explored for the treatment of periprosthetic inflammation at lower doses. Appropriate ester linking of EM to a neutral PAMAM dendrimer enables improved intracellular uptake and pharmacological activity of EM in RAW 264.7 macrophage cell lines, which are the target cells for the in vivo treatment.Figure optionsDownload high-quality image (144 K)Download as PowerPoint slide