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

• Published in: Nanomedicine 2011-06, Vol.7 (3), p.284-294
• Main Authors: Bosnjakovic, Admira, MS, Mishra, Manoj K., PhD, Ren, Weiping, PhD, Kurtoglu, Yunus E., PhD, Shi, Tong, BS, Fan, Dianna, MS, Kannan, Rangaramanujam M., PhD
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Cell Death - drug effects; Dendrimers - chemical synthesis; Dendrimers - chemistry; Dendrimers - pharmacology; Drug delivery; Drug Delivery Systems; Erythromycin; Erythromycin - pharmacology; Erythromycin - therapeutic use; Inflammation - drug therapy; Inflammation - pathology; Internal Medicine; L-Lactate Dehydrogenase - metabolism; Lipopolysaccharides - pharmacology; Macrophages; Macrophages - cytology; Macrophages - drug effects; Mice; Microbial Sensitivity Tests; Nitrites - metabolism; Nylons - chemical synthesis; Nylons - chemistry; Nylons - pharmacology; PAMAM dendrimer; Particle Size; Periprosthetic inflammation; Polyamines - chemical synthesis; Polyamines - chemistry; Polyamines - pharmacology; Prosthesis-Related Infections - drug therapy; Staphylococcus aureus - drug effects; Static Electricity
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2010.10.008

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. 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.