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.


BACKGROUND
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.
Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan 48202, USA.
Admira
A
Bosnjakovic
Manoj K
MK
Mishra
Weiping
W
Ren
Yunus E
YE
Kurtoglu
Tong
T
Shi
Dianna
D
Fan
Rangaramanujam M
RM
Kannan
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems; D004917:Erythromycin / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009573:Nitrites / Q000378:metabolism; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016459:Prosthesis-Related Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects; D055672:Static Electricity
D000900:Anti-Bacterial Agents; D050091:Dendrimers; D008070:Lipopolysaccharides; D009573:Nitrites; D009757:Nylons; C520550:PAMAM-G4; C531249:Poly(amidoamine); D011073:Polyamines; D004917:Erythromycin; D007770:L-Lactate Dehydrogenase