Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle

Abstract

The recent WHO report on antibiotic resistances shows a dramatic increase of microbial resistance against antibiotics. With only a few new antibiotics in the pipeline, a different drug delivery approach is urgently needed. We have obtained evidence demonstrating the effectiveness of a cell based drug delivery system that utilizes the innate immune system as targeting carrier for antibacterial drugs. In this study we show the efficient loading of neutrophil granulocytes with chlorhexidine and the complete killing of E. coli as well as Fusobacterium necrophorum in in-vitro studies. Fusobacterium necrophorum causes hepatic abscesses in cattle fed high grain diets. We also show in a mouse model that this delivery system targets infections of F. necrophorum in the liver and reduces the bacterial burden by an order of magnitude from approximately 2•106 to 1•105.

Posaconazole-Loaded Leukocytes as a Novel Treatment Strategy Targeting Invasive Pulmonary Aspergillosis

“…Furthermore, treatment with these drugloaded cells in a mouse model of F. necrophorum infection resulted in a significant reduction in bacterial burden, suggesting effective targeted delivery of chlorhexidine via neutrophils (197). The results of these two reports and the current study provide compelling evidence for the further study of cell-mediated drug delivery as a means of improving the efficacy of existing antimicrobials and as a strategy to overcome the barriers associated with traditional drug delivery methods.…”

Peptide nanosponges designed for rapid uptake by leukocytes and neural stem cells

“…28 Among them are stem cells, 29 monocytes/macrophages 30,31 and neutrophils. 32,33 Neural stem cells, which can be, principally, cultured and matched to patient-types, have been successfully utilized for cell-mediated therapies in rodent models, 22,27,34 as well as neutrophils 35,36 and monocytes. 10,23,24,27 The use of autologous cells has the potential of developing truly patient specic therapies, and also of signicantly lowering the regulatory barriers for cell-based human cancer therapies.…”

Evaluation of the antimicrobial activity and compressive strength of a dental cement modified using plant extract mixture

“…2. This can be explained on the basis that M. luteus is very sensitive to chlorhexidine which can be efficiently taken up by the bacteria according to Wendel et al [38]. The antimicrobial activity might be attributed to the different phytochemical constituents in each of the three incorporated PE.…”