title: 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.
authors.affiliation: Department of Chemical Engineering, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Sebastian O
authors.initials: SO
authors.lastname: Wendel
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Sailesh
authors.initials: S
authors.lastname: Menon
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas, United States of America; University of Ha'il, Ha'il, Saudi Arabia.
authors.forename: Hamad
authors.initials: H
authors.lastname: Alshetaiwi
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Tej B
authors.initials: TB
authors.lastname: Shrestha
authors.affiliation: Department of Chemistry, Augustana College, Rock Island, Illinois, United States of America.
authors.forename: Lauren
authors.initials: L
authors.lastname: Chlebanowski
authors.affiliation: Department of Statistics, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Hsu
authors.affiliation: Department of Chemistry, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Bossmann
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas, United States of America.
authors.forename: Deryl L
authors.initials: DL
authors.lastname: Troyer
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000627:therapeutic use; D002417:Cattle; D002418:Cattle Diseases / Q000382:microbiology / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002710:Chlorhexidine / Q000008:administration & dosage* / Q000627:therapeutic use; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D004926:Escherichia coli / Q000187:drug effects; D005675:Fusobacterium necrophorum / Q000187:drug effects; D008100:Liver Abscess / Q000382:microbiology / Q000628:therapy / Q000662:veterinary*; D051379:Mice; D016982:Micrococcus luteus / Q000737:chemistry*; D009504:Neutrophils / Q000737:chemistry / Q000382:microbiology / Q000637:transplantation*
chemical_list: D000891:Anti-Infective Agents, Local; D002710:Chlorhexidine