Dextrin conjugation to colistin inhibits its toxicity, cellular uptake and acute kidney injury in vivo

Author:

Varache Mathieu1ORCID,Rizzo Siân1,Sayers Edward J.2ORCID,Newbury Lucy3,Mason Anna3,Liao Chia-Te4,Chiron Emilie1,Bourdiec Nathan1,Jones Adam15,Fraser Donald J.3,Taylor Philip R.46,Jones Arwyn T.2ORCID,Thomas David W.14,Ferguson Elaine L.1ORCID

Affiliation:

1. Advanced Therapies Group, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, CF14 4XY, UK

2. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, CF10 3NB, UK

3. Wales Kidney Research Unit, Division of Infection and Immunity, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Cardiff, CF14 4XN, UK

4. Systems Immunity Research Institute, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK

5. Cellular Pathology Department, University Dental Hospital, Cardiff and Vale University Health Board, Cardiff, CF14 4XY, UK

6. UK Dementia Research Institute at Cardiff, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK

Abstract

The acute kidney injury (AKI) and dose-limiting nephrotoxicity, which occurs in 20–60% of patients following systemic administration of colistin, represents a challenge in the effective treatment of multi-drug resistant Gram-negative infections.

Funder

Medical Research Council

Wellcome Trust

Publisher

Royal Society of Chemistry (RSC)

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