Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 179, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.addr.2021.113916
Keywords
Glycoside hydrolases; Drug delivery systems; Clinical development; Targeted delivery; Enzyme therapeutics
Categories
Funding
- Australia Government Research Training Stipend
- Department of Education and Training Endeavour Postgraduate Leadership Award
- Hospital Research Foundation
- National Institutes of Health [R33A1119116-03]
- United States Army Medical Research and Materiel Command (USAMRMC) [W81XWH-15-PRMRPIIRA, AM-25]
- Hospital for Sick Children Proof of Principle Grant
- Canadian Institutes of Health Research [43998, 81361, FDN154327]
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Biofilm-dispersing enzymes have the potential to enhance microbial susceptibility to antibiotics and immune cells by degrading the extracellular polymeric matrix, but face challenges of denaturation and degradation in vivo. Drug delivery systems offer promise in overcoming these challenges through encapsulation and protection, providing a targeted therapeutic approach for biofilm-associated infections.
Biofilm-dispersing enzymes degrade the extracellular polymeric matrix surrounding bacterial biofilms, disperse the microbial community and increase their susceptibility to antibiotics and immune cells. Challenges for the clinical translation of biofilm-dispersing enzymes involve their susceptibility to denaturation, degradation, and clearance upon administration in vivo. Drug delivery systems aim to overcome these limitations through encapsulation, stabilization and protection from the exterior environment, thereby maintaining the enzymatic activity. Smart drug delivery systems offer target specificity, releasing payloads at the site of infection while minimizing unnecessary systemic exposure. This review highlights critical advances of biofilm-dispersing enzymes as a novel therapeutic approach for biofilm-associated infections. We explore how smart, bio-responsive delivery systems overcome the limiting factors of biofilm-dispersing enzymes and summarize the key systems designed. This review will guide future developments, focusing on utilizing selective and specific therapies in a targeted fashion to meet the unmet therapeutic needs of biofilm infections. (C) 2021 Elsevier B.V. All rights reserved.
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