title: Hyaluronan/Tannic Acid Nanoparticles Via Catechol/Boronate Complexation as a Smart Antibacterial System.
abstract: Nanoparticles based on hyaluronic acid (HA) are designed to deliver tannic acid (TA) as an antimicrobial agent. The presence of HA makes these particles potentially useful to target bacteria that colonize cells presenting HA membrane receptors (e.g. CD44), such as macrophages. HA bearing 3-aminophenyl boronic acid groups (HA-APBA) is reacted with TA, yielding nanoparticles with a size that decreases with decreasing HA molecular weight (e.g. 200 nm for 44 kDa, 400 nm for 737 kDa). The boronate esters make the nanoparticles stable at physiological pH, but their hydrolysis in an acidic environment (pH = 5) leads to swelling/solubilization, therefore potentially allowing TA release in endosomal compartments. We have assessed the nanoparticle toxicity profile (on RAW 264.7 macrophages) and their antimicrobial activity (on E. coli and on both methicillin-sensitive and -resistant S. aureus). The antibacterial effect of HA-APBA/TA nanoparticles was significantly higher than that of TA alone, and has very similar activity to TA coformulated with a reducing agent (ascorbic acid), which indicates both the nanoparticles to protect TA catechols from oxidation, and the effective release of TA after nanoparticle internalization. Therefore, there is potential for these nanoparticles to be used in stable, effective, and potentially targetable nanoparticle-based antimicrobial formulations.
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK.|Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
authors.forename: Elita
authors.initials: E
authors.lastname: Montanari
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Arianna
authors.initials: A
authors.lastname: Gennari
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Pelliccia
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gourmel
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Enrique
authors.initials: E
authors.lastname: Lallana
authors.affiliation: Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Matricardi
authors.affiliation: Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McBain
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Tirelli
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001897:Boronic Acids / Q000737:chemistry*; D002396:Catechols / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D006820:Hyaluronic Acid / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D013211:Staphylococcus aureus / Q000187:drug effects; D013634:Tannins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001897:Boronic Acids; D002396:Catechols; D004337:Drug Carriers; D013634:Tannins; D006820:Hyaluronic Acid; C034221:catechol
keywords: catechols; hyaluronan; intracellular bacteria; pH-sensitive