Antimicrobial and antioxidant amphiphilic random copolymers to address medical device-centered infections.
Microbial biofilms are known to support a number of human infections, including those related to medical devices. This work is focused on the development of novel dual-function amphiphilic random copolymers to be employed as coatings for medical devices. Particularly, copolymers were obtained by polymerization of an antimicrobial cationic monomer (bearing tertiary amine) and an antioxidant and antimicrobial hydrophobic monomer (containing hydroxytyrosol, HTy). To obtain copolymers with various amphiphilic balance, different molar ratios of the two monomers were used. (1)H NMR and DSC analyses evidenced that HTy aromatic rings are able to interact with each other leading to a supra-macromolecular re-arrangement and decrease the copolymer size in water. All copolymers showed good antioxidant activity and Fe(2+) chelating ability. Cytotoxicity and hemolytic tests evidenced that the amphiphilic balance, cationic charge density and polymer size in solution are key determinants for polymer biocompatibility. As for the antimicrobial properties, the lowest minimal inhibitory concentration (MIC = 40 μg/mL) against Staphylococcus epidermidis was shown by the water-soluble copolymer having the highest HTy molar content (0.3). This copolymer layered onto catheter surfaces was also able to prevent staphylococcal adhesion. This approach permits not only prevention of biofilm infections but also reduction of the risk of emergence of drug-resistant bacteria. Indeed, the combination of two active compounds in the same polymer can provide a synergistic action against biofilms and suppress reactive species oxygen (ROS), known to promote the occurrence of antibiotic resistance.
Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Vincenzo
V
Taresco
Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Fernanda
F
Crisante
Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Iolanda
I
Francolini
Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Andrea
A
Martinelli
Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Lucio
L
D'Ilario
Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Lucia
L
Ricci-Vitiani
Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Mariachiara
M
Buccarelli
ENEA-UTTAMB, C.R. Casaccia, Via Anguillarese 301, 00100 Rome, Italy.
Loris
L
Pietrelli
Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy. Electronic address: antonella.piozzi@uniroma1.it.
Antonella
A
Piozzi
D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D057785:Catheters / Q000382:microbiology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002614:Chelating Agents / Q000737:chemistry; D004864:Equipment and Supplies / Q000382:microbiology*; D004912:Erythrocytes / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D057446:Hydrodynamics; D007477:Ions; D007501:Iron / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D010851:Picrates / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D016459:Prosthesis-Related Infections / Q000188:drug therapy* / Q000382:microbiology; D066244:Proton Magnetic Resonance Spectroscopy; D012995:Solubility; D013501:Surface-Active Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014867:Water / Q000737:chemistry
D000890:Anti-Infective Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D002614:Chelating Agents; D006454:Hemoglobins; D007477:Ions; D010851:Picrates; D011108:Polymers; D013501:Surface-Active Agents; D014867:Water; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron
Amphiphilic copolymers; Antimicrobial polymers; Antioxidant polymers; Hydroxytyrosol; Medical device infections