Studio del meccanismo d’azione e dei parametri strutturali di nuovi materiali ad azione antimicrobica

The increased demand of new and more effective materials able to reduce and prevent microbiological contamination is one of the great challenges of scientific research. In the last decade, the use of antimicrobial polymers has aroused a huge interest in the scientific community because they are effective, safe and able to avoid spreading multidrug-resistant microorganisms. Recently, Dr. Lorella Izzo of the University of Salerno developed a new family of non-leaching antimicrobial copolymers having star-type architecture A(BC)n (n = 1, 2, 4) containing m-PEG (block A), methylmethacrylate (MMA), and nonquaternized 2-(dimethylamino)ethyl methacrylate (DMAEMA) (blocks BC). Preliminary studies conducted on this copolymer have shown that their antimicrobial properties depends on the DMAEMA monomers and are strongly related to the topological structure of the composing copolymers. The first goal of my PhD project was to assess whether the antimicrobial and hemolytic activity of PEG(MMA-DMAEMA)n was influenced by the change of the three main components of copolymers: balance between charge density (AAEMA) and hydrophobicity (MMA), polymer architecture and variation of the N-substituent groups. To this aim, two new series of insoluble copolymers surfaces PEG(MMA-AAEMA)n-like were synthesized. They consisted inA(BC), A(BC)2 and A(BC)4 architectures, different ratio between AAEMA/MMA and different N-alkyl substituents of alkyl-aminoethyl methacrylates (AAEMAs: methyl, Me; ethyl, Et; isopropyl, i-Pr; and tert-butyl, t-Bu). We found that the antimicrobial activity of films was dependent on the amount of surface charge density rather than the hydrophobicity and they did not induce any hemolytic activity. The second objective of this project was to investigate the mechanism of action of these antimicrobial surfaces on gram-negative bacteria Escherichia coli. It has been shown that the copolymers cause an alteration of bacteria’s outer membrane permeability after 30 minutes of treatment, instead the cells died after treatments longer than 60 minutes. However, the bactericidal action of copolymers did not depend by the interaction with intracellular receptor because they directly interact with the cell membranes. Considering that the cationic pedant groups of AAEMA are not long enough to completely penetrate the cell wall, it has been suggested that the copolymers after the electrostatic interaction with bacteria surfaces interact with the LPS molecules causing the loss of stability of the outer membrane and the dead of bacteria. These findings provided enough evidence to speculate the mechanism of action of new antimicrobial surfaces PEG(MMA-AAEMA)n. [edited by author]