Antimicrobial peptides (AMPs) are among the most promising biomolecules for the development of new drugs to fight multidrug-resistant (MDR) bacteria and biofilm-associated infections. Although many natural and synthetic AMPs have good antimicrobial activity against MDR bacteria, their use is still limited by low cell permeability and oral bioavailability, limited stability, and some toxicity. The inclusion of AMPs in liposomes could protect them from degradation, increasing their bioavailability and reducing their toxicity [1,2]. This research was focused on some AMPs derived from a peptide isolated in an Antarctic fish [3] whose activity against ESKAPE (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter sp.) pathogenic bacteria [4] and different Candida species [5] had already been shown. For each AMP, depending on its physico-chemical properties and its antibacterial mechanism of action, the optimal liposome formulation was developed, by exploring anionic, cationic and neutral liposomal formulations, consisting of saturated and unsaturated lipids, also in presence of cholesterol. The lipid composition and the lipid/AMP molar ratio were varied and different preparation protocols were investigated in order to obtain stable and monodisperse formulations with the highest AMP entrapment efficiency, as determined by UV measurements. The colloidal stability of liposomes over time was evaluated by Dynamic Light Scattering (DLS) and ? potential measurements; the morphological characterization was carried out by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Finally, the ability of the selected liposomal formulations to interact with liposomes mimicking the bacterial cell membrane was assessed by fluorescence resonance energy transfer (FRET) experiments. The most promising candidates will be tested in in vitro and in vivo models for toxicity, pharmacokinetics and antibacterial efficacy. This work was carried out in the frame of the project NANOPEPTOBAT (Project n° A0375-2020-36557) funded by Regione Lazio within the call "Progetti Gruppi di Ricerca 2020" POR FESR Lazio 2014-2020.
Liposomes as drug delivery system for artic fish-derived antimicrobial peptides (AMPs)
Fabiana Pandolfi;Cecilia Bombelli;Francesca Ceccacci;Stefano Borocci;
2022
Abstract
Antimicrobial peptides (AMPs) are among the most promising biomolecules for the development of new drugs to fight multidrug-resistant (MDR) bacteria and biofilm-associated infections. Although many natural and synthetic AMPs have good antimicrobial activity against MDR bacteria, their use is still limited by low cell permeability and oral bioavailability, limited stability, and some toxicity. The inclusion of AMPs in liposomes could protect them from degradation, increasing their bioavailability and reducing their toxicity [1,2]. This research was focused on some AMPs derived from a peptide isolated in an Antarctic fish [3] whose activity against ESKAPE (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter sp.) pathogenic bacteria [4] and different Candida species [5] had already been shown. For each AMP, depending on its physico-chemical properties and its antibacterial mechanism of action, the optimal liposome formulation was developed, by exploring anionic, cationic and neutral liposomal formulations, consisting of saturated and unsaturated lipids, also in presence of cholesterol. The lipid composition and the lipid/AMP molar ratio were varied and different preparation protocols were investigated in order to obtain stable and monodisperse formulations with the highest AMP entrapment efficiency, as determined by UV measurements. The colloidal stability of liposomes over time was evaluated by Dynamic Light Scattering (DLS) and ? potential measurements; the morphological characterization was carried out by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Finally, the ability of the selected liposomal formulations to interact with liposomes mimicking the bacterial cell membrane was assessed by fluorescence resonance energy transfer (FRET) experiments. The most promising candidates will be tested in in vitro and in vivo models for toxicity, pharmacokinetics and antibacterial efficacy. This work was carried out in the frame of the project NANOPEPTOBAT (Project n° A0375-2020-36557) funded by Regione Lazio within the call "Progetti Gruppi di Ricerca 2020" POR FESR Lazio 2014-2020.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
