Nanoparticulate Antibiotic Systems as Antibacterial Agents and Antibiotic Delivery Platforms to Fight Infections

Abstract

Today’s human society, product of decades of progress in all fields of knowledge, would have been unimaginable without the discovery of antibiotics and more generally of antimicrobials. However, from the beginning, the scientific community was aware that microorganisms through various strategies were able to hinder and render vain antibiotic action. Common examples are the phenomena of persistence, tolerance, and resistance, up to the creation of the feared bacterial biofilms. Antibiotics are a precious but equally labile resource that must be preserved but at the same time reinforced to safeguard their effectiveness. Nanoparticulate systems such as nanobactericides, with their inherent antibacterial activity, and nanocarriers, which operate as drug delivery systems for conventional antibiotics, are innovative therapies made available by nanotechnology. Inorganic nanoparticles are effective both as nanobactericides (AgNPs, ZnONPs, and TiO2NPs) and as nanocarriers (AgNPs, AuNPs, ZnONPs, and TiO2NPs) against sensitive and multi-drug-resistant bacterial strains. Liposomes are among the most studied and flexible antibiotic delivery platforms: conventional liposomes allow passive targeting at the mononuclear phagocytic system (MPS); “stealth” liposomes prevent macrophage uptake so as to eradicate infections in tissues and organs outside MPS; thanks to their positive charge, cationic liposomes interact preferentially with bacterial and biofilm surfaces, acting as innate antibacterials as well as drug delivery systems (DDS); fusogenic liposomes have fluid bilayers that promote fusion with microbial membranes; and finally, ligand-targeted liposomes provide active targeting at infection sites. Dendrimers are among the most recent and attractive nanoparticulate systems, thanks to their multibranched nanoarchitecture, which equipped them with multiple active sites for loading antibiotics and also interacting with bacteria. Finally, nanoantibiotics represent a new hopeful generation of antibiotic candidates capable of increasing or even restoring the clinical efficacy of “old” antibiotics rendered useless by the resistance phenomena.

Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields

“…Topical administration of antimicrobials onto the skin provides many advantages since it offers a high local load of the antimicrobial. Moreover, due to the pleiotropic mechanisms of action, AMPs can contribute to fight ESKAPE infections as well as to regulate various mechanisms including the host processes of inflammation and wound healing ( Kang et al, 2014 ; Vassallo et al, 2020 ). However, AMPs intended to treat chronic skin and soft tissue infections should not (i) be absorbed from the wound or infection site into the systemic circulation; (ii) rouse allergic sensitization.…”

Vantagens da utilização de antibióticos encapsulados em lipossomas para o combate de infecções causadas por enterobactérias

“…Os estudos da literatura sobre a entrega de antibióticos encapsulados em lipossomas comprovam que essa estratégia terapêutica é mais eficaz do que a entrega de antibióticos livres frente a infecções causadas por enterobactérias (El-Hammadi & Arias, 2019;Trucillo et al, 2020;Vassallo et al, 2020). Além disso, devido ao significado clínico da resistência bacteriana, as pesquisas têm sido intensificadas a fim de possibilitar a utilização de fármacos com espectro de ação limitada frente a isolados resistentes, que pode ser promovida por meio da encapsulação em lipossomas (Cé et al, 2021).…”

Inorganic Nanoparticles and Composite Films for Antimicrobial Therapies

“…While all types of NPs have been intensively studied for drug delivery applications, inorganic NPs provide more suitable features that ensure the protection and bioavailability of the drug with targeted action, limited adverse reactions to the organism, and higher efficiency due to improved drug transport and penetration [ 6 , 25 , 26 ]. Among the envisaged disease treatments, antimicrobial therapies are of considerable importance due to the possibility of developing alternative antimicrobial agents with the ability to destroy or inhibit the growth of antimicrobial-resistant pathogens [ 26 , 27 , 28 , 29 ]. In this regard, inorganic NPs demonstrated increased effectiveness both as nanobiocides due to their intrinsic antimicrobial properties and as nanocarriers for antimicrobial drugs [ 28 ].…”

“…Among the envisaged disease treatments, antimicrobial therapies are of considerable importance due to the possibility of developing alternative antimicrobial agents with the ability to destroy or inhibit the growth of antimicrobial-resistant pathogens [ 26 , 27 , 28 , 29 ]. In this regard, inorganic NPs demonstrated increased effectiveness both as nanobiocides due to their intrinsic antimicrobial properties and as nanocarriers for antimicrobial drugs [ 28 ]. This is of particular importance, as antimicrobial resistance, which results in standard treatment inefficiency and the subsequent persistence and spreading of infections, has become a global public health emergency [ 28 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

“…In this regard, inorganic NPs demonstrated increased effectiveness both as nanobiocides due to their intrinsic antimicrobial properties and as nanocarriers for antimicrobial drugs [ 28 ]. This is of particular importance, as antimicrobial resistance, which results in standard treatment inefficiency and the subsequent persistence and spreading of infections, has become a global public health emergency [ 28 , 30 , 31 , 32 , 33 , 34 , 35 ]. Precisely, according to the available statistics, there are up to 700,000 deaths due to antimicrobial resistance worldwide annually, with the number expected to rise to 10 million deaths by 2050 [ 28 , 36 ].…”