Many nanotechnology-based antimicrobials and antimicrobial-delivery-systems have been developed over the past decades with the aim to provide alternatives to
antibiotic treatment of infectious-biofilms across the human body. Antimicrobials can be loaded into nanocarriers to protect them against de-activation, and to reduce their toxicity and potential, harmful side-effects. Moreover, antimicrobial nanocarriers such as
micelles, can be equipped with stealth and pH-responsive features that allow self-targeting and accumulation in infectious-biofilms at high concentrations. Micellar and liposomal nanocarriers differ in hydrophilicity of their outer-surface and inner-core.
Micelles are self-assembled, spherical core-shell structures composed of single layers of
surfactants, with hydrophilic head-groups and hydrophobic tail-groups pointing to the micellar core.
Liposomes are composed of
lipids, self-assembled into bilayers. The hydrophilic head of the
lipids determines the surface properties of
liposomes, while the hydrophobic tail, internal to the bilayer, determines the fluidity of liposomal-membranes. Therefore, whereas
micelles can only be loaded with hydrophobic antimicrobials, hydrophilic antimicrobials can be encapsulated in the hydrophilic, aqueous core of
liposomes and hydrophobic or amphiphilic antimicrobials can be inserted in the
phospholipid bilayer. Nanotechnology-derived
liposomes can be prepared with diameters <100-200 nm, required to prevent reticulo-endothelial rejection and allow penetration into infectious-biofilms. However, surface-functionalization of
liposomes is considerably more difficult than of
micelles, which explains while self-targeting, pH-responsive
liposomes that find their way through the blood circulation toward infectious-biofilms are still challenging to prepare. Equally, development of
liposomes that penetrate over the entire thickness of biofilms to provide deep killing of biofilm inhabitants still provides a challenge. The liposomal
phospholipid bilayer easily fuses with bacterial cell membranes to release high antimicrobial-doses directly inside bacteria. Arguably, protection against de-activation of
antibiotics in liposomal nanocarriers and their fusogenicity constitute the biggest advantage of liposomal antimicrobial carriers over antimicrobials free in
solution. Many Gram-negative and Gram-positive bacterial strains, resistant to specific
antibiotics, have been demonstrated to be susceptible to these
antibiotics when encapsulated in liposomal nanocarriers. Recently, also progress has been made concerning large-scale production and long-term storage of
liposomes. Therewith, the remaining challenges to develop self-targeting
liposomes that penetrate, accumulate and kill deeply in infectious-biofilms remain worthwhile to pursue.