Abstract
Liposomes are closed bilayer structures spontaneously formed by hydrated phospholipids that are widely used as efficient delivery systems for drugs or antigens, due to their capability to encapsulate bioactive hydrophilic, amphipathic, and lipophilic molecules into inner water phase or within lipid leaflets. The efficacy of liposomes as drug or antigen carriers has been improved in the last years to ameliorate pharmacokinetics and capacity to release their cargo in selected target organs or cells. Moreover, different formulations and variations in liposome composition have been often proposed to include immunostimulatory molecules, ligands for specific receptors, or stimuli responsive compounds. Intriguingly, independent research has unveiled the capacity of several phospholipids to play critical roles as intracellular messengers in modulating both innate and adaptive immune responses through various mechanisms, including (i) activation of different antimicrobial enzymatic pathways, (ii) driving the fusion–fission events between endosomes with direct consequences to phagosome maturation and/or to antigen presentation pathway, and (iii) modulation of the inflammatory response. These features can be exploited by including selected bioactive phospholipids in the bilayer scaffold of liposomes. This would represent an important step forward since drug or antigen carrying liposomes could be engineered to simultaneously activate different signal transduction pathways and target specific cells or tissues to induce antigen-specific T and/or B cell response. This lipid-based host-directed strategy can provide a focused antimicrobial innate and adaptive immune response against specific pathogens and offer a novel prophylactic or therapeutic option against chronic, recurrent, or drug-resistant infections.
Highlights
Liposomes are small artificial spherical vesicles constituted by one or more phospholipid bilayers with the polar groups of phospholipids oriented to the inner and outer aqueous phase
This formulation was subjected to several critical issues, such as the instability in plasma and short blood circulation half-life, due to their interaction with high- and low-density lipoproteins that resulted in the rapid release of the encapsulated drug into the plasma, and the efficient liposome uptake and removal from circulation by the macrophage system
The size was shown to be a crucial determinant for circulation half-life of liposomes, as their elimination by phagocytes is directly correlated to the liposome diameter: MLV with diameters ranging from 500 to 5,000 nm are quickly removed by phagocytes, whereas ULV with diameters between 20 and 50 nm show the less propensity to be internalized by macrophages [5], but are characterized by a low volume available for drug entrapment
Summary
Independent research has unveiled the capacity of several phospholipids to play critical roles as intracellular messengers in modulating both innate and adaptive immune responses through various mechanisms, including (i) activation of different antimicrobial enzymatic pathways, (ii) driving the fusion–fission events between endosomes with direct consequences to phagosome maturation and/or to antigen presentation pathway, and (iii) modulation of the inflammatory response. These features can be exploited by including selected bioactive phospholipids in the bilayer scaffold of liposomes.
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