Agriculture Reference
In-Depth Information
have a single lipid bilayer. ULVs can be further classified into small unilamellar
vesicles (SUVs) and large unilamellar vesicles (LUVs) depending on their size
range (Jesorka and Owar
2008
). The challenge in making liposomes for antimicro-
bial delivery is to achieve the formation of homogeneous structures with adequate
properties and good encapsulation efficiency. Thus, several parameters must be
considered when selecting the method for liposome preparation, including the
physicochemical characteristics of the lipid ingredients and the substances to be
enclosed within the liposomes, particle size, polydispersity, zeta potential, expected
shelf life, batch-to-batch reproducibility, and the possibility for large-scale produc-
tion of safe and efficient products (Sharma and Sharma
1997
; Mozafari et al.
2008
).
Liposomes, in particular ULVs, are not spontaneously formed. In general, an
adequate energy input (sonication, extrusion, homogenization, shaking, or heating)
is supplied to phospholipid suspension in aqueous environment (Jesorka and Owar
2008
). The encapsulation of antimicrobial substances into liposomes is often
achieved by the thin-film hydration method or by the reversed-phase method
(Brandelli
2012
). In the first method, a lipid film is hydrated with an aqueous buffer
containing the antimicrobial substance, at a temperature above the phase transition
temperature of lipids. The resulting population of MLVs is further processed by
membrane extrusion or sonication to obtain SUVs of uniform size. In the reversed-
phase method, a solution containing the antimicrobial substance is dropped into the
lipid solution to form a water-in-oil emulsion. This emulsion is sonicated yielding
reverse micelles. After the organic solvent is evaporated, a viscous organogel is
formed, which is reverted to nanoliposomes after addition of ultrapure water
(Mertins et al.
2005
).
From the first description of the liposome structure in 1965, extensive studies on
their fundamental properties including lipid polymorphisms, lipid-protein and
lipid-drug interactions, and mechanisms of liposome disposition were developed,
and the potential application of liposomes as a drug delivery vehicle was thoroughly
recognized and started being transferred to practice in the 1980s. Liposomes were
originally introduced to the cosmetic market by Dior in 1986, and subsequently,
Doxil (doxorubicin liposomes) became the first liposome-based drug delivery
system approved by the US Food and Drug Administration (FDA) in 1995
(Zhang et al.
2010a
). Liposomes are the most extensively used antimicrobial drug
delivery system. As the liposomes contain both lipid and aqueous phases, they can
be used for the entrapment and delivery of hydrophilic, hydrophobic, and amphi-
philic molecules. An important feature of liposomes is its lipid bilayer structure,
which can directly fuse with cell membranes, releasing drug contents to the
microbial membranes or the interior of the microorganism. In addition, the lipo-
some surface can be easily modified with “stealth” materials to improve their
stability. Polyethylene glycol (PEG) has been frequently conjugated to liposome
surface to create a layer that prolongs the shelf life of liposomes in the bloodstream
(Milla et al.
2012
). The surface of liposomes can be also modified by the addition of
targeting ligands such as antibodies or lectins, which can bind selectively to
microorganisms or infected cells and then release the drug contents to exert its
antimicrobial effect.
