10.3.2.2 Liposomes
Liposome is a spherical vesicle which is composed of one or multiple bilayers
[112]. The size of liposome can range from tens of nanometers to several
micrometers. Compared with other nanocarriers, liposomes possess many advantages, such as excellent biocompatibility and biodegradability, low toxicity and
immunogenicity [113]. Thus, liposomes have been widely investigated as vehicle
for chemo drugs and genes since its first description in 1961 [114]. However, one of
the most disadvantages is the poor stability. In order to improve their stability and
endow liposomes with some new functionality, different strategies have been
adopted to modify the surface of liposomes [115, 116]. Unlike protein nanoparticles
whose modification is predominantly achieved by chemical reaction, both physical
and chemical modification are widely adopted for liposome preparation [117, 118].
Physical functionalization strategies include adsorption with surfactants, coating
with polymers and layer-by-layer electrostatic deposition [119]. Huang et al.
reported that the formation of elastic liposomes with Tween 80 could greatly
improve their stability [120]. The as-prepared liposomes were employed as drug
carriers, which could not only protect the encapsulated drug from enzymatic
degradation in gastrointestinal fluids, but also successfully deliver the drug to the
blood and brain in a sustained manner. As the presence of dipalmitoylphosphatidylcholine (DPPC) and stearyl amine, the liposomes were positively charged
and they were easily coated with negatively charged polymeric molecules with high
stability. Jain et al. developed polyelectrolyte-coated liposome via layer-by-layer
electrostatic deposition for the oral delivery of doxorubicin (DOX) [121]. Stearyl
amine containing liposomes were firstly coated with anionic PAA and then the
cationic polyallyl amine hydrochloride (PAH) was introduced by a layer-by-layer
electrostatic deposition strategy. The obtained liposomes possessed a robust
structure after formulation optimization and were used for delivery of DOX.
Occasionally, the loaded cargo (e.g. doxorubicin or bisphosphonates) in liposomes
can serve as a ‘physical attractor and stabilizer’ for radioisotopes (e.g.
64 Cu/
52 Mn/
89 Zr) loading via metal-p electron interactions (Fig. 10.5b) [122, 123].
Another study used liposome to encapsulate folate-conjugated DFO for radiolabeling of
89
Zr via ligand exchange [124].
The chemical modification strategies of liposomes could be categorized into
pre-modification and post-modification methods. In pre-modification methods, the
ingredients were firstly modified with functional molecules (PEG, targeting ligands,
or stimuli-responsive linkers) before their self-assembly into liposomes [125, 126]
while in post-modification techniques, liposomes were incubated with micelles
formed from functional molecules to form functionalized liposomes. Although the
pre-modification methods are tedious and difficult for quality control compared with
the latter ones, they were more widely adopted to synthesize functional liposomes
as this method can maintain the integrity of liposomes to a better extent while the
latter method is only applicable in some specific liposome. For example, during the
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D. Chen and H. Hong
Liposome is a spherical vesicle which is composed of one or multiple bilayers
[112]. The size of liposome can range from tens of nanometers to several
micrometers. Compared with other nanocarriers, liposomes possess many advantages, such as excellent biocompatibility and biodegradability, low toxicity and
immunogenicity [113]. Thus, liposomes have been widely investigated as vehicle
for chemo drugs and genes since its first description in 1961 [114]. However, one of
the most disadvantages is the poor stability. In order to improve their stability and
endow liposomes with some new functionality, different strategies have been
adopted to modify the surface of liposomes [115, 116]. Unlike protein nanoparticles
whose modification is predominantly achieved by chemical reaction, both physical
and chemical modification are widely adopted for liposome preparation [117, 118].
Physical functionalization strategies include adsorption with surfactants, coating
with polymers and layer-by-layer electrostatic deposition [119]. Huang et al.
reported that the formation of elastic liposomes with Tween 80 could greatly
improve their stability [120]. The as-prepared liposomes were employed as drug
carriers, which could not only protect the encapsulated drug from enzymatic
degradation in gastrointestinal fluids, but also successfully deliver the drug to the
blood and brain in a sustained manner. As the presence of dipalmitoylphosphatidylcholine (DPPC) and stearyl amine, the liposomes were positively charged
and they were easily coated with negatively charged polymeric molecules with high
stability. Jain et al. developed polyelectrolyte-coated liposome via layer-by-layer
electrostatic deposition for the oral delivery of doxorubicin (DOX) [121]. Stearyl
amine containing liposomes were firstly coated with anionic PAA and then the
cationic polyallyl amine hydrochloride (PAH) was introduced by a layer-by-layer
electrostatic deposition strategy. The obtained liposomes possessed a robust
structure after formulation optimization and were used for delivery of DOX.
Occasionally, the loaded cargo (e.g. doxorubicin or bisphosphonates) in liposomes
can serve as a ‘physical attractor and stabilizer’ for radioisotopes (e.g.
64 Cu/
52 Mn/
89 Zr) loading via metal-p electron interactions (Fig. 10.5b) [122, 123].
Another study used liposome to encapsulate folate-conjugated DFO for radiolabeling of
89
Zr via ligand exchange [124].
The chemical modification strategies of liposomes could be categorized into
pre-modification and post-modification methods. In pre-modification methods, the
ingredients were firstly modified with functional molecules (PEG, targeting ligands,
or stimuli-responsive linkers) before their self-assembly into liposomes [125, 126]
while in post-modification techniques, liposomes were incubated with micelles
formed from functional molecules to form functionalized liposomes. Although the
pre-modification methods are tedious and difficult for quality control compared with
the latter ones, they were more widely adopted to synthesize functional liposomes
as this method can maintain the integrity of liposomes to a better extent while the
latter method is only applicable in some specific liposome. For example, during the
198
D. Chen and H. Hong