Recent Advances with Liposomes as Drug Carriers - Advanced Biomaterials and Biodevices - page 87

liposome at lower pH conditions was demonstrated [94], and such sen-
sitive polymers have been successfully used with liposomal prepara-
tions for the delivery of DNA [95]. In another interesting study, Hiraka
et al. developed pH-sensitive liposomes to deliver Fe-porphyrin for
its anti-cancer ef ects [96]. h e hypothesis was that Fe-porphyrin
would cause cell death by the generation of reactive oxygen species.
Non- PEG polymers like polyampholytes [97] and poly(hydroxypropyl)
methacrylamides [98] have also been successfully used to take advantage
of this pH-triggered ef ect. Although a majority of pH-sensitive release
systems depend on an exogenous change in pH, there exist few examples
of release by internal acidii cation. Recently Wehunt et al. designed a car-
rier composed of pH-sensitive lipids, wherein the application of an HCL
cotransporter allows for internal acidii cation and subsequent release of
the encapsulated cargo [99]. In another approach, Yao et al. made use of a
pH-sensitive peptide incorporated into the liposome with the idea of fus-
ing with endosomal membranes at low pH and subsequently delivering the
contents into the cell ef ectively [100].
3.2.3.2 Enzyme-SensitiveLiposomes
Another approach uses liposomal coatings degradable by extra-cellular
enzymes [101]. Recently, there has been a lot of interest in the use of matrix
metallo-proteinases (MMPs) to trigger the release of liposomal contents
[102]. Various MMPs have been implicated in a variety of disease mod-
els and thus serve as viable targets for assisted release of nanocarriers.
Banerjee et al. demonstrated the use of an MMP-9 cleavable lipopeptide
[103]. h e cleavage of the lipopeptide compromised the structural integrity
of the liposome thus releasing the encapsulated carboxyl uorescein dye.
Phospholipase 2-sensitive liposomes were also developed for the delivery
of siRNA [104]. Liposomes with a glutathione-reducible PEG coating were
also used to ef ectively deliver DNA to the cells [105].
3.2.3.3 Ultrasound-TriggeredLiposomes
For the development of ultrasound-sensitive liposomes, it is imperative that
the liposome contains substantial air pockets in addition to its drug cargo,
i.e. could be considered liposomal microbubbles [106]. It was hypothesized
that the application of external ultrasound at the target site would allow the
liposomes accumulated there to break open and release their cargo [107].
Studies have also shown that the liposome-membrane composition greatly
af ects the sensitivity of liposomes to ultrasound [108]. Echogenic lipo-
somes have thus been successfully developed for the delivery of drugs like