Biomedical Engineering Reference
In-Depth Information
3.5
Conclusions and Future Directions
In summary, signii cant progress has already been made in the area of
liposomal therapeutics, and liposomes have come a long way as the car-
rier of choice for the delivery of pharmaceutical drugs. As this chapter
has reviewed current research on liposomes within a six year window,
certain trends have been identii ed. h ere has not been too much focus
on exploratory research with 'classical' and long-circulation liposomes
as these have already been well established over the past two decades.
Current research in the use of passively targeted liposomes has laid a
lot of onus on the use of stimuli-sensitive and triggered release systems
enabling us with more control to prevent of -target toxicities [270, 271].
In the case of targeted liposomes, there has been much more focus
on the use of engineered peptides from phage libraries for the selec-
tive delivery of drugs to the target site [272]. h ere is also a lot of evi-
dence to suggest that targeted liposomes even when PEGylated are still
taken up by the MPS or have been seen to cause non-specii c interac-
tions in healthy tissues, which express the target receptor. h e use of
dual-ligand combinations seeks to address both these issues. Using two
dif erent ligands not only allows for more selectivity, but also allows
us to go to a much lower overall ligand concentration if a synergistic
relationship is established between the ligands used. However, the use
of high-ai nity ligands, especially in tumor therapies, may also result
in the 'barrier ef ect' [273]. h e liposomes bind to the i rst cell in the
tumor with so much ai nity that they are unable to penetrate into the
tumor tissue ef ectively. h is accumulation at the i rst line of cells blocks
of access to the other formulations preventing deeper penetration.
It is becoming more evident that diseases like cancer are evolving to
become able to overcome traditional chemotherapeutics by developing
drug resistance etc. To combat this, many researchers have been develop-
ing strategies like the use of combination therapeutics, such as loading
dif erent drugs into the same liposome while simultaneously according
it stimulus-sensitive and targeting functions in the hope of developing
the ideal 'smart' carrier. Another contemporary approach has been the
use of various combination therapies such as treatment with radiation or
a chemotherapeutic agent to sensitize the cells to the primary treatment
modality. h ese have been summarized in Table 3.2. h e results from all
these approaches certainly seem encouraging and represent a very prom-
ising path for liposomal drug delivery systems.
