The artificial cell design: liposomes - Artificial Cells, Cell Engineering and Therapy - page 81

Active carriers
As far as so-called `active' carriers are concerned, a comprehensive account is
outside the scope of this chapter. Recently, thermosensitive liposomes have been
described which are able to accumulate in tumours because of their long-
circulating properties (see below) and to release doxorubicin in response to local
heating (Ishida et al., 2000; Chen et al., 2004). Release of doxorubicin from
liposomes has also been achieved by high-intensity focused ultrasound (Yuh et
al., 2005).
Another type of active carrier which is attracting much attention at the
moment is liposomes containing magnetic iron particles, or magnetoliposomes
(reviewed by Ito et al., 2005). These carrier systems have potential both as
contrast agents for magnetic resonance imaging and for guided drug delivery to
tumours, especially when long-circulating formulations are used to take
advantage of the so-called EPR effect (Martina et al., 2005). Since these
systems can be destabilized by hyperthermia, they could be used for site-specific
release of an encapsulated drug. The attachment of a tumour-specific ligand at
the surface would further enhance the efficacy of this approach (Kullberg et al.,
2005).
3.3.4 Long-circulating liposomes
Despite encouraging results with these `conventional' carrier systems, much
research has been devoted towards designing carriers with modified distribution
and new therapeutic applications. One major axis is the development of
sterically stabilized, or `Stealth TM ', carriers which undergo greatly reduced
opsonization and uptake by the mononuclear phagocyte system and therefore
open up new perspectives for applications by the intravenous route. Secondly,
since internalization of colloidal carriers usually leads to the lysosomal compart-
ment, it may be necessary to modify the intracellular distribution of the carrier.
This is particularly true when the encapsulated drug is a nucleic acid. Delivery
systems are necessary for this type of molecule because they are susceptible to
nuclease-mediated degradation in the circulation and penetrate poorly through
membranes. However, they are also susceptible to nuclease attack within the
lysosomes and their site of action is either in the cytoplasm in the case of an
antisense or small interfering RNA strategy or in the nucleus in the case of gene
replacement or anti-gene therapy. Thus, systems have been developed which
either fuse with the plasma membrane or have a pH-sensitive configuration
which changes conformation in the lysosomes and allows escape of the
encapsulated material into the cytoplasm. Finally, the ultimate goal would be to
be able to direct the drug carrier system to a specific cell type; that is, to develop
a third-generation carrier.