Biomedical Engineering Reference
In-Depth Information
microenvironments thus exposing the targeting ligands. Similarly, Zhu
et al.
developed a liposomal formulation targeted with 2C5 and TATp
and coated with a MMP-2 sensitive PEG-based polymer [252].
In recent years, there have been a number of studies involving the
delivery of a combination of drugs encapsulated in the same liposome
with the hope of eliciting a synergistic ef ect [253, 254]. Drug resistance
represents a major obstacle in the treatment of many cancers with con-
ventional liposomal systems encapsulating just one drug. Liposomes for
the combined delivery of transforming growth factor inhibitor as well as
interleukin-2 for increased tumor immunotherapy were developed [255].
Belogurov
et al.
demonstrated the use of mannosylated liposomes encap-
sulating three myelin basic protein peptides for the ef ective treatment
of experimental autoimmune encephalomyelitis in rats [256]. Liposomes
co-loaded with irinotecan and phytic acid were also developed and their
cytotoxic ef ects on colon tumors were evaluated
in vitro
and
in vivo
in
a murine xenograt model [257]. Inhalable liposomes co-loaded with
paclitaxel and a vitamin E analog signii cantly inhibited murine mam-
mary tumors when compared to single treatments [258]. Liposomes con-
taining a combination of specii c P-gp inhibitors and anti-cancer drugs
also represent a novel approach to overcoming multi-drug resistance in
tumors [259]. Liposomes co-loaded with vincristine and quinacrine have
also proved to be ei cient in overcoming resistant human leukemia in a
murine xenograt model [260]. In a recent study, Raju
et al
developed vita-
min E - conjugated Trastuzumab liposome containing docetaxel [261].
To try to overcome multidrug resistance at a gene level, many groups
have employed the use of liposomal systems co-loaded with either siRNA
[262] or DNA [263, 264] and a cytotoxic drug. Similarly, anti-ganglioside
liposomes co-loaded with c-myc antisense oligoneucleotide and doxo-
rubicin showed signii cant tumor growth inhibition [265]. h e hypoth-
esis is that the oligonucleotide sensitizes the cell to doxorubicin. Another
approach has been the use of apoptosis-inducing ligands like TRAIL to
sensitize the cell to conventional anti-cancer drugs to improve therapeu-
tic ef ects [266]. Similarly, peptide-targeted liposomes containing pacli-
taxel and the gene encoding for TRAIL showed increased cytotoxicity in
a murine glioma model [267]. Recently Sawant
et al.
demonstrated the
use of palmitoyl ascorbate (PA)-modii ed liposomes loaded with pacli-
taxel as a novel combination for the treatment of cancer [268, 269]. It was
shown that PA causes cytotoxicity by increasing the formation of reactive
oxygen species.
