Biomedical Engineering Reference
In-Depth Information
Rh
rhodamine
DDS
drug delivery system
STPP
stearyl triphenyl phosphonium
Rh-123
rhodamine-123
PCL
paclitaxel
LSD
lysosomal storage diseases
ERT
enzyme replacement therapy
RhB
octadecyl derivative of rhodamine B
C
12
FDG
5-dodecanoylamino fluorescein di-b-D-galactopyranoside
1
Introduction
It is now well understood that nanocarrier-mediated drug delivery can control the
disposition of a drug within the body. The term 'targeting' in nanocarrier-mediated
drug delivery often involves binding of the nanocarrier to a cell-surface receptor
(receptors that are preferentially expressed/over-expressed on the target cell) fol-
lowed by internalization of the nanocarrier via the endocytic pathway. The problem,
however, is that any nanocarrier entering the cell via the endocytic pathway becomes
entrapped in the endosome and eventually ends up in the lysosome, where active
degradation under the action of the lysosomal enzymes takes place. This problem is
particularly critical for nucleic acids, peptidic drugs that are sensitive to degradation.
As a result, only a small fraction of such an unaffected substance appears in the cell
cytoplasm. So far, multiple but only partially successful attempts have been made to
bring various macromolecular drugs and drug-loaded pharmaceutical carriers
directly into the cell cytoplasm, bypassing the endocytic pathway. Methods such as
microinjection or electroporation used for the delivery of membrane-impermeable
molecules in cell experiments are invasive in nature and can damage the cellular
membrane (Chakrabarti et al.
1989
; Arnheiter and Haller
1988
). Non-invasive meth-
ods such as the use of pH-sensitive carriers, including pH-sensitive liposomes
(which at low pH inside endosomes destabilize endosomal membrane and liberate
the entrapped drug into the cytoplasm) (Straubinger et al.
1985
; Torchilin
2005b
)
and cell-penetrating molecules (Torchilin
2005b, 2007b
; Sawant and Torchilin
2010
)
are much more efficient. These approaches assume that just the cell cytosol delivery
is adequate for the final action of a drug or nucleic acid.
However, it has become increasingly evident that it is also necessary to control
the nanocarrier's disposition within the cell. Many drugs must be delivered to spe-
cific cell organelles such as nuclei (the target for gene and antisense therapy), lyso-
somes (the target for the delivery of deficient lysosomal enzymes in therapy of
lysosomal storage diseases), and mitochondria (the target for pro-apoptotic antican-
cer drugs) to exert their therapeutic action. Thus, the focus has now moved towards
targeting the nanocarrier or its cargo to an individual cell organelle.
Liposomes (mainly, for water soluble drugs) and micelles (for poorly soluble
drugs) can be considered as prototype nanocarriers. Liposomes are artificial
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