Biomedical Engineering Reference
In-Depth Information
absorptive-mediated transcytosis, or by receptor-mediated transcytosis.
Hence, by manipulating the liposome structures, they can be constructed
to be temperature or pH sensitive to permit controlled release of their con-
tents. The dual problems of mediating BBB transport and inhibiting periph-
eral clearance of liposomes were solved by the combined use of PEGylation
technology and chimeric peptide technology [115]. After surface modifica-
tion of liposomes with these substances, they behave as a sterically stabi-
lized one, due to enhanced hydrophilicity imparted by polymers' hydrophilic
chains, a lower contact angle between particles and phagocytic cells of body,
and due to the lesser interaction between serum opsonins, thereby prevent-
ing opsonisation. Constructed temperature-sensitive liposomes loaded
with doxorubicin in combination with local hyperthermia, show a com-
plete regression of human tumor xenografts in all the mice studied [116].
The encapsulation of doxorubicin in polyethylene glycol-coated liposomes
(Doxil/Caelyx [PLD]), was developed to enhance the safety and efficacy of
conventional doxorubicin. The liposomes alter pharmacologic and pharma-
cokinetic parameters of conventional doxorubicin, so that drug delivery to
the tumor is enhanced while toxicity normally associated with conventional
doxorubicin is decreased. In preclinical models, PLD produced remission
and cure against many cancers, including tumors of the breast, lung, ovaries,
prostate, colon, bladder, and pancreas, as well as lymphoma, sarcoma, and
myeloma. PLD appeared to overcome multidrug resistance, possibly as the
result of increased intracellular concentrations and an interaction between
the liposome and P-glycoprotein function [117]. Several phase II studies
showed promising activity of PLD in recurrent ovarian cancer patients with
response rate ranging from 16 to 25% [118].
Bevacizumab is a recombinant humanized monoclonal antibody that in-
hibits VEGF, a growth factor ligand responsible for angiogenesis. Results
from several phase III clinical trials comprising colorectal, non-small cell
lung and breast cancer, demonstrate that bevacizumab results in superior
patient response rates. Bevacizumab can be used as a targeting moiety to
enhance the NPs efficacy. For this reason, bevacizumab-labeled cationic
liposomes have been developed, to improve targeting to several pancre-
atic cancer cell lines including Capane1, HPAFeII, and PANCe1 [119].
Bevacizumab-conjugated liposomes had modest impacts on cell viabil-
ity in vitro, and demonstrated increased cellular uptake by PANCe1 cells
grown in the presence of VEGF. Protein stabilization of liposomes is being
studied to deliver hydrophobic drugs such as docetaxel for cancer therapy.
Docetaxel is encapsulated into the liposome bi-layer and stabilized by albu-
min to prevent rapid drug leakage (ATI-1123). The results of ATI-1123 ef-
ficacy studies in human xenograft mice models for prostate, pancreatic, and
non-small-cell lung cancer showed partial tumor regression in 90% of the
PC3 tumor xenograft model, and improved efficacy in the pancreas model
[120]. Small-interfering RNA fragments have been found to suppress gene
