Biomedical Engineering Reference
In-Depth Information
in tumor vascular permeability. In a recent study, in vivo murine U87MG
glioblastoma multiforme model, liposomal topotecan increased survival
more than 20-fold [258]. The efficiency of liposomal and other NP-based
drug delivery systems, such as colloidal nonlipidic coated polymeric NPs,
microspheres, and micelles, is enhanced by targeting of various molecules.
In a novel research, MPEGylated PCL nanoparticles containing paclitaxel
were prepared by the emulsion and evaporation technique. C6 glioblastoma
cell viability studies showed that MPEG-NP/paclitaxel could produce
higher or at least comparable cytotoxicity than Taxol injection. As demon-
strated by in vivo real-time fluorescence imaging analysis in intracranial C6
glioblastoma bearing mice, the MPEGylated PCL nanoparticles displayed
much stronger fluorescence signal in tumor tissue, and larger area-under-
curve than non-MPEGylated PCL nanoparticles. The therapeutic improve-
ment of MPEG-NP/paclitaxel in vivo against intracranial C6 glioblastoma
was also obtained based on the effect of passive tumor targeting [198]. One
interesting approach consists of coating a NP with polysorbate 80, which
adsorbs apolipoproteins B and E, and allows receptor-mediated endocytosis
by brain capillary endothelial cells. In these studies, 40% of the rats treated
with doxorubicin loaded nanoparticles survived the duration of the study
(6 months), with no evidence of residual tumor. Similarly, PEGylated doxo-
rubicin loaded solid lipid nanoparticles can enhance delivery across the BBB
after intravenous administration in rabbits [259]. Doxorubicin was pres-
ent in the brain only after administration of the nanoparticle formulation
and the extent of doxorubicin transport was dependent on the extent of
PEG modification. Recently, a promising chemotherapeutic drug (SN-38)
incorporated in micelles was compared with CPT-11, a prodrug of SN-38,
for the glioblastoma treatment in mice. The growth-inhibitory effects of
the drug-loaded micelles were 34- to 444-fold more potent than those of
CPT-11. In addition, when the drug was incorporated in the nanovectors, a
significantly potent anti-tumor activity against an orthotopic glioblastoma
multiforme xenograft and significantly longer survival rates than CPT-11
were observed [260].
A new strategy to achieve selective drug delivery to tumor tissue is mag-
netic targeting. This approach has the advantage of enhancing the attraction
of drug-loaded magnetic NPs in cancer cells by using an externally ap-
plied magnetic field [194]. Among the other polymer-derived drug delivery
systems, the nanoconjugate Polycefin (based on polymalic acid) has been
studied in animal models of human glioma, using intracranial injections of
human cancer cells. Antiangiogenic results have been obtained in rats by
injection, in vivo, of human glioma U87MG xenografts [261]. A novel study
aimed to examine the applicability of polyethyleneimine (PEI)-modified
magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to
brain tumors. The obtained data show that cationic magnetic nanoparticles
GPEI exhibit high cell penetration ability and low cell toxicity. In addition,
