Biomedical Engineering Reference
In-Depth Information
(PLGA) and PLA have been developed for drug delivery.
145
These polymeric
NMs have been effective in delivering their contents to intracellular targets.
In another study, a degradable, polyamine ester polymer, polybutanediol
diacrylate co amino pentanol (C32), a diptheria toxin suicide gene (
DT-A
)
driven by a prostate-specific promoter was directly injected into normal prostate
and prostate tumors in mice.
146
This C32/
DT-A
system resulted in notable size
decrease and apoptosis in 50% of normal prostate. A single injection of C32/
DT-A-triggered apoptosis in 80% of tumor cells present in the tissue; therefore,
it is expected that multiple NP injection would trigger a great percentage of
prostate tumor cells apoptosis.
MDR is known to develop through a variety of molecular mechanisms in
tumor cells. The enzyme, glucosylceramide synthase, is responsible for the acti-
vation of ceramide, the proapoptotic mediator, to glucosylceramide, a nonfunc-
tional moiety. This molecule is overexpressed by a number of MDR tumor types
and has been implicated in cell survival during chemotherapy. Investigation of
the therapeutic strategy of coadministering ceramide with TAX in an attempt to
restore apoptotic signaling and overcome MDR in a human ovarian cancer cell
line using modified poly(epsilon-caprolactone) (PEO-PCL) NPs to encapsulate
and deliver the therapeutic agents for enhanced efficacy was carried out.
147
The
studies showed that MDR cancer cells can be completely eradicated by this
approach and that MDR cells can be resensitized to a dose of TAX near the IC
50
of non-MDR cells. Molecular analysis of activity showed that the efficacy of
this therapeutic approach is due to a restoration in apoptotic signaling exhibiting
the potential for clinical use to overcome MDR.
5.9.1.1 Polylactic Glycolic Acid
NMs have a great risk of aggregation during storage, transport, and dispersion.
Degradation of the outer polymer coating can also be affected by particle size.
As an example, the rate of PLGA degradation was found to increase as the par-
ticle made from this polymer increased in size.
148
This degradation process is
believed to result from PLGA degradation products that easily diffuse through
shorter distances in smaller NPs, whereas the polymer matrix of larger particles
increases the time of release due to the greater distance that may cause autocata-
lytic degradation of the polymer.
149
PLGA has been widely studied for various medical applications. It has
also been extensively reported for drug delivery for different drugs and dis-
eases.
8,54,59,150,151,152,153,154
Seju et al.
152
focused on the use of PLGA for the
delivery of olanzapine (OZ), a second-generation or atypical antipsychotic drug
which selectively binds to central dopamine D
2
and serotonin (5-HT
2c
) recep-
tors. This drug has poor bioavailability due to hepatic first-pass metabolism
and low permeability into the brain that is due to efflux by P-glycoproteins.
152
They prepared PLGA using nanoprecipitation technique and characterized by
entrapment efficiency, particle size, zeta potential, modulated temperature dif-
ferential scanning calorimetry, and X-ray diffraction.
152
The NP showed a mean
