Biomedical Engineering Reference
In-Depth Information
a 2:1 concentration ratio showed the highest antitumor activity to three different
types of tumor cells that were studied.
In another study, the length of time for PLGA circulation in the bloodstream
was investigated using TAX-loaded chitosan and polyethylene glycol-coated
PLGA (PLGA-CS-PEG) NMs.
160
This study also looked at efficiency of encap-
sulation of hydrophobic drugs and evasion of phagocytic uptake by reducing
opsonization by blood proteins to increase the bioavailability of the drug by
optimizing the concentration of CS and PEG.
160
The efficiency of uptake and in
vitro cytotoxicity was evaluated in various cancer cell lines representing retino-
blastoma, breast cancer, and pancreatic cancer. The studies showed prolonged
blood circulation of the PLGA-CS-PEG NPs as well as reduced macrophage
uptake with minimal sequestration in the liver. This in vitro study showed the
synergistic effect of PEG-CS drug delivery NMs for prolonged blood circulation.
5.9.1.2 Liposome
Liposomes have been demonstrated to be useful for delivering pharmaceutical
agents. These systems use “contact-facilitated drug delivery,” which involves
binding or interaction with the targeted cell membrane allowing for enhanced
lipid-lipid exchange with the lipid monolayer of the NP, thereby accelerating
the convective flux of lipophilic drugs (e.g. TAX) to dissolve through the outer
lipid membrane of the NMs to targeted cells.
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These types of nanosystems can
serve as drug depots exhibiting prolonged release kinetics and long persistence
at the target site.
Medina et al.
81
developed PET tracers which irreversibly bound to EGFR.
They used a liposomal NP delivery system to alter the pharmacokinetic profile
and improve tumor targeting of highly lipophilic but otherwise promising can-
cer imaging tracers, such as the EGFR inhibitor SKI 243. In their study, they
compared the pharmacokinetics and tumor targeting of the bare EGFR kinase-
targeting radiotracer SKI 212243 (SKI 243) with that of the same tracer embed-
ded in liposomes. The results indicated that SKI 243 and liposomal SKI 243
were both taken up by tumor xenografts but liposomal SKI 243 remained in the
blood longer and consequently exhibited a three- to six-fold increase in uptake
in the tumor among several other organs.
NPs can be formulated to deliver drugs across several biological barri-
ers.
162,163
Antineoplastics, antiviral drugs, and several other types of drugs are
markedly hindered because of inability of these molecules to cross the BBB
which can be overcome with the application of NPs to deliver across this barrier.
It has been reported that NPs can cross the BBB following the opening of TJs
by hyperosmotic mannitol that may provide sustained delivery of therapeutic
agents for diseases that are difficult to treat like brain tumors.
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In another study, amorphous drug/polymer NPs were prepared from ethyl
cellulose and UK-157,147 (systematic name (3S,4R)-[6-(3-hydroxyphenyl)
sulfonyl]-2,2,3-trimethyl-4-(2-methyl-3-oxo-2,3-dihydropyridazin-6-yloxy)-
3-chromanol), a potassium channel opener, using sodium glycocholate (NaGC)
