Carrier-mediated and artificial-cell targeted cancer drug delivery - Artificial Cells, Cell Engineering and Therapy - page 478

means of improving the tumor-specific delivery of anticancer agents by rapidly
releasing drug from the liposome when hypothermia is applied to the tumor area
(Mendelson et al., 2005).
21.2.2 Nanoparticles
ABI-007 is the first protein-stabilized nanoparticle approved by the FDA
(Gradishar, 2006; Socinski, 2006; Ibrahim et al., 2002). ABI-007 is an albumin
stabilized nanoparticle formulation of paclitaxel designed to overcome the
solubility issues associated with paclitaxel that require the need for solvents such
as cremophor, which have been associated with infusion-related reactions and
requires the need for premedication and other incompatibilities with certain IV
bags or tubing (Gradishar, 2006; Ibrahim et al., 2002). The albumin-stabilized
nanoparticle results in a more rapid distribution out of the vascular compartment
and provides a tumor targeting mechanism. The albumin receptor-mediated
transport on the endothelial cell wall with in blood vessels facilitates the passage
of ABI-007 from the bloodstream into the underlying tumor tissue (Gradishar,
2006; Ibrahim et al., 2002).
Similar to liposomal agents, the dosage of ABI-007 is determined by the
paclitaxel content of the formulation (Gradishar, 2006; Ibrahim et al., 2002).
The approved regimen for ABI-007 is 260mg/m 2 IV over 30 min every 3 weeks
which is higher than the usual dose range for paclitaxel (i.e. 135±200 mg/m 2 )
(Gradishar, 2006; Socinski, 2006). In addition there was a lower incidence of
myelosuppression after administration of ABI-007 than previously seen with
similar doses of paclitaxel (Ibrahim et al., 2002). The other toxicities associated
with ABI-007 were similar to high-dose, short-infusion paclitaxel including
sensory neuropathy and mucositis. Keratopathy, a relatively unique toxicity also
associated with ABI-007 was reported by Ibrahim et al. (2002). Thus, as with
liposomal formulations, administration of a drug in a nanoparticle formulation
can alter the pharmacokinetic, tissue and tumor distribution, and toxicity pattern.
Also similar to liposomal agents, the mechanism by which the albumin
stabilized nanoparticle is catabolized and paclitaxel is released is unclear.
21.2.3 Microspheres
Microencapsulation is an emerging technology in the development of bio-
artifical organs for drug, protein and delivery systems (Haque et al., 2005).
Bioencapsulation technology offers several advantages and has shown
promising results for the treatment of diseases. For all of these applications,
appropriate performance of the microcapsules is critically dependent on the
properties of the capsular membrane {P2}. Several studies have encapsulated
bacterial cells for potential therapeutic applications using oral administration,
such as in kidney failure uremia, cancer therapy, diarrhea, cholesteremia and