Nanoparticles for the Oral Administration of Cancer Therapies - Intracellular Delivery: Fundamentals and Applications - page 498

a supersaturated amount of the drug. In this context, Gao and collaborators used a
typical SEDDS (formulated with Cremophor ® EL and a mixture of ethanol and
glyceryl dioleate) mixed with hydroxypropylmethylcellulose for the oral delivery
of paclitaxel. This formulation displayed a fourfold higher bioavailability of the
anticancer drug that when formulated as Taxol ® . Co-administration of this
S-SEDDS-paclitaxel formulation with cyclosporine A (as inhibitor of the P-gp)
resulted in significantly higher absolute bioavailability of paclitaxel (threefold
higher than without the inhibitor of the P-gp) (Gao et al. 2003 ).

Lipid Nanoparticles

Solid lipid nanoparticles are devices made from lipids that are solid at room tem-
perature. In the body, they can be erosioned and degraded by bile salts and pancreatic
lipase (Roger et al. 2010a ). In principle, these systems are specifically designed for
the controlled release of lipophilic compounds such as paclitaxel (Cai et al. 2010 ).
Thus, paclitaxel-loaded lipid nanocapsules demonstrated a threefold increase in the
oral bioavailability of this anticancer drug in comparison with Taxol ® orally
administered. This effect on the oral paclitaxel bioavailability would be directly
related to the presence of the surfactant Solutol ® HS15, which would inhibit the
P-glycoprotein efflux system. Besides, lymphatic transport of paclitaxel and the
nanocapsule structure might also be beneficial for the oral permeability of paclitaxel
(Roger et al. 2010b ; Peltier et al. 2006 ). However, in some cases, solid lipid nano-
particles can present an insufficient drug loading capacity due to drug expulsion
after polymorphic transition during storage (Almeida and Souto 2007 ).

3.3.2 Polymer Nanoparticles

Nanoparticles that combine bioadhesive properties with a certain inhibitory capacity
of the P-gp extrusion system and cytochrome P-450 complex can be an adequate
strategy for oral chemotherapy. Then, a high therapeutic efficacy and less side effects
of the drug can thus be expected. Another advantage from these polymer nano-
particles can be their inherent properties to control the release of the loaded drug,
which may be of interest to obtain sustained and prolonged release of the drug.
In this way, it was reported a novel bioadhesive drug delivery system based on
the combination between poly(d,l-lactide-co-glycolide) nanoparticles and mont-
morillonite (PLGA/MMT) for the oral delivery of paclitaxel. Paclitaxel-loaded
PLGA/MMT nanoparticles were prepared by the emulsion/solvent evaporation
method and montmorillonite was incorporated in the formulation as a matrix mate-
rial component, which also plays the role of a co-emulsifier in the nanoparticle
preparative process. Besides, these nanoparticles were coated with trastuzumab
(human epidermal growth factor receptor-2 antibody or HER2). Trastuzumab “deco-
ration” of nanoparticles significantly increased their cellular uptake by a human
breast cancer cell line (SK-BR-3) and Caco-2 (Sun et al. 2008 ; Dong and Feng 2005 ).