Nanoparticles for the Oral Administration of Cancer Therapies - Intracellular Delivery: Fundamentals and Applications - page 497

carriers are capable of reducing the surface tension of the drug and, then, improve
its dissolution. However, these drugs (especially weakly basic drugs) may come out
of the formulation due to solubilization in the gastric fluid and may precipitate in
the intestinal fluid on gastric emptying. Thus, the maximum advantage of a lipid
formulation could only be drawn if the drug remains in lipid solution throughout its
residence in the gastrointestinal tract. However, the performance of lipid formulations
and the fate of the drug in the gastrointestinal tract depend on three different phe-
nomenons that occur simultaneously: dispersion, dilution and digestion of the
formulation. Dispersion of the formulation due to gastric agitation results in increased
exposure of the inner surfaces of the formulation, dilution in the gastric fluid results
in partitioning of the drug in the external fluid phase and enzymatic breakdown of
the lipid in the gastrointestinal tract can result in change in their composition, struc-
ture and potential loss of their solvent capacity. The digestion of the lipid vehicle
in the presence of gastric lipase results in reduction in their solubilization capacity
(Mohsin et al. 2009 ; Kaukonen et al. 2004 ). However, the precipitated drug may be
resolubilized by both the exogenous and the endogenous lipids in the form of
colloidal species in the intestinal region which would depend on several factors, like
the lipophilicity of the drug, the nature of the colloidal phases produced on digestion
of the different lipids and the kinetics of drug transfer between the digesting formu-
lation and the colloidal phases produced (Chakraborty et al. 2009 ).
Nanoemulsions
Nanoemulsions and self-emulsified drug delivery systems (SEDDS) have been
extensively used for oral administration of lipophilic compounds. Nanoemulsions
are heterogeneous systems consisting of two immiscible liquids in which one liquid
is dispersed as droplets within the other liquid (Singh and Vingkar 2008 ). Self-
nanoemulsified drug delivery systems are isotropic mixtures of oil, surfactant,
cosurfactant and drug that form fine oil-in-water (o/w) nanoemulsions upon mild
agitation in aqueous media (Nazzal et al. 2002 ). They are stabilized by an interfacial
film of surfactant molecules with a typical droplet size lower than 100 nm, which
guarantees efficient absorption of the droplets (Cai et al. 2010 ). These systems
improve the oral bioavailability of lipophilic drugs by different mechanisms including
drug solubilisation and protection against enzymatic degradation. In addition, the
small size of these droplets increases the interphase between the lipophilic droplet
and the aqueous medium of the gut facilitating a homogeneous and wide distribution
of the drug along the gastrointestinal tract.
However these systems usually need the presence of large amount of surfactant
agents, which can be of interest to modify the permeability of the membrane (Gao
2003, 2009 ); although, at the same time, may induce gastrointestinal side-effects.
In an attempt to reduce the surfactant side-effects and achieve rapid absorption of
poorly soluble drugs, it has been proposed a new class of supersaturable formulations
based on SEDDS formulations (S-SEDDS) (Gao 2003, 2009 ). The S-SEDDS con-
tain a reduced amount of surfactant and a thickening agent to temporarily stabilize