Lessons Learned from Pharmaceutical Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 123

et al. They suspect that the ELVIS effect can be transformed to other inflammatory
tissue as well, when they share similar pathophysiological features, such as vascular
leakage and activated inflammatory cells (Yuan et al. 2012). Another opportunity to
make use of passive targeting via pathophysiological changes is the particle accumu-
lation in inflamed areas of the intestinal epithelium (Schmidt et al. 2013; Lamprecht,
Schafer, and Lehr 2001).
To summarize, unique size and surface properties of nanoparticles give them the
chance to accumulate, for example, in tumor tissue, due to endothelial defectiveness.
Models like the EPR and also the ELVIS effect give nanoparticulate carrier systems
the possibility of passively targeting the site of action.
In contrast to passive targeting, active targeting, known as the modification of
carriers' surface with appropriate ligands to specifically target required pathological
sites in the body, is a more advanced approach. In addition, nanopharmaceuticals
offer unique formulation possibilities for the delivery of biopharmaceuticals, which
are often limited by chemical instability during formulation and storage, enzymatic
degradation in vivo , thus poor bioavailability. Besides stability issues of biopharma-
ceutics, bioavailability is also diminished due to the low permeability of biophar-
maceutics across cell barriers (Cleland, Daugherty, and Mrsny 2001). Due to the
progress in biotechnology, biopharmaceutics, such as proteins, peptides, and nucleic
acids, are currently representing a large fraction of compounds in drug develop-
ment pipelines (Wong 2009). Although parenteral application is the typical route
to deliver biopharmaceuticals and is so far the least expensive and quickest strategy
for commercialization, noninvasive routes of administration would still be favored.
Therefore, nanotechnology can play an important role in the delivery of such com-
pounds. They can not only serve as delivery agents but also protect the drug from
degradation and can furthermore control release and enhance permeation via cell
membranes (Almeida and Souto 2007).
Although there are only a few formulations on the market yet (a selection can be
found in Table 6.1) the impact of reformulated or novel nanoparticle-based formu-
lations on medicine and health care is more than promising. Figure 6.2 provides a
scheme to summarize the achievable advantages via nanoformulations.
6.5.2 n anoPharmaCeutiCals on the m arket
In the following section, examples of regulatory approved and thus marketed nano-
medicine products will be presented to illustrate their use for pharmaceutical appli-
cations. Examples of nanocrystals will be shown first, followed by two examples of
liposomal formulations (carrier systems). In particular, their formulation as well as
their advantage over conventional (i.e., non-nano) formulations will be explained. In
addition, an overview of various marketed formulations is shown in Table 6.1.
6.5.2.1 Rapamune ® (Sirolimus)
Although sirolimus failed in its original purpose as an antibiotic, it is today the
most potent immunosuppressive agent for the prevention of graft rejection in organ
transplantation. Its highly hydrophobic structure makes it practically insoluble in
water. Hence, bioavailability is greatly reduced. An oral lipid-based solution of