Anna Giulia Cattaneo, M.D.
In recent years new technologies entered the field biomedical
sciences. They are based on a poorly studied, and innovative,
field of knowledge: namely, the science at nanoscale.
The chemicals behave in a completely unusual manner, when
at least one dimension is not greater than 100 nm, and they
show new properties in comparison with bulk materials. The
exploitation of nanoparticles (3D nano), nanowires (2D nano)
and nanosheets (1D nano) has been explosive in the last ten
years in the fields of material science and biotechnologies,
and the nanomedicine is emerging as the application of these
discoveries in the field of human health.
The most important property of nanomaterials is that they
are a subclass of colloids; therefore their behaviour is mimicking
the biological fluids and the cellular environments, both
the citoplasmic and the extracellular ones.
Despite their great promises, the nanomaterials approved
for the use in humans at a late experimental phase, or accepted
for clinical use, are by far very few.
The term nanodrug is restricted to formulations in which the
active molecule is contained in nanoparticles, embedded in
a polymeric shell acting as a transporter and a protective
coating. The shell is mostly of lipidic nature, mainly liposomic,
in other cases, the lipidic layer is substituted by an organic
polymer. The most strikingly properties of these formulations
are summarized by higher activity with lower systemic toxicity,
thanks to the ability of the drug to release "in situ"
in a prolonged and sustained manner. The release "in
situ" can be enhanced by the functionalization of the
nanoparticles surface with antibodies or other specific ligands
for molecules expressed by the target tissue. This is the
case of some antitumor agents, like the paclitaxel, the doxorubicin
and the cisplatin. The liposomal cytarabine is generally reserved
for the intrathecal use. These formulations are used in the
case of serious intolerance or resistance to the traditional
formulation, or when the cancer develops a resistance to classical
multidrug treatments. Trials on the use of nanodrugs in oncology,
especially focused on the needs of older people are practically
A different type of nanomaterials useful for medical uses
are those having their nanodimension restricted to the porosity
(e.g. the "mesoporous" silicon), those releasing
nanoparticles or those supported by a net of nanofibres. At
least several types of these nanomaterials can be precious
and innovative for the amelioration of the geriatric care,
and are dedicated to pathologies frequently seen in geriatric
The first to be mentioned, for the simplicity of use and
the wide field for applications, are protective coatings releasing
silver NPs and hydrogels for poorly healing wound, well performing
even in the case of burn lesions. However clinical trials
on the pressure wounds in older people are lacking, despite
the great frequency of these pathology.
A similar principle - the release of nanoparticles by a device
exceeding the nanoscale - support the ability of central venous
catheters (CVC) impregnated with nanoAg (AgTive©) to
avoid the bacterial growth. Implantable devices releasing
nanoparticulated drugs are successfully used to prevent stent
restenosis following cardiovascular surgery.
Another area of exploitation of nanotechnologies is the bone
and tissue repair. Implanted scaffolds of mesoporous silicon,
or other materials, offer a good substrate for the re-growth
of tissues and for remineralisation and repair of injured
bones. This is another hot area in geriatrics; unfortunately
the state of the art is in this case limited to the experiments
The unique physical chemistry of nanomaterials offers another
area of application, thanks to their particular bioavailability.
The nanoparticles, in fact, are able to reach the central
nervous system not only crossing the blood-brain-barrier,
but even through a passive diffusion across the "lamina
cribra" of the ethmoid, if inhaled. This property, well
defined and useful for the treatment of leukemic meningitis
in children, or even for the treatment of cerebral metastasis
in adults, has been postulated to be of benefit for the prevention
or cure of degenerative cerebral diseases common in aged people,
through the inhibition of free radical, of aggregation of
amyloids and peptides, or for gene-directed therapy (Ann N
Y Acad Sci. 2007; 1122:219-30). These studies move their first
steps in the lab, and their clinical application seems to
be, unfortunately, reserved to the future.
Much more interesting and current, in my opinion, are the
application to another poorly accessible district of the body,
namely the posterior pole of the eye. Nanodevices of mesoporous
silicon (a material with nanopores) embedding antinflammatory
drugs are available and able to promote a sustained and prolonged
release of the active molecule to the retina, offering a valuable
means to treat the age-related macular degeneration. This
type of treatment has been proposed for FDA approval even
to cure the diabetic retinopathy.
The variety of uses of nanomaterials for the cure of diseases
affecting the eye is discussed in recent works, evaluating
their usefulness in avoiding or stopping macular degeneration
and neovascularisation of the retinal or the choroid. Experiments
with implanted nanofibres scaffolds, obtained the axonal regeneration
of optic fibres sufficient to permit some degree of vision
regression of blindness in hamsters with severed optical trait
(Proc Natl Acad Sci U S A. 2006; 103:5054-9).
Despite these exciting perspectives and results, the advancement
of clinical exploitation of nanotechnologies is much slower
than the fervid experimental area in the general field. The
unusual physical-chemistry characterizing these materials
is at the basis of their innovative properties which make
them interesting, but is also the main hindrance to the knowledge
of their potential toxicity, unpredictable form the knowledge
about the corresponding traditional formulations. The surprising
properties of molecules at nanoscale, in fact, prohibit any
inference on their behaviour as toxic agents, and the study
in this field are very scarce at the present.
In summary, this Editorial presents a perspective for a lively
and innovative medicine, and opens the discussion for a rejuvenated
approach to the treatment of a number of ailments affecting
older people. If rejuvenation does not apply to the humans
beings, it must affect at least the human sciences and their
exploitations, with benefits for the older person too.
DBSF, Università dell'Insubria
via J.H. Dunant,3 - 21100 Varese
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