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New insight in medicine: can the rejuvenation of knowledge be useful for the older patient? Torna agli editoriali

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 inexistent.

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 departments.

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 in animals.

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.

Present address:
DBSF, Università dell'Insubria
via J.H. Dunant,3 - 21100 Varese

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