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Title: NANOTECHNOLOGIES:


1
NANOTECHNOLOGIES THE NEW GENERATION OF MEDICINE
Dr Mariano Licciardi
2
NANOTECHNOLOGIES NANOMEDICINE
NANOPHARMACEUTICALS
NANOPHARMACEUTICALS represent an emerging field
where the nanoscale element may refer to either
the size of the drug particle or to a therapeutic
delivery system. These therapeutic systems may be
defined as a complex system consisting of at
least two components, one of which is the active
ingredient. In this field the concept of
nanoscale is the range from 1 to 500 nm.
3
NANOPHARMACEUTICALS have the finality to optimize
drug delivery, bioavailability and in general
increase the efficacy of already known drug
molecules respect traditional dosage forms in
terms of
  • - chemical stability,
  • - promote selective drug accumulation into the
    target organs or cells,
  • - decrease administered dose,
  • decrease side and toxic effects,
  • - allow administration through all administration
    routes.

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Our research is focused on the preparation and
characterization of bicompatible polymers useful
to prepare nanopharmaceutical devices for
pharmaceutical and biomedical applications. In
particular our interest is addressed to some
synthetic polyaminoacids, such as
a,b-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA)
and a,b-polyaspartylhydrazide (PAHy). Both
polymers have attracted great interest, since
they are highly water soluble, non toxic, non
antigenic, non teratogenic and easily produced in
large quantities and at low cost. In particular,
the biocompatible polymers that we have
investigated, have been used as starting
materials to prepare
  • macromolecular prodrugs,
  • polymeric micelles,
  • polymer-protein complexes,
  • polycations for gene therapy
  • nanoparticles

6
a,b-poly (N-2-hydroxyethylaspartamide) (PHEA)
a,b-polyasparthylhydrazide (PAHy)
7
  • MACROMOLECULAR PRODRUGS

In macromolecular conjugates, active agents are
covalently linked to hydrophilic polymeric
carrier by hydrolizable bonds or spacers, so that
the hydrolysis of active agent/polymer linkage is
necessary to its release and to obtain the
effect. The main advantage of these systems is
constituted by their ability to efficiently
protect linked drug molecules, to increase
water-solubility, to increase bioavailabity and
modulate drug targeting and biodistribution.
1 nm d 20 nm
8
Examples of drugs linked to our polymers
Alclofenac, Naproxen,Ketoprofen Ibuprofen,
Diflunisal, Indometacin, Biphenilacetic acid
Amantadine,Aciclovir, Ganciclovir, Zidovudine
  • FANS
  • Antiviral DRUGS

Citarabine Taxol Gemcitabine
  • ANTICANCER DRUGS

9
RESULTS
Increase water solubility and chemical stability
of Taxol
PHEA-2-SUCCINYLTAXOL CONJUGATE
Promote passive targeting to a specific
organ liver
Eur. J. Pharm. Biopharm. 58, 151 (2004)
10
RESULTS
Promote selective drug targeting (mediated
by oxytocin receptors) inside ovarian and breast
tumors

Eur. J. Pharm. Biopharm. 66 (2007) 182
11
POLYMERIC MICELLES
Polymeric micelles are colloidal systems obtained
by self-assembling of amphiphilic copolymers
above critical aggregation concentration (CAC).
In the polymeric micelle the drug can be
incorporated by physical or upon chemical linking
to polymeric surfactant. The ability of polymeric
micelles to promote drug absorption is correlated
to the increase of cell membrane crossing, thus
strongly improving drug bioavailability.
10 nm d 200 nm
12
PHEA-PEG-C16
PAHy-PEG-C16
13
TUMOR DISTRIBUTION PROFILE
PHEA-PEG-C16 micelles slow and progressive
tumor accumilation after parenteral
administration in rat.
J. Control. Release, 89, 285 (2003)
14
INCREASED TAMOXIFEN SOLUBILITY AND CELL UPTAKE
Macromol. Biosci. 4, (2004) 1028
15
Polymer-protein complexes Polymeric complexes are
nanodevices formed by synthetic copolymers
properly designed in order to complex small
molecules or macromolecules by physical
interactions. Colloidal resulting systems are
able to strongly stabilize and protect peptide
and protein molecules, allowing their
administration for different administration
routes.
Application fields include successful oral
delivery of peptides, proteins and vaccines.
16
RESULTS AFTER ORAL ADMINISTRATION OF INSULIN
COMPLEXES
GOLD MEDAL AT SALON INTERNATIONAL DES INVENTIONS
GENEVE 2008
Patent N. RM2007A000327
International Application n. PCT/IT/2008/000376
17
INTERPOLYECTROLITE COMPLEXES
Polyplexes (InterPolyElectrolyte Complexes,
IPECs) are obtained by electrostatic interaction
between cationic polymers (positively charged)
and genetic material (such as plasmids or nucleic
acid based drugs, negatively charged)
these systems are able to condense genetic
material (until to colloidal size), in order to
make possible its introduction into cells and
besides they protect DNA from nuclease
degradation improving transfection efficiency.
50 nm d 500 nm
18
RESULTS PHEA and PAHy cationic copolymers have
been showed to be non toxic and able to transfect
plasmid to cells in vitro
J. Control. Release 131 (2008) 54
Nanomedicine 4(2) (2009) 291
Nanomedicine 5(2) (2010) 243
19
Nanoparticles Polymeric nanoparticles are drug
loaded nanomatrices obtained by chemical or
physical crosslinking of properly derivatized
synthetic (PHEA, PAHy) or natural
(polysaccarides) polymers. Nanoparticles can
incorporate high amount of active molecules (high
drug loading capacity) and control drug release
rate and biodistribution.
10 nm d 500 nm
20
PREPARATION OF POLYMERIC NANOPARTICLES BASED ON
PHEA COPOLYMERS
RESULTS Stealth nanoparticles based on PHEA
copolymers allowed successfully to escape
reticulo-endotelial system reducing non
productive effects and immunitary response.
PEG shell
macrophages
Biomacromolecules 7 (2006) 3083
21
CONCLUSIONS Nanotechnologies represent today a
very promising approach to design and obtain drug
and gene delivery systems with the aim to solve
the problems connected with the traditional
dosage forms. In the Laboratory of
Biocompatible Polymers of the University of
Palermo different nanotechnologies have been
produced for drug and gene delivery These
nanotechnologies have been successfully proposed
in nanomedicine, diagnostics and cosmetics. We
hope that research in this field could go on
obtaining more and more promising results.
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