multifunctional nanocarriers encapsulating anti-alzheimer drug for nasal delivery to central nervous

130 Pages·2012·2.95 MB·English

Alma Mater Studiorum – Università di Bologna

DOTTORATO DI RICERCA IN

SCIENZE FARMACEUTICHE

Ciclo XXIV

Settore Concorsuale di afferenza: 03/D2

Settore Scientifico disciplinare: CHIM/09

MULTIFUNCTIONAL NANOCARRIERS ENCAPSULATING
ANTI-ALZHEIMER DRUG FOR NASAL DELIVERY TO
CENTRAL NERVOUS SYSTEM

Presentata da: Giuseppe Corace

Coordinatore Dottorato Relatore

Chiar.mo Prof. Maurizio Recanatini Chiar.mo Prof. Vittorio Zecchi

Esame finale anno 2012

“Imagination is more important than knowledge.
For knowledge is limited to all we now know and understand,
while imagination embraces the entire world,
and all there ever will be to know and understand”

Albert Einstein
To my Family
ACKNOWLEDGMENTS

I would like to express my gratitude to my supervisor, Prof. Vittorio
Zecchi for his guidance and knowledge, and all the Drug Delivery
Group, to Dr. Federica Bigucci, Dr.TeresaCerchiara and
especially to my unofficial supervisor, Dr. Barbara Luppi who
supported me with an invaluable assistance, support and guidance
during the research work and thesis revision.
I express my sincerest gratitude to Dr. Cristina Cavallari, Prof.
Lorenzo Rodriguez and Prof. Adamo Fini for their scientific and
friendly support, which never came less, always accompanying me since
I was a master student.
I am deeply thankful to Prof. Silvana Hrelia, Dr. Cristina
Angeloni and Dr. Elisa Motori (Dep. Biochemistry “G.
Moruzzi”) for their studies on neuronal cultures and especially for
their willingness and kindness.
I would like to express a special thanks to Prof. Martin Brandl and
his entire Research Group (Drug Delivery, Institut for Fysik,
Kemi og Farmaci, Odense, Denmark), to Prof. Annette
Bauer-Brandl, Prof. Judith Kuntsche, Prof. Paul Stain,
Max di Cagno, Sarah Fischer, Ulla M. Brinkmann Trettenes,
Kerstin Frank and technical support staff (Tina Christiansen and
Karen Elmquist) for their hospitality, when I spent my period of
research abroad.
Thanks also goes out to my master students (Stefano Palmieri,
Francesca Cordeschi, Elena Monti, Anna Paola Nunzella,
Valentina Iaia, Mariangela Conserva, Mirko Montagnoli,
Alice Delucca, Luca Mancini, Yari Delvecchio, Silvia Lelli),
teach them has humanly enriched me
Finally, the biggest thanks goes to my Family for giving me the
strength to follow my dreams.

Giuseppe Corace

LIST OF PAPERS DISCUSSED

This thesis includes the papers listed below:

1. Barbara Luppi; Federica Bigucci; Giuseppe Corace; Alice Delucca; Teresa
Cerchiara; Milena Sorrenti; Laura Catenacci; Anna Maria Di Pietra; Vittorio
Zecchi. Albumin nanoparticles carrying permeation enhancers for nasal
delivery of tacrine hydrochloride.
Eur. J. Pharm. Biopharm. 44(4):559-65; 2011
Reproduced with permission. License Number: 2861131055273. © 2011
Elsevier

2. Giuseppe Corace, Barbara Luppi, Cristina Angeloni, Elisa Motori, Silvana
Hrelia, Paul C. Stein, Martin Brandl, Roberto Gotti and Vittorio Zecchi
Multifunctional Liposomes For Nasal Delivery Of The Anti-Alzheimer Drug
Tacrine Hydrochloride. Part 1: Formulation, Characterization, In-Vitro/Ex-
Vivo Permeability And Neuronal Uptake Evaluation
In preparation for the Journal of Controlled Release

3. Giuseppe Corace, Barbara Luppi, Cristina Angeloni, Elisa Motori, Silvana
Hrelia, Paul C. Stein, Martin Brandl, Roberto Gotti and Vittorio Zecchi
Multifunctional Liposomes For Nasal Delivery Of The Anti-Alzheimer Drug
Tacrine Hydrochloride. Part 2: Tocopherol Lateral Diffusion And
Neuroprotective Effect Evaluation.
In preparation for the Journal of Controlled Release
My contribution:
I contributed to all part of above papers except for the thermal analyses (TGA and
DSC) reported in the paper 1, that were performed by Dr. Milena Sorrenti and Dr.
Laura Catenacci (Department of Pharmaceutical Science, University of Pavia, Pavia,
Italy), the evaluation of Tacrine Log D by NMR reported in paper 2, that was
performed in collaboration with Prof. Paul C. Stein (Department of Physics,
Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark), the
quantification of the Tacrine in the neuronal extract by HPLC reported in the paper 2,
that was performed by and in collaboration with Prof. Roberto Gotti (Department of
Pharmaceutical Sciences, University of Bologna, Bologna, Italy) the neurotoxicity
and neuroprotection reported in paper 3, that were performed by and in collaboration
with Dr. Elisa Motori, Dr. Cristina Angeloni and Prof. Silvana Hrelia (Department of
Biochemistry “G. Moruzzi”, University of Bologna, Bologna, Italy).