PASUT GIANFRANCO

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Structure Department of Pharmaceutical and Pharmacological Sciences
Telephone 0498275694
Qualification Professore ordinario
Scientific sector CHIM/09 - APPLIED TECHNOLOGICAL PHARMACEUTICS
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(updated on 27/06/2013 16:58)

Proposals for thesis
Proposed thesis are focused on the research aims presented in the "Research Area" section.
Pasut has several international collaborations that can be taken into consideration for the thesis subject.

Curriculum Vitae
Gianfranco Pasut is Assistant Professor of “Formulation of Biotech Drug” at the Department of Pharmaceutical and Pharmacological Sciences, University of Padova (Italy) since 2006.
He received a Master degree in Pharmaceutical Chemistry and Technology in 1999 and a PhD in Pharmaceutical Sciences in 2003, both from the University of Padova. In 2001, during his PhD program he was at the Rheumatology Dept, Medical School, University of Pennsylvania (USA) and in 2007 he was “Visiting Scientist” at the School of Pharmacy, University of Reading (UK).
His current research interests are focused on using polymers for the delivery of protein and small drugs. Studies have taken into consideration either synthetic or natural polymers such as poly(ethylene glycol) (PEG), poly (2-Ethyl 2-Oxazoline), hyaluronic acid, polyglutamic acid and polysialyc acid. Pasut has developed several protein conjugates and studied new approaches of protein-polymer conjugation also base on enzymatic approaches of conjugation by exploiting the selectivity of transglutaminase. In the field of drug delivery of small drugs, he investigated new targeted conjugates and conjugates for combination therapy for the treatment of cancer.
Research interest are also dedicated to the development of new PEG-dendron-phospholipids derivatives for the preparation of stealth liposomes with extended stability and half-life in vivo.
He has published 45 articles, 11 book chapters and he is the co-inventor of 9 patents.

Research areas
Nanomedicines have developed rapidly and their use is changing the world of medicine, leading to improved drug efficacy, fewer side effects and better patient compliance. Personalized nanomedicines are expected to be the future of clinical practice, but some aspects such as the development of feasible drug delivery systems must be solved before their use can be upscaled. An intense collaboration with pharmaceutical industries is necessary to ensure a balance between innovation and feasibility.
The aim of a drug delivery system is to increase the effectiveness of therapeutic protocols and at the same time to reduce toxicity and overall treatment costs. Out of the array of drug delivery approaches available, polymer conjugation is emerging because of its applicability to both low MW drugs and proteins. A water soluble polymer can confer several properties to linked molecules: i) increased half-life due to reduced kidney clearance, ii) protection against degrading enzymes or reduced uptake by reticulo-endothelial system (RES), thanks to the polymer steric hindrance iii) augmentation of water solubility, particularly relevant for some anticancer drugs with low solubility, iv) prevention of immunogenicity of heterologous proteins and v) selective tumour accumulation, coined, the ‘enhanced permeability and retention’ (EPR) effect which does not apply to low molecular weight drugs, which freely extravasate also from the normal vessels of healthy tissues, thus causing general toxicity.
My research focuses on two streams of study dealing with:
a) Polymer-drug conjugates
Over the past three decades, cancer research has not only been focused on understanding the molecular basis of cancer and in testing new small organic compounds but also in studying and exploring the potential of drug delivery systems.
Poly(ethylene glycol) (PEG) has a particular structure with only two functionalizable groups, which makes it possible to prepare conjugates with a precise chemical structure. We developed several high loading PEGs by synthesizing the dendron structure at one or both of the polymer’s ends. Those new polymers offer great control over the number of drug molecules coupled per polymer chain, and when an heterobifunctional PEG is used it is also possible to create well defined conjugates with the desired ratio between the polymer:drug:targeting agent. Other polymers are also studies, such as hyaluronic acid polyglutamic acid polysialic acid, poly(2-N-ethyl oxazoline), etc.
b) Polymer-protein conjugates
The rationale behind polymer conjugation is to prolong the plasma half-life of therapeutically active agents by increasing their hydrodynamic volume and hence reducing the kidney excretion rate. Polymer chains can, moreover, inhibit the approach of antibodies, proteolytic enzymes or cells on the surface of conjugated proteins, an effect obtained by steric hindrance of polymer chains.
We have developed several PEGs conjugates with therapeutic proteins, such as human growth hormone (hGH), granulocyte colony stimulating factor, asparaginase, interferon alpha, salmon calcitonin, insulin and a PEG-hGH conjugate has been tested in monkeys.
Researches are also focused on the study of microbial transglutaminase (mTGase) as an enzyme for enzymatic polymer conjugation. mTGase-mediated PEGylation presents two important advantages: i) the modification of glutamine, a residue that otherwise cannot be modified with chemical methods and ii) the enzyme selectivity.

Publications
Greco F, Arif I, Botting R, Fante C, Quintieri L, Clementi C, Schiavon O, Pasut G. Polysialic acid as a drug carrier: evaluation of a new polysialic acid–epirubicin conjugate and its comparison against established drug carriers. Polym Chem, 2013;4:1600-1609
da Silva Freitas D, Mero A, Pasut G. Chemical and Enzymatic Site Specific PEGylation of hGH. Bioconjug Chem, 2013;24:456-463
Miller K, Clementi C, Polyak D, Eldar-Boock A, Benayoun L, Barshack I, Shaked Y, Pasut G, Satchi-Fainaro R. Poly(ethylene glycol)-paclitaxel-alendronate self-assembled micelles for the targeted treatment of breast cancer bone metastases. Biomaterials, 2013;34:3795-3806
Mero A, Pasqualin M, Campisi M, Renier D, Pasut G. Conjugation of hyaluronan to proteins. Carbohydr Pol, 2013;92(2):2163-2170
Pasut G, Veronese FM. State of the art in PEGylation: the great versatility achieved after forty years of research. J Control Release. 2012;161(2):461-72
Mero A, Ishino T, Chaiken I, Veronese FM, Pasut G. Multivalent and flexible PEG-nitrilotriacetic acid derivatives for non-covalent protein pegylation. Pharm Res. 2011;28(10):2412-21
Clementi C, Miller K, Mero A, Satchi-Fainaro R, Pasut G. Dendritic poly(ethylene glycol) bearing paclitaxel and alendronate for targeting bone neoplasms. Mol Pharm. 2011;8(4):1063-72
Mero A, Schiavon M, Veronese FM, Pasut G. A new method to increase selectivity of transglutaminase mediated PEGylation of salmon calcitonin and human growth hormone. J Control Release. 2011;154(1):27-34
Pasut G, Greco F, Mero A, Mendichi R, Fante C, Green RJ, Veronese FM. Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action. J Med Chem. 2009;52(20):6499-502.
Pasut G, Veronese FM. PEG conjugates in clinical development or use as anticancer agents: an overview. Adv Drug Deliv Rev. 2009;61(13):1177-88
Pasut G, Mero A, Caboi F, Scaramuzza S, Sollai L, Veronese FM. A new PEG-beta-alanine active derivative for releasable protein conjugation. Bioconjug Chem. 2008;19(12):2427-31
Pasut G, Canal F, Dalla Via L, Arpicco S, Veronese FM, Schiavon O. Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acid. J Control Release. 2008;127(3):239-48
Pasut G, Sergi M, Veronese FM. Anti-cancer PEG-enzymes: 30 years old, but still a current approach. Adv Drug Deliv Rev. 2008;60(1):69-78.

List of taught course units in A.Y. 2018/19
Degree course code (?) Degree course track Course unit code Course unit name Credits Year Period Lang. Teacher in charge
ME2193 COMMON MEP5070484 11 2nd Year First
semester
ENG GIANFRANCO PASUT
FA1733 COMMON MEP3052598 6 5th Year First
semester
ENG GIANFRANCO PASUT