Objective During their life time one from three people will suffer from cancer and due to inadequate treatment one from four will die. The main objective of this proposal is to prepare a new generation of tumour targeting polymer conjugates of anticancer drugs with improved therapeutic performance, based on soluble, biodegradable high molecular weight polymers, and to bring at least one of them up to the level of clinical evaluation.Rationale: Polymer conjugates of anticancer drug containing bound active moieties are used to improve pharmacokinetics, prolonging antitumour activity and decreasing protein immunogenicity. This technique allows concentrating the drug in solid tumour tissue by enhanced capillary permeability and retention (EPR) effect. This effect is strictly dependent on the molecular weight of the conjugates, the higher the molecular weight the higher the selectivity achievable. The first generation of polymer conjugates, N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymer conjugates with doxorubicin and poly(ethyleneglycol) (PEG)-L-asparaginase (Oncaspar) although promising, cannot be considered optimised since their polymer chain lacks biodegradability.This restricts use to low molecular weight compounds that can be excreted, but do not for that reason exploit the full potentiality of the technique. The new polymer conjugates object of the proposal: The proposed polymeric systems will be based on high molecular weight water-soluble functionalised polyesters of novel structure.In particular, they will show the following features: a) high molecular weight; b) biodegradable backbone; c) water solubility, achieved by the presence of poly (ethyleneglycol) or other hydrophilic segments; d) novel peptide and pH sensitive spacers which are stable in blood but selectively cleaved within the tumour; d) peptide (eg. Vapreotide or LHRHanalogues or aminosugar moieties) as targeting side substituents.The outcome of the project will be significantly improved polymer conjugates of the following anticancer drugs: doxorubicin (as a model), Ara C, mitomycinC, neocarcinostatin or taxol.Structure of the Consortium: The consortium is composed of 3 industrial and 4 academic partners of internationally confirmed expertise in biology, medicine, polymer and organic chemistry, materials science and pharmaceutics. BE97-4133 Fields of science natural scienceschemical sciencesorganic chemistrynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencespolymer sciencesmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepharmacology and pharmacypharmacokinetics Programme(s) FP4-BRITE/EURAM 3 - Specific research and technological development programme in the field of industrial and materials technologies, 1994-1998 Topic(s) 0201 - Materials engineering Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator Università degli Studi di Milano EU contribution No data Address Via Venezian 21 20133 Milano Italy See on map Links Website Opens in new window Total cost No data Participants (7) Sort alphabetically Sort by EU Contribution Expand all Collapse all DEBIO Recherche Pharmaceutique Switzerland EU contribution No data Address 146,Route du Levant 1920 Martigny See on map Total cost No data POLYMER LABORATORIES LTD United Kingdom EU contribution No data Address Essex Road CHURCH STRETTON See on map Links Website Opens in new window Total cost No data PolyPeptide Laboratories A/S Denmark EU contribution No data Address 2,Herredsvejen 3400 Hillerod See on map Total cost No data The School of Pharmacy, University ofLondon United Kingdom EU contribution No data Address 29-39,Brunswick Square WC1N 1AX London See on map Total cost No data UNIVERSITY OF ABERDEEN United Kingdom EU contribution No data Address Polwarth Building, Foresterhill AB25 2ZD ABERDEEN See on map Total cost No data UNIVERSITY OF WALES CARDIFF United Kingdom EU contribution No data Address King Edward VII Avenue, Redwood Building CF10 3XF CARDIFF See on map Total cost No data Università degli Studi di Padova Italy EU contribution No data Address Via F. Marzolo 5 35131 Padova See on map Total cost No data
