The HemDelStim project has set as its main scientific objective the opening of a new approach and a new scientific direction for the treatment of patients with chronic renal dysfunction and liver cancer. Unlike the therapeutic approach so far, which involves performing the hemodialysis process (to replace kidney function) and performing chemotherapy in parallel with this procedure, the project aimed to combine the two, in an intelligent way, with a minimal impact on the body. The drug used to treat liver cancer (doxorubicin) was encapsulated in supramolecular or polymeric architectures, the release being made strictly based on a stimulus – the tumor marker for this type of cancer (alpha fetoprotein). For this intelligent release, the concept of 'responsive drug delivery stimuli' – supramolecular or polymeric architectures containing doxorubicin functionalized with monoclonal antibody for alpha fetoprotein – was used. The presence of alpha fetoprotein in the blood undergoing dialysis will cause bursting of the encapsulars and release of doxorobicin. Supramolecular or polymeric architectures containing alpha fetoprotein monoclonal antibody surface, with encapsulated doxorubicin, were immobilized on polysulfone membranes for hemodialysis (membranes containing anticoagulants on the surface). The combination of the two therapeutic procedures – hemodialysis and stimulated drug release, represents the main novelty element of the project.
Specifically, polysulfone polymeric membranes were obtained, functionalized with anticoagulants and supramolecular or polymeric architectures with encapsulated doxycycline. The first objective involved the synthesis of supermolecule or polymeric architectures with the ability to release doxycillin under the action of a stimulus – the tumor marker for liver cancer. Two different modalities were chosen in order to be able to choose an optimum following the analyses and evaluations carried out. The optimum chosen after the tests performed was represented by supramolecular architectures based on cyclodextrin. The second objective involved the synthesis of polysulfone membranes with immobilized anticoagulant and supramolecular or polymeric architectures for controlled release of doxorubicin. Also in the field of anticoagulants, the project proposed an innovative approach by replacing heparin with vitamin E. The third objective involved the complete evaluation of materials both in terms of cytotoxicity and hemotoxicity, as well as in terms of filtering capacities of hemodialysis membranes (UV-Viz evaluation of creatinine, urea retention, uric acid and salts from synthetic food solutions), as well as evaluation of the controlled release capacity of doxorubicin in the presence of increased concentrations of alphafetoprotein in the feed solution. The main element of originality is represented by the combination of the two therapeutic procedures (hemodialysis and controlled release of drugs under the action of stimuli – tumor marker), without any previous literature reference.
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