We successfully prepared and characterized a hyaluronic acid- and folic acid-based hydrogel for the delivery of cisplatin (GEL-CIS) with the aim to induce specific and efficient incorporation of CIS into ovarian cancer (OC) cells, improve its antineoplastic effect and avoid CIS-resistance. The slow and controlled release of the drug from the polymeric network and its swelling degree at physiologic pH suggested its suitability for CIS delivery in OC. We compared here the effects of pure CIS to that of GEL-CIS on human OC cell lines, either wild type or CIS-resistant, in basal conditions and in the presence of macrophage-derived conditioned medium, mimicking the action of tumor-associated macrophages in vivo. GEL-CIS inhibited OC cell growth and migration more efficiently than pure CIS and modulated the expression of proteins involved in the Epithelial Mesenchymal Transition, a process playing a key role in OC metastatic spread and resistance to CIS.
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