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Polymer-based delivery vehicle for cisplatin

D.B. Vieira, C.F.M. Menck, A.M. Carmona-Ribeiro
University of São Paulo, BR

Keywords: cisplatin, quitosan, cationic nanoparticles


Cisplatin (CisPt) is one of the most widely used agents to treat a variety of tumors, but dose-limiting toxicities or intrinsic and acquired resistance limit its application. We report a unique strategy to deliver cisplatin to melanoma cells by sandwiched the drug between two oppositely charged polyelectrolytes: chitosan (CH) and carboxymethylcellulose (CMC), yielding cationic nanoparticles that presented optimal colloid stability. Moreover, the relevance of chitosan structure was investigated by testing two chitosans with different degrees of acetylation of the glucosamine monomer. Both chitosans formed colloidal particles of similar sizes when mixed with CMC. However, only the chitosan with high charge densities formed stable complexes with CMC to deliver efficiently the drug. By using drug-CMC-CH nanoparticles, cytostatic effects of free and encapsulated drug toward melanoma cells, where estimated by using the XTT assay, showing that the chemotherapeutic drug is very cytotoxic in melanoma cells. The effectiveness of encapsulated drug against melanoma cells is approximately one order of magnitude greater than that of free drug. The strategy of delivering CisPt to melanoma cancer cells opens up avenues for systemic targeted therapy against this cancer using platinum drugs. More broadly, by targeting tumor-specific antigens, using similarly engineered nanoparticles, it may be possible to selectively deliver a therapeutic dose of platinum drugs to a myriad of cancers. Further studies with relevant animal models are needed. Financial support: FAPESP and CNPq.
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