Romanian Society of Pharmaceutical Sciences

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PDMAEMA/SILK SERICIN HYBRID NANOCARRIERS FOR EFFICIENT DELIVERY OF 5-FLUOROURACIL AND OXALIPLATIN TO HUMAN COLORECTAL ADENOCARCINOMA TUMOUR CELLS

ARIANA HUDIȚĂ 1,2, DIANA IULIANA STANCIU 1, MIRELA VIOLETA ȘERBAN 1, BIANCA GĂLĂȚEANU 1*, IONUȚ-CRISTIAN RADU 3, EUGENIA TANASĂ 4, CĂTĂLIN ZAHARIA 3, GEORGE-TRAIAN-ALEXANDRU BURCEA-DRAGOMIROIU 5, CRISTIAN-DANIEL MARINECI 5, OCTAV GINGHINĂ 6,7

1 Faculty of Biology, University of Bucharest, Bucharest, Romania
2 Research Institute of the University of Bucharest, University of Bucharest, Bucharest, Romania
3 Faculty of Chemical Engineering and Biotechnology, University of Science and Technology Politehnica Bucharest, Bucharest, Romania
4 Faculty of Applied Science, National University of Science and Technology Politehnica Bucharest, Bucharest, Romania
5 Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
6 Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, Romania
7 Department of Surgery 3, “Prof. Dr. Al. Trestioreanu” Institute of Oncology Bucharest, Romania

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Colorectal cancer (CRC) remains a significant concern in gastrointestinal oncology, ranking high in both mortality and incidence for both sexes. The standard chemotherapeutic regimen includes 5-fluorouracil (5-FU) and oxaliplatin (OXP), administered alone or as combinatorial therapy, their use being associated with severe side effects. In this study, we report the synthesis and characterisation of 5-fluorouracil (5-FU) and oxaliplatin (OXP)-loaded hybrid nanoparticles based on silk sericin and poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) for targeted CRC therapy. The hybrid nanoparticles exhibited excellent biocompatibility, maintaining the viability and proliferation of human adenocarcinoma cells (HT-29) in their unloaded form. In vitro, cytotoxicity assays revealed that 5-FU/OXP-loaded nanoparticles significantly reduced cell viability, disrupted mitochondrial integrity and altered the cytoskeleton structure of HT-29 cells. The hybrid nanoparticles are ideal for drug protection and are being used as tools to reduce the systemic toxicity induced by free drugs. These findings suggest that sericin/PDMAEMA-based hybrid nanoparticles are a promising delivery system for 5-FU and OXP in CRC treatment. Further research should focus on in vivo studies to validate the efficacy and safety of these hybrid nanoparticles in animal models.