article · Pharmaceutics
Repurposing established medicines offers an alternative route for developing cancer therapies. Research evaluated the anti-tumour effects of niflumic acid, a non-steroidal anti-inflammatory drug, combined with ceramides into PEGylated cerosome vesicles. The optimised topical gel formulation demonstrated high drug entrapment, structural stability, and more than double the skin permeation rate of standard niflumic acid gel in laboratory tests. In mice with solid Ehrlich carcinoma, the topical gel substantially lowered tumour volume and improved survival rates. Biological analysis showed that the formulation suppressed key cancer growth pathways, including EGFR, ERK, and microRNA-21-5p, alongside reductions in inflammatory and proliferative markers like COX-2 and cyclin D1. The treatment also increased antioxidant capacity and stimulated programmed cancer cell death.
Repurposing existing medications can accelerate cancer research by building upon established drug safety profiles. This work shows that loading a conventional anti-inflammatory medicine into nanoscale lipid carriers enhances skin penetration and halts tumour growth in animal models, demonstrating how advanced drug delivery systems can unlock new therapeutic uses for familiar pharmaceuticals.
This work could inform the development of non-invasive topical therapies for localized skin tumours, of interest to pharmaceutical developers and dermatological oncology companies. Because testing is limited to ex vivo rat skin and in vivo mouse models, the technology remains at an early preclinical stage, requiring substantial clinical validation, safety testing, and manufacturing scale-up before commercial application.
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Background/Objectives: Repurposing existing drugs may represent a promising strategy for effective cancer therapy. This study was the first to investigate the augmented antitumor therapeutic effect achieved by co-incorporating the NSAID Niflumic acid (NIF) with ceramides into PEGylated cerosomes (NIF-loaded PEG-CERs) in a novel platform that targets specifically the MAPK-ERK signaling pathway and miR-21-5p modulation. Methods: The prepared formulae were statistically optimized utilizing a full factorial design and the optimal formula (C5) was further incorporated into a topical gel and evaluated for ex vivo rat skin permeation, and tested in vivo in a subcutaneous solid Ehrlich carcinoma (SEC) mice model. Results: The optimal formula (C5) showed tubular elongated morphology with higher EE% (96.71 ± 0.0), lower vesicular size (VS) and PDI values, 292.95 ± 0.78 nm and 0.47 ± 0.0 respectively. A high ZP value (−37.5 ± 0.57 mV) was in accordance with stability results showing good stability of the optimal formula (C5). Permeability studies exhibited 2.02-fold higher skin permeation compared to pure NIF gel. A significant decrease in tumor volume and marked improvement in survival rate in SEC mice were confirmed by downregulation of EGFR, ERK1, ERK2, and miR-21-5p expression. Furthermore, an increase in total antioxidant capacity and caspase-3 levels was observed, accompanied by significant suppression in cyclin D1, MMP-2, COX-2, and MDA levels. Finally, histopathological analysis revealed the superior antitumor effect of C5 gel together with immunohistochemical assay showing the lowest BCL-2-positive staining, indicating the restoration of physiological apoptotic balance. Conclusions: Based on the previous findings, NIF-loaded PEG-CERs offer augmented therapeutic potential for efficient topical skin cancer management in an SEC mice model.
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DOI: 10.3390/pharmaceutics18091125
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