Drug delivery to tumours using a novel 5-FU derivative encapsulated into lipid nanocapsules

Abstract

In this work, a novel lipophilic 5-fluorouracil (5-FU) derivative was synthesised and encapsulated into lipid nanocapsules (LNC). 5-FU was modified with lauric acid to give a lipophilic mono-lauroyl-derivative (5-FU-C12, MW of about 342 g/mol, yield of reaction 70%). 5-FU-C12 obtained was efficiently encapsulated into LNC (encapsulation efficiency above 90%) without altering the physico-chemical characteristics of LNC. The encapsulation of 5-FU-C12 led to an increased stability of the drug when in contact with plasma being the drug detectable until 3 h following incubation. Cytotoxicity assay carried out using MTS on 2D cell culture showed that 5-FU-C12-loaded LNC had an enhanced cytotoxic effect on glioma (9L) and human colorectal (HTC-116) cancer cell line in comparison with 5-FU or 5-FU-C12. Then, HCT-116 tumour spheroids were cultivated and the reduction of spheroid volume was measured following treatment with drug-loaded LNC and drugs alone. Similar reduction on spheroids volume was observed following the treatment with drug-loaded LNC, 5-FU-C12 and 5-FU alone, while blank LNC displayed a reduction in cell viability only at high concentration. Globally, our data suggest that the encapsulation increased the activity of the 5-FU-C12. However, in-depth evaluations of LNC permeability into spheroids are needed to disclose the potential of these nanosystems for cancer treatment.

Keywords:

• 5-Fluorouracil
• lipid nanoparticles
• cancer treatment
• nanomedicine

Acknowledgement

Authors are thankful to Pierre-Yves Dugas from the Univ Lyon, Université Claude Bernard Lyon 1, CNRS, C2P2 UMR 5265, for his kind help and expertise for cryoTEM observation.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work has been carried out within the research programme of NICHE, financially supported by EuroNanoMed-II (4th call); RESOLVE, financially supported by EuroNanoMed-III (8th call), and ITMO Cancer within the frame of the Programme Plan Cancer 2014–2019 [no. PC201507].