Anticancer Activity of Phospholipid-Dexibuprofen Conjugates Loaded in Nanostructured Lipid Carriers.

PURPOSE

In our work, we focused on the development of nanostructured lipid carriers (NLCs) loaded with dexibuprofen (DXI) and their application for cancer therapy by proposing the binding of phospholipids with this non-steroidal anti-inflammatory drug (NSAID) to obtain new delivery systems.

METHODS

We successfully synthesized seven conjugates with good yields, four of which are new, and have not been previously published in the literature. The structures of the obtained conjugates were confirmed and comparative in vitro studies of their antiproliferative activity were conducted, along with molecular modeling to assess their therapeutic potential.

RESULTS

1-DXI-2-hydroxy--glycero-3-phosphocholine (DXI-LPC), 1-DXI-2-oleoyl--glycero-3-phosphocholine (DXI-OA-PC) and 1-oleoyl-2-DXI--glycero-3-phosphocholine (OA-DXI-PC) showed selectivity for cancer cells, influencing the cell cycle and inducing apoptosis. Encapsulation of heterosubstituted conjugates with increased lipophilic character in NLC resulted in DXI-PA-PC-NLC and DXI-OA-PC-NLC with favorable size (around 150 nm) and polydispersity index of 0.15, high encapsulation efficacy (above 99%), long-term stability, and modified release profile (51.4% and 48.9% of DXI released from DXI-PA-PC-NLC and DXI-OA-PC-NLC, respectively). Antiproliferative assays confirmed enhanced activity of synthesized products and their increased accumulation in cancer cells.

CONCLUSION

This study describes the synthesis of new conjugates of DXI and phospholipids and their nanotechnological formulations for potential use in cancer therapy.