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

Abstract

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-sn-glycero-3-phosphocholine (DXI-LPC), 1-DXI-2-oleoyl-sn-glycero-3-phosphocholine (DXI-OA-PC) and 1-oleoyl-2-DXI-sn-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.

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Materials

Dexibuprofen (DXI), fatty acids (stearic and oleic), triethylamine (TEA), dibutyltin (IV) oxide (DBTO), 4-(N,N-dimethylamino)pyridine (DMAP), N,N′-dicyclohexylcarbodiimide (DCC), N,N-dimethylformamide (DMF), oxalyl chloride, celite® 110, Dowex® 50WX8 H+ (ion-exchange resin), refined beeswax (BW), Tween® 80 (polysorbate 80), Nile red (NR), methanol, ethanol and acetonitrile of HPLC grade were purchased from Merck (Darmstadt, Germany). Glycero-3-phosphocholine (GPC) was ordered from Bachem AG (Bubendorf, Switzerland). Miglyol® 812 was acquired from Roig Farma SA (Terrassa, Spain), while indium (purity ≥99.95%) was supplied by Fluka (Buchs, Switzerland). Deionized water was prepared using a Millipore® Milli-Q® system (Merck KGaA) (Millipore, Darmstadt, Germany). Camptothecin (CPT) was purchased from (Sigma-Aldrich, Darmstadt, Germany). All other solvents were of analytical grade.

Thiruchenthooran V, Świtalska M, Maciejewska G, Palko-Łabuz A, Bonilla-Vidal L, Espina M, Luisa Garcia M, Wietrzyk J, Souto EB, Sánchez-López E, Gliszczyńska A. Anticancer Activity of Phospholipid-Dexibuprofen Conjugates Loaded in Nanostructured Lipid Carriers. Int J Nanomedicine. 2025;20:6999-7019
https://doi.org/10.2147/IJN.S512505