pH/thermo-responsive nucleolipid-containing liposomes for triggering delivery of doxorubicin

GARCÍA, MÓNICA C*; CALDERÓN-MONTAÑO, JOSÉ; RUEDA, MANUELA; LONGHI, MARCELA; RABASCO, ANTONIO; LÓPEZ-LÁZARO, MIGUEL; PRIETO-DAPENA, FRANCISCO; GONZÁLEZ-RODRÍGUEZ, MARÍA LUISA*

Otro; ° Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2020+1); 2021

The pH gradient between normal and tumoral tissues, and their rapid metabolism that induces hyperthermia encourage the development of pH- and thermo-sensitive liposomes (Lip) as nanocarriers for anticancer drugs. Nucleolipids have been studied as scaffolding material of Lip mainly for cancer therapy. Hence, we report the use of 1,2-dipalmitoyl-sn-glycero-3-(cytidine diphosphate) (DG-CDP) for developing pH/thermo-sensitive nucleolipid-containing Lip based on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol for triggering delivery of doxorubicin (Dox). Thin-film hydration and transmembrane pH-gradient methods were used to prepare the Lip and for Dox loading, respectively. Morphological and interfacial properties, and encapsulation efficiency (EE%) were analyzed. Drug release studies toward different media (pH 7.4 and 5.1 at 37 °C and 42 °C) and cytotoxic activity against breast and ovarian cancer cells were analyzed. Unloaded and Dox-loaded Lip exhibited nano-scale sizes (415-535 nm), acceptable polydispersity indexes (<0.3), almost spherical shapes, and negative Z-potential (–23- –14.7 mV) because of the phosphate groups of DG-CDP. High EE% was achieved (82 %) and althought an efficient control in the Dox release towards both receptor media was observed, the release of Dox was triggered at acidic pH and hyperthermia temperature, demonstrating responsiveness to both stimuli. Dox-encapsulated Lip preserved its antiproliferative activity against cancer cells. Overall, Lip-Dox showed promising properties for cancer nanomedicine.