Daunorubicin (DNR) and
cardiolipin (CL) were co-delivered using thermosensitive
liposomes (TSLs).
1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1-myristoyl-2-stearoyl-sn-glycero-3-phosphocholine (MSPC),
cholesterol, 1,2-distearoyl-sn-glycero-3-
phosphoethanolamine-N-[methoxy(
polyethylene glycol)-2000] or
DSPE-
mPEG (2000) and CL were used in the formulation of
liposomes at a molar ratio of 57:40:30:3:20, respectively. CL forms raft-like microdomains that may relocate and change
lipid organization of the outer and inner mitochondrial membranes. Such transbilayer
lipid movement eventually leads to membrane permeabilization. TSLs were prepared by thin-film hydration (drug:
lipid ratio 1:5) where DNR was encapsulated within the aqueous core of the
liposomes and CL acted as a component of the
lipid bilayer. The
liposomes exhibited high drug encapsulation efficiency (>90%), small size (~115 nm), narrow size distribution (polydispersity index ~0.12), and a rapid release profile under the influence of mild
hyperthermia. The
liposomes also exhibited ~4-fold higher cytotoxicity against MDA-MB-231 cells compared to DNR or
liposomes similar to DaunoXome® (p < 0.001). This study provides a basis for developing a co-delivery system of DNR and CL encapsulated in
liposomes for treatment of
breast cancer.