Development of a stable and high loaded liposomal formulation of lapatinib with enhanced therapeutic effects for breast cancer in combination with Caelyx®: In vitro and in vivo evaluations.

[Display omitted] • Lapatinib is a hydrophobic molecule. • Therapeutic effects of lapatinib can be enhanced using drug delivery systems. • Encapsulating lapatinib in a pegylated liposomal formulation can enhance therapeutic outcomes. • Liposomal lapatinib shows promising effects on inhibiting cell proliferation and inducing autophagy and apoptosis. • Co-administration of liposomal lapatinib with liposomal doxorubicin improves the survival time. Lapatinib, a dual tyrosine kinase inhibitor, has poor water solubility, which results in poor and incomplete absorption from the gastrointestinal tract. To overcome this obstacle, we designed a stable and high-loaded liposomal formulation encapsulating lapatinib and examined its therapeutic efficacy in vitro and in vivo on TUBO and 4T1 cell lines. We also assessed the impact of liposomal lapatinib on the extent of the tumor and spleen-infiltrating lymphocytes and the autophagy and apoptosis gene expression within the tumor site. Our results showed that liposomal lapatinib inhibits cell proliferation and significantly induces autophagy and apoptosis compared to control groups. Moreover, when it used in combination with liposomal doxorubicin, it extended the time to end from 22.4 ± 3.5 in the control group to 40 days in the TUBO cell line and from 29.2 ± 1.7 to 38.6 ± 2.2 days in 4T1 triple-negative breast cancer cell line, which reveals its promising effects on the survival of tumor-bearing mice. Our results indicated the need for further evaluations to understand liposomal lapatinib's potential effects on autophagy, apoptosis, and particularly on immune system cells. [ABSTRACT FROM AUTHOR]