Co-delivery of gemcitabine and salinomycin in PEGylated liposomes for enhanced anticancer efficacy against colorectal cancer

Abstract

Colorectal cancer remains one of the major causes of morbidity and mortality in both developed and emerging countries. Cancer stem cells (CSCs) are a subpopulation of cells within the tumor mass harboring stem cell characteristics, considered responsible for tumor initiation, growth, relapse, and treatment failure. Lately, it has become clear that both CSCs and non-CSCs have to be eliminated for the successful eradication of cancer. Drug delivery systems have been extensively employed to enhance drug efficacy. In this study, salinomycin (SAL), a selective anti-CSC drug, and gemcitabine (GEM), a conventional anticancer drug, were co-loaded in liposomes and tested for optimal therapeutic efficacy. We employed the Design of Experiments approach to develop and optimize a liposomal delivery system for GEM and SAL. The antiproliferative effect of the liposomes was evaluated in SW-620 human colorectal cancer cells. The GEM and SAL-loaded liposomes exhibited adequate size, polydispersity, zeta potential, and drug content. The in vitro release study showed a sustained release of GEM and SAL from the liposomes over 72 h. Moreover, no sign of liposome aggregation was seen over 1 month and in a biological medium (FBS). The in vitro cytotoxic effects of the co-loaded liposomes were superior to that of single GEM either in free or liposomal form. The combination therapy using GEM and SAL co-loaded in liposomes could be a promising strategy for tackling colorectal cancer.

Keywords:

• Cancer stem cells
• colorectal cancer
• design of experiments
• gemcitabine
• liposomes
• salinomycin

Author contributions

Conception and design of the study: TLR, SA and TI. Methodology and execution: TLR, TI, SA, JA, BNI, RL and SR. Acquisition, analysis and interpretation of data: TLR, TI, SA, BM, JA, BNI, RL, SR and TI. Drafting and revision of the paper: TLR, TI, SA, BM, JA, BNI, RL, SR and TI. Final approval of the paper: TLR, TI, SA, BM, JA, BNI, RL, SR and TI. All authors agree to be accountable for all aspects of the work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data supporting the results or analyses presented in this paper are available from the corresponding author upon request.

Additional information

Funding

This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS - UEFISCDI, project number PN-III-P1-1.1-PD-2019–0781, within PNCDI III.