Synergistic co-loading of vincristine improved chemotherapeutic potential of pegylated liposomal doxorubicin against triple negative breast cancer and non-small cell lung cancer

The current work aims to explore the biological characteristics of vincristine synergistic co-loading into pegylated liposomal doxorubicin in non-indicated modalities of non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). The combinatorial liposome prepared by active co-loading of the drugs against modified ammonium ion gradient exhibited 95% encapsulation of both drugs. The cellular uptake studies using confocal microscopy and flow cytometry showed significantly increased uptake of dual drug formulation as against liposomal doxorubicin. The co-loaded liposome formulation had significantly increased cell cycle arrest in G(2)/M phase with subsequent apoptosis and reduced cell viability in both tumor cell lines than doxorubicin liposome. This carrier exhibited similar acute toxicity, pharmacokinetic and tissue distribution profiles with significant increase in tumor regression as compared to liposomal doxorubicin. These results indicate that co-encapsulation of vincristine into clinically used pegylated liposomal doxorubicin significantly improved in-vitro and in-vivo therapeutic efficacy against NSCLC and TNBC. (C)2020 Elsevier Inc. All rights reserved.

Automated summary

This study explored the biological characteristics of co-loading vincristine with pegylated liposomal doxorubicin in non-small cell lung cancer and triple negative breast cancer. Results showed significantly increased cellular uptake, cell cycle arrest, apoptosis, and reduced cell viability with the co-loaded liposome formulation compared to doxorubicin liposome, leading to improved therapeutic efficacy in vitro and in vivo against NSCLC and TNBC.