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

• Published in: Nanomedicine 2021-01, Vol.31, p.102320-102320, Article 102320
• Main Authors: Ghosh, Saikat, Lalani, Rohan, Maiti, Kuntal, Banerjee, Shubhadeep, Bhatt, Himanshu, Bobde, Yamini Shankar, Patel, Vivek, Biswas, Swati, Bhowmick, Subhas, Misra, Ambikanandan
• Format: Article
• Language: English
• Subjects: Breast cancer; Doxorubicin; Liposome; Lung cancer; Vincristine
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2020.102320

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 G2/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. Synergistic vincristine co-loading into clinically used pegylated liposomal doxorubicin resulted in significantly increased cellular uptake, reduction in cellular viability and wound healing of dual drug liposome in A549 and MDA-MB 231 cell lines as compared to liposomal doxorubicin. Mechanistically it was found to have shifted the cell cycle arrest in G2/M phase to the sub-G0 phase which resulted in improved apoptotic potential of this new formulation in both cell lines. The dual carrier presented similar maximum tolerated dose, pharmacokinetic and tissue distribution profiles to clinically used formulation besides having significantly improved tumor regression against NSCLC and TNBC. [Display omitted] •Synergistic co-loading of vincristine with doxorubicin in pegylated liposome.•No significant change in physicochemical characteristic properties.•Significant improvement in apoptosis and reduced viability.•Significantly improved in-vitro and in-vivo therapeutic efficacy in NSCLC and TNBC.•Exhibited similar acute toxicity, pharmacokinetic and tissue distribution profiles