Engineered liposomes bearing camptothecin analogue for tumour targeting:in vitroandex-vivostudies

Topotecan (TPT) is a semi-synthetic, water-soluble derivative of camptothecin, which inhibits the action of topoisomerase I in the S-phase of the cell cycle leading to cell death. For the effective delivery of TPT to cancer cells, pH-sensitive sialic acid modified liposomes were developed. These liposomes were prepared by the thin-film hydration method using the active loading technique. Vesicle size, polydispersity index (PDI), zeta potential, and percentage entrapment efficiency were determined to be 167 +/- 3.78 nm, 0.243, -8.39 mV, and 79.88 +/- 1.67%, respectively. The pH-sensitive sialic acid (SA) conjugated liposomes enhanced the drug release at acidic pH 4 (92.33 +/- 4.21%) as compared to physiological pH 7.4 (63.11 +/- 4.51%). A Sulforhodamine B (SRB) cytotoxicity assay was performed in Murine sarcoma S180 cell lines and the GI(50)value of free TPT, Lipo, P-Lipo, SA-P-Lipo, and Adriamycin (ADR) were determined to be 10.07 +/- 0.15, 27.33 +/- 1.01, 28.76 +/- 0.87, 15.7 +/- 0.45, and 11.5 +/- 0.21 mu g/mL, respectively. Results obtained from the apoptosis study revealed that cell death by a combination of early apoptosis and apoptosis caused by SA-P-Lipo was similar to 24 fold higher than the control. These results demonstrated that pH-sensitive sialic acid conjugated liposomes will be a potential formulation for improving the antitumor efficacy of TPT. However, further research is necessitated to expedite its applicability in clinical regimen in order to ascertain its safety and efficacy.

Automated summary

This study developed pH-sensitive sialic acid modified liposomes for delivering Topotecan to cancer cells, showing enhanced drug release under acidic conditions. The cytotoxicity assay in murine sarcoma cells demonstrated significantly higher cell death induced by SA-P-Lipo compared to the control.