Engineered liposomes bearing camptothecin analogue for tumour targeting: in vitro and ex-vivo studies

Abstract

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 GI₅₀ 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 µg/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 ∼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.

Keywords:

• Liposomes
• Topotecan (TPT)
• sialic acid
• pH-sensitive
• active loading

Acknowledgements

We are highly thankful for financial support obtained from AICTE Fellowship to Miss Shivani Saraf and also Lipoid (Germany) for providing gift samples of lipids. Authors report no potential conflict of interest. We are also thankful to the Sophisticated Instruments Centre of Dr H S Gour Vishwavidyalaya, Sagar MP India for providing NanoPlus Zeta/nanoparticle analyzer (Particulate Systems, Norcross, GA, U.K.) and Beckman Coulter EPICS XL flow cytometer as well as Transmission Electron Microscope (Transmission Electron Microscope-4x JEOL. Japan) facility for the analysis of our formulations.

Disclosure statement

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