Co-delivery of paclitaxel and etoposide prodrug by human serum albumin and PLGA nanoparticles: synergistic cytotoxicity in brain tumour cells

Abstract

The aims of this study were to develop co-delivery systems of paclitaxel (PTX) and etoposide prodrug (4’-O-benzyloxycarbonyl-etoposide, ETP-cbz) based on non-cross-linked human serum albumin (HSA) and poly(lactide-co-glycolide) nanoparticles and to evaluate the synergistic potential of these drugs in vitro. The nanoformulations were prepared by the high-pressure homogenisation technique and characterised using DLS, TEM, SEM, AFM, HPLC, CZE, in-vitro release, and cytotoxicity in human and murine glioma cells. All nanoparticles had 90-150 nm in size and negative ζ-potentials. The Neuro2A cells were the most sensitive to both HSA- and PLGA-based co-delivery systems (IC₅₀ 0.024 µM and 0.053 µM, respectively). The drugs’ synergistic effect (combination index < 0.9) was observed in the GL261 cells for both types of co-delivery formulations and in the Neuro2A cells for the HSA-based system. These nanodelivery systems may be useful to improve combination chemotherapy for brain tumour treatment. To our knowledge, this is the first report describing the non-cross-linked HSA-based co-delivery nanosuspension which was prepared using nab™ technology.

Keywords:

• Co-delivery
• сytotoxicity
• etoposide pro-drug
• HSA nanoparticles
• GL261 glioma cells
• Neuro-2a neuroblastoma cells
• paclitaxel
• PLGA nanoparticles
• synergistic effect

Acknowledgements

The authors are grateful to Evonik Nutrition and Care GmbH (Hanau, Germany) and CPH Pharma b.v. (Amsterdam, Netherlands) for providing Resomer^® 502H. The authors are grateful to the IPCE RAS Joint Research Centre for Physical Methods of Research (CKP FMI IPCE RAS) for the SEM study of the nanoparticle samples and to the D. I. Mendeleev Center for Collective Use of Scientific Equipment for performing the analytical tests.

Author contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (Grant No. 075–15-2020–792, Unique identifier RF-190220X0031).