Dual drug loaded polypeptide delivery systems for cancer therapy

Abstract

The present study was aimed to prepare and examine in vitro novel dual-drug loaded delivery systems. Biodegradable nanoparticles based on poly(L-glutamic acid-co-D-phenylalanine) were used as nanocarriers for encapsulation of two drugs from the paclitaxel, irinotecan, and doxorubicin series. The developed delivery systems were characterised with hydrodynamic diameters less than 300 nm (PDI < 0.3). High encapsulation efficiencies (≥75%) were achieved for all single- and dual-drug formulations. The release studies showed faster release at acidic pH, with the release rate decreasing over time. The release patterns of the co-encapsulated forms of substances differed from those of the separately encapsulated drugs, suggesting differences in drug-polymer interactions. The joint action of encapsulated drugs was analysed using the colon cancer cells, both for the dual-drug delivery sytems and a mixture of single-drug formulations. The encapsulated forms of the drug combinations demonstrated comparable efficacy to the free forms, with the encapsulation enhancing solubility of the hydrophobic drug paclitaxel.

Keywords:

• Polypeptides
• polymeric particles
• antitumor drugs
• irinotecan
• doxorubicin
• paclitaxel
• co-encapsulation
• combination of drugs
• dual drug delivery systems

Acknowledgements

Centre for Molecular and Cell Technologies of the Research Park of Saint-Petersburg State University is acknowledged for TEM analysis.

Disclosure statement

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

Additional information

Funding

This research was funded by Russian Science Foundation. The work on the development of formulations and some biological experiments was carried out within the project No. 20–73-00222. The release, cytotoxicity and TEM studies were performed as part of project No. 21–73-20104.