Delivery of pemetrexed by magnetic nanoparticles: design, characterization, in vitro and in vivo assessment

Abstract

Drug-loaded magnetic nanoparticles have been developed because of the advantages of specific drug targeting in cancer treatment. Pemetrexed (PEM) is a multi-targeting antifolate agent that is effective for the treatment of many cancers, for example, non-small cell lung cancer. Here, PEM loaded magnetic O-carboxymethyl chitosan (O-CMC) nanoparticles were prepared to deliver PEM on tumor tissue with an external magnetic field. The modification of chitosan to O-CMC was confirmed by FTIR analysis. Nanoparticle synthesis was performed via ionic gelation method. The diameter of magnetic O-CMC nanoparticles (MCMC) was found to be 130.1 ± 22.96 nm. After PEM loading, diameter was found to be 123.9 ± 11.42 nm. The drug release of PEM loaded MCMC (PMCMC) was slower in physiological medium than in acidic medium. A549-luc-C8 and CRL5807 cell lines were used for MTT test which showed that IC₅₀ values of nanoparticles were lower than PEM. The antitumor efficiency of PMCMC in xenograft tumor model was examined with in vivo imaging system (IVIS) and caliper and with hematological analyses. In vivo studies revealed that PMCMC had targeted antitumor activity in A549-luc-C8-tumor-bearing mice compared to PEM. As a result, it was suggested that PMCMC have great potential for the treatment of non-small cell lung cancer.

Keywords:

• A549-luc-C8
• magnetic targeting
• nanoparticle
• non-small cell lung cancer
• O-carboxymethyl chitosan
• pemetrexed

Author contributions

Senay Şanlıer and Güliz Ak were responsible for the conception and design of the study, analysis, and interpretation of the data. Didem Aksu and Eda Çapkın contributed to the all experimental section. Ilgın Kımız helped during cell culture analysis and Özge Sarı contributed to in vivo studies.

Acknowledgments

We would like to thank Dursun Demiroz for drawing the non-chemical illustrations.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We would like to thank Ege University Scientific Research Project Office, Ege Üniversitesi (Project ID: 2013 ILAM 002) for the financial support.