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

被引:10
作者
Ak, Guliz [1 ,2 ]
Aksu, Didem [1 ]
Capkin, Eda [1 ]
Sari, Ozge [2 ]
Gebologlu, Ilgin Kimiz [3 ]
Sanlier, Senay Hamarat [1 ,2 ]
机构
[1] Ege Univ, Dept Biochem, Fac Sci, Izmir, Turkey
[2] Ege Univ, Ctr Drug Res & Dev & Pharmacokinet Applicat, Izmir, Turkey
[3] Ege Univ, Inst Nat & Appl Sci, Bioengn Grad Programme, Izmir, Turkey
关键词
A549-luc-C8; magnetic targeting; nanoparticle; non-small cell lung cancer; O-carboxymethyl chitosan; pemetrexed; LUNG-CANCER CELLS; DRUG-DELIVERY; CHITOSAN NANOPARTICLES; RELEASE; NANOCARRIER;
D O I
10.1080/10826068.2019.1692220
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:215 / 225
页数:11
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