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Preparation and Evaluation of Stearylamine-Bearing Pemetrexed Disodium-Loaded Cationic Liposomes In Vitro and In Vivo

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Abstract

Pemetrexed disodium (PMX) stands out in the treatment of non-small cell lung cancer (NSCLC), but with short half-life and toxic side effects. This study was to design cationic liposomes for targeting delivery PMX to the lungs. The PMX cationic liposome was prepared by thin-film hydration using stearylamine (SA) as the positive component of charge-regulating charge. Then, the PMX cationic liposome (SA-PMX-Lips) was characterized by particle size, morphology, entrapment efficiency (EE), and drug loading (DL). Finally, the drug release behavior in vitro, the pharmacokinetic study, and tissue distribution of SA-PMX-Lips were evaluated separately, with PMX solution (PMX-Sol) and PMX liposome (PMX-Lips) as the control. According to results, SA-PMX-Lips were spherical and the particle size was 219.7 ± 4.97 nm with a narrow polydispersity index (PDI) (0.231 ± 0.024) and a positive zeta potential 22.2 ± 0.52 mV. Its EE was 92.39 ± 1.94% and DL was 9.15 ± 0.07%. The results of in vitro and in vivo experiments showed that SA-PMX-Lips released slowly, prolonged retention time and increased the value of AUC. More notably, SA-PMX-Lips could improve the accumulation of drugs in the lungs and the relative uptake rate (Re) was 2.35 in the lungs, which indicated its lung targeting. In summary, SA-PMX-Lips showed the potential for the effective delivery of PMX and the treatment of NSCLC.

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Acknowledgments

The authors thank the University of Pharmaceutical Science, Shandong University, for providing facilities. The paper is funded by Major Scientific and Technological Innovation Project of Shandong Province (2918CXGC1411), Shandong Key Research and Development Program(2018GSF121006).

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  1. Kongfang He and Jingjing Liu contributed equally to this work.

Authors and Affiliations

  1. The School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Ji’nan, Shandong Province, China

    Kongfang He, Jingjing Liu, Yanyun Hao, Xuehua Yang & Guihua Huang

  2. Qilu Children’s Hospital of Shandong University, Ji’nan, China

    Yan Gao

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  1. Kongfang He
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Correspondence to Guihua Huang.

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He, K., Liu, J., Gao, Y. et al. Preparation and Evaluation of Stearylamine-Bearing Pemetrexed Disodium-Loaded Cationic Liposomes In Vitro and In Vivo. AAPS PharmSciTech 21, 193 (2020). https://doi.org/10.1208/s12249-019-1586-6

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