4.7 Article

Synthesis and in vitro cytotoxicity evaluation of star-shaped polymethacrylic conjugates with methotrexate or acitretin as potential antipsoriatic prodrugs

期刊

EUROPEAN JOURNAL OF PHARMACOLOGY
卷 866, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.ejphar.2019.172804

关键词

Me45; NHDF; HaCaT; BEAS-2B cell lines; In vitro assays: MTT; Apoptosis; Cell cycle; Star-shaped polymethacrylic conjugates; Methotrexate; Acitretin; Antipsoriatic prodrugs

资金

  1. Polish National Science Center from the Silesian University of Technology in Gliwice [UMO-2016/23/D/ST5/01312, 2017/25/B/NZ4/01550, 02/010/BK_19/0143]
  2. EU Innovative Economy Program (POIG) project [02.01.00-00-166/08]
  3. POIG project [02.03.01-00-040/13]
  4. Biotechnology Centre of the Silesian University of Technology [POIG.02.01.00-00-166/08]

向作者/读者索取更多资源

Water-soluble polymer-drug conjugates were obtained and analyzed towards their potential use as prodrugs for two hydrophobic antipsoriatic agents, including methotrexate (MTX) and acitretin (AC). The conjugation efficacy of MTX decreased with a decreasing molar ratio of N,N-dimethylaminoethyl methacrylate (DMAEMA) repeating units in the polymethacrylic chains. Cytotoxicity of positively charged (from +5 to +10 mV) nano-and microparticles (3-1500 nm in DMEM at 37 degrees C) were estimated by in vitro MTT and Annexin-V apoptosis assays on Me45, NHDF, HaCaT and BEAS-2B cell lines. Further, cell cycle analysis revealed arrest in G0/G1 phase in melanoma cells, while neither apoptosis induction nor cell cycle arrest occurred in normal epidermal and epithelial cells. Tested conjugates displayed a novel cytostatic effect in Me45 cells and a pro-apoptotic effect in HaCaT cells. Epithelial BEAS-2B cells were the most sensitive to the tested conjugates and responded via induction of necrosis. Cell line models allowed for characterization of the biologically relevant potential action of pro-drugs. Additionally, a skin in vitro evaluation assay provided the first known evidence of side-effect reduction with pro-drug use. Histological examinations confirmed the lack of negative effects of conjugates on the skin and showed no irritating properties.

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