Verapamil delivery systems on the basis of mesoporous ZSM-5/KIT-6 and ZSM-5/SBA-15 polymer nanocomposites as a potential tool to overcome MDR in cancer cells

Margarita Popova, Rositsa Mihaylova, Georgi Momekov, Denitsa Momekova, Hristina Lazarova, Ivalina Trendafilova, Violeta Mitova, Neli Koseva, Judith Mihályi, Pavletta Shestakova, Petko St. Petkov, Hristiyan A. Aleksandrov, Georgi N. Vayssilov, Spiro Konstantinov, Ágnes Szegedi

Research output: Contribution to journalArticle

Abstract

ZSM-5/KIT-6 and ZSM-5/SBA-15 nanoparticles were synthesized and further modified by a post-synthesis method with [sbnd](CH2)3SO3H and [sbnd](CH2)3NHCO(CH2)2COOH groups to optimize their drug loading and release kinetic profiles. The verapamil cargo drug was loaded by incipient wetness impregnation both on the parent and modified nanoporous supports. Nanocarriers were then coated with a three-layer polymeric shell composed of chitosan-k-carrageenan-chitosan with grafted polysulfobetaine chains. The parent and drug loaded formulations were characterized by powder XRD, N2 physisorption, thermal analysis, AFM, DLS, TEM, ATR-FT-IR and solid state NMR spectroscopies. Loading of verapamil on such nanoporous carriers and their subsequent polymer coating resulted in a prolonged in vitro release of the drug molecules. Quantum-chemical calculations were performed to investigate the strength of the interaction between the specific functional groups of the drug molecule and [sbnd](CH2)3SO3H and [sbnd]CH2)3NHCO(CH2)2COOH groups of the drug carrier. Furthermore, the ability of the developed nanocomposites to positively modulate the intracellular internalization and thereby augment the antitumor activity of the p-gp substrate drug doxorubicin was investigated in a comparative manner vs. free drug in a panel of MDR positive (HL-60/Dox, HT-29) and MDR negative (HL-60) human cancer cell lines using the Chou-Talalay method.

Original languageEnglish
Pages (from-to)460-472
Number of pages13
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume142
DOIs
Publication statusPublished - Sep 2019

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Keywords

  • Delivery systems
  • Multi-drug resistance
  • Surface modification
  • Verapamil
  • Zeolite/mesoporous silica nanocomposites

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Cite this

Popova, M., Mihaylova, R., Momekov, G., Momekova, D., Lazarova, H., Trendafilova, I., Mitova, V., Koseva, N., Mihályi, J., Shestakova, P., St. Petkov, P., Aleksandrov, H. A., Vayssilov, G. N., Konstantinov, S., & Szegedi, Á. (2019). Verapamil delivery systems on the basis of mesoporous ZSM-5/KIT-6 and ZSM-5/SBA-15 polymer nanocomposites as a potential tool to overcome MDR in cancer cells. European Journal of Pharmaceutics and Biopharmaceutics, 142, 460-472. https://doi.org/10.1016/j.ejpb.2019.07.021