期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 142, 期 -, 页码 460-472出版社
ELSEVIER
DOI: 10.1016/j.ejpb.2019.07.021
关键词
Zeolite/mesoporous silica nanocomposites; Surface modification; Verapamil; Delivery systems; Multi-drug resistance
资金
- Bulgarian National Science Fund [H 09/18]
- Bulgarian -Hungarian Inter -Academic Exchange Agreement
ZSM-5/ICIT-6 and ZSM-5/SBA-15 nanoparticles were synthesized and further modified by a post-synthesis method with -(CH2)(3)SO3H and -(CH2)(3)NHCO(CH2)(2)COOH 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, N-2 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 -(CH2)(3)SO3H and -(CH2)(3)NHCO(CH2)(2)COOH 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.
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