Niosomal encapsulation enhances thymoquinone-induced apoptosis in androgen-independent prostate cancer: an integrated DFT, docking, ADMET and cellular study.

Authors

Gulsah Gedik, Gorkem Dulger, Ilker Kiliccioglu, Ahmad Badreddin Musatat, Aysegul Akkoyunlu, Ugur Karagoz

Published in

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. Pages 115287. Nov 03, 2026. Epub Nov 03, 2026.

Abstract

Thymoquinone (TQ), the principal bioactive constituent of Nigella sativa seed oil, engages multiple anticancer pathways but is limited clinically by a sub-hourly plasma half-life and rapid hepatic clearance. We report a Span 60/cholesterol niosomal carrier (TQ-NIO) evaluated in PC-3 and LNCaP prostate cancer cells within an integrated quantum-chemical and target-engagement framework. TQ-NIO formed sub-micron vesicles (341.2 ± 12.1 nm; PDI 0.63 ± 0.13; ζ = -29.1 ± 0.8 mV) with 81.3 ± 0.8 % encapsulation efficiency and Korsmeyer-Peppas-controlled Fickian release (n = 0.28) over 72 h. Encapsulation halved the WST-1 IC₅₀ of TQ in androgen-independent PC-3 cells (24 h: 13.5 → 6.5 µg mL^-1; 48 h: 9.4 → 4.1 µg mL^-1), while shifts in LNCaP cells were minimal, a cell-line-selective response. In PC-3, TQ-NIO amplified caspase-3/-9 activation 2.6-2.7-fold, raised p53 (3.7-fold) and Bax (2.4-fold), and suppressed Bcl-2 (0.50-fold) and survivin (0.40-fold); HUVECs retained near-control morphology. Free TQ inhibited violacein production in Chromobacterium violaceum (zone 20.3 ± 0.6 mm), and the niosomal form preserved anti-biofilm activity against Escherichia coli at dilutions where free TQ failed. Calculations at the B3LYP-D4/def2-TZVP level assigned TQ super-electrophilic character (ω ≈ 7.3 eV) with C7/C8 as Michael-acceptor centers and O4 as the dominant nucleophilic anchor, while docking against five oncologically relevant targets returned modest binding energies (-4.70 to -5.78 kcal mol^-1) indicating possible interactions rather than demonstrated target engagement or functional inhibition. Niosomal encapsulation enhanced the in vitro antiproliferative and apoptosis-associated effects of TQ, particularly in PC-3 cells.

PMID:
42977097
Bibliographic data and abstract were imported from PubMed on 04 Nov 2026.

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