Fiza Ur Rehman, Syeda Sohaila Naz, Muhammad Junaid Dar, Annum Malik, Maimoona Qindeel, Francesco Baino, Fazli Wahid, Abbas Rahdar, Saeeda Munir, Sara Qaisar, Kifayat Ullah Shah, Mahtab Razlansari,
Volume 19, Issue 2 (June-Biomaterials Special Issue- 2022)
Abstract
Neoplastic cells have co-opted inflammatory receptors and signaling molecules that potentiate inflammation. Activated inflammatory pathways lead to neo-angiogenesis, lymph-angiogenesis, immunosuppression, tumor growth, proliferation and metastasis. This cancer-sustaining inflammation is a critical target to arrest cancer growth. Multiple drug resistance, high cost, low oral bioavailability and serious side effects have rendered conventional cytotoxic chemotherapeutics less impressive. The aim of this research was to achieve cancer debulking and proliferation prevention by limiting ‘cancer-sustaining’ tumor niche inflammation through non-conventional oral approach employing anti-inflammatory agents and avoiding conventional cytotoxic agents. Synergistic anti-inflammatory agents, i.e. celecoxib as selective COX-2 inhibitor and montelukast as cysteinyl leukotriene receptor antagonist, were selected. Silver nanoparticles (AgNPs) were used as nanocarriers because of their efficient synergistic anti-neoplastic effects and excellent oral drug delivery potential. Specifically, selected drugs were co-conjugated onto AgNPs. Synthesized nanoparticles were then surface-modified with poly(vinyl alcohol) to control particle size, avoid opsonization/preferred cellular uptake and improve dispersion. Surface plasmon resonance analysis, particle size analysis, DSC, TGA, XRD, FTIR and LIBS analysis confirmed the successful conjugation of drugs and efficient polymer coating with high loading efficiency. In-vitro, the nanoparticles manifested best and sustained release in moderately acidic (pH 4.5) milieu enabling passive tumor targeting potential. In-vivo, synthesized nanoparticles exhibited efficient dose-dependent anti-inflammatory activity reducing the dose up to 25-fold. The formulation also manifested hemo-compatibility, potent anti-denaturation activity and dose-dependent in-vitro and in-vivo anti-cancer potential against MCF-7 breast cancer and Hep-G2 liver cancer cell lines in both orthotopic and subcutaneous xenograft cancer models. The anti-inflammatory nanoparticles manifested tumor specific release potential exhibiting selective cytotoxicity at cancerous milieu with slightly acidic environment and activated inflammatory pathways. The formulation displayed impressive oral bioavailability, sustained release, negligible cytotoxicity against THLE-2 normal human hepatocytes, low toxicity (high LD50) and wide therapeutic window. Results suggest promise of developed nanomaterials as hemo-compatible, potent, cheaper, less-toxic oral anti-inflammatory and non-conventional anti-cancer agents.
Ahabboud Malika, Najwa Gouitaa, Ahjyaje Fatimazahra, Lamcharfi Taj-Dine, Abdi Farid,
Volume 20, Issue 1 (March 2023)
Abstract
In this paper, Pb1-xFex(Zr0.52Ti0.48)O3 (PFZT) nanopowders, with x from 0.00 up to 0.20, were synthesized by using the sol-gel method. The PFZT samples were characterized by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), and impedance spectroscopy. According to the experimental results, PFZT combines rhombohedral and tetragonal symmetries for all the samples without a change in phase structure. The SEM investigation indicated that the grains are homogeneous with regular form and the average grain size of PFZT ceramics changed with Fe concentration. The dielectric characterizations show that the dielectric permittivity increases with increasing temperature, and the Fe amount shifts down the temperature of transition. Moreover, a dielectric resonance phenomenon is observed for all the PFZT ceramics.
Ahabboud Malika, Gouitaa Najwa, Ahjyaje Fatimazahra, Lamcharfi Taj-Dine, Abdi Farid, Haddad Mustapha,
Volume 21, Issue 0 (IN PRESS 2024)
Abstract
This paper reports the preparation and characterization of (1-x) PbZr0.52Ti0.48O3 -xBiFeO3 (1-x)PZTxBFO) (x= 0.00, 0.15, 0.30, 0.45, 0.60 and 1.00) multiferroic ceramics which were prepared by a sol-gel method for PZT and hydrothermal reaction process for BFO. The perovskite structure of the composite system was confirmed by X-ray diffraction and Raman spectroscopy, while the composite microstructure w:as char:acterized by scanning electron microscopy. XRD results and Rietveld analysis for the (1-x)PZT-xBFO composites confirm the coexistence of these three phases; rhombohedral (R3m) and tetragonal phases (P4mm) for pure PZT and only the rhombohedral phase (R3c) for pure BFO. Raman spectroscopy of the (1-x)PZT-xBFO composites shows two clear bands around 150 and 180 cm-1. When the BFO content increases, the intensities of Raman modes are decreased. The SEM results suggested a formation of agglomerate and form into large complex clusters as BFO increased and a higher grain size was obtained for the BFO sample compared with the other composites. The EDS spectra of our pellets show that all the characteristic lines of the chemical elements Pb, Zr, Ti, and O and Bi, Fe, and O are present for the PZT and BFO materials respectively. The temperature-dependent dielectric constant shows different behavior dependent on BFO content. Indeed, the dielectric properties are found to be improved with an increase in dopant concentration of BFO in PZT, and novel dielectric behavior, resonance, and antiresonance, were obtained.
