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3D-Printing-Assisted Synthesis of Paclitaxel-Loaded Niosomes Functionalized by Cross-Linked Gelatin/Alginate Composite: Large-Scale Synthesis and In-Vitro Anti-Cancer Evaluation Publisher Pubmed



Hosseini F1 ; Mirzaei Chegeni M2 ; Bidaki A1 ; Zaer M3 ; Abolhassani H4 ; Seyedi SA5 ; Nabipoorashrafi SA5 ; Ashrafnia Menarbazari A6 ; Moeinzadeh A7 ; Farmani AR8 ; Tavakkoli Yaraki M9
Authors
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Authors Affiliations
  1. 1. Chemical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran
  2. 2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  3. 3. Biomedical Engineering Department, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran
  4. 4. Department of Biomedical Engineering, University of Rochester, Rochester, 14627, NY, United States
  5. 5. Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran, Iran
  6. 6. Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran
  7. 7. Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Tissue Engineering, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
  9. 9. School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, 2109, NSW, Australia

Source: International Journal of Biological Macromolecules Published:2023


Abstract

Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60–80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications. © 2023