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  1. Sharifzadeh G, Hosseinkhani H
    Adv Healthc Mater, 2017 Dec;6(24).
    PMID: 29057617 DOI: 10.1002/adhm.201700801
    Recent advances and applications of biomolecule-responsive hydrogels, namely, glucose-responsive hydrogels, protein-responsive hydrogels, and nucleic-acid-responsive hydrogels are highlighted. However, achieving the ultimate purpose of using biomolecule-responsive hydrogels in preclinical and clinical areas is still at the very early stage and calls for more novel designing concepts and advance ideas. On the way toward the real/clinical application of biomolecule-responsive hydrogels, plenty of factors should be extensively studied and examined under both in vitro and in vivo conditions. For example, biocompatibility, biointegration, and toxicity of biomolecule-responsive hydrogels should be carefully evaluated. From the living body's point of view, biocompatibility is seriously depended on the interactions at the tissue/polymer interface. These interactions are influenced by physical nature, chemical structure, surface properties, and degradation of the materials. In addition, the developments of advanced hydrogels with tunable biological and mechanical properties which cause no/low side effects are of great importance.
  2. Sharifzadeh G, Hezaveh H, Muhamad II, Hashim S, Khairuddin N
    Mater Sci Eng C Mater Biol Appl, 2020 May;110:110609.
    PMID: 32204060 DOI: 10.1016/j.msec.2019.110609
    Vaginal drug delivery is regarded as a promising route against women-related health issues such as unwanted pregnancies and sexually transmitted infections. However, only a very few studies have been reported on the use of hydrogel rings with low cytotoxicity for vaginal drug delivery applications. Moreover, the effect of nanoparticles on hydrogel vaginal rings has not been clearly evaluated. To overcome these challenges, we hereby developed nanocomposite hydrogel rings based on polyacrylamide-sodium carboxymethyl cellulose-montmorillonite nanoparticles in the ring-shaped aluminum mold for controlled drug delivery. The hydrogel rings were synthesized by using N,N'-methylene bisacrylamide, N,N,N',N'-tetramethyl ethylene diamine, and ammonium persulfate, as a crosslinker, accelerator, and initiator, respectively. The obtained rings were 5.5 cm in diameters and 0.5 cm in rims. Chemical structures of the nanocomposite rings were confirmed by Fourier transform infrared, and Nuclear Magnetic Resonance spectroscopies. Additionally, the swelling ratio of hydrogels was appeared to be adjusted by the introduction of nanoparticles. In vitro release experiment of methylene blue, as a hydrophilic model drug, revealed that the nanocomposite rings could not only reduce burst effect (almost more than twice), but also achieve prolonged release for 15 days in the vaginal fluid simulant which mimic the vaginal conditions at pH of almost 4.2, and a temperature of 37 °C. Importantly, the resultant hydrogel rings with or without various concentrations of montmorillonite showed low cytotoxicity toward human skin fibroblasts. Furthermore, different antibacterial activities against Escherichia coli were observed for various concentrations of montmorillonite in hydrogels. These results suggest the great potential of montmorillonite-based hydrogel rings for vaginal drug delivery.
  3. Hosseinkhani H, Domb AJ, Sharifzadeh G, Nahum V
    Pharmaceutics, 2023 Mar 06;15(3).
    PMID: 36986717 DOI: 10.3390/pharmaceutics15030856
    The development of biological methods over the past decade has stimulated great interest in the possibility to regenerate human tissues. Advances in stem cell research, gene therapy, and tissue engineering have accelerated the technology in tissue and organ regeneration. However, despite significant progress in this area, there are still several technical issues that must be addressed, especially in the clinical use of gene therapy. The aims of gene therapy include utilising cells to produce a suitable protein, silencing over-producing proteins, and genetically modifying and repairing cell functions that may affect disease conditions. While most current gene therapy clinical trials are based on cell- and viral-mediated approaches, non-viral gene transfection agents are emerging as potentially safe and effective in the treatment of a wide variety of genetic and acquired diseases. Gene therapy based on viral vectors may induce pathogenicity and immunogenicity. Therefore, significant efforts are being invested in non-viral vectors to enhance their efficiency to a level comparable to the viral vector. Non-viral technologies consist of plasmid-based expression systems containing a gene encoding, a therapeutic protein, and synthetic gene delivery systems. One possible approach to enhance non-viral vector ability or to be an alternative to viral vectors would be to use tissue engineering technology for regenerative medicine therapy. This review provides a critical view of gene therapy with a major focus on the development of regenerative medicine technologies to control the in vivo location and function of administered genes.
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