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    Safe Personalized Treatment Recommendation System for Multimorbidity

    , M.Sc. Thesis Sharif University of Technology Ghasempour, Elahe (Author) ; Habibi, Jafar (Supervisor)
    Abstract
    Multimorbidity in an individual is a typical and increasing condition and a major challenge in healthcare. The goal of treatment recommendation for such patients is to decide the most effective combination of treatments. Doctors typically prescribe medication based on their intuition and experience. However, due to knowledge gaps or unintended biases, often times these clinical decisions can be sub-optimal. Broad adoption and usage of electronic health records (EHRs) in the last decade has opened up a great opportunity to leverage healthcare data to improve clinical decisions.In this approach we use EHR and drug-drug interaction (DDI) information to prescribe medications. We use multiple... 

    Synthesis of water dispersible reduced graphene oxide via supramolecular complexation with modified β-cyclodextrin

    , Article International Journal of Polymeric Materials and Polymeric Biomaterials ; Volume 66, Issue 5 , 2017 , Pages 235-242 ; 00914037 (ISSN) Pourjavadi, A ; Eskandari, M ; Hosseini, S. H ; Nazari, M ; Sharif University of Technology
    Taylor and Francis Inc  2017
    Abstract
    A noncovalent functionalization of the edges of reduced graphene oxide (RGO) with β-cyclodextrin-graft-hyperbranched polyglycerol (β-CD-g-HPG) was successfully performed via a host-guest interaction. The results showed that β-CD-g-HPG disperses the graphene sheets better than pure β-CD or HPG. The resulted supramolecular structure is stable in neutral water medium more than one week. However, in acidic medium the host-guest interaction is collapsed and graphene nanosheets precipitate. © 2017, Copyright © Taylor & Francis  

    Paclitaxel/β-CD-g-PG inclusion complex: An insight into complexation thermodynamics and guest solubility

    , Article Journal of Molecular Liquids ; Volume 208 , August , 2015 , Pages 145-150 ; 01677322 (ISSN) Zarrabi, A ; Vossoughi, M ; Sharif University of Technology
    Elsevier  2015
    Abstract
    Paclitaxel as one of the most effective anticancer drugs has low aqueous solubility. This inevitably reveals its commercial formulation in Cremophor EL®/ethanol mixture. However, this formulation leads to several severe side effects such as hypersensitivity reactions, neurotoxicity and nephrotoxicity. Inclusion complexation has been introduced as a practical approach in increasing paclitaxel aqueous solubility. To this end, a hybrid nanocarrier system based on hyperbranched polyglycerol and β-cyclodextrin is designed with key components uniquely structured at nanoscale and evaluated according to medical requirements. Paclitaxel is included in the hydrophobic cavity of cyclodextrin as guest... 

    Observer-Based Output Feedback Linearization Control with Application to HIV Dynamics

    , Article Industrial and Engineering Chemistry Research ; Volume 54, Issue 10 , January , 2015 , Pages 2697-2708 ; 08885885 (ISSN) Hajizadeh, I ; Shahrokhi, M ; Sharif University of Technology
    American Chemical Society  2015
    Abstract
    This paper presents the feedback linearization control of HIV infection. A multi-input multi-output (MIMO) dynamic nonlinear HIV infection model for this purpose has been used. For this purpose, three widely used drugs are considered. A Luenberger-like nonlinear observer (LNO) is designed for estimation of unavailable states. To minimize the side effects of drugs, the concentration of ZDV which has the highest side effect is fixed to a minimum value and the external controllers parameters are obtained by maximizing an objective function. In the control design, limitations on drug consumption and unavailability of all states are taken into account. The closed-loop stability has been... 

    Microfluidic-based multi-organ platforms for drug discovery

    , Article Micromachines ; Volume 7, Issue 9 , 2016 ; 2072666X (ISSN) Rezaei Kolahchi, A ; Khadem Mohtaram, N ; Pezeshgi Modarres, H ; Mohammadi, M. H ; Geraili, A ; Jafari, P ; Akbari, M ; Sanati Nezhad, A ; Sharif University of Technology
    MDPI AG 
    Abstract
    Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of such platforms is still far from reality. Recent advances in physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling, micro- and nanotechnology, and in silico modeling have enabled single- and multi-organ platforms for investigation of new chemical agents and tissue-tissue interactions. This review provides an overview of the principles of designing... 

    Smart mesoporous silica nanoparticles for controlled-release drug delivery

    , Article Nanotechnology Reviews ; Volume 5, Issue 2 , 2016 , Pages 195-207 ; 21919089 (ISSN) Karimi, M ; Mirshekari, H ; Aliakbari, M ; Sahandi Zangabad, P ; Hamblin, M. R ; Sharif University of Technology
    Walter de Gruyter GmbH  2016
    Abstract
    Stimuli-responsive controlled-release nanocarriers are promising vehicles for delivery of bioactive molecules that can minimize side effects and maximize efficiency. The release of the drug occurs when the nanocarrier is triggered by an internal or external stimulus. Mesoporous silica nanoparticles (MSN) can have drugs and bioactive cargos loaded into the high-capacity pores, and their release can be triggered by activation of a variety of stimulus-responsive molecular "gatekeepers" or "nanovalves." In this mini-review, we discuss the basic concepts of MSN in targeted drug-release systems and cover different stimulus-responsive gatekeepers. Internal stimuli include redox, enzymes, and pH,... 

    Investigating reliable conditions for hewl as an amyloid model in computational studies and drug interactions

    , Article Journal of Chemical Information and Modeling ; Volume 59, Issue 12 , 2019 , Pages 5218-5229 ; 15499596 (ISSN) Kalhor, H. R ; Jabbary, M ; Sharif University of Technology
    American Chemical Society  2019
    Abstract
    A number of conformational diseases in humans have been associated with protein/peptide fibrillation known as amyloid. Although extensive studies have been conducted in understanding the molecular basis of amyloid formation, a detailed mechanism is still missing. Experimentally, HEWL (hen egg white lysozyme) has been exploited ubiquitously as a model protein for amyloid fibrillation and drug inhibition. However, computational studies investigating fibril formation of HEWL have been a difficult task to perform mainly due to high stability of lysozymes and the absence of crystal structures of HEWL fibril oligomers. In this study, we have examined various conditions of HEWL amyloid formation... 

    The effect of chitosan and PEG polymers on stabilization of GF-17 structure: A molecular dynamics study

    , Article Carbohydrate Polymers ; Volume 237 , 2020 Asadzadeh, H ; Moosavi, A ; Arghavani Hadi, J ; Sharif University of Technology
    Elsevier Ltd  2020
    Abstract
    We examine the interactions of chitosan and polyethylene glycol (PEG) with antimicrobial peptide GF-17 to identify a suitable carrier to improve the peptide drug delivery systems. To this end, the molecular dynamics simulations are used to determine the interactions of a typical antimicrobial peptide GF-17 with the chitosan and PEG polymers. The findings indicate the great potential of the peptide to maintain its secondary structure in the adjacent to chitosan polymers. During the interaction with chitosan polymers, the structure of the peptide has smaller fluctuations compared to the PEG polymers. Also, in the presence of both the polymers, the PEG polymers are situated closer to the... 

    Combined effects of electric stimulation and microgrooves in cardiac tissue-on-a-chip for drug screening

    , Article Small Methods ; Volume 4, Issue 10 , 2020 Ren, L ; Zhou, X ; Nasiri, R ; Fang, J ; Jiang, X ; Wang, C ; Qu, M ; Ling, H ; Chen, Y ; Xue, Y ; Hartel, M.C ; Tebon, P ; Zhang, S ; Kim, H.-J ; Yuan, X ; Shamloo, A ; Dokmeci, M. R ; Li, S ; Khademhosseini, A ; Ahadian, S ; Sun, W ; Sharif University of Technology
    John Wiley and Sons Inc  2020
    Abstract
    Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip... 

    Evaluation of anti-cancer and anti-metastatic effects of folate-PEGylated niosomes for co-delivery of letrozole and ascorbic acid on breast cancer cells

    , Article Molecular Systems Design and Engineering ; Volume 7, Issue 9 , 2022 , Pages 1102-1118 ; 20589689 (ISSN) Bourbour, M ; Khayam, N ; Noorbazargan, H ; Tavakkoli Yaraki, M ; Asghari Lalami, Z ; Akbarzadeh, I ; Eshrati Yeganeh, F ; Dolatabadi, A ; Mirzaei Rad, F ; Tan, Y. N ; Sharif University of Technology
    Royal Society of Chemistry  2022
    Abstract
    Fighting with cancer requires the delivery of different therapeutics to the target cancerous cells by taking advantage of the synergistic effects of complementary medicine. Herein, we present a folate-PEGylated niosome as an efficient nanocarrier for targeted co-delivery of hydrophobic letrozole (L) and hydrophilic ascorbic acid (A) to breast cancer cells. The formulation of the niosomal nanocarrier was optimized by varying the ratio of cholesterol and surfactants to maximize the drug loading and minimize the size of nanocarriers. The optimum drug carriers were further functionalized with folate-PEG molecules to enhance the efficiency of drug delivery to the breast cancer cells and prevent... 

    Controlled release of doxorubicin from electrospun PEO/chitosan/graphene oxide nanocomposite nanofibrous scaffolds

    , Article Materials Science and Engineering C ; Volume 48 , March , 2015 , Pages 384-390 ; 09284931 (ISSN) Ardeshirzadeh, B ; Aboutalebi Anaraki, N ; Irani, M ; Roshanfekr Rad, L ; Shamshiri, S ; Sharif University of Technology
    Elsevier Ltd  2015
    Abstract
    Polyethylene oxide (PEO)/chitosan (CS)/graphene oxide (GO) electrospun nanofibrous scaffolds were successfully developed via electrospinning process for controlled release of doxorubicin (DOX). The SEM analysis of nanofibrous scaffolds with different contents of GO (0.1, 0.2, 0.5 and 0.7 wt.%) indicated that the minimum diameter of nanofibers was found to be 85 nm for PEO/CS/GO 0.5% nanofibers. The π-π stacking interaction between DOX and GO with fine pores of nanofibrous scaffolds exhibited higher drug loading (98%) and controlled release of the DOX loaded PEO/CS/GO nanofibers. The results of DOX release from nanofibrous scaffolds at pH 5.3 and 7.4 indicated strong pH dependence. The... 

    Bacterial components as naturally inspired nano-carriers for drug/gene delivery and immunization: set the bugs to work?

    , Article Biotechnology Advances ; Volume 36, Issue 4 , 2018 , Pages 968-985 ; 07349750 (ISSN) Farjadian, F ; Moghoofei, M ; Mirkiani, S ; Ghasemi, A ; Rabiee, N ; Hadifar, S ; Beyzavi, A ; Karimi, M ; Hamblin, M. R ; Sharif University of Technology
    Elsevier Inc  2018
    Abstract
    Drug delivery is a rapidly growing area of research motivated by the nanotechnology revolution, the ideal of personalized medicine, and the desire to reduce the side effects of toxic anti-cancer drugs. Amongst a bewildering array of different nanostructures and nanocarriers, those examples that are fundamentally bio-inspired and derived from natural sources are particularly preferred. Delivery of vaccines is also an active area of research in this field. Bacterial cells and their components that have been used for drug delivery, include the crystalline cell-surface layer known as “S-layer” bacterial ghosts, bacterial outer membrane vesicles, and bacterial products or derivatives (e.g.... 

    Optimization and characterization of tannic acid loaded niosomes for enhanced antibacterial and anti-biofilm activities

    , Article Advanced Powder Technology ; 2020 Heidari, F ; Akbarzadeh, I ; Nourouzian, D ; Mirzaie, A ; Bakhshandeh, H ; Sharif University of Technology
    Elsevier B.V  2020
    Abstract
    The purpose of this study was to prepare and characterize an optimized system of tannic acid-loaded niosomes as a potential carrier for antibacterial and anti-biofilm delivery. The niosomal formulation was optimized using response surface methodology (RSM). The effects of the molar ratio of surfactant to cholesterol, drug concentration, and molar ratio of Span 60 to Tween 60 on particle size and drug entrapment efficiency of the niosomal nanocarrier were studied. The optimized nanoparticles were characterized in terms of the morphology, in vitro release profile, and antibacterial properties. Moreover, Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC)... 

    Probe into the molecular mechanism of ibuprofen interaction with warfarin bound to human serum albumin in comparison to ascorbic and salicylic acids: Allosteric inhibition of anticoagulant release

    , Article Journal of Chemical Information and Modeling ; Volume 61, Issue 8 , 2021 , Pages 4045-4057 ; 15499596 (ISSN) Kalhor, H. R ; Taghikhani, E ; Sharif University of Technology
    American Chemical Society  2021
    Abstract
    The release of anticoagulant drugs such as warfarin from human serum albumin (HSA) has been important not only mechanistically but also clinically for patients who take multiple drugs simultaneously. In this study, the role of some commonly used drugs, including s-ibuprofen, ascorbic acid, and salicylic acid, was investigated in the release of warfarin bound to HSA in silico. The effects of the aforementioned drugs on the HSA-warfarin complex were investigated with molecular dynamics (MD) simulations using two approaches; in the first perspective, molecular docking was used to model the interaction of each drug with the HSA-warfarin complex, and in the second approach, drugs were positioned... 

    Natural polymers decorated mof-mxene nanocarriers for co-delivery of doxorubicin/pCRISPR

    , Article ACS Applied Bio Materials ; Volume 4, Issue 6 , 2021 , Pages 5106-5121 ; 25766422 (ISSN) Rabiee, N ; Bagherzadeh, M ; Jouyandeh, M ; Zarrintaj, P ; Saeb, M. R ; Mozafari, M ; Shokouhimehr, M ; Varma, R. S ; Sharif University of Technology
    American Chemical Society  2021
    Abstract
    A one-pot and facile method with assistance of high gravity was applied for the synthesis of inorganic two-dimensional MOF-5 embedded MXene nanostructures. The innovative inorganic MXene/MOF-5 nanostructure was applied in co-delivery of drug and gene, and to increase its bioavailability and interaction with the pCRISPR, the nanomaterial was coated with alginate and chitosan. The polymer-coated nanosystems were fully characterized, and the sustained DOX delivery and comprehensive cytotoxicity studies were conducted on the HEK-293, PC12, HepG2, and HeLa cell lines, demonstrating acceptable and excellent cell viability at both very low (0.1 μg.mL-1) and high (10 μg·mL-1) concentrations. The... 

    Fabrication and evaluation of controlled release of doxorubicin loaded UiO-66-NH2 metal organic frameworks

    , Article International Journal of Engineering, Transactions B: Applications ; Volume 34, Issue 8 , 2021 , Pages 1874-1881 ; 1728144X (ISSN) Rakhshani, N ; Hassanzadeh Nemati, N ; Ramezani Saadatabadi, A ; Sadrnezhaad, S. K ; Sharif University of Technology
    Materials and Energy Research Center  2021
    Abstract
    The metal-organic frameworks (MOFs) due to their large specific surface area and high biocompatibility are suitable as carriers for drug delivery systems (DDSs). In the present study, doxorubicin (DOX) as an anticancer drug was loaded into UiO-66-NH2 MOFs to decrease the adverse side effects of pristine DOX use and to increase its efficiency through the controlled release of DOX from MOFs. The MOFs were synthesized via microwave heating method and characterized using X-ray diffraction, scanning electron microscopy, and Brunauer-Emmett- Teller analysis. The drug loading efficiency, drug release profiles from synthesized MOFs and pharmacokinetic studies were investigated. The biocompatibility... 

    Modeling of an ultrasound system in targeted drug delivery to abdominal aortic aneurysm: a patient-specificin silico study based on ligand-receptor binding

    , Article IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control ; Volume 69, Issue 3 , 2022 , Pages 967-974 ; 08853010 (ISSN) Shamloo, A ; Boroumand, A ; Ebrahimi, S ; Kalantarnia, F ; Maleki, S ; Moradi, H ; Sharif University of Technology
    Institute of Electrical and Electronics Engineers Inc  2022
    Abstract
    Targeted drug delivery methods have shown a significant impact on enhancing drug delivery efficiency and reducing drug side effects. While various stimuli have been used to promote the drug delivery process, applying ultrasound (US) waves to control drug particles through the human body, noninvasively, has drawn the scientist's attention. However, microcarriers delivery reaches the aneurysmal artery by US waves that exert volumetric forces on blood, and drug carriers, which can therefore affect blood flow patterns and movement pathways of drug carriers, have not yet been studied. In this study, we developed a 3-D patient-specific model of abdominal aortic aneurysm (AAA) to evaluate the... 

    Green carbon-based nanocomposite biomaterials through the lens of microscopes

    , Article Emergent Materials ; Volume 5, Issue 3 , 2022 , Pages 665-671 ; 25225731 (ISSN) Rabiee, N ; Ahmadi, S ; Rabiee, M ; Bagherzadeh, M ; Vahabi, H ; Jouyandeh, M ; Saeb, M. R ; Sharif University of Technology
    Springer Nature  2022
    Abstract
    In this work, a green synthesis method was designed and practiced to develop bioactive and biocompatible carbon-based nanocomposites biomaterials. ZnO nanoparticles were synthesized in assistance of leaf extracts and added to a composite nanostructure composed of the reduced graphene oxide (rGO) and multi-walled carbon nanotubes (MWCNT). The resulting green nanocomposite revealed ability to make π-π interactions, hydrogen bonding, and van der Waals interactions with the doxorubicin (DOX). Then, the surface morphology of the synthesized nanocomposite was investigated, and the interrelationship between the surface morphology, relative cell viability, and drug uptake and release behavior were... 

    Plant protein-based hydrophobic fine and ultrafine carrier particles in drug delivery systems

    , Article Critical Reviews in Biotechnology ; Volume 38, Issue 1 , 2018 , Pages 47-67 ; 07388551 (ISSN) Malekzad, H ; Mirshekari, H ; Sahandi Zangabad, P ; Moosavi Basri, S. M ; Baniasadi, F ; Sharifi Aghdam, M ; Karimi, M ; Hamblin, M. R ; Sharif University of Technology
    Taylor and Francis Ltd  2018
    Abstract
    For thousands of years, plants and their products have been used as the mainstay of medicinal therapy. In recent years, besides attempts to isolate the active ingredients of medicinal plants, other new applications of plant products, such as their use to prepare drug delivery vehicles, have been discovered. Nanobiotechnology is a branch of pharmacology that can provide new approaches for drug delivery by the preparation of biocompatible carrier nanoparticles (NPs). In this article, we review recent studies with four important plant proteins that have been used as carriers for targeted delivery of drugs and genes. Zein is a water-insoluble protein from maize; Gliadin is a 70% alcohol-soluble... 

    Stimulus-responsive sequential release systems for drug and gene delivery

    , Article Nano Today ; Volume 34 , 2020 Ahmadi, S ; Rabiee, N ; Bagherzadeh, M ; Elmi, F ; Fatahi, Y ; Farjadian, F ; Baheiraei, N ; Nasseri, B ; Rabiee, M ; Tavakoli Dastjerd, N ; Valibeik, A ; Karimi, M ; Hamblin, M. R ; Sharif University of Technology
    Elsevier B.V  2020
    Abstract
    In recent years, a range of studies have been conducted with the aim to design and characterize delivery systems that are able to release multiple therapeutic agents in controlled and programmed temporal sequences, or with spatial resolution inside the body. This sequential release occurs in response to different stimuli, including changes in pH, redox potential, enzyme activity, temperature gradients, light irradiation, and by applying external magnetic and electrical fields. Sequential release (SR)-based delivery systems, are often based on a range of different micro- or nanocarriers and may offer a silver bullet in the battle against various diseases, such as cancer. Their distinctive...