Sharif Digital Repository

With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate... 

Mitochondria is a major regulator of inducing tumor apoptosis and it is as a prime target for chemotherapy. Anticancers need to access specific tumor cells and also pass through different barriers such as outer and inner membranes of mitochondria. Targeted accumulation of paclitaxel (PTX) within the mitochondria was achieved by direct conjugation of PTX with triphenylphosphonium (TPP) as a mitochondrial membrane-permeable cation. PTX-TPP prodrug was synthesized by pH-sensitive ester bond between the hydroxyl function of PTX and the carboxylic function of TPP. This ester bond is only cleaved by the mitochondrial aldehyde dehydrogenase. Prodrug was loaded in the albumin nanoparticles by... 

In this work, a novel carrier based-on modified graphene oxide was designed for co-delivery of hydrophobic and hydrophilic anticancer drugs (curcumin (Cur) and doxorubicin (DOX) as the model of drugs). The hydroxyl groups at the edges of graphene oxide (GO) sheets were used as the initiation sites for growing poly(epichlorohydrin) (PCH) chains. Then, hyperbranched polyglycerol (HPG) was grafted on the hydroxyl end groups of PCH (PCH-g-HPG). Pendant chlorines in the main chain of GO-PCH-g-HPG were replaced with hydrazine. The modification of GO sheets with oxygen-rich polymers increased water solubility of graphene oxide. Doxorubicin was loaded onto the nanocarrier by covalent bonding with... 

This study aimed to synthesize methoxy polyethylene glycol propionaldehyde (mPEG20,000-ALD) for the preparation of PEGylated nanoliposomal cisplatin. Nanocarriers such as liposomes are developed for a wide range of drug delivery systems. PEG with high molecular weight (Mw) is used to coat the liposomes. In this study, simulated Fourier transform infrared (FTIR) spectra of mPEG-ALD were obtained using density functional theory (DFT) calculations and then compared with actual FTIR spectrum of mPEG20,000-ALD (Mw = 20 kDa). We found that the intensity of C = O stretching vibration at 1,700 cm-1 related to the carbonyl functional group of mPEG20,000-ALD was very weak. The results of DFT... 

Formation of the amyloid beta (Aβ) peptide aggregations represents an indispensable role in appearing and progression of Alzheimer disease. β-sheet breaker peptides can be designed and modified with different amino acids in order to improve biological properties and binding affinity to the amyloid beta peptide. In the present study, three peptide sequences were designed based on the hopeful results of LIAIMA peptide and molecular docking studies were carried out onto the monomer and fibril structure of amyloid beta peptide using AutoDock Vina software. According to the obtained interactions and binding energy from docking, the best-designed peptide (D-GABA-FPLIAIMA) was chosen and... 

The global COVID-19 pandemic has affected the world’s population by causing changes in behavior, such as social distancing, masking, restricting people’s movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of... 

Background: Numerous studies have described the neuroprotective effect of lithium in spinal cord injury in addition to its ameliorative impact on pain sensation. In the present study, we aim to examine the efficacy of 85 mg/kg as well as 50 mg/kg dosage of the lithium chloride (LiCl) through oral consumption in spinal cord injured rats and their effect on gene expression of three candidate genes, corresponding to the hyper-sensitization. Methods: Adult Wistar (male) rats were divided into four experimental groups: control; oral administration of LiCl with 85 mg/kg and 50 mg/kg dosage; and 10 % sucrose receiver as the vehicle. BBB and heat plantar tests were performed weekly throughout four... 

Simvastatin, a well-known antihyperlipidemic drug, has antibacterial activity against a broad range of bacteria, especially Staphylococcus aureus. In present study, a nanoemulsion gel-based formulation containing Simvastatin was developed for infected wound therapy. Therefore, different formulations of Simvastatin nanoemulsion were prepared. Based on droplet size, polydispersity index and zeta potential, the best nanoemulsion formulation containing Simvastatin was selected for development of nanoemulsion gel formulation of drug using carbomer 934 as gelling agent. Thermodynamic stability of Simvastatin nanoemulsion was assessed at different conditions. The in vitro antibacterial activity... 

Breast cancer is one of the most prevalent causes of cancer mortality in women. In order to increase patient prognosis and survival rates, new technologies are urgently required to deliver therapeutics in a more effective and efficient manner. Niosome nanoparticles have been recently employed as therapeutic platforms capable of loading and carrying drugs within their core for both mono and combination therapy. Here, niosome-based nanoscale carriers were investigated as a targeted delivery system for breast cancer therapy. The platform developed consists of niosomes loaded with letrozole and cyclophosphamide (NLC) and surface-functionalized with a folic-acidtargeting moiety (NLCPFA). Drug... 

The oxidation-reduction (redox)–responsive micelle system is based on a diselenide-containing triblock copolymer, poly(ε-caprolactone)-bis(diselenide-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate) [PCL-(SeSe-mPEG/PEG-FA)2]. This has helped in the development of tumor-targeted delivery for hydrophobic anticancer drugs. The diselenide bond, as a redox-sensitive linkage, was designed in such a manner that it is located at the hydrophilic–hydrophobic hinge to allow complete collapse of the micelle and thus efficient drug release in redox environments. The amphiphilic block copolymers self-assembled into micelles at concentrations higher than the critical micelle concentration (CMC)... 

In this work, the synthesized graphene oxide/TiO2/doxorubicin (GO/TiO2/DOX) composites were loaded into the chitosan/poly(lactic acid) (PLA) solutions to fabricate the electrospun chitosan/PLA/GO/TiO2/DOX nanofibrous scaffolds via electrospinning process. The synthesized composites and nanofibers were characterized using X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis. Three-factor three-level central composite design was used to determine the influence of PLA to chitosan ratio, TiO2/DOX content and GO/TiO2/DOX content on the release of DOX from nanofibrous scaffolds. Drug loading efficiency and drug release behavior from... 

In this study, optimized cephalexin-loaded niosomal formulations based on span 60 and tween 60 were prepared as a promising drug carrier system. The niosomal formulations were characterized using a series of techniques such as scanning electron microscopy, Fourier transformed infrared spectroscopy, dynamic light scattering, and zeta potential measurement. The size and drug encapsulation efficiency are determined by the type and composition of surfactant. The developed niosomal formulations showed great storage stability up to 30 days with low change in size and drug entrapment during the storage, making them potential candidates for real applications. Moreover, the prepared niosomes showed... 

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... 

Background: Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic... 

Oxaliplatin (OXA) has been widely used for treatment of colorectal cancer. In this study, to enhance antitumor and apoptosis efficacy, OXA was encapsulated in a novel folate conjugated hyaluronic acid coated alginate nanogels (F/HA/AL/OXA). The F/HA/AL/OXA nanogels were prepared by cross-linking process. The physico-chemical properties of F/HA/AL/OXA nanogels were characterized using scanning electron microscopy, transmission electron microscopy, fourier transform infrared spectroscopy, dynamic light scattering, and fluorescent spectrophotometry. The in-vitro antitumor activity of free OXA, AL, HA/AL, HA/AL/OXA and F/HA/AL/OXA nanogels were assessed using MTT assay against colorectal cancer... 

Background: Type-2 diabetes mellitus is characterized by insulin resistance and impaired insulin secretion in the human body. Many endeavors have been made in terms of controlling and reducing blood glucose via the medium of automated controlling tools to increase precision and efficiency and reduce human error. Recently, reinforcement learning algorithms are proved to be powerful in the field of intelligent control, which was the motivation for the current study. Methods: For the first time, a reinforcement algorithm called normalized advantage function (NAF) algorithm has been applied as a model-free reinforcement learning method to regulate the blood glucose level of type-2 diabetic... 

Although simvastatin (SIM) has been proven to be a powerful agent against myocardial ischemia/reperfusion (MI/R) injury, poor water solubility, short half-life, and low bioavailability have made it futile while using conventional drug delivery system. Hence, this study aims to investigate therapeutic efficacy of SIM-loaded nano-niosomes on MI/R injury. Surface active agent film hydration method was used to synthesize nano-niosomes. The physicochemical properties of nano-niosomes were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, niosomes were characterized in entrapment efficiency (EE) and releasing pattern. Male Wistar rats were... 

At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. More specifically for drug delivery purposes, the use of nanoparticles is attracting increasing attention due to their unique capabilities and their negligible side effects not only in cancer therapy but also in the treatment of other ailments. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with proper surface architecture and conjugated targeting ligands/proteins have attracted a great deal of attention for drug delivery applications. This review covers recent advances in the development of SPIONs together... 

Porphyrins are organic compounds that continue to attract much theoretical interest, and have been called the “pigments of life”. They have a wide role in photodynamic and sonodynamic therapy, along with uses in magnetic resonance, fluorescence and photoacoustic imaging. There is a vast range of porphyrins that have been isolated or designed, but few of them have real clinical applications. Due to the hydrophobic properties of porphyrins, and their tendency to aggregate by stacking of the planar molecules they are difficult to work with in aqueous media. Therefore encapsulating them in nanoparticles (NPs) or attachment to various delivery vehicles have been used to improve delivery... 

Recent advances in biomaterials, microfabrication, microfluidics, and cell biology have led to the development of organ-on-a-chip devices that can reproduce key functions of various organs. Such platforms promise to provide novel insights into various physiological events, including mechanisms of disease, and evaluate the effects of external interventions, such as drug administration. The neuroscience field is expected to benefit greatly from these innovative tools. Conventional ex vivo studies of the nervous system have been limited by the inability of cell culture to adequately mimic in vivo physiology. While animal models can be used, their relevance to human physiology is uncertain and...