Sharif Digital Repository

Easily assembled and biocompatible chitosan/hyaluronic acid nanoparticles with multiple stimuli-responsive ability are ideally suited for efficient delivery of therapeutic agents under specific endogenous triggers. We report a simple and versatile strategy to formulate oxidative stress and pH-responsive chitosan/hyaluronic acid nanocarriers with high encapsulation efficiencies of small drug molecules and nerve growth factor protein. This is achieved through invoking the dual role of a thioketal-based weak organic acid to disperse and functionalize low molecular weight chitosan in one-pot. Thioketal embedded chitosan/hyaluronic acid nanostructures respond to oxidative stress and show... 

Despite a diverse range of active pharmaceutical agents currently at our disposal, high morbidity rate diseases continue to pose a major health crisis globally. One of the important parameters in this regard is the controlled cargo delivery at desired sites. Among a variety of synthetic and natural macromolecular systems, chitosan, an abundant biopolymer, offers a platform for tailored architectures that could have high loading capacity of cargo, target and deliver. Stimuli directed accumulation of vehicles and drug release is an area of direct relevance to biomedical applications. In this review, we highlight essential characteristics of modified chitosan that present themselves for... 

Upon incubation of nanoparticles in biological fluids, a new layer called the protein corona is formed on their surface affecting the interactions between nanoparticles and targeted cells during the endocytosis process. In the present study, a mathematical model based on the diffusion of membrane mobile receptors is proposed. Opposing the endocytosis proceeding, membrane bending and tension energies are named as resistant energy. Also, the binding energy and free-energy associated with the configurational entropy are collectively termed promoter energy. Utilizing this model, endocytosis of gold nanoparticle (GNP) is simulated to explore the biological media effect. The results reveal that... 

Cell-laden hydrogel microcapsules enable the high-throughput production of cell aggregates, which are relevant for three-dimensional tissue engineering and drug screening applications. However, current microcapsule production strategies are limited by their throughput, multistep protocols, and limited amount of compatible biomaterials. We here present a single-step process for the controlled microfluidic production of single-core microcapsules using enzymatic outside-in cross-linking of tyramine-conjugated polymers. It was hypothesized that a physically, instead of the conventionally explored biochemically, controlled enzymatic cross-linking process would improve the reproducibility,... 

In this study, an impulsive state feedback controller has been proposed for the treatment of hepatitis-C-infected patients under Pegylated-Interferon (PEG-IFN-α2b) therapy. The Neumann model has been utilized as the representative of the hepatitis C virus (HCV) dynamics. In order to consider the drug efficacy variation between injections, the pharmacokinetics/pharmacodynamics (PK/PD) equations have been included in the model. The impulsive nature of the drug injection also has been considered in the disease dynamics. In the proposed treatment method, the drug dose limitation has been addressed as an input nonlinearity. The asymptotical stability of the control method under the impulsive... 

Bioactive glass has been used clinically in bone repair applications for bone grafting because of its prominent physiochemical and osteogenic properties. Various attempts have been made to enhance bioactive glass efficiency in combination with other biomaterials such as antibiotics and growth factors. In present study, we developed a modification of bioactive glass nanoparticles that insured long term antibacterial effect. Bioactive glass nanoparticles (BGNs) were functionalized with (3-Aminopropyl) triethoxysilane (APTS), then vancomycin (VAN) was immobilized onto BGNs-APTS via EDC/NHS cross-linking process. Another study group namely BGNs-VAN was synthesized as a control group without any... 

Coaxial electrospinning with the ability to use simultaneously two separate solvents provides a promising strategy for drug delivery. Nevertheless, controlled release of hydrophilic and sensitive therapeutics from slow biodegradable polymers is still challenging. To address this gap, we fabricated core-sheath fibers for dual delivery of lysozyme, as a model protein, and phenytoin sodium as a small therapeutic molecule. The sheath was processed by a gelatin solution while the core fibers were fabricated from an aqueous gelatin/PVA solution. Microstructural studies by transmission and scanning electron microscopy reveal the formation of homogeneous core-sheath nanofibers with an outer and... 

A Zn-Rich (GaN)1−x(ZnO)xnanostructure was synthesized with the assistance of a high-gravity technique in order to reduce the reaction time and temperature. The synthesized inorganic nanomaterial has been applied in both drug and gene delivery systems, and as the first fully inorganic nanomaterial, it was investigated in a comprehensive cellular investigation as well. In order to increase the potential bioavailability, as well as the interactions with the pCRISPR, the nanomaterial was enriched with additional Zn ions. The nanomaterial and the final nanocarrier were characterized at each step before and after any biological analysisviaFESEM, AFM, TEM, FTIR and XRD. The polymer coated... 

Phosphatidylcholine (PC) possesses amphiphilic characteristics to form vesicles or liposome nanoparticles and can be utilized to deliver essential nutrients such as proteins, peptide antigens, and essential fatty acids. In this study, an attempt has been made to obtain purified PC and evaluate its potential in nanoliposome synthesis and its corresponding drug release profile. In this regard, four physical separation techniques comprising extraction, precipitation, static, and dynamic adsorption were assessed and applied to purify PC from soybean lecithin. Different solvents and the ratio of lecithin to solvent were used to achieve the highest PC percentage. The results of an HPLC test showed... 

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... 

One of the antibiotics used to treat infections is streptomycin sulfate that inhibits both Gram-negative and -positive bacteria. Nanoparticles are suitable carriers for the direct delivery and release of drug agents to infected locations. Niosomes are one of the new drug delivery systems that have received much attention today due to their excellent biofilm penetration property and controlled release. In this study, niosomes containing streptomycin sulfate were prepared by using the thin layer hydration method and optimized based on the size, polydispersity index (PDI), and encapsulation efficiency (EE%) characteristics. It was found that the Span 60-to-Tween 60 ratio of 1.5 and the... 

Since the injection of the oncolytic viruses in the virotherapy process reduces the toxicity and drug resistance inherent in the chemotherapy; chemovirotherapy as a novel combination therapy has become an efficient cancer treatment. The primary purpose of this paper is to design a robust optimal control strategy for the chemovirotherapy through which the tumor density decreases to its stable condition with limited drug and virus delivery. This desired treatment should be responsive in the presence of input disturbances and parametric uncertainties. In this regard, an ODE (Ordinary Differential Equation) mathematical model of the chemovirotherapy process presenting the connection between the... 

Exploring efficient chemotherapy would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. As in vivo experimental methods are unable to isolate or control individual factors of the TME, and in vitro models often cannot include all the contributing factors, some questions are best addressed with mathematical models of systems biology. In this study, we establish a multi-scale mathematical model of the TME to simulate three-dimensional tumor growth and angiogenesis and then implement the model for an array of chemotherapy approaches to elucidate the effect of TME conditions and drug scheduling on controlling tumor progression. The... 

Diatoms are unicellular microalga found in soil and almost every aquatic environment (marine and fresh water). Biogenic silica and diatoms are attractive for biotechnological and industrial applications, especially in the field of biomedicine, industrial/synthetic manufacturing processes, and biomedical/pharmaceutical sciences. Deposition of silica by diatoms allows them to create micro- or nanoscale structures which may be utilized in nanomedicine and especially in drug/gene delivery. Diatoms with their unique architectures, good thermal stability, suitable surface area, simple chemical functionalization/modification procedures, ease of genetic manipulations, optical/photonic... 

Hybrid bioactive inorganic-organic carbon-based nanocomposites of reduced graphene oxide (rGO) nanosheets enlarged with multi-walled carbon nanotubes (MWCNTs) were decorated to provide a suitable space forin situgrowth of CoNi2S4and green-synthesized ZnO nanoparticles. The ensuing nanocarrier supplied π-π interactions between the DOX drug and a stabilizing agent derived from leaf extracts on the surface of ZnO nanoparticles and hydrogen bonds; gene delivery of (p)CRISPR was also facilitated by chitosan and alginate renewable macromolecules. Also, these polymers can inhibit the potential interactions between the inorganic parts and cellular membranes to reduce the potential cytotoxicity.... 

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... 

Herein, the NH2-UiO-66 metal organic framework (MOF) has been green synthesized with the assistance of high gravity to provide a suitable and safe platform for drug loading. The NH2-UiO-66 MOF was characterized using a field-emission scanning electron microscope, transmission electron microscope (TEM), X-ray diffraction, and zeta potential analysis. Doxorubicin was then encapsulated physically on the porosity of the green MOF. Two different stimulus polymers, p(HEMA) and p(NIPAM), were used as the coating agents of the MOFs. Doxorubicin was loaded onto the polymer-coated MOFs as well, and a drug payload of more than 51% was obtained, which is a record by itself. In the next step, pCRISPR was... 

The design of advanced nanobiomaterials to improve analytical accuracy and therapeutic efficacy has become an important prerequisite for the development of innovative nanomedicines. Recently, phospholipid nanobiomaterials including 2-methacryloyloxyethyl phosphorylcholine (MPC) have attracted great attention with remarkable characteristics such as resistance to nonspecific protein adsorption and cell adhesion for various biomedical applications. Despite many recent reports, there is a lack of comprehensive review on the phospholipid nanobiomaterials from synthesis to diagnostic and therapeutic applications. Here, we review the synthesis and characterization of phospholipid nanobiomaterials... 

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... 

In the current study, gold nanoparticles (AuNPs) were prepared using the green synthesis method using Artemisia annua extract, loaded into niosomes, and investigated their cytotoxicity and apoptotic effects. To optimize the niosomal formulation containing AuNPs, the effects of surfactants: cholesterol molar ratio, Span 60: Tween 60 M ratio, and AuNP concentration (µg/mL) were investigated. After examining the drug release profile, mathematical models were assessed to predict release kinetic. The cytotoxicity of noisome encapsulated AuNPs and free AuNPs was evaluated against human ovarian cancer cell line (A2780) by MTT assay. The apoptotic/necrosis ratio was studied using flow cytometry as...