Sharif Digital Repository

In this work, an efficient treatment strategy for hepatitis C disease using interferon (IFN) has been proposed on the basis of the back-stepping control technique. The basic model of the hepatitis C virus (HCV) has been considered for controller design. To tackle the problem of model parameter variations, the adaptive version of the back-stepping method has been utilized. For applying the proposed treatment, all states should be available while only the viral load is measured. To solve this problem, a nonlinear Luenberger-like observer has been designed to estimate the unmeasured states. In the proposed treatment, limitation of the drug efficacy has been taken into account. Asymptotical... 

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... 

In this study, a stable observer-based feedback controller has been designed for treatment of hepatitis C infectious disease under interferon (IFN) therapy. In order to consider the memory behavior and uncertain nature of this biological system, an unknown dynamics fractional-order (FO) model has been utilized for describing the interactions between the healthy cells, infected cells, and hepatitis C virus (HCV). To cope with unknown dynamics, the fuzzy logic system (FLS) has been utilized. Limitation of the drug efficacy due to its negative side effects has been taken into account as an input saturation. In order to estimate the unknown states which are required for treatment, a full-order... 

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... 

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,... 

Tissue adhesives have been widely used for preventing wound leaks, sever bleeding, as well as for enhancing drug delivery and biosensing. However, only a few among suggested platforms cover the circumstances required for high-adhesion strength and biocompatibility, without toxicity. Antibacterial properties, controllable degradation, encapsulation capacity, detectability by image-guided procedures and affordable price are also centered to on-demand tissue adhesives. Herein we overview the history of tissue adhesives, different types of polysaccharide-based tissue adhesives, their mechanism of gluing, and different applications of polysaccharide-based tissue adhesives. We also highlight the... 

A new composite adaptive control strategy is developed for both of the reduction of cancer tumor volume and the online identification of tumor parameters during the drug delivery process in chemotherapy. This control strategy is developed for three different nonlinear mathematical cell-kill models of the cancer tumor including the log-kill hypothesis, Norton-Simon hypothesis and Emax hypothesis. All of these models are considered to have fully parametric uncertainties. The stability, tracking convergence and parameters identification convergence during the chemotherapy process are proved using the Lyapunov method. For the first time, the parameters identification of the uncertain... 

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... 

Targeted drug delivery (TDD) to abdominal aortic aneurysm (AAA) using a controlled and efficient approach has recently been a significant challenge. In this study, by using magnetic microbubbles (MMBs) under a magnetic field, we investigated the MMBs performance in TDD to AAA based on the amount of surface density of MMBs (SDMM) adhered to the AAA lumen. The results showed that among the types of MMBs studied in the presence of the magnetic field, micromarkers are the best type of microbubble with a −50 % increase in SDMM adhered to the critical area of AAA. The results show that applying a magnetic field causes the amount of SDMM adhered to the whole area of AAA to increase −1.54 times... 

This work focused on the design of new pH-responsive nanoparticles for controlled delivery of anticancer drug doxorubicin (Dox). Nanoparticles of poly(methacrylic acid)-polysorbate 80-grafted starch (PMAA-PS 80-g-St) were synthesized by using a one-pot method that enabled simultaneous grafting of PMAA and PS 80 onto starch and nanoparticle formation in an aqueous medium. The particles were characterized by FTIR, 1H NMR, TEM, DLS, and potentiometric titration. Dox loading and in vitro release from the nanoparticles were investigated. The FTIR and 1H NMR confirmed the chemical composition of the graft terpolymer. The nanoparticles were relatively spherical with narrow size distribution and... 

This work was intended to develop a new cross-linked gelatinized starch-xanthan gum hydrogel system, to characterize the properties of the new material, and to explore its potential applications in controlled drug delivery. Cross-linked starch-xanthan gum polymers were synthesized with varying levels of xanthan gum and sodium trimetaphosphate (STMP). The reaction of starch-xanthan gum polymers with STMP was examined using solid 31P NMR spectroscopy and FTIR. Morphology of the films made from the new polymers was studied by scanning electron microscopy. The swelling properties and the network parameters such as gel mesh size of the films were investigated. The permeation of solutes with... 

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... 

Forced and free vibrational analyses of viscoelastic nanotubes containing fluid under a moving load in complex environments incorporating surface effects are conducted based on the nonlocal strain gradient theory and the Rayleigh beam model. To model the internal nanoflow, the slip boundary condition is employed. Adopting the Galerkin discretization approach, the reduced-order dynamic model of the system is acquired. Analytical and numerical methods are exploited to determine the dynamic response of the system. The impacts of geometry, scale parameter ratio, Knudsen number, fluid velocity, rotary inertia parameter, viscoelastic parameter, surface residual stress, surface elastic modulus, and... 

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug... 

Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in... 

The composition and topology of metal-organic frameworks (MOFs) are exceptionally tailorable; moreover, they are extremely porous and represent an excellent Brunauer–Emmett–Teller (BET) surface area (≈3000–6000 m2·g−1). Nanoscale MOFs (NMOFs), as cargo nanocarriers, have increasingly attracted the attention of scientists and biotechnologists during the past decade, in parallel with the evolution in the use of porous nanomaterials in biomedicine. Compared to other nanoparticle-based delivery systems, such as porous nanosilica, nanomicelles, and dendrimer-encapsulated nanoparticles, NMOFs are more flexible, have a higher biodegradability potential, and can be more easily functionalized to meet... 

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... 

Ordered perpendicular TiO2 nanotubes (TNT) with 405 to 952 nm length and 60 to 90 nm diameter were grown via 40 to 120 min anodization of Ti6Al4V flat substrates. The samples were called TNT-40, -60, -80, -100, and -120. Vancomycin was loaded on the bare and anodized electrodes by separate immersion and electrophoretic (EP) deposition procedures. EP loading resulted in storage capacity of 5221.86 μg cm-2 for TNT-80 which was much higher than 1036.75 μg cm-2 of immersed sample. Drug release comprised of three stages: (i) burst release (78% for the bare, and 23% for the TNT-80 sample), (ii) gradual transport (21% for the bare, and 64% for the TNT-80 sample), and (iii) equilibrium. Transfer...