Sharif Digital Repository

In this study, a semi-conductive nanocomposite for electrically controlled drug delivery is introduced. Hydrolyzed collagen known as a naturally abundant polypeptide was modified with polycaprolactone. This modification changed the mechanical properties of the hydrolyzed-collagen. A hydrogel compound was synthesized through radical co-polymerization of acrylic acid on the backbone of this biocompatible polymer in the presence of a crosslinker. The reaction parameters affecting the water absorbency of the hydrogel were optimized using Taguchi method. In situ polymerization of aniline, incorporated conductive nanofiber pathways throughout the hydrogel matrix. 1H NMR, TGA, AFM, SEM, FTIR,... 

A new robust adaptive controller is developed for the control of the hepatitis B virus (HBV) infection inside the body. The non-linear HBV model has three state variables: uninfected cells, infected cells and free viruses. A control law is designed for the antiviral therapy such that the volume of infected cells and the volume of free viruses are decreased to their desired values which are zero. One control input represents the efficiency of drug therapy in inhibiting viral production and the other control input represents the efficiency of drug therapy in blocking new infection. The proposed controller ensures the stability and robust performance in the presence of parametric and... 

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... 

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,... 

Spontaneous generation of nanobubbles (NBs) was developed by using a controllable platform of superfast microvortices, based on turbulent jet flows in the presence of graphene oxide (GO) sheets. Very high energy dissipation rates through discharging warm water into cold N2 aqueous solutions resulted in creation of micro/submicro-vortices. Shear stresses in these domains generated gas local supersaturations, leading to the formation of high concentration (∼109 mL−1) of stable NBs. Introducing GO sheets into the microvortex system resulted in effective manipulation of NBs by providing energetically favorable sites for prompt heterogeneous nucleation as well as stronger shear rate fluctuations.... 

Arrayed Ti6Al4V nanotubes (TNT) coated with hydroxyapatite (HA) were synthesized via electrochemical anodization method. Paracetamol was loaded onto TNT-HA electrode. Effects of anodization, nanotube formation and hydroxyapatite deposition on sorption and release of the drug were investigated. Saturation time of paracetamol on the anodized samples was 30% shorter than the hydroxyapatite-coated samples. Release behavior of the loaded drug was studied by (a) plunging the probe into phosphate buffered saline (PBS), (b) sampling the drug-loaded PBS at different times and (c) analyzing the solution via ultraviolet-visible (UV-vis) spectroscopy. Results showed that HA electrodes hold higher... 

The purpose of this study was to produce an intelligent superabsorbent polymer (SAP) to be used as a pH sensitive matrix for the controlled delivery of drugs. Novel types of highly swelling SAPs were prepared by grafting crosslinked acrylic acid-co-acrylamide (AA-co-AAm) chains onto pectin by free-radical polymerization. The superabsorbent formation was confirmed by Fourier transform infrared spectroscopic (FT-IR) and scanning electron microscopy (SEM). The controlled release behavior of ibuprofen (IBU) from the superabsorbent polymer was investigated. SAP structural-property relationships that affect its controlled release behavior were determined. Analysis of the results indicated that it... 

In the context of controlled release drug delivery approaches, the systems providing zero-order release kinetics have special advantages. Through employing these systems, drug concentration could be maintained within the therapeutic window over release time; thus maximum effectiveness alongside minimized side effects of the drug are achieved. However, obtaining zero-order drug release is extremely challenging. One of the main obstacles is the fact that implemented devices should be designed to overcome the decreasing mass transfer driving force, especially, in polymeric systems in which diffusion mechanism is dominant. In this study, we developed a new configuration of a polymeric matrix... 

Oral administration is a pillar of the pharmaceutical industry and yet it remains challenging to administer hydrophilic therapeutics by the oral route. Smart and controlled oral drug delivery could bypass the physiological barriers that limit the oral delivery of these therapeutics. Micro- and nanoscale technologies, with an unprecedented ability to create, control, and measure micro- or nanoenvironments, have found tremendous applications in biology and medicine. In particular, significant advances have been made in using these technologies for oral drug delivery. In this review, we briefly describe biological barriers to oral drug delivery and micro and nanoscale fabrication technologies.... 

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... 

A three-dimensional model has been developed to describe the multiphase release of macromolecular drugs encapsulated in a hydrogel. The heterogeneity of network mesh size was considered by assigning varying diffusion coefficients to the network lattices randomly. Using a stochastic approach, the random nature of diffusion of drug molecules was captured within the network. The simplest form of distribution containing two diffusion coefficients was tested. To generate the drug release profiles for experimental validation under the limitation of computational cost, a simple scaling relationship was employed. Unlike the single-diffusivity model, the dual-diffusivity model showed good agreement... 

Swimming microrobots have a variety of applications including drug delivery, sensing, and artificial fertilization. Their small size makes onboard actuation very hard, and therefore an external source such as the magnetic field is a practical way to steer and move the robot. In this paper, we have designed a novel microrobot steered by magnetic paddles. We have also discussed design parameters where, based on the conducted simulation, the robot speed reaches 520 um/s. It is shown that the microrobot speed depends on the robot paddle dimensions. According to the microrobots motion characteristics and their different reactions to the same input, we have designed a steering strategy for... 

In the past few years, laser-assisted methods have greatly influenced biomedical studies due to less invasive ways of treatment and higher precision. New stimuli-responsive drug carriers are still explored by scientists to achieve a better spatiotemporal control of drug carriers by using visible to NIR light instead of phototoxic ultra-violet irradiation. Due to their biocompatibility and high loading capacity of hydrophilic drugs, hydrogels have been used extensively in this area. However, poor cellular uptake and restricted loading of hydrophobic drugs are challenges that should be addressed. In this study, a previously known nanogel system based on chitosan and poly(N-isopropylacrylamide)... 

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... 

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... 

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... 

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... 

With the high rate of mortality associated with breast cancer among women, breast cancer treatment has attracted great deal of attention globally. To reduce the exposure of body organs to high cytotoxicity of the common chemotherapeutic drugs, local co-delivery of selected chemotherapeutics has emerged as a solution. In this work, an electrospun composite including a co-drug-loaded graphene oxide-based nanocarrier is fabricated for local anticancer applications. To increase dispersion and cellular uptake of graphene oxide (GO), first, the hydroxyl groups at the edges of GO are grafted by poly (epichlorohydrin) (PCH) to form GO-PCH. Then, the hydroxyl end groups of PCH are grafted (g) with... 

The present study proposes an exact solution for the release kinetic of a solute from inside a hollow cylindrical polymeric matrix into an infinite medium when the initial concentration of the solute (A) is greater than the solubility limit (Cs). A combination of analytical and numerical methods was used to calculate the solute concentration profile and the release rate. The model was developed for two different conditions including: (1) The release medium was flowing through the hollow cylinder in which the boundary layer may be neglected, and (2) The release medium inside the hollow cylinder was stagnant where the boundary layer needed to be considered. The results indicated that the...