Sharif Digital Repository

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... 

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... 

Magnetic micelle nanoparticles with thermoresponsive behavior were designed for thermo-triggered paclitaxel delivery. For this purpose, thermoresponsive triblock copolymer poly(N-isopropyl acrylamide)-b-polycaprolactone-b-poly(N-isopropyl acrylamide) was prepared. The magnetic micelle was formed by self-assembly of triblock copolymer on the magnetite which was coated by oleic acid. The size of the magnetic micelle was between 30–40 nm reported by transmission electron microscopy. Also, dynamic light scattering indicated the hydrodynamic diameter was thermal dependent. Moreover, the drug release profile showed thermo-triggered release of paclitaxel. Thus, the smart nanocarrier has potential... 

Magnetic micelle nanoparticles with thermoresponsive behavior were designed for thermo-triggered paclitaxel delivery. For this purpose, thermoresponsive triblock copolymer poly(N-isopropyl acrylamide)-b-polycaprolactone-b-poly(N-isopropyl acrylamide) was prepared. The magnetic micelle was formed by self-assembly of triblock copolymer on the magnetite which was coated by oleic acid. The size of the magnetic micelle was between 30–40 nm reported by transmission electron microscopy. Also, dynamic light scattering indicated the hydrodynamic diameter was thermal dependent. Moreover, the drug release profile showed thermo-triggered release of paclitaxel. Thus, the smart nanocarrier has potential... 

Systematic delivery of therapeutic agents to specific sites, with a stimulus-responsive drug release profile is currently a rapidly growing area. Mesoporous silica nanoparticles (MSNs) are the useful platforms as drug/gene delivery systems due to their unique properties including the ability to control the pore size, high porosity, and morphology, which can directly affect the mechanism and profile of drug release. The appropriate fabrication strategy can tailor the particle shape and size, leading to enhanced delivery and release mechanisms. The MSN surface can be modified by using either organic or inorganic molecules to induce smart and site-specific drug delivery and release.... 

In the present study, the tri-layer nanofibers were synthesized via triaxial electrospinning process to control the sustained delivery of Doxorubicin (DOX), Paclitaxel (PTX) and 5- fluorouracil (5-FU) anticancer drugs from nanofibers. The 5-FU molecules were incorporated into the core solution (chitosan/polyvinyl alcohol (CS/PVA)) to fabricate the CS/PVA/5-FU inner layer of nanofibers. The intermediate layer was prepared from poly(lactic acid)/chitosan (PLA/CS) nanofibers. The DOX and PTX molecules were initially loaded into the g-C3N4 nanosheets and following were incorporated into the PLA/CS solution to fabricate the outer layer of nanofibers. The synthesized nanosheets and nanofibers were... 

Titanium does not react well with the human tissues and due to its bio-inert nature the surface modification has yet to be well-studied. In this study, the sonoelectrochemical process has been carried out to generate TiO2 nanotube arrays on implantable Ti 6–4. All the prepared nanotubes fill with the vancomycin by immersion and electrophoresis method. Drug-releasing properties, antibacterial behavior, protein adsorption and cell attachment of drug-modified nanotubes are examined by UV–vis, flow cytometry, modified disc diffusion, BSA adsorption, and FESEM, respectively. The most uniform morphology, appropriate drug release, cell viability behavior and antibacterial properties can be achieved... 

The multistep release of therapeutic agents in the theranostic particulate systems has remained as a challenge in smart drug delivery. In this study, superparamagnetic nanoparticles of Fe3O4 were coated with a blend of F127/F68 grades of pluronic in order to adjust the lower critical solution temperature (LCST) and consequently engineering of the release temperature. Pluronic as a biocompatible thermo-sensitive polymer is frequently used as a self-emulsifying drug delivery system. Magnetite nanoparticles with double layer coating of oleic acid and pluronic F127 have been reported as an on-demand smart carrier for hydrophobic drugs. LCST was examined using differential scanning calorimetry... 

One of the main issues of wastewater treatment is the silica deposition in steam turbines. Evaporation of silica with the steam in adequate concentration is one of the main sources of scale formation in steam turbines. In this study, the authors introduce the utilization of a genetic-based approach—gene expression programming (GEP)—for solubility prognostication of the silica in superheated steam of boilers with respect to water silica content and pressure. The result of GEP mathematical approach is a new algebraic formula to achieve our goals. Developed model predicts the silica solubility in the range of 0.8–22.1 MPa and 1–500 mg/kg for pressure and boiler water silica content,... 

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... 

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... 

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... 

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... 

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... 

Breast cancer incidence has increased in recent decades. In the present study, an optimum formulation of chitosan (CS)-adorned niosome-based nanocarriers for co-delivery of doxorubicin (DOX) and vincristine (VIN) was developed for the treatment of breast cancer to reduce drug doses and overcome multidrug resistance. The three-level Box-Behnken method was utilized to optimize the particles in terms of size, polydispersity index (PDI), entrapment efficacy (EE (%)), and percent of drug release (%). The release rate of two drugs from CS-adorned nanoparticles (DOX+VIN/Nio/CS) in acidic and physiological pH is less than uncoated niosome (DOX+VIN/Nio). In addition, acidic pH increases the release... 

Herein, a novel type of multifunctional magnetic nanoparticles with dual thermal and pH-responsive behavior was fabricated as the carrier for delivery of doxorubicin (DOX). Fe3O4@SiO2 magnetic nanoparticles, were grafted with polymer brushes consisting of poly (NIPAM-co-GMA) (PNG) chains via surface initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. The polymer brushes were then modified with hydrazine groups as DOX binding sites. The prepared multifunctional magnetic nanoparticles were characterized by FT-IR, 1H NMR, XPS, TGA, DLS, VSM, GPC, TEM, and XRD analysis. The in vitro drug release of the multifunctional magnetic nanoparticles was examined at 37 °C... 

Atherosclerotic plaques and thrombosis are chronic inflammatory complications and the main manifestations of cardiovascular diseases (CVD), the leading cause of death globally. Achieving non/minimal-invasive therapeutic means for these implications in the coronary network is vital and has become an interdisciplinary concern. Accordingly, smart drug delivery systems, specifically based on micro- and nanoparticles, as a promising method to offer non/minimal-invasive therapeutic mechanisms are under active research. Notably, computational models enable us to study, design, and predict treatment strategies based on smart drug delivery systems with less time and cost compared with conventional... 

The aim of this work was to synthesize molecularly imprinted polymer-poly ethylene glycol-folic acid (MIP-PEG-FA) nanoparticles for use as a controlled release carrier for targeting delivery of paclitaxel (PTX) to cancer cells. MIP nanoparticles were synthesized by a mini-emulsion polymerization technique and then PEG-FA was conjugated to the surface of nanoparticles. Nanoparticles showed high drug loading and encapsulation efficiency, 15.6 ± 0.8 and 100%, respectively. The imprinting efficiency of MIPs was evaluated by binding experiments in human serum. Good selective binding and recognition were found in MIP nanoparticles. In vitro drug release studies showed that MIP-PEG-FA have a... 

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)... 

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...