Sharif Digital Repository

Conventional chemotherapy methods impact both normal and cancerous cells; therefore, it is essential to design novel drug delivery systems in order to reduce drugs’ side effects. Having high retention time in blood and the capability of crossing blood-brain barriers are the characteristics of nano-scaled drug delivery systems.The research thesis is about the synthesis and characterization of the light-sensitive biocompatible nanogels with the core-shell structure with the intention of Doxorubicin anti-cancer drug delivery. These smart nanogels possess a hydrophobic core coated with hydrophilic starch polymeric chain modified with beta-cyclodextrin. The formation of the core-shell structure... 

Drug targeting to specific organs and tissues has become one of the critical endeavors of the new century. Magnetic nanoparticles have gained a lot of attention in biomedical and industrial application. Doxorubicin is an effective anti-cancer drug in the treatment of many types of cancers. The aim of this study is to load doxorubicin on stimuli-responsive nanocarriers. These nanocarriers are prepared from magnetic nanoparticles. Then these magnetic nanparticles are coated by copolymer of poly(glycidyl methacrylate) then reacted with hydrazine and hydrazide functional group is formed that can chemically be bonded with the anticancer drug doxorubicin via a hydrazone bond formation. This... 

In recent decades, due to the significant growth of implants’ application and considering the infection of the implants as the most momentous factor in implantation failure, study on the controlled drug release and other biologically active agents in modern drug delivery systems has attracted many kinds of research throughout the world and efforts are being made to use regulated drug delivery systems for implantation which is also the purpose of this current scientific work.To achieve this, the anodizing process was used to fabricate titanium oxide nanotubes (TNTs) to increase the absorption capacity of the drug in the implants and these TNTs were formed regularly and uniformly in an organic... 

Most natural folate derivatives are highly sensitive to temperature, oxygen and light and their stability depends on food process condition. Alginate and pectin were evaluated for folic acid encapsulation and increasing its stability. By combining them and optimising encapsulation condition the efficiency was enhanced up to 90% . Furthermore, using polymers in combined form caused decrease in folic acid leakage from capsules in acidic condition of stomach. First of all, the time of encapsulation was measured which was 140-180 minutes. In this study the effect of Calcium Chloride concentration on encapsulation was studied. Therefore, two variables were selected which were pectin to algine... 

In this thesis, nanocomposites based on magnetic graphene oxide and iron oxide nanoparticles coated with smart polymeric materials (by polymerization of monomers such as glycidyl methacrylate, acrylic acid, and N-isopropyl acrylamide) via Reversible Addition−Fragmentation Chain-Transfer (RAFT) polymerization were successfully synthesized. The combination of large surface area in nanoparticles and different functional groups in polymeric layers can give unique properties to nanocomposites. Therefore, we synthesized various smart nanocomposites with this perspective. After synthesizing these nanocomposites, smart magnetic nanoparticles were characterized by FT-IR, NMR, XPS, TGA, DLS, VSM, GPC,... 

In this research, we developed a drug release system of two biocompatible and biodegradable polymers and biocompatible ceramic nanoparticles. Hydrogels of sodium alginate (SA) were crosslinked using calcium chloride. The SA hydrogels were blended with polyvinyl pyrrolidone (PVP) and mixed with hydroxyapatite nanoparticles (HAP) to make hydrogel nanocomposites in the form of microbeads as drug carriers. Ciprofloxacin was selected as a model antibiotic drug for treatment of bone infection. It was found that SA and PVP form hydrogen bonds and are miscible at whole range of concentrations. Indeed, the SA/PVP blends may be considered as interpenetrating polymer networks (IPNs). HAP nanoparticles... 

1- Mesoporous silica materials have been found to possess pore sizes ranging from 2 -10 nm alongside 2D-hexagonal and 3D-cubic structural features. The specific properties of nanoparticles of the mesoporous silica family, such as the collected size, porosity, morphology, and high chemical stability, make them among the best drug delivery systems and catalysts. Designing the catalysts with advanced structures that effectively locate the transition metals and create active centres onto the surfaces of mesoporous silica materials has attracted extraordinary attention. According to many studies, mesoporous silica materials without organic functional groups cannot be used as catalysts in chemical... 

Smart heat-sensitive polymers play a unique role in drug delivery systems due to reversible behavior in response to environmental changes, especially temperature changes. Among the heat-sensitive polymers, UCST polymers due to their specific behavior and very little-known polymers with this feature are the subject of many new researches. In the present study, New designed temperature-sensitive polymers with UCST capability based on acrylamide and vinyl acetate were synthesized. These copolymers were synthesized in different percentages of acrylamide by free radical polymerization in solution conditions. All polymers compounds were characterized by H-NMR, FT-IR, DSC and GPC measurements. The... 

The main goal of this study is to prepare and investigate stimuli responsive structures that respond to the light and other environmental triggers. Also, investigating their applications in biological fields such as: drug delivery and tissue engineering, in addition to the application of these materials in the field of chemical sensors that show color change with changes in solvent, electric field and metal ions. In the matter of drug delivery, guest-host interactions were used to release anticancer drugs, in such a way that with ultraviolet light irradiation and simultaneously with the formation of the cis isomer, the connections between azobenzene groups and cyclodextrin rings are... 

In recent years, the tendency to use biodegradable and biocompatible polymer nanoparticles for drug delivery applications has been increasing, the reason for this being the possibility of precise control of the drug release rate, ease of use, and no need for external Surgery after the release of the drug, increases the therapeutic efficiency of the drug and reduces the side effects with its precise transfer. In this research work, drug carrier nanocomposites were prepared from polylactic acid (PLA), polyethylene glycol (PEG) and hydroxyapatite (HAp) and for the controlled release of ciprofloxacin (CIP). It was used to treat bone infections. The drug loading efficiency for nano-carriers was... 

Manufacturing in many industries, such as electronics, petrochemical, automotive, and food, has long relied on continuous approaches, while the pharmaceutical industry has traditionally been processed in batch reactors. Since the beginning of the third millennium, continuous drug synthesis has received attention due to its multiple advantages over batch systems, which include process safety, adaptability, controllability, economic efficiency, scale-up, and enhancing performance. In this project, the pharmaceutical intermediate 1,4-benzodiazepine, which is usable as a precursor of diazepam and flurazepam, is continuously synthesized in a 400 microliters integrated micromixer and microreactor... 

Several studies based on anti- cancer, anti- metastatic and anti- tumor effects of curcumin have been reported . Besides these benefits, the therapeutic efficacy of curcumin is limited due to its poor aqueous solubility, extensive first-pass metabolism, inadequate tissue absorption and degradation at alkaline pH, which severely diminishes its bioavailability. In this project we seek to solve some of the problems with nanoscience to work more effectively. In the past decade, mesoporous silica nanoparticles (MSNs) have found widespread application as controlled drug delivery systems. Recent reports on the design of capped and gated MSN-based systems have shown promise in preventing premature... 

Nowadays, advanced and inexpensive pre-clinical methods for investigating the effects of anti-cancer drugs are expanding. One of the latest three-dimensional laboratory modeling for evaluating the effects of drugs is the use of tumor-on-chip technology, which actually models the physiological system of the body through three-dimensional scaffolds, multicellular cultures, and shaped vascular systems. In this study, three-dimensional culture of cancer cells was performed in the form of spheroids. A chip of U-shaped microstructures with and without gaps was used to trap cells and form cancer spheroids. We simulated the simultaneous effect of drug and oxygen concentration distribution inside the... 

Idiopathic pulmonary fibrosis is the most common type of pulmonary fibrosis that causes ulcers inside the lungs. In addition to Nintedanib, Pirfenidone is currently the only compound approved by the US Food and Drug Administration in 2014 for the treatment of idiopathic pulmonary fibrosis. Meanwhile, in the pharmaceutical industry, drug synthesis is usually done through batch-wise processes, and pirfenidone is currently only produced through batch-wise processes. Hence, this study aims to change the synthesis method of this drug, which is traditionally performed through batch-wise processes, to a continuous flow process. Therefore, a micro-reactor technology can be adopted which offers a... 

Search for effective methods for treating cancer requires a deep understanding of the tumor microenvironment and its role in cancerous tumor growth and progression. Mathematical modeling methods, which have fewer limitations than experimental methods for examining the microcirculation of cancer in detail, are suggested to answer many questions about the behavior and dynamics of cancerous tumors. In the present study, a multi-scale mathematical model of the three-dimensional tumor microenvironment, including molecular, cellular, and tissue scales, is presented. In this model, important aspects of tumor microenvironmental dynamics including tumor growth, angiogenesis, cancer metabolism, and... 

The development of technologies and some defects in medicine caused to emerge a new approach called precision medicine. Unlike the traditional medicine, medical experts do best treatment for each patient based on his genetic characteristics in this approach. Predicting drug response on cancer cell lines is one of the most vital challenges in this area. Various approaches have been proposed to construct predicting models while the substantial distinctions between resistant and sensitive cell lines had been neglected in them. Here, we propose a new approach for constructing the predictive model. In our approach, we utilized the distinctions between sensitive and resistant cell lines and also... 

In recent years, batch systems were often used in the synthesis of pharmaceuticals. Nowadays, due to the possibility of more optimal conditions in flow systems, such as better mixing and optimal performance of heat transfer and mass transfer, process safety, reduction of retention time, and ease in increasing the scale of the process, the use of flow systems has been expanded. B-hydroxysulfone is a pharmaceutical intermediate in the production of bicalutamide, which is used in the treatment of prostate cancer and is used in many organic and biological processes. The reaction time in batch systems is about 17 to 20 hours, and in the flow system, the retention time has reached about 180-90... 

With the rapid development of biotechnology, peptide and protein drugs are now playing an increasingly important role in therapeutics. Compared with chemical drugs, peptide and protein drugs have some limitations such as low stability and rapid deactivation. Biodegradable and biocompatible polymeric micro carriers have been shown to have a high potential for the delivery of peptides and proteins. Among these polymers, alginate has been widely investigated as a biomaterial. Alginates are natural polysaccharide polymers isolated from brown seaweed. Bovine serum albumin (BSA) loaded calcium alginate microspheres produced in this study by a modified w/o emulsification method. The influence of... 

The aim of this study is to devise innovative compounds that impede the function of CK2α enzyme by incorporating amino acids and sugars into their molecular structure. CK2α, a catalytic subunit of CK2 enzyme, operates autonomously and is the only continuously active kinase that does not require an upstream regulator. Emerging evidence highlights CK2α's crucial role in various cancers and infectious diseases, including Covid-19, indicating that suppressing its function could provide a promising approach to improve patient outcomes. To accomplish this objective, the drug design process must take into account both pharmacokinetic and pharmacodynamic properties. Pharmacokinetics, encompassing... 

In this study the transport and deposition of pharmaceutical particles delivered by a commercial metered dose inhaler (MDI) is investigated in a combination of human upper airways, inhaler, and spacer. The emphasis of the present work is on the effects of evaporation of ethanol from particles, inlet momentum of particles, and use of spacer on their transport and deposition phenomena. The pharmaceutical particles are typically delivered with high initial momentum to human upper airways. It is believed that this initial momentum is responsible for increased undesirable deposition of particles in upper airways, especially in case of particles larger than 1 micrometer in diameter. In the present...