Journal of Applied Research of Chemical -Polymer Engineering

Abstract Abstract
Research Subject: Breast cancer is one of the most common cancer in the world with the highest mortality rate in women. Chemotherapy is the typical therapy for the cancer. However, it has side effects due to damage to healthy cells. Targeted drug delivery by nano carriers to the cancerous cells reduces the toxic side effects on normal cells. Serum albumin is a widely used drug carrier because of its availability, ease of preparation, and binding ability to various ligands. Attachment of iron oxide nanoparticles to albumin can control their distribution by applying an external magnetic field.
Research Approach: In this study, albumin nanoparticles attached to superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized and loaded with 5-Fluorouracil (5-FU) anticancer drug by using the desolvation technique. The produced nanoparticles were characterized in terms of size, surface charge, and drug entrapment, by dynamic light scattering (DLS) and UV-Vis spectrophotometry. The cytotoxic effects of 5FU-loaded magnetic albumin nanoparticles and free 5FU on MCF7 cells were evaluated with the MTT assay. The internalization of nanoparticles in MCF-7 cells was confirmed by Prussian blue staining. In the end, the effects of nanoparticles on cell cycle and apoptosis were evaluated by flow cytometry using propidium iodide.
Main Results: The mean particle size and zeta potential of 5FU loaded albumin nanoparticles and albumin magnetic nanoparticles were 220 nm, -25.8 mV, and 221 nm, -28 mV respectively. Drug entrapment efficiency and drug loading efficiency were also, 20%, 1%, and 15.8%, and 0.06% for albumin nanoparticles and magnetic albumin nanoparticles in turn. The drug-loaded magnetic albumin nanoparticles showed higher cytotoxicity than the free drug on MCF-7 cells. The flow cytometry cell cycle analysis showed more cytotoxicity of albumin nanoparticles in comparison with other groups. According to these results, it can be said that 5-FU loaded magnetic albumin nanoparticles were more effective and deserve further studies in the cancer treatment.
Keywords: Albumin magnetic nanoparticles, 5-fluorouracil, targeted drug delivery, MCF-7 cell line

Abstract Research subject: Low solubility of pharmaceutical compounds leads to increasing the required drug dosage and their side effects as well as reducing their therapeutic efficiency. Producing pharmaceutical micro/nanoparticles with homogenous morphology and narrow size distribution is one of the confirmed approaches for their solubility enhancement. So, selection and designing an appropriate method for this purpose is one of the most important research fields of pharmaceutical industries. Over the past three decades, supercritical carbon dioxide (sc-CO₂) based methods as a clean and green technologies have been received much attention in various fields of pharmaceutical industries. However, in order to design and development of these methods for producing micro/nanoparticles, determination of the compounds solubility in sc-CO₂ is essential.
Research approach: In this research, well known empirical models (Adachi and Lu, Ch and Madras, Hozahzbr et al., Bian et al., Mendez-Santiago-Teja), as well as the artificial neural network model were applied for prediction the solubility of six anticancer drugs (Aprepitant, 5-Fluorouracil, Imatinib mesylate, Capecitabine, Letrozole, Docetaxel) in sc-CO₂.
In order to evaluate the accuracy of these models, a comparison was made between the calculated solubility values and the available experimental data, based on several statistical criteria, such as the average absolute relative deviation (AARD%), adjusted correlation coefficient (R_adj) and F-value.
Main results: According to obtained results, Adachi and Lu model with AARD% value of 12.12% and R_adj value of 0.97 provided acceptable results for solubility of mentioned drugs in sc-CO₂. Also, in comparison between empirical and artificial neural network models, the latter one with AARD% value of 1.65% and R_adj value of 0.9960 was appointed as the most appropriate model for correlation of drugs solubility data.

Abstract Metformin enhances insulin's effect and increases cells’ sensitivity to insulin. In this paper, nanocomposite was designed and used in the metformin release system, which was able to release the required drug in a controlled manner. In this research, nanoparticles of zinc oxide (ZnO) were prepared via the sol-gel method. The experimental design central composite response surface method was applied for the optimization of the nanoparticles based on varied variables such as the weight of zinc acetate (gr) (X ₁) and the volume of triethanolamine (ml) (X₂). The particle size of the optimized nanoparticle was reported to be 28 ± 21.27 nm; zeta potential and PdI were 25.54 ± 1.64 mV, 0.168 ± 0.05 respectively. The chitosan polymer was used to improve environmental compatibility and increase drug release control; finally, metformin was loaded on the optimized nanocomposite. Structural properties were analyzed using scanning electron microscopy (SEM) X-Ray Diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and Dynamic Light Scattering (DLS). The SEM images showed that the average nanocomposite size was 40 nm. The results of XRD patterns and SEM images were also consistent with each other and the average particle size was the same. Infrared spectrophotometry showed the presence of chitosan used to coat nanoparticles on their surfaces and confirmed the loading of metformin. An in-vitro metformin release from the nanocomposite was conducted in PBS (pH=7.4) and analyzed by a spectrophotometer at 233 nm. Metformin has a high solubility in water, and since it is difficult to prepare a slow release form of high-solubility drugs, the aim of this study was to design a slow-release formulation of metformin with a suitable profile that could control release without explosive release for up to 120 hours.

Abstract Research subject: The use of nanoparticles, especially nano-antibiotics, increases their efficacy. More uniform release of antibiotics is one of the benefits of being nano. They can also be made using ointment or banderol to absorb through the skin to the infection, thereby reducing its side effects. Amoxicillin is one of the most widely used antibiotics in the world which can be prevented by increasing the use of other strong antibiotics if promoted as nanoparticles. Determining the mechanism of nanoparticle formation of this drug is an important factor for its commercial production.
Research approach: The purpose of this study was to determine the nucleation mechanism and time of induction of crystallization of amoxicillin nanoparticles in the presence of surface active agents ‘CTAB’ and ‘SDS’. Therefore, the effect of amoxicillin concentration and stabilizing concentration on the crystallization process was investigated. In this project, a combination of inductive-reactive crystallization was used. In this method, amoxicillin sodium was produced with sodium hydroxide, amoxicillin sodium, has a much higher solubility in water. Then, by adding hydrochloric acid, amoxicillin will be recovered and supersaturated. SEM and DLS analyzes were used to determine the properties of amoxicillin nanoparticles. All the experiments were repeated twice.
Main results: The results show that particles with a mean size of 50 nm were formed, and the particle stability was confirmed up to one week after formation. The results of the experiments show that the nucleation mechanism is the primary type with an average explanatory factor (R²) equal to 0.9887 and adding a stabilizing agent has no effect on the nucleation mechanism.

Abstract Research subject: Parkinson’s disease is a neurodegnerative disorder with no treatment due to the blood brain barrier (BBB) existence. The cure for this disease is Dopamine a chemical molecule.
Research approach: This study investigates biodegradable naoparticles (NPs) carrying dopamine (DA) across the blood–brain barrier. Ion polymerization and solvent methods were used to achieve this goal. Particle size, zeta potential, entrapment efficiency and in vitro drug release behavior, at pH 7 were examined.
Main results: The empty nanoparticles and drug-loaded nanoparticles were found to be spherical in shape and fluffy exterior, with mono-modal size distribution and negative zeta-potentials of increasing average sizes 90 to 120 nm simultaneously. Fourier transform infrared (FTIR) spectra demonstrated the polymerization of nBCA monomers and encapsulation of DA inside poly (butylcyanoacrylate) (PBCA).Thermal characteristics of the copolymer were investigated by Fourier-transform infrared spectroscopy (FTIR). Drug loading efficiency was around 25%.The in-vitro drug release profile of DA -loaded PBCA nanoparticles prepared from ion polymerization following solution techniques exhibited a gradual release; more than 20 ٪w/w of the drug was released after 51 h. The results showed that the DA–PBCA nanocapsules could be an effective carrier for hydrophilic agents. In this study, PBCA-NSPs were successfully generated as a delivery system for DA, providing a promising approach to improve the therapy of PDs.

Abstract The use of genetic engineering tools to produce industrial strains, especially from non-model microorganisms such as cyanobacteria, is always subject to limitations. In this research, a system-oriented method was used to design a culture medium instead of strain designing and its ability to increase ethanol production by Synechocystis sp. PCC 6803 was experimentally evaluated. In this method, compounds are added to the medium to regulate the activity of target enzymes not for the purpose of being consumed by the cells, and thus, the designed culture medium eliminates the intracellular constraints on the production. A metabolic model was used to determine the minimum level of ethanol production and to identify genes that increase or decrease of their expression increase this minimum level. Then, regulators of the enzyme expressed by the target genes were extracted from the Brenda database and their effect on the production was evaluated experimentally and design of experiment was performed to optimize the concentration of the selected compounds. Among the compounds identified, two inhibitors (salicylic acid and mercuric chloride) and one activator (pyruvate) were selected to be added to the medium and their concentration was optimized using the central composite design method. The proposed regulatory medium increased the production of ethanol from 352 to 1116 mg/l, indicating the effectiveness of the added regulatory compounds on the cyanobacteria metabolism. The proposed system-oriented method can be used to design medium culture for other important bio-products such as recombinant proteins.