Search results for: drug release kinetics

Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

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The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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Authors: Susmita Roy, Madhavan Nallani

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In recent years' polymersomes, self-assembled polymeric vesicles emerge from block copolymers, have been widely investigated due to their enhance stability and unique advantageous properties compared to their phospholipid counterpart, liposomes, dendrimers, and micelles. It provides a distinctive platform for advanced therapeutics and the creation of complex (bio) catalytically active systems for research in Nanomedicine and synthetic biology. Inspired by nature, where compartmentalization of biological components is all ubiquitous, we are interested in developing a platform technology of self-assembled multifunctional compartments with applications in areas from targeted drug/gene delivery, biosensing, pharmaceutical to cosmetics. Polymersome surfaces can be a proper choice of derivatization with a controlled amount of functional groups. To achieve site-specific targeting of polymersomes, biological recognition motives can be attached to the polymersomes surface by standard bioconjugation techniques, (like esterification, amidation, thiol-maleimide coupling, click-chemistry routes or other coupling methods). Herein, we are developing easy going, one-step bioconjugation strategies for site-specific surface functionalized biodegradable polymeric and/or polymer-lipid hybrid vesicles for targeted drug delivery. Biodegradable polymer, polycaprolactone-b-polyethylene glycol (PCL-PEG), polylactic acid-b-polyethylene glycol (PLA-PEG) and phospholipid, 1-palmitoyl-2- oleoyl-sn-glycero-3-phosphocholine (POPC) has been widely used for numerous vesicle formulations. Some of these drug-loaded formulations are being tested on mice for controlled release. These surface functionalized polymersomes are also appropriate for membrane protein reconstitution/insertion, antibodies conjugation and various bioconjugation with diverse targeted molecules for controlled drug delivery.

Keywords: drug delivery, membrane protein, polymersome, surface modification

Procedia PDF Downloads 143

Authors: Peter K. Galenko, Stefanie Koch, Markus Rettenmayr, Robert Wonneberger, Evgeny V. Kharanzhevskiy, Maria Zamoryanskaya, Vladimir Ankudinov

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We analyze the structure of undercooled melts, crystal growth kinetics and amorphous/crystalline microstructure of rapidly solidifying glass-forming Pd-based and CuZr-based alloys. A dendrite growth model is developed using a combination of the kinetic phase-field model and mesoscopic sharp interface model. The model predicts features of crystallization kinetics in alloys from thermodynamically controlled growth (governed by the Gibbs free energy change on solidification) to the kinetically limited regime (governed by atomic attachment-detachment processes at the solid/liquid interface). Comparing critical undercoolings observed in the crystallization kinetics with experimental data on melt viscosity, atomistic simulation's data on liquid microstructure and theoretically predicted dendrite growth velocity allows us to conclude that the dendrite growth kinetics strongly depends on the cluster structure changes of the melt. The obtained data of theoretical and experimental investigations are used for interpretation of microstructure of samples processed in electro-magnetic levitator on board International Space Station in the frame of the project "MULTIPHAS" (European Space Agency and German Aerospace Center, 50WM1941) and "KINETIKA" (ROSKOSMOS).

Keywords: dendrite, kinetics, model, solidification

Procedia PDF Downloads 106

Authors: Akbar Esmaeili, Zahra Salarieh

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Cerium oxide nanoparticles (nano-series) are used as catalysts in industrial applications due to their free radical scavenging properties. Given that free radicals play an essential role in the pathology of many neurological diseases, we investigated the use of nanocrystals as a potential therapeutic agent for oxidative damage. This project synthesized nano-series from a new and environmentally friendly bio-pathway. Investigation of cerium nitrate in culture medium containing inoculated Lactobacillus acidophilus strain before incubation produces nano-series. Loaded with glatiramer acetate (GA) was formed by coating carboxymethylcellulose (CMC) and CeO2. FE-SEM analysis showed nano-series in the 9-11 nm range, spherical shape, and uniform particle size distribution. Cubic nanoparticles containing anti-multiple sclerosis (anti-Ms) treatment called GA were used. Glycerol monostearate (GMS) was used as a fat base, and evening primrose extract was used as an anti-inflammatory in cubosomes. Design-Expert® software was used to study the effects of different formulation factors on the properties of GAloaded cubic dispersions. Thirty GA-labeled cubic dispersions were prepared with GA-labeled carboxymethylcellulose and evaluated in vitro. The results showed an average nano-series size of 89.02 and a zeta potential of -49.9. Cubosomes containing GA-CMC/CeO2 showed a stable release profile for 180 min. The results showed that cubosomes containing GA-CMC/CeO2 could be a promising drug carrier with normal release behavior.

Keywords: ciochemistry, biotechnology, molecular, biology

Procedia PDF Downloads 34

Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

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Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

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Authors: M. Rahimnejad, B. Vahidi, B. Ebrahimi Hoseinzadeh, F. Yazdian, P. Motamed Fath, R. Jamjah

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In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

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Authors: Avdhesh K. Sharma

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Formulation for drying and pyrolysis process in packed beds at slow heating rates is presented. Drying of biomass particles bed is described by mass diffusion equation and local moisture-vapour-equilibrium relations. In gasifiers, volatilization rate during pyrolysis of biomass is modeled by using apparent kinetic rate expression, while product compositions at slow heating rates is modeled using empirical fitted mass ratios (i.e., CO/CO₂, ME/CO₂, H₂O/CO₂) in terms of pyrolysis temperature. The drying module is validated fairly with available chemical kinetics scheme and found that the testing zone in gasifier bed constituted of relatively smaller particles having high airflow with high isothermal temperature expedite the drying process. Further, volatile releases more quickly within the shorter zone height at high temperatures (isothermal). Both, moisture loss and volatile release profiles are found to be sensitive to temperature, although the influence of initial moisture content on volatile release profile is not so sensitive.

Keywords: modeling downdraft gasifier, drying, pyrolysis, moist woody biomass

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Authors: Stanely Nsubuga

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Background In Uganda, injection drug use is a growing but less studied problem. Preventing the transition to injection drug use may help prevent blood-borne viral transmission, but little is known about when and how people transition to injection drug use. A greater understanding of this transition process may aid in the country’s efforts to prevent the continued growth of injection drug use, HIV, and hepatitis C Virus (HCV) infection among people who inject drugs (PWID). Methods Using a rapid situation assessment framework, we conducted semi-structured interviews among 125 PWID (102 males and 23 females)—recruited through outreach and snow-ball sampling. Participants were interviewed about their experiences on when and how they transitioned into injection drug use and these issues were also discussed in 12 focus groups held with the participants. Results All the study participants started their drug use career with non-injecting forms including chewing, smoking, and sniffing before transitioning to injecting. Transitioning was generally described as a peer-driven and socially learnt behavior. The participants’ social networks and accessibility to injectable drugs on the market and among close friends influenced the time lag between first regular drug use and first injecting—which took an average of 4.5 years. By the age of 24, at least 81.6% (95.7% for females and 78.4% for males) had transitioned into injecting. Over 84.8% shared injecting equipment during their first injection, 47.2% started injecting because a close friend was already injecting, 26.4% desired to achieve a greater “high” (26.4%) which could reflect drug-tolerance, and 12% out of curiosity.

Keywords: People who Use Drugs, transition, injection drug use, Uganda

Procedia PDF Downloads 114

Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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Authors: Norma Binti Alias, Che Rahim Che The, Norfarizan Mohd Said, Sakinah Abdul Hanan, Akhtar Ali

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This paper discusses on the transportation of magnetic drug targeting through blood within vessels, tissues and cells. There are three integrated mathematical models to be discussed and analyze the concentration of drug and blood flow through magnetic nanoparticles. The cell therapy brought advancement in the field of nanotechnology to fight against the tumors. The systematic therapeutic effect of Single Cells can reduce the growth of cancer tissue. The process of this nanoscale phenomena system is able to measure and to model, by identifying some parameters and applying fundamental principles of mathematical modeling and simulation. The mathematical modeling of single cell growth depends on three types of cell densities such as proliferative, quiescent and necrotic cells. The aim of this paper is to enhance the simulation of three types of models. The first model represents the transport of drugs by coupled partial differential equations (PDEs) with 3D parabolic type in a cylindrical coordinate system. This model is integrated by Non-Newtonian flow equations, leading to blood liquid flow as the medium for transportation system and the magnetic force on the magnetic nanoparticles. The interaction between the magnetic force on drug with magnetic properties produces induced currents and the applied magnetic field yields forces with tend to move slowly the movement of blood and bring the drug to the cancer cells. The devices of nanoscale allow the drug to discharge the blood vessels and even spread out through the tissue and access to the cancer cells. The second model is the transport of drug nanoparticles from the vascular system to a single cell. The treatment of the vascular system encounters some parameter identification such as magnetic nanoparticle targeted delivery, blood flow, momentum transport, density and viscosity for drug and blood medium, intensity of magnetic fields and the radius of the capillary. Based on two discretization techniques, finite difference method (FDM) and finite element method (FEM), the set of integrated models are transformed into a series of grid points to get a large system of equations. The third model is a single cell density model involving the three sets of first order PDEs equations for proliferating, quiescent and necrotic cells change over time and space in Cartesian coordinate which regulates under different rates of nutrients consumptions. The model presents the proliferative and quiescent cell growth depends on some parameter changes and the necrotic cells emerged as the tumor core. Some numerical schemes for solving the system of equations are compared and analyzed. Simulation and computation of the discretized model are supported by Matlab and C programming languages on a single processing unit. Some numerical results and analysis of the algorithms are presented in terms of informative presentation of tables, multiple graph and multidimensional visualization. As a conclusion, the integrated of three types mathematical modeling and the comparison of numerical performance indicates that the superior tool and analysis for solving the complete set of magnetic drug delivery system which give significant effects on the growth of the targeted cancer cell.

Keywords: mathematical modeling, visualization, PDE models, magnetic nanoparticle drug delivery model, drug release model, single cell effects, avascular tumor growth, numerical analysis

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Authors: Lali Khurtsia, Vano Tsertsvadze

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Georgian drug policy is directed to reduce the supply of drugs. Retrospective analysis has shown that law enforcement activities have been followed by the expulsion of particular injecting drugs. The demand remains unchanged and drugs are substituted by the hand-made, even more dangerous homemade drugs entered the market. To find out expected new trends on the Georgian drug market, qualitative study was conducted with Georgian drug users to determine drug supply routes. It turned out that drug suppliers and consumers for safety reasons and to protect their anonymity, use Skype to make deals. IT in illegal drug trade is even more sophisticated in the worldwide. Trading with Bitcoins in the Darknet ensures high confidentiality of money transactions and the safe circulation of drugs. In 2014 largest Bitcoin mining enterprise in the world was built in Georgia. We argue that the use of Bitcoins and Darknet by Georgian drug consumers and suppliers will be an incentive to response adequately to the government's policy of restricting supply in order to satisfy market demand for drugs.

Keywords: bitcoin, darknet, drugs, policy

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Jung Hyun Kim, Gyo Woo Lee

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In this study, the enhancement of the heat release performance of an extruded-type heat sink to prepare the large-capacity solar inverter thru the flow holes in the base plate near the heat sources was investigated. Optimal location and number of the holes in the baseplate were determined by using a commercial computation program. The heat release performance of the shape-modified heat sink was measured experimentally and compared with that of the simulation. The heat sink with 12 flow holes in the 18-mm-thick base plate has a 8.1% wider heat transfer area, a 2.5% more mass flow of air, and a 2.7% higher heat release rate than those of the original heat sink. Also, the surface temperature of the base plate was lowered 1.5°C by the holes.

Keywords: heat sink, forced convection, heat transfer, performance evaluation, flow holes

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Authors: Khaliun Nyambayar, Nomindari Azzaya, Batkhuyag Purevjav

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Pharmacovigilance was officially introduced in Mongolia in 2003, in accordance with the Health Minister Order 183 for the registry of adverse drug reactions (ADR), approved in 2006 and was reviewed in 2010. This study was designed to evaluate the incidence and common types of adverse drug reactions among hospitalized children, the frequency of adverse drug reaction reported by health care providers, and the follow-up processes resulting from adverse drug reactions. A retrospective study of paediatric patients who experienced an adverse drug reaction from 2015 to 2019, extracted from the “yellow” card at the State Research Center for Maternal and Child Health, (city). A total of 417 adverse drug reactions were reported with an overall incidence was 80 (21.5%). Adverse reactions resulting from the use of antibiotics (particularly gentamycin, cephalosporins, and vancomycin) were usually mild. ADR’s were reported by physicians and nurses (93.8%), pharmacists (6.25%). Although documentation of physician notification occurred for 93% of adverse drug reactions, only 29% of cases were documented in the patient's medical chart, 13% included follow-up education for individuals involved, and 10% were updated in the allergy profile of the hospital computer system. Measures to improve the detection and reporting of adverse drug reactions by all health care professionals should be improved, to enhance our understanding of the nature and impact of these reactions in children.

Keywords: adverse drug reaction, pediatric, yellow card, Mongolia

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Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Nanosized environmentally responsive materials are of special interest for various applications, including targeted drug to a considerable potential for treatment of many human diseases. The important technological advantages of nanoparticles (NPs) usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic (water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. As the next step of this research an evaluation of biocompatibility and bioavailability of the synthesized NPs has been performed, using two stable human cell culture lines – HeLa and A549. This part of study is still in progress now.

Keywords: amino acids, biodegradable polymers, nanoparticles (NPs), non-toxic building blocks

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Authors: Pram Abhayawardhana, Ali Reza Nazmi, Hossein Najaf Zadeh

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This study examines the use of additive manufacturing (AM) to develop sustainable and intelligent agricultural formulations that can gradually release fertilisers. AM offers the ability to design customised formulations with precise geometries and controlled release properties while taking into account their mechanical, chemical, and environmental properties. The study specifically investigates the use of an aerogel matrix mixed with a potential fertiliser in agriculture. Highly porous 3D printed aerogel structures were designed to enable the slow release of fertilisers. The performance of the formulated mixture is evaluated against other commonly used materials for slow-release applications. The findings suggest that the 3D printed gel made has great potential for slow-release fertilisers, providing an environmentally friendly solution for agricultural practices. The combination of AM technology and sustainable materials can play a vital role in mitigating the negative environmental impact of traditional fertilisers, as well as improving the efficiency and sustainability of agricultural production.

Keywords: 3D printing, hydrogel, aerogel, fertiliser, agriculture

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Authors: Shideh Mohseni Movahed, Mansoureh Safari

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Intelligent drug delivery systems (IDDS) are innovative technological innovations and clinical way to advance current treatments. These systems differ in technique of therapeutic administration, intricacy, materials and patient compliance to address numerous clinical conditions that require different pharmacological therapies. IDDS capable of releasing an active molecule at the proper site and at a amount that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism is particularly appealing. In this paper, we describe the most recent advances in the development of intelligent drug delivery systems.

Keywords: drug delivery systems, IDDS, medicine, health

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

Procedia PDF Downloads 160

Authors: Fanjun Zhou

Abstract:

In today's drug-ridden society, drug injection is gradually becoming more popular and has hidden danger to IDUs (injection drug users) such as infectious diseases. According to reports, 67% of IDUs reported improper disposal at some point over the prior 30 days, leading to a proliferation of injection needles on the streets. In recent years, the number of cases of children or ordinary people unintentionally picking up needles have increased. Various needle remover inventions have begun to surface, but the existing ones are either expensive, unportable, or risky for IDUs. In order to effectively alleviate the proliferation of drug injection needles and improve the invention of needle removers, a miniature portable needle remover and receptacle is invented. The device for capturing and storing syringe needles contains an upper lid portion mounted tightly onto the lower box portion through an interlock system on the opposing sides of the device with a breaking-twisting mechanism to remove the needle. The invention is intended to be affordable to the general public, safe enough for IDUs to use, reliable enough not to harm others, and effective in breaking needles from the syringe. This report is conducted in the hope of spreading awareness of the dangers of drug injection and to provide a way to mitigate this drug rampant situation.

Keywords: needle remover, drug injection, injection drug users, portable, receptacle

Procedia PDF Downloads 80

Authors: M. A. Khanday, Aasma Rafiq, Khalid Nazir

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This paper is an attempt to establish the mathematical models to understand the distribution of drug administration in the human body through oral and intravenous routes. Three models were formulated based on diffusion process using Fick’s principle and the law of mass action. The rate constants governing the law of mass action were used on the basis of the drug efficacy at different interfaces. The Laplace transform and eigenvalue methods were used to obtain the solution of the ordinary differential equations concerning the rate of change of concentration in different compartments viz. blood and tissue medium. The drug concentration in the different compartments has been computed using numerical parameters. The results illustrate the variation of drug concentration with respect to time using MATLAB software. It has been observed from the results that the drug concentration decreases in the first compartment and gradually increases in other subsequent compartments.

Keywords: Laplace transform, diffusion, eigenvalue method, mathematical model

Procedia PDF Downloads 323

Authors: Yu-Chen Chang, Yen-Ping Peng, Wei-Yu Chen, Ku-Fan Chen

Abstract:

Contamination of soil and groundwater has become a serious and widespread environmental problem. In this study, sustained-release persulfate tablets were developed using persulfate powder and a modified cellulose binder for organic-contaminated groundwater remediation. Conventional cement-based persulfate-releasing materials were also synthesized for the comparison. The main objectives of this study were to: (1) evaluate the release rates of the remedial tablets; (2) obtain the optimal formulas of the tablets; and (3) evaluate the effects of the tablets on the subsurface environment. The results of batch experiments show that the optimal parameter for the preparation of the persulfate-releasing tablet was persulfate:cellulose = 1:1 (wt:wt) with a 5,000 kg F/cm2 of pressure application. The cellulose-based persulfate tablet was able to release 2,030 mg/L of persulfate per day for 10 days. Compared to cement-based persulfate-releasing materials, the persulfate release rates of the cellulose-based persulfate tablets were much more stable. Moreover, since the tablets are soluble in water, no waste will be produced in the subsurface. The results of column tests show that groundwater flow would shorten the release time of the tablets. This study successfully developed unique persulfate tablets based on green remediation perspective. The efficacy of the persulfate-releasing tablets on the removal of organic pollutants needs to be further evaluated. The persulfate tablets are expected to be applied for site remediation in the future.

Keywords: sustained-release persulfate tablet, modified cellulose, green remediation, groundwater

Procedia PDF Downloads 272

Authors: Tinomuvonga Manenji Zhou, Eubert Mahofa, Tatenda Crispen Madzokere

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The nanostructured formulation can increase fertilizer efficacy and uptake ratio of the soil nutrients in agriculture production and save fertilizer resources. Controlled release modes have properties of both release rate and release pattern of nutrients, for fertilizers that are soluble in water might be correctly controlled. Nanoparticles can reduce the rate at which fertilizer nutrients are in the soil by leaching. A slow release NPK-hydroxyapatite nano hybrid fertilizer was synthesized using exfoliated bentonite as filler material. A simple, scalable method was used to synthesize the nitrogen-phosphorus hydroxyapatite nano fertilizer, where calcium hydroxide, phosphoric acid, and urea were used as precursor material, followed by the incorporation of potassium through a liquid grinding method. The product obtained was an NPK-hydroxyapatite nano hybrid fertilizer. A quantitative analysis was done to determine the percentage of nitrogen, phosphorus, and potassium in the hybrid fertilizer. AAS was used to determine the percentage of potassium in the fertilizer. An accelerated water test was conducted to compare the nutrient release behavior of nutrients between the synthesized NPK-hydroxyapatite nano hybrid fertilizer and commercial NPK fertilizer. The rate of release of Nitrogen, phosphorus, and potassium was significantly lower in the synthesized NPK hydroxyapatite nano hybrid fertilizer than in the convectional NPK fertilizer. The synthesized fertilizer was characterized using XRD. NPK hydroxyapatite nano hybrid fertilizer encapsulated in exfoliated bentonite thus prepared can be used as an environmentally friendly fertilizer formulation which could be extended to solve one of the major problems faced in the global fertilization of low nitrogen, phosphorus, and potassium use efficiency in agriculture.

Keywords: NPK hydroxyapatite nano hybrid fertilizer, bentonite, encapsulation, low release

Procedia PDF Downloads 85

Authors: Abraham J. Domb

Abstract:

Nearly every eye disorder and treatment of post operated eyes evolve around ocular drug delivery. Most ocular diseases are treated with repeated topical applications administered as eye drops. Various attempts have been made to improve drug bioavailability by increasing both the retention of the drug in the pre-corneal area and the penetration of the drug through the cornea. However, currently marketed products are associated with vision blurring, irritability, patient discomfort, toxicity, low drug bioavailability, manufacturing difficulties and inadequate aqueous stability. It has been suggested to use iontophoresis for the non-invasive delivery of drugs. The iontophoretic device is composed of a control panel, two electrodes, a cylindrical well for the insertion of a disposable hydrogel, and a disposable hydrogel pellet. The drug-loaded hydrogel is attached to a cylindrical well at the edge of the electrode of the device and placed onto the eye. The device applies a variable electrical current that can vary from 0.1 mA to 1.5 mA for pre-set periods from 10 seconds to 300 seconds. The iontophoretic device developed in the lab was found to be effective in the delivery of the drugs: gentamicin, water-soluble steroids, and various anticancer agents. When testing in rabbits for safety, the device was considered to be non-toxic and effective.

Keywords: iontophoresis, eye disorder, drug delivery, hydrogel

Procedia PDF Downloads 64

Authors: Jigar N. Shah, Hiral J. Shah, Praful D. Bharadia

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The major challenge faced by formulation scientists in transdermal drug delivery system is to overcome the inherent barriers related to skin permeation. The stratum corneum layer of the skin is working as the rate limiting step in transdermal transport and reduce drug permeation through skin. Many approaches have been used to enhance the penetration of drugs through this layer of the skin. The purpose of this study is to investigate the development and evaluation of a combined approach of drug carriers and iontophoresis as a vehicle to improve skin permeation of an analgesic drug. Iontophoresis is a non-invasive technique for transporting charged molecules into and through tissues by a mild electric field. It has been shown to effectively deliver a variety of drugs across the skin to the underlying tissue. In addition to the enhanced continuous transport, iontophoresis allows dose titration by adjusting the electric field, which makes personalized dosing feasible. Drug carrier could modify the physicochemical properties of the encapsulated molecule and offer a means to facilitate the percutaneous delivery of difficult-to-uptake substances. Recently, there are some reports about using liposomes, microemulsions and polymeric nanoparticles as vehicles for iontophoretic drug delivery. Niosomes, the nonionic surfactant-based vesicles that are essentially similar in properties to liposomes have been proposed as an alternative to liposomes. Niosomes are more stable and free from other shortcoming of liposomes. Recently, the transdermal delivery of certain drugs using niosomes has been envisaged and niosomes have proved to be superior transdermal nanocarriers. Proniosomes overcome some of the physical stability related problems of niosomes. The proniosomal structure was liquid crystalline-compact niosomes hybrid which could be converted into niosomes upon hydration. The combined use of drug carriers and iontophoresis could offer many additional benefits. The system was evaluated for Encapsulation Efficiency, vesicle size, zeta potential, Transmission Electron Microscopy (TEM), DSC, in-vitro release, ex-vivo permeation across skin and rate of hydration. The use of proniosomal gel as a vehicle for the transdermal iontophoretic delivery was evaluated in-vitro. The characteristics of the applied electric current, such as density, type, frequency, and on/off interval ratio were observed. The study confirms the synergistic effect of proniosomes and iontophoresis in improving the transdermal permeation profile of selected analgesic drug. It is concluded that proniosomal gel can be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.

Keywords: iontophoresis, niosomes, permeation enhancement, transdermal delivery

Procedia PDF Downloads 367

Authors: Sharif Abdelghany

Abstract:

Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

Procedia PDF Downloads 361

Authors: M. Fatmi, T. Chihi, M. A. Ghebouli, B. Ghebouli

Abstract:

This work presents the experimental results of the differential scanning calorimetry (DSC), hardness measurements (Hv) and XRD analysis, for order to investigate the kinetics of precipitation phenomena in Al-7%wt. Mg alloy. In the XRD and DSC curves indicates the formation of the intermediate precipitation of β-(Al3Mg2) phase respectively. The activation energies associated with the processes have been determined according to the three models proposed by Kissinger, Ozawa, and Boswell. Consequently, the nucleation mechanism of the precipitates can be explained. These phases are confirmed by XRD analysis.

Keywords: discontinuous precipitation, hardening, Al–Mg alloys, mechanical and mechatronics engineering

Procedia PDF Downloads 396

Authors: Asfa Hussain, Chee Tang, Mien Nguyen

Abstract:

Introduction: The safe usage of medications is dependent on clear, well-documented prescribing. Medical drug charts should be regularly checked to ensure that they are fit for purpose. Aims: The purpose of this study was to evaluate whether the Isabel Hospice drug charts were effective or prone to medical errors. The aim was to create a comprehensive palliative care drug chart in line with medico-legal guidelines and to minimise drug administration and prescription errors. Methodology: 50 medical drug charts were audited from March to April 2020, to assess whether they complied with medico-legal guidelines, in a hospice within East of England. Meetings were held with the larger multi-disciplinary team (MDT), including the pharmacists, nursing staff and doctors, to raise awareness of the issue. A preliminary drug chart was created, using the input from the wider MDT. The chart was revised and trialled over 15 times, and each time feedback from the MDT was incorporated into the subsequent template. In the midst of the COVID-19 pandemic in September 2020, the finalised drug chart was trialled. 50 new palliative drug charts were re-audited, to evaluate the changes made. Results: Prescribing and administration errors were high prior to the implementation of the new chart. This improved significantly after introducing the new drug charts, therefore improving patient safety and care. The percentage of inadequately documented allergies went down from 66% to 20% and incorrect oxygen prescription from 40% to 16%. The prescription drug-drug interactions decreased by 30%. Conclusion: It is vital to have clear standardised drug charts, in line with medico-legal standards, to allow ease of prescription and administration of medications and ensure optimum patient-centred care. This closed loop audit demonstrated significant improvement in documentation and prevention of possible fatal drug errors and interactions.

Keywords: palliative care, drug chart, medication errors, drug-drug interactions, COVID-19, patient safety

Procedia PDF Downloads 159