Search results for: drug kinetics
1789 Biosurfactant-Mediated Nanoparticle Synthesis by Bacillus subtilis
Authors: Satya Eswari Jujjavarapu, Swasti Dhagat, Lata Upadhyay, Reecha Sahu
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Silver nanoparticles have a broad range of antimicrobial and antifungal properties ranging from soaps, pastes to sterilization and drug delivery systems. These can be synthesized by physical, chemical and biological methods; biological methods being the most popular owing to their non-toxic nature and reduced energy requirements. Microbial surfactants, produced on the microbial cell surface or excreted extracellularly are an alternative to synthetic surfactants for the production of silver nanoparticles. Hence, they are also called as green molecules. Microbial lipopeptide surfactants (biosurfactant) exhibit anti-tumor and anti-microbial properties and can be used as drug delivery agents. In this study, biosurfactant was synthesized by using a strain of acillus subtilis. The biosurfactant thus produced was analysed by emulsification assay, oil spilling test, and haemolytic test. Biosurfactant-mediated silver nanoparticles were synthesised by microwave irradiation of the culture supernatant and further characterized by UV–vis spectroscopy for a range of 400-600 nm. The UV–vis spectra showed a surface plasmon resonance vibration band at 410 nm corresponding to the peak of silver nanoparticles.Keywords: biosurfactant, Bacillus subtilis, silver nano particle, lipopeptide
Procedia PDF Downloads 2331788 Ionic Liquids-Polymer Nanoparticle Systems as Breakthrough Tools to Improve the Leprosy Treatment
Authors: A. Julio, R. Caparica, S. Costa Lima, S. Reis, J. G. Costa, P. Fonte, T. Santos De Almeida
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The Mycobacterium leprae causes a chronic and infectious disease called leprosy, which the most common symptoms are peripheral neuropathy and deformation of several parts of the body. The pharmacological treatment of leprosy is a combined therapy with three different drugs, rifampicin, clofazimine, and dapsone. However, clofazimine and dapsone have poor solubility in water and also low bioavailability. Thus, it is crucial to develop strategies to overcome such drawbacks. The use of ionic liquids (ILs) may be a strategy to overcome the low solubility since they have been used as solubility promoters. ILs are salts, liquid below 100 ºC or even at room temperature, that may be placed in water, oils or hydroalcoholic solutions. Another approach may be the encapsulation of drugs into polymeric nanoparticles, which improves their bioavailability. In this study, two different classes of ILs were used, the imidazole- and the choline-based ionic liquids, as solubility enhancers of the poorly soluble antileprotic drugs. Thus, after the solubility studies, it was developed IL-PLGA nanoparticles hybrid systems to deliver such drugs. First of all, the solubility studies of clofazimine and dapsone were performed in water and in water: IL mixtures, at ILs concentrations where cell viability is maintained, at room temperature for 72 hours. For both drugs, it was observed an improvement on the drug solubility and [Cho][Phe] showed to be the best solubility enhancer, especially for clofazimine, where it was observed a 10-fold improvement. Later, it was produced nanoparticles, with a polymeric matrix of poly(lactic-co-glycolic acid) (PLGA) 75:25, by a modified solvent-evaporation W/O/W double emulsion technique in the presence of [Cho][Phe]. Thus, the inner phase was an aqueous solution of 0.2 % (v/v) of the above IL with each drug to its maximum solubility determined on the previous study. After the production, the nanosystem hybrid was physicochemically characterized. The produced nanoparticles had a diameter of around 580 nm and 640 nm, for clofazimine and dapsone, respectively. Regarding the polydispersity index, it was in agreement of the recommended value of this parameter for drug delivery systems (around 0.3). The association efficiency (AE) of the developed hybrid nanosystems demonstrated promising AE values for both drugs, given their low solubility (64.0 ± 4.0 % for clofazimine and 58.6 ± 10.0 % for dapsone), that prospects the capacity of these delivery systems to enhance the bioavailability and loading of clofazimine and dapsone. Overall, the study achievement may signify an upgrading of the patient’s quality of life, since it may mean a change in the therapeutic scheme, not requiring doses of drug so high to obtain a therapeutic effect. The authors would like to thank Fundação para a Ciência e a Tecnologia, Portugal (FCT/MCTES (PIDDAC), UID/DTP/04567/2016-CBIOS/PRUID/BI2/2018).Keywords: ionic liquids, ionic liquids-PLGA nanoparticles hybrid systems, leprosy treatment, solubility
Procedia PDF Downloads 1371787 Strategies of Drug Discovery in Insects
Authors: Alaaeddeen M. Seufi
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Many have been published on therapeutic derivatives from living organisms including insects. In addition to traditional maggot therapy, more than 900 therapeutic products were isolated from insects. Most people look at insects as enemies and others believe that insects are friends. Many beneficial insects rather than Honey Bees, Silk Worms and Shellac insect could insure human-insect friendship. In addition, insects could be MicroFactories, Biosensors or Bioreactors. InsectFarm is an amazing example of the applied research that transfers insects from laboratory to market by Prof Mircea Ciuhrii and co-workers. They worked for 18 years to derive therapeutics from insects. Their research resulted in production of more than 30 commercial medications derived from insects (e.g. Imunomax, Noblesse, etc.). Two general approaches were followed to discover drugs from living organisms. Some laboratories preferred biochemical approach to purify components of the innate immune system of insects and insect metabolites as well. Then the purified components could be tested for many therapeutic trials. Other researchers preferred molecular approach based on proteomic studies. Components of the innate immune system of insects were then tested for their medical activities. Our Laboratory team preferred to induce insect immune system (using oral, topical and injection routes of administration), then a transcriptomic study was done to discover the induced genes and to identify specific biomarkers that can help in drug discovery. Biomarkers play an important role in medicine and in drug discovery and development as well. Optimum biomarker development and application will require a team approach because of the multifaceted nature of biomarker selection, validation, and application. This team uses several techniques such as pharmacoepidemiology, pharmacogenomics, and functional proteomics; bioanalytical development and validation; modeling and simulation to improve and refine drug development. Our Achievements included the discovery of four components of the innate immune system of Spodoptera littoralis and Musca domestica. These components were designated as SpliDef (defesin), SpliLec (lectin), SpliCec (cecropin) and MdAtt (attacin). SpliDef, SpliLec and MdAtt were confirmed as antimicrobial peptides, while SpliCec was additionally confirmed as anticancer peptide. Our current research is going on to achieve something in antioxidants and anticoagulants from insects. Our perspective is to achieve something in the mass production of prototypes of our products and to reach it to the commercial level. These achievements are the integrated contributions of everybody in our team staff.Keywords: AMPs, insect, innate immunitty, therappeutics
Procedia PDF Downloads 3661786 Identification of Potent and Selective SIRT7 Anti-Cancer Inhibitor via Structure-Based Virtual Screening and Molecular Dynamics Simulation
Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi
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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation
Procedia PDF Downloads 671785 Title: Real World Evidence a Tool to Overcome the Lack of a Comparative Arm in Drug Evaluation in the Context of Rare Diseases
Authors: Mohamed Wahba
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Objective: To build a comparative arm for product (X) in specific gene mutated advanced gastrointestinal cancer using real world evidence to fulfill HTA requirements in drug evaluation. Methods: Data for product (X) were collected from phase II clinical trial while real world data for (Y) and (Z) were collected from US database. Real-world (RW) cohorts were matched to clinical trial base line characteristics using weighting by odds method. Outcomes included progression-free survival (PFS) and overall survival (OS) rates. Study location and participants: Internationally (product X, n=80) and from USA (Product Y and Z, n=73) Results: Two comparisons were made: trial cohort 1 (X) versus real-world cohort 1 (Z), trial cohort 2 (X) versus real-world cohort 2 (Y). For first line, the median OS was 9.7 months (95% CI 8.6- 11.5) and the median PFS was 5.2 months (95% CI 4.7- not reached) for real-world cohort 1. For second line, the median OS was 10.6 months (95% CI 4.7- 27.3) for real-world cohort 2 and the median PFS was 5.0 months (95% CI 2.1- 29.3). For OS analysis, results were statistically significant but not for PFS analysis. Conclusion: This study provided the clinical comparative outcomes needed for HTA evaluation.Keywords: real world evidence, pharmacoeconomics, HTA agencies, oncology
Procedia PDF Downloads 831784 Application of Liquid Chromatographic Method for the in vitro Determination of Gastric and Intestinal Stability of Pure Andrographolide in the Extract of Andrographis paniculata
Authors: Vijay R. Patil, Sathiyanarayanan Lohidasan, K. R. Mahadik
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Gastrointestinal stability of andrographolide was evaluated in vitro in simulated gastric (SGF) and intestinal (SIF) fluids using a validated HPLC-PDA method. The method was validated using a 5μm ThermoHypersil GOLD C18column (250 mm × 4.0 mm) and mobile phase consisting of water: acetonitrile; 70: 30 (v/v) delivered isocratically at a flow rate of 1 mL/min with UV detection at 228 nm. Andrographolide in pure form and extract Andrographis paniculata was incubated at 37°C in an incubator shaker in USP simulated gastric and intestinal fluids with and without enzymes. Systematic protocol as per FDA Guidance System was followed for stability study and samples were assayed at 0, 15, 30 and 60 min intervals for gastric and at 0, 15, 30, 60 min, 1, 2 and 3 h for intestinal stability study. Also, the stability study was performed up to 24 h to see the degradation pattern in SGF and SIF (with enzyme and without enzyme). The developed method was found to be accurate, precise and robust. Andrographolide was found to be stable in SGF (pH ∼ 1.2) for 1h and SIF (pH 6.8) up to 3 h. The relative difference (RD) of amount of drug added and found at all time points was found to be < 3%. The present study suggests that drug loss in the gastrointestinal tract takes place may be by membrane permeation rather than a degradation process.Keywords: andrographolide, Andrographis paniculata, in vitro, stability, gastric, Intestinal HPLC-PDA
Procedia PDF Downloads 2411783 Assessment of Knowledge, Attitude, and Practice of Health Care Professionals and Factors Associated with Adverse Drug Reaction Reporting in Public and Private Hospitals of Islamabad
Authors: Zaka Nisa, Farooq Sher
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Adverse drug reactions (ADRs) underreporting is a great challenge to Pharmacovigilance. Health care professionals have to consider ADR reporting as their professional obligation, an effective system of ADR reporting is important to improve patient health care and safety. The present study is designed to assess the knowledge, attitude, practice and factors associated with ADR reporting by health care professionals (physicians and pharmacists) in public and private hospitals of Pakistan. A pretested questionnaire was administered to 384 physicians and pharmacists in public and private hospitals. Respondents were evaluated for their knowledge, attitude, and practice related to ADR reporting. The data was analyzed using the SPSS statistical software, the factors which encourage and discourage respondents in reporting ADRs were determined. Most of the respondents have shown a positive attitude towards ADR reporting. The response rate was 95.32%. Of the 367 questionnaires, including 333 (86.5%) physicians and 34 (8.8%) pharmacists with the mean age 28.34 (SD= 6.69), most of the respondents showed poor ADR reporting knowledge (83.1%). The majority of respondents (78.2%) showed positive attitude towards ADR reporting and only (12.3%) hospitals have good ADR reporting practice. Knowledge of respondents in public hospitals (8.6%) was less as compare to those in the private hospitals (29.7%) (P < 0.001). Attitude of respondents in private hospitals was more positive (92.4%) than those in public hospitals (68.8%) (P < 0.001). No significant difference was observed in practicing of ADR reporting in public (11.8%) and private hospitals (13.1%) (P value 0.89). Seriousness of ADR, unusualness of reaction, new drug involvement and confidence in diagnosis of ADR were the factors which encourage respondents to report ADR, however, lack of knowledge regarding where and how to report ADR, lack of access to ADR reporting form, managing patients was more important than reporting ADR, legal liability issues were the factors which discourage respondents to report ADR. The study reveals poor knowledge and practice regarding ADR reporting. However positive attitude was seen regarding ADR reporting. There is a need of educational training for health care professionals as well as genuine and continuous efforts are required by Government and health authorities to ensure the proper implementation of ADR reporting system in all of the hospitals.Keywords: adverse drugs reactions (ADR), pharmacovigilance, spontaneous ADR reporting, knowledge of ADR, attitude of health care profesionals, practice of ADR reporting
Procedia PDF Downloads 2521782 In situ Immobilization of Mercury in a Contaminated Calcareous Soil Using Water Treatment Residual Nanoparticles
Authors: Elsayed A. Elkhatib, Ahmed M. Mahdy, Mohamed L. Moharem, Mohamed O. Mesalem
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Mercury (Hg) is one of the most toxic and bio-accumulative heavy metal in the environment. However, cheap and effective in situ remediation technology is lacking. In this study, the effects of water treatment residuals nanoparticles (nWTR) on mobility, fractionation and speciation of mercury in an arid zone soil from Egypt were evaluated. Water treatment residual nanoparticles with high surface area (129 m 2 g-1) were prepared using Fritsch planetary mono mill. Scanning and transmission electron microscopy revealed that the nanoparticles of WTR nanoparticles are spherical in shape, and single particle sizes are in the range of 45 to 96 nm. The x-ray diffraction (XRD) results ascertained that amorphous iron, aluminum (hydr)oxides and silicon oxide dominating all nWTR, with no apparent crystalline iron–Al (hydr)oxides. Addition of nWTR, greatly increased the Hg sorption capacities of studied soils and greatly reduced the cumulative Hg released from the soils. Application of nWTR at 0.10 and 0.30 % rates reduced the released Hg from the soil by 50 and 85 % respectively. The power function and first order kinetics models well described the desorption process from soils and nWTR amended soils as evidenced by high coefficient of determination (R2) and low SE values. Application of nWTR greatly increased the association of Hg with the residual fraction. Meanwhile, application of nWTR at a rate of 0.3% greatly increased the association of Hg with the residual fraction (>93%) and significantly increased the most stable Hg species (Hg(OH)2 amor) which in turn enhanced Hg immobilization in the studied soils. Fourier transmission infrared spectroscopy analysis indicated the involvement of nWTR in the retention of Hg (II) through OH groups which suggest inner-sphere adsorption of Hg ions to surface functional groups on nWTR. These results demonstrated the feasibility of using a low-cost nWTR as best management practice to immobilize excess Hg in contaminated soils.Keywords: release kinetics, Fourier transmission infrared spectroscopy, Hg fractionation, Hg species
Procedia PDF Downloads 2281781 Formulation Design and Optimization of Orodispersible Tablets of Diphenhydramine Hydrochloride Having Adequate Mechanical Strength
Authors: Jiwan P. Lavande, A. V. Chandewar
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In the present study, orodispersible tablets of diphenhydramine hydrochloride were prepared using croscarmellose sodium, crospovidone and camphor, menthol (as subliming agents) in different ratios and ODTs prepared with superdisintegrants were compared with ODTs prepared with camphor and menthol (subliming agents) for the following evaluation of in vitro disintegration time, dispersion time, wetting time, hardness and water absorption ratio. Results revealed that the tablets of all formulations have acceptable physical parameters. The drug and excipients compatibility study was evaluated using FTIR technique and has not detected any incompatibility. The in vitro release of drug from DC6 formulation was quick when compared to other formulations. Stability study was carried out as per ICH guidelines for three months and results revealed that upon storage disintegration time of tablets had not shown any significant difference. Microscopic study of different formulations of sublimed tablets showed formation of pores for the tablets prepared by sublimation method. Thus, conclusion can be made that the stable orodispersible tablets of diphenhydramine hydrochloride can be developed for the rapid release of diphenhydramine hydrochloride.Keywords: orodispersible tablet, subliming agent, super disintegrants, diphenhydramine hydrochloride
Procedia PDF Downloads 2271780 New Strategy for Breeding of Artemisia annua L. for a Sustainable Production of the Antimalarial Drug Artemisinin
Authors: Nadali Babaeian Jelodar, Chan Lai Keng, Arvind Bhatt, Laleh Bordbar, Leow E Shuen, Kamaruzaman Mohamed
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Recently artemisinin (the endoperoxide sesquiterpene lactone) has received considerable attention because of its antimalarial activity. It is isolated from the aerial part of the Artemisia annua L. Artemisinin is very difficult to synthesise also its production by mean of cell, tissue or organ cultures is very low. Presently, only its extraction from A. annua L. plants remains the only source of the drug. The reported yield of artemisinin from leaves of A. annua L. is very low and unstable, with yields typically less than 1% of leaf dry weight. To increase the percentage of artemisinin, researchers have been engaged in developing new varieties. A review concerning the breeding of A. annua L. is presented. The aim of this review is to bring together most of the available scientific research papers about the breeding conducted on the genus A. annua L., which is currently scattered across various publications. Through this review the authors hope to attract the attention of breeders throughout the world to focus on the unexplored potential of A. annua L. species. Also the future scope of this plant has been emphasized with a view of the importance of breeding of A. annua L. for increasing of artemisinin content. By releasing of new cultivar of A. annua L. and cultivation of this plant offers the opportunity to optimize yield and achieve a uniform, high quality product.Keywords: Artemisia annua L., breeding, artemisinin, cultivation, medicinal plant
Procedia PDF Downloads 2581779 A Hybrid of BioWin and Computational Fluid Dynamics Based Modeling of Biological Wastewater Treatment Plants for Model-Based Control
Authors: Komal Rathore, Kiesha Pierre, Kyle Cogswell, Aaron Driscoll, Andres Tejada Martinez, Gita Iranipour, Luke Mulford, Aydin Sunol
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Modeling of Biological Wastewater Treatment Plants requires several parameters for kinetic rate expressions, thermo-physical properties, and hydrodynamic behavior. The kinetics and associated mechanisms become complex due to several biological processes taking place in wastewater treatment plants at varying times and spatial scales. A dynamic process model that incorporated the complex model for activated sludge kinetics was developed using the BioWin software platform for an Advanced Wastewater Treatment Plant in Valrico, Florida. Due to the extensive number of tunable parameters, an experimental design was employed for judicious selection of the most influential parameter sets and their bounds. The model was tuned using both the influent and effluent plant data to reconcile and rectify the forecasted results from the BioWin Model. Amount of mixed liquor suspended solids in the oxidation ditch, aeration rates and recycle rates were adjusted accordingly. The experimental analysis and plant SCADA data were used to predict influent wastewater rates and composition profiles as a function of time for extended periods. The lumped dynamic model development process was coupled with Computational Fluid Dynamics (CFD) modeling of the key units such as oxidation ditches in the plant. Several CFD models that incorporate the nitrification-denitrification kinetics, as well as, hydrodynamics was developed and being tested using ANSYS Fluent software platform. These realistic and verified models developed using BioWin and ANSYS were used to plan beforehand the operating policies and control strategies for the biological wastewater plant accordingly that further allows regulatory compliance at minimum operational cost. These models, with a little bit of tuning, can be used for other biological wastewater treatment plants as well. The BioWin model mimics the existing performance of the Valrico Plant which allowed the operators and engineers to predict effluent behavior and take control actions to meet the discharge limits of the plant. Also, with the help of this model, we were able to find out the key kinetic and stoichiometric parameters which are significantly more important for modeling of biological wastewater treatment plants. One of the other important findings from this model were the effects of mixed liquor suspended solids and recycle ratios on the effluent concentration of various parameters such as total nitrogen, ammonia, nitrate, nitrite, etc. The ANSYS model allowed the abstraction of information such as the formation of dead zones increases through the length of the oxidation ditches as compared to near the aerators. These profiles were also very useful in studying the behavior of mixing patterns, effect of aerator speed, and use of baffles which in turn helps in optimizing the plant performance.Keywords: computational fluid dynamics, flow-sheet simulation, kinetic modeling, process dynamics
Procedia PDF Downloads 2021778 Insight into the Physical Ageing of Poly(Butylene Succinate)
Authors: I. Georgousopoulou, S. Vouyiouka, C. Papaspyrides
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The hydrolytic degradation of poly(butylene succinate) (PBS) was investigated when exposed to different humidity-temperature environments. To this direction different PBS grades were submitted to hydrolysis runs. Results indicated that the increment of hydrolysis temperature and relative humidity induced significant decrease in the molecular weight and thermal properties of the bioplastic. Τhe derived data can be considered to construct degradation kinetics based on carboxyl content variation versus time.Keywords: hydrolytic degradation, physical ageing, poly(butylene succinate), polyester
Procedia PDF Downloads 2801777 Long-Term Results of Coronary Bifurcation Stenting with Drug Eluting Stents
Authors: Piotr Muzyk, Beata Morawiec, Mariusz Opara, Andrzej Tomasik, Brygida Przywara-Chowaniec, Wojciech Jachec, Ewa Nowalany-Kozielska, Damian Kawecki
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Background: Coronary bifurcation is one of the most complex lesion in patients with coronary ar-tery disease. Provisional T-stenting is currently one of the recommended techniques. The aim was to assess optimal methods of treatment in the era of drug-eluting stents (DES). Methods: The regis-try consisted of data from 1916 patients treated with coronary percutaneous interventions (PCI) using either first- or second-generation DES. Patients with bifurcation lesion entered the analysis. Major adverse cardiac and cardiovascular events (MACCE) were assessed at one year of follow-up and comprised of death, acute myocardial infarction (AMI), repeated PCI (re-PCI) of target ves-sel and stroke. Results: Of 1916 registry patients, 204 patients (11%) were diagnosed with bifurcation lesion >50% and entered the analysis. The most commonly used technique was provi-sional T-stenting (141 patients, 69%). Optimization with kissing-balloons technique was performed in 45 patients (22%). In 59 patients (29%) second-generation DES was implanted, while in 112 pa-tients (55%), first-generation DES was used. In 33 patients (16%) both types of DES were used. The procedure success rate (TIMI 3 flow) was achieved in 98% of patients. In one-year follow-up, there were 39 MACCE (19%) (9 deaths, 17 AMI, 16 re-PCI and 5 strokes). Provisional T-stenting resulted in similar rate of MACCE to other techniques (16% vs. 5%, p=0.27) and similar occurrence of re-PCI (6% vs. 2%, p=0.78). The results of post-PCI kissing-balloon technique gave equal out-comes with 3% vs. 16% of MACCE in patients in whom no optimization technique was used (p=0.39). The type of implanted DES (second- vs. first-generation) had no influence on MACCE (4% vs 14%, respectively, p=0.12) and re-PCI (1.7% vs. 51% patients, respectively, p=0.28). Con-clusions: The treatment of bifurcation lesions with PCI represent high-risk procedures with high rate of MACCE. Stenting technique, optimization of PCI and the generation of implanted stent should be personalized for each case to balance risk of the procedure. In this setting, the operator experience might be the factor of better outcome, which should be further investigated.Keywords: coronary bifurcation, drug eluting stents, long-term follow-up, percutaneous coronary interventions
Procedia PDF Downloads 1981776 Resveratrol Incorporated Liposomes Prepared from Pegylated Phospholipids and Cholesterol
Authors: Mont Kumpugdee-Vollrath, Khaled Abdallah
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Liposomes and pegylated liposomes were widely used as drug delivery system in pharmaceutical field since a long time. However, in the former time, polyethylene glycol (PEG) was connected into phospholipid after the liposomes were already prepared. In this paper, we intend to study the possibility of applying phospholipids which already connected with PEG and then they were used to prepare liposomes. The model drug resveratrol was used because it can be applied against different diseases. Cholesterol was applied to stabilize the membrane of liposomes. The thin film technique in a laboratory scale was a preparation method. The liposomes were then characterized by nanoparticle tracking analysis (NTA), photon correlation spectroscopy (PCS) and light microscopic techniques. The stable liposomes can be produced and the particle sizes after filtration were in nanometers. The 2- and 3-chains-PEG-phospholipid (PL) caused in smaller particle size than the 4-chains-PEG-PL. Liposomes from PL 90G and cholesterol were stable during storage at 8 °C of 56 days because the particle sizes measured by PCS were almost not changed. There was almost no leakage of resveratrol from liposomes PL 90G with cholesterol after diffusion test in dialysis tube for 28 days. All liposomes showed the sustained release during measuring time of 270 min. The maximum release amount of 16-20% was detected with liposomes from 2- and 3-chains-PEG-PL. The other liposomes gave max. release amount of resveratrol only of 10%. The release kinetic can be explained by Korsmeyer-Peppas equation.Keywords: liposome, NTA, resveratrol, pegylation, cholesterol
Procedia PDF Downloads 1781775 Heterogeneous Catalytic Ozonation of Diethyl Phthalate
Authors: Chedly Tizaoui, Hussain Mohammed, Lobna Mansouri, Nidal Hilal, Latifa Bousselmi
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The degradation of diethyl phthalate (DEP) was studied using heterogeneous catalytic ozonation. Activated carbon was used as a catalyst. The degradation of DEP with ozone alone was slow while catalytic ozonation increased degradation rates. Second-order reaction kinetics was used to describe the experimental data, and the corresponding rate constant values were 1.19 and 3.94 M-1.s-1 for ozone and ozone/activated carbon respectively.Keywords: ozone, heterogeneous catalytic ozonation, diethyl phthalate, endocrine disrupting chemicals
Procedia PDF Downloads 3401774 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model
Authors: Ziyad S. Haidar
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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology
Procedia PDF Downloads 721773 Localisation of Fluorescently Labelled Drug-Free Phospholipid Vesicles to the Cartilage Surface of Rat Synovial Joints
Authors: Sam Yurdakul, Nick Baverstock, Jim Mills
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TDT 064 (FLEXISEQ®) is a drug-free gel used to treat osteoarthritis (OA)-associated pain and joint stiffness. It contains ultra-deformable phospholipid Sequessome™ vesicles, which can pass through the skin barrier intact. In six randomized OA studies, topical TDT 064 was well tolerated and improved joint pain, physical function and stiffness. In the largest study, these TDT 064-mediated effects were statistically significantly greater than oral placebo and equivalent to celecoxib. To understand the therapeutic effects of TDT 064, we investigated the localisation of the drug-free vesicles within rat synovial joints. TDT 064 containing DiO-labelled Sequessome™ vesicles was applied to the knees of four 6-week-old CD® hairless rats (10 mg/kg/ joint), 2–3 times/day, for 3 days (representing the recommended clinical dose). Eighteen hours later, the animals and one untreated control were sacrificed, and the knee joints isolated, flash frozen and embedded in Acrytol Mounting Media™. Approximately 15 sections (10 µm) from each joint were analysed by fluorescence microscopy. To investigate whether the localisation of DiO fluorescence was associated with intact vesicles, an anti-PEG monoclonal antibody (mAb) was used to detect Tween, a constituent of Sequessome™ vesicles. Sections were visualized at 484 nm (DiO) and 647 nm (anti-PEG mAb) and analysed using inForm 1.4 (Perkin Elmer, Inc.). Significant fluorescence was observed at 484 nm in sections from TDT 064-treated animals. No non-specific fluorescence was observed in control sections. Fluorescence was detected as discrete vesicles on the cartilage surfaces, inside the cartilaginous matrix and within the synovial space. The number of DiO-labelled vesicles in multiple fields of view was consistent and >100 in sections from four different treated knees. DiO and anti-PEG mAb co-localised within the collagenous tissues in four different joint sections. Under higher magnification (40x), vesicles were seen in the intercellular spaces of the synovial joint tissue, but no fluorescence was seen inside cells. These data suggest that the phospholipid vesicles in TDT 064 localize at the surface of the joint cartilage; these vesicles may therefore be supplementing the phospholipid deficiency reported in OA and acting as a biolubricant within the synovial joint.Keywords: joint pain, osteoarthritis, phospholipid vesicles, TDT 064
Procedia PDF Downloads 4411772 Biosorption Kinetics, Isotherms, and Thermodynamic Studies of Copper (II) on Spirogyra sp.
Authors: Diwan Singh
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The ability of non-living Spirogyra sp. biomass for biosorption of copper(II) ions from aqueous solutions was explored. The effect of contact time, pH, initial copper ion concentration, biosorbent dosage and temperature were investigated in batch experiments. Both the Freundlich and Langmuir Isotherms were found applicable on the experimental data (R2>0.98). Qmax obtained from the Langmuir Isotherms was found to be 28.7 mg/g of biomass. The values of Gibbs free energy (ΔGº) and enthalpy change (ΔHº) suggest that the sorption is spontaneous and endothermic at 20ºC-40ºC.Keywords: biosorption, Spirogyra sp., contact time, pH, dose
Procedia PDF Downloads 4181771 Calcein Release from Liposomes Mediated by Phospholipase A₂ Activity: Effect of Cholesterol and Amphipathic Di and Tri Blocks Copolymers
Authors: Marco Soto-Arriaza, Eduardo Cena-Ahumada, Jaime Melendez-Rojel
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Background: Liposomes have been widely used as a model of lipid bilayer to study the physicochemical properties of biological membrane, encapsulation, transport and release of different molecules. Furthermore, extensive research has focused on improving the efficiency in the transport of drugs, developing tools that improve the release of the encapsulated drug from liposomes. In this context, the enzymatic activity of PLA₂, despite having been shown to be an effective tool to promote the release of drugs from liposomes, is still an open field of research. Aim: The aim of the present study is to explore the effect of cholesterol (Cho) and amphipathic di- and tri-block copolymers, on calcein release mediated by enzymatic activity of PLA2 in Dipalmitoylphosphatidylcholine (DPPC) liposomes under physiological conditions. Methods: Different dispersions of DPPC, cholesterol, di-block POE₄₅-PCL₅₂ or tri-block PCL₁₂-POE₄₅-PCL₁₂ were prepared by the extrusion method after five freezing/thawing cycles; in Phosphate buffer 10mM pH 7.4 in presence of calcein. DPPC liposomes/Calcein were centrifuged at 15000rpm 10 min to separate free calcein. Enzymatic activity assays of PLA₂ were performed at 37°C using the TBS buffer pH 7.4. The size distribution, polydispersity, Z-potential and Calcein encapsulation of DPPC liposomes was monitored. Results: PLA₂ activity showed a slower kinetic of calcein release up to 20 mol% of cholesterol, evidencing a minimum at 10 mol% and then a maximum at 18 mol%. Regardless of the percentage of cholesterol, up to 18 mol% a one-hundred percentage release of calcein was observed. At higher cholesterol concentrations, PLA₂ showed to be inefficient or not to be involved in calcein release. In assays where copolymers were added in a concentration lower than their cmc, a similar behavior to those showed in the presence of Cho was observed, that is a slower kinetic in calcein release. In both experimental approaches, a one-hundred percentage of calcein release was observed. PLA₂ was shown to be sensitive to the 4-(4-Octadecylphenyl)-4-oxobutenoic acid inhibitor and calcium, reducing the release of calcein to 0%. Cell viability of HeLa cells decreased 7% in the presence of DPPC liposomes after 3 hours of incubation and 17% and 23% at 5 and 15 hours, respectively. Conclusion: Calcein release from DPPC liposomes, mediated by PLA₂ activity, depends on the percentage of cholesterol and the presence of copolymers. Both, cholesterol up to 20 mol% and copolymers below it cmc could be applied to the regulation of the kinetics of antitumoral drugs release without inducing cell toxicity per se.Keywords: amphipathic copolymers, calcein release, cholesterol, DPPC liposome, phospholipase A₂
Procedia PDF Downloads 1551770 Effective Infection Control Measures to Prevent Transmission of Multi-Drug Resistant Organisms from Burn Transfer Cases in a Regional Burn Centre
Authors: Si Jack Chong, Chew Theng Yap, Wan Loong James Mok
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Introduction: Regional burn centres face the spectra of introduced multi-drug resistant organisms (MDRO) from transfer patients resident in MDRO endemic countries. MDRO can cause severe nosocomial infection, which in massive burn patients, will lead to greater morbidity and mortality and strain the institution financially. We aim to highlight 4 key measures that have effectively prevented transmission of imported MDRO. Methods: A case of Candida auris (C. auris) from a massive burn patient transferred from an MDRO endemic country is used to illustrate the measures. C. auris is a globally emerging multi-drug resistant fungal pathogen causing nosocomial transmission. Results: Infection control measures used to mitigate the risk of outbreak from transfer cases are: (1) Multidisciplinary team approach involving Infection Control and Infectious Disease specialists early to ensure appropriate antibiotics use and implementation of barrier measures, (2) aseptic procedures for dressing change with strict isolation and donning of personal protective equipment in the ward, (3) early screening of massive burn patient from MDRO endemic region, (4) hydrogen peroxide vaporization terminal cleaning for operating theatres and rooms. Conclusion: The prevalence of air travel and international transfer to regional burn centres will need effective infection control measures to reduce the risk of transmission from imported massive burn patients. In our centre, we have effectively implemented 4 measures which have reduced the risks of local contamination. We share a recent case report to illustrate successful management of a potential MDRO outbreak resulting from transfer of massive burn patient resident in an MDRO endemic area.Keywords: burns, burn unit, cross infection, infection control
Procedia PDF Downloads 1441769 Mucoadhesive Chitosan-Coated Nanostructured Lipid Carriers for Oral Delivery of Amphotericin B
Authors: S. L. J. Tan, N. Billa, C. J. Roberts
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Oral delivery of amphotericin B (AmpB) potentially eliminates constraints and side effects associated with intravenous administration, but remains challenging due to the physicochemical properties of the drug such that it results in meagre bioavailability (0.3%). In an advanced formulation, 1) nanostructured lipid carriers (NLC) were formulated as they can accommodate higher levels of cargoes and restrict drug expulsion and 2) a mucoadhesion feature was incorporated so as to impart sluggish transit of the NLC along the gastrointestinal tract and hence, maximize uptake and improve bioavailability of AmpB. The AmpB-loaded NLC formulation was successfully formulated via high shear homogenisation and ultrasonication. A chitosan coating was adsorbed onto the formed NLC. Physical properties of the formulations; particle size, zeta potential, encapsulation efficiency (%EE), aggregation states and mucoadhesion as well as the effect of the variable pH on the integrity of the formulations were examined. The particle size of the freshly prepared AmpB-loaded NLC was 163.1 ± 0.7 nm, with a negative surface charge and remained essentially stable over 120 days. Adsorption of chitosan caused a significant increase in particle size to 348.0 ± 12 nm with the zeta potential change towards positivity. Interestingly, the chitosan-coated AmpB-loaded NLC (ChiAmpB NLC) showed significant decrease in particle size upon storage, suggesting 'anti-Ostwald' ripening effect. AmpB-loaded NLC formulation showed %EE of 94.3 ± 0.02 % and incorporation of chitosan increased the %EE significantly, to 99.3 ± 0.15 %. This suggests that the addition of chitosan renders stability to the NLC formulation, interacting with the anionic segment of the NLC and preventing the drug leakage. AmpB in both NLC and ChiAmpB NLC showed polyaggregation which is the non-toxic conformation. The mucoadhesiveness of the ChiAmpB NLC formulation was observed in both acidic pH (pH 5.8) and near-neutral pH (pH 6.8) conditions as opposed to AmpB-loaded NLC formulation. Hence, the incorporation of chitosan into the NLC formulation did not only impart mucoadhesive property but also protected against the expulsion of AmpB which makes it well-primed as a potential oral delivery system for AmpB.Keywords: Amphotericin B, mucoadhesion, nanostructured lipid carriers, oral delivery
Procedia PDF Downloads 1561768 Study of the Influence of Refractory Nitride Additives on Hydrogen Storage Properties of Ti6Al4V-Based Materials Produced by Spark Plasma Sintering
Authors: John Olorunfemi Abe, Olawale Muhammed Popoola, Abimbola Patricia Idowu Popoola
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Hydrogen is an appealing alternative to fossil fuels because of its abundance, low weight, high energy density, and relative lack of contaminants. However, its low density presents a number of storage challenges. Therefore, this work studies the influence of refractory nitride additives consisting of 5 wt. % each of hexagonal boron nitride (h-BN), titanium nitride (TiN), and aluminum nitride (AlN) on hydrogen storage and electrochemical characteristics of Ti6Al4V-based materials produced by spark plasma sintering. The microstructure and phase constituents of the sintered materials were characterized using scanning electron microscopy (in conjunction with energy-dispersive spectroscopy) and X-ray diffraction, respectively. Pressure-composition-temperature (PCT) measurements were used to assess the hydrogen absorption/desorption behavior, kinetics, and storage capacities of the sintered materials, respectively. The pure Ti6Al4V alloy displayed a two-phase (α+β) microstructure, while the modified composites exhibited apparent microstructural modifications with the appearance of nitride-rich secondary phases. It is found that the diffusion process controls the kinetics of the hydrogen absorption. Thus, a faster rate of hydrogen absorption at elevated temperatures ensued. The additives acted as catalysts, lowered the activation energy and accelerated the rate of hydrogen sorption in the composites relative to the monolithic alloy. Ti6Al4V-5 wt. % h-BN appears to be the most promising candidate for hydrogen storage (2.28 wt. %), followed by Ti6Al4V-5 wt. % TiN (2.09 wt. %), whereas Ti6Al4V-5 wt. % AlN shows the least hydrogen storage performance (1.35 wt. %). Accordingly, the developed hydride system (Ti6Al4V-5h-BN) may be competitive for use in applications involving short-range continuous vehicles (~50-100km) as well as stationary applications such as electrochemical devices, large-scale storage cylinders in hydrogen production locations, and hydrogen filling stations.Keywords: hydrogen storage, Ti6Al4V hydride system, pressure-composition-temperature measurements, refractory nitride additives, spark plasma sintering, Ti6Al4V-based materials
Procedia PDF Downloads 551767 Pegylated Liposomes of Trans Resveratrol, an Anticancer Agent, for Enhancing Therapeutic Efficacy and Long Circulation
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
Procedia PDF Downloads 5791766 Comparative Acaricidal Efficacy of Fluralaner vs Oral Ivermectin Against Tick Infestation in Dogs
Authors: Tayyaba Zahra, Shehla Gul Bokhari, Asim Khalid Mahmood, Raheela Akhtar, Khizar Matloob
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In Pakistan, dogs are commonly infested with ticks, especially in summers, causing not only dermatological issues but also systemic problems. Persistence of tick infestation often leads to heavy losses. Different acaricides are locally available with variable efficacy; however, recurrence of infestation is commonly reported. The present study was thus designed to compare the efficacy of a novel drug Fluralaner and conventionally used Ivermectin against tick infestation. Dogs positive for tick infestation were randomly divided into 2 groups viz, Groups A and B having 8 dogs each. Ticks were enumerated manually from the whole body of dogs at day 0 before the administration of drugs Dogs in Group A were treated with Fluralaner at day 0, and dogs in Group B were treated with Ivermectin. Post-treatment, ticks were counted again at days 7, 14, 21, 28, and 35. At day 07 of the study, no tick was found on the dogs treated with Fluralaner, while many ticks were present on the dogs treated with Ivermectin showing an efficacy up to 50%. On the consecutive follow-up evaluations, similar results were found for Fluralaner while the efficacy of Ivermectin was further reduced to less than 50%. Furthermore, Fluralaner treated dogs had better RBC counts, PCV, Hgb concentration, LFTs, RFTs post-treatment than the dogs treated with Ivermectin. Statistically, oral Fluralaner proved a more effective drug (P≤0.05)than oral Ivermectin against tick infestation in dogs.Keywords: fluralaner, ivermectin, dogs, tick infestations
Procedia PDF Downloads 1931765 Nutraceutical Potential of Mushroom Bioactive Metabolites and Their Food Functionality
Authors: Jackson Ishara, Ariel Buzera, Gustave N. Mushagalusa, Ahmed R. A. Hammam, Judith Munga, Paul Karanja, John Kinyuru
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Numerous mushroom bioactive metabolites, including polysaccharides, eritadenine, lignin, chitosan, mevinolin, and astrakurkurone have been studied in life-threatening conditions and diseases such as diabetes, cardiovascular, hypertension, cancer, DNA damage, hypercholesterolemia, and obesity attempting to identify natural therapies. These bioactive metabolites have shown potential as antiviral and immune system strengthener natural agents through diverse cellular and physiological pathways modulation with no toxicity evidence, widely available, and affordable. In light of the emerging literature, this paper compiles the most recent information describing the molecular mechanisms that underlie the nutraceutical potentials of these mushroom metabolites suggesting their effectiveness if combined with existing drug therapies. The findings raise hope that these mushroom bioactive metabolites may be utilized as natural therapies considering their therapeutic potential while anticipating further research designing clinical trials and developing new drug therapies while encouraging their consumption as a natural adjuvant in preventing and controlling life-threatening conditions and diseases.Keywords: bioactive metabolites, food functionality, health-threatening conditions, mushrooms, nutraceutical
Procedia PDF Downloads 941764 Nutrigenetic and Bioinformatic Analysis of Rice Bran Bioactives for the Treatment of Lifestyle Related Disease Diabetes and Hypertension
Authors: Md. Alauddin, Md. Ruhul Amin, Md. Omar Faruque, Muhammad Ali Siddiquee, Zakir Hossain Howlader, Mohammad Asaduzzaman
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Diabetes and hypertension are the major lifestyle related diseases. The α-amylase and angiotensin converting enzymes (ACE) are the key enzymes that regulate diabetes and hypertension. The aim was to develop a drug for the treatment of diabetes and hypertension. The Rice Bran (RB) sample (Oryza sativa; BRRI-Dhan-84) was collected from the Bangladesh Rice Research Institute (BRRI), and rice bran proteins were isolated and hydrolyzed by hydrolyzing enzyme alcalase and trypsin. In vivo experiment suggested that rice bran bioactives has an effect on regulating the expression of several key gluconeogenesis and lipogenesis-regulating genes, such as glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, and fatty acid synthase. The above genes have a connection of regulating the glucose level, lipids profile as well as act as an anti-inflammatory agent. A molecular docking, bioinformatics and in vitro experiments were performed. We found rice bran protein hydrolysates significantly (<0.05) influence the peptide concentration in the case of trypsin, alcalase, and (trypsin + alcalase) digestion. The in vitro analysis found that protein hydrolysate significantly (<0.05) reduced diabetic and hypertension as well as oxidative stress. A molecular docking study showed that the YY and IP peptide have a significantly strong binding affinity to the active site of the ACE enzyme and α-amylase with -7.8Kcal/mol and -6.2Kcal/mol, respectively. The Molecular dynamics (MD) simulation and Swiss ADME data analysis showed that less toxicity risk, good physicochemical properties, pharmacokinetics, and drug-likeness with drug scores 0.45 and 0.55 of YY and IP peptides, respectively. Thus, rice bran bioactive could be a good candidate for the treatment of diabetes and hypertension.Keywords: anti-hypertensive and anti-hyperglycemic, anti-oxidative, bioinformatics, in vitro study, rice bran proteins and peptides
Procedia PDF Downloads 551763 Improving the Utility of Social Media in Pharmacovigilance: A Mixed Methods Study
Authors: Amber Dhoot, Tarush Gupta, Andrea Gurr, William Jenkins, Sandro Pietrunti, Alexis Tang
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Background: The COVID-19 pandemic has driven pharmacovigilance towards a new paradigm. Nowadays, more people than ever before are recognising and reporting adverse reactions from medications, treatments, and vaccines. In the modern era, with over 3.8 billion users, social media has become the most accessible medium for people to voice their opinions and so provides an opportunity to engage with more patient-centric and accessible pharmacovigilance. However, the pharmaceutical industry has been slow to incorporate social media into its modern pharmacovigilance strategy. This project aims to make social media a more effective tool in pharmacovigilance, and so reduce drug costs, improve drug safety and improve patient outcomes. This will be achieved by firstly uncovering and categorising the barriers facing the widespread adoption of social media in pharmacovigilance. Following this, the potential opportunities of social media will be explored. We will then propose realistic, practical recommendations to make social media a more effective tool for pharmacovigilance. Methodology: A comprehensive systematic literature review was conducted to produce a categorised summary of these barriers. This was followed by conducting 11 semi-structured interviews with pharmacovigilance experts to confirm the literature review findings whilst also exploring the unpublished and real-life challenges faced by those in the pharmaceutical industry. Finally, a survey of the general public (n = 112) ascertained public knowledge, perception, and opinion regarding the use of their social media data for pharmacovigilance purposes. This project stands out by offering perspectives from the public and pharmaceutical industry that fill the research gaps identified in the literature review. Results: Our results gave rise to several key analysis points. Firstly, inadequacies of current Natural Language Processing algorithms hinder effective pharmacovigilance data extraction from social media, and where data extraction is possible, there are significant questions over its quality. Social media also contains a variety of biases towards common drugs, mild adverse drug reactions, and the younger generation. Additionally, outdated regulations for social media pharmacovigilance do not align with new, modern General Data Protection Regulations (GDPR), creating ethical ambiguity about data privacy and level of access. This leads to an underlying mindset of avoidance within the pharmaceutical industry, as firms are disincentivised by the legal, financial, and reputational risks associated with breaking ambiguous regulations. Conclusion: Our project uncovered several barriers that prevent effective pharmacovigilance on social media. As such, social media should be used to complement traditional sources of pharmacovigilance rather than as a sole source of pharmacovigilance data. However, this project adds further value by proposing five practical recommendations that improve the effectiveness of social media pharmacovigilance. These include: prioritising health-orientated social media; improving technical capabilities through investment and strategic partnerships; setting clear regulatory guidelines using multi-stakeholder processes; creating an adverse drug reaction reporting interface inbuilt into social media platforms; and, finally, developing educational campaigns to raise awareness of the use of social media in pharmacovigilance. Implementation of these recommendations would speed up the efficient, ethical, and systematic adoption of social media in pharmacovigilance.Keywords: adverse drug reaction, drug safety, pharmacovigilance, social media
Procedia PDF Downloads 781762 Zingiberaceous Plants as a Source of Anti-Bacterial Activity: Targeting Bacterial Cell Division Protein (FtsZ)
Authors: S. Reshma Reghu, Shiburaj Sugathan, T. G. Nandu, K. B. Ramesh Kumar, Mathew Dan
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Bacterial diseases are considered to be one of the most prevalent health hazards in the developing world and many bacteria are becoming resistant to existing antibiotics making the treatment ineffective. Thus, it is necessary to find novel targets and develop new antibacterial drugs with a novel mechanism of action. The process of bacterial cell division is a novel and attractive target for new antibacterial drug discovery. FtsZ, a homolog of eukaryotic tubulin, is the major protein of the bacterial cell division machinery and is considered as an important antibacterial drug target. Zingiberaceae, the Ginger family consists of aromatic herbs with creeping rhizomes. Many of these plants have antimicrobial properties.This study aimed to determine the anti-bacterial activity of selected Zingiberaceous plants by targeting bacterial cell division protein, FtsZ. Essential oils and methanol extracts of Amomum ghaticum, Alpinia galanga, Kaempferia galanga, K. rotunda, and Zingiber officinale were tested to find its antibacterial efficiency using disc diffusion method against authentic bacterial strains obtained from MTCC (India). Essential oil isolated from A.galanga and Z.officinale were further assayed for FtsZ inhibition assay following non-radioactive malachite green-phosphomolybdate assay using E. coli FtsZ protein obtained from Cytoskelton Inc., USA. Z.officinale essential oil possess FtsZ inhibitory property. A molecular docking study was conducted with the known bioactive compounds of Z. officinale as ligands with the E. coli FtsZ protein homology model. Some of the major constituents of this plant like catechin, epicatechin, and gingerol possess agreeable docking scores. The results of this study revealed that several chemical constituents in Ginger plants can be utilised as potential source of antibacterial activity and it can warrant further investigation through drug discovery studies.Keywords: antibacterial, FtsZ, zingiberaceae, docking
Procedia PDF Downloads 4681761 Comparison of the Effects of Alprazolam and Zaleplon on Anxiety Levels in Patients Undergoing Abdominal Gynecological Surgery
Authors: Shekoufeh Behdad, Amirhossein Yadegari, Leila Ghodrati, Saman Yadegari
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Context: Preoperative anxiety is a common psychological reaction experienced by all patients undergoing surgery. It can have negative effects on the patient's well-being and even impact surgical outcomes. Therefore, finding effective interventions to reduce preoperative anxiety is important in improving patient care. Research Aim: The aim of this study is to compare the effects of oral administration of zaleplon (5 mg) and alprazolam (0.5 mg) on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Methodology: This study is a double-blind, randomized clinical trial conducted after receiving approval from the university's ethics committee and obtaining written informed consent from the patients. The night before the surgery, patients were randomly assigned to receive either 0.5 mg of alprazolam or 5 mg of zaleplon orally. Anxiety levels, measured using a 10-cm visual analog scale, and hemodynamic variables (blood pressure and heart rate) were assessed before drug administration and on the morning of the operation after the patient entered the pre-operation room. Findings: The study found that there were no significant differences in mean anxiety levels or hemodynamic variables before and after administration of either drug in both groups (P value > 0.05). This suggests that both 0.5 mg of alprazolam and 5 mg of zaleplon effectively reduce preoperative anxiety in women undergoing abdominal surgery without serious side effects. Theoretical Importance: This study contributes to the understanding of the effectiveness of alprazolam and zaleplon in reducing preoperative anxiety. It adds to the existing literature on pharmacological interventions for anxiety management, specifically in the context of gynecological abdominal surgery. Data Collection: Data for this study were collected through the assessment of anxiety levels using a visual analog scale and measuring hemodynamic variables, including systolic, diastolic, and mean arterial blood pressures, as well as heart rate. These measurements were taken before drug administration and on the morning of the surgery. Analysis Procedures: Statistical analysis was performed to compare the mean anxiety levels and hemodynamic variables before and after drug administration in the two groups. The significance of the differences was determined using appropriate statistical tests. Questions Addressed: This study aimed to answer the question of whether there are differences in the effects of alprazolam and zaleplon on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Conclusion: The oral administration of both 0.5 mg of alprazolam and 5 mg of zaleplon the night before surgery effectively reduces preoperative anxiety in women undergoing abdominal surgery. These findings have important implications for the management of preoperative anxiety and can contribute to improving the overall surgical experience for patients.Keywords: zaleplon, alprazolam, premedication, abdominal surgery
Procedia PDF Downloads 741760 Upconversion Nanoparticle-Mediated Carbon Monoxide Prodrug Delivery System for Cancer Therapy
Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu
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Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.
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