Search results for: drug carriers
1791 Health and the Politics of Trust: Multi-Drug-Resistant Tuberculosis in Kathmandu
Authors: Mattia Testuzza
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Public health is a social endeavour, which involves many different actors: from extremely stratified, structured health systems to unofficial networks of people and knowledge. Health and diseases are an intertwined individual and social experiences. Both patients and health workers navigate this public space through relations of trust. Trust in healthcare goes from the personal trust between a patient and her/his doctor to the trust of both the patient and the health worker in the medical knowledge and the healthcare system. Trust it is not a given, but it is continuously negotiated, given and gained. The key to understand these essential relations of trust in health is to recognise them as a social practice, which therefore implies agency and power. In these terms, health is constantly public and made public, as trust emerges as a meaningfully political phenomenon. Trust as a power relation can be observed at play in the implementation of public health policies such as the WHO’s Directly-Observed Theraphy Short-course (DOTS), and with the increasing concern for drug-resistance that tuberculosis pose, looking at the role of trust in the healthcare delivery system and implementation of public health policies becomes significantly relevant. The ethnographic fieldwork was carried out in four months through observation of the daily practices at the National Tuberculosis Center of Nepal, and semi-structured interviews with MultiDrug-Resistant Tuberculosis (MDR-TB) patients at different stages of the treatment, their relatives, MDR-TB specialised nurses, and doctors. Throughout the research, the role which trust plays in tuberculosis treatment emerged as one fundamental ax that cuts through all the different factors intertwined with drug-resistance development, unfolding a tension between the DOTS policy, which undermines trust, and the day-to-day healthcare relations and practices which cannot function without trust. Trust also stands out as a key component of the solutions to unforeseen issues which develop from the overall uncertainty of the context - for example, political instability and extreme poverty - in which tuberculosis treatment is carried out in Nepal.Keywords: trust, tuberculosis, drug-resistance, politics of health
Procedia PDF Downloads 2541790 Encapsulation of Venlafaxine-Dowex® Resinate: A Once Daily Multiple Unit Formulation
Authors: Salwa Mohamed Salah Eldin, Howida Kamal Ibrahim
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Introduction: Major depressive disorder affects high proportion of the world’s population presenting cost load in health care. Extended release venlafaxine is more convenient and could reduce discontinuation syndrome. The once daily dosing also reduces the potential for adverse events such as nausea due to reduced Cmax. Venlafaxine is an effective first-line agent in the treatment of depression. A once daily formulation was designed to enhance patient compliance. Complexing with a resin was suggested to improve loading of the water soluble drug. The formulated systems were thoroughly evaluated in vitro to prove superiority to previous trials and were compared to the commercial extended release product in experimental animals. Materials and Methods: Venlafaxine-resinates were prepared using Dowex®50WX4-400 and Dowex®50WX8-100 at drug to resin weight ratio of 1: 1. The prepared resinates were evaluated for their drug content, particle shape and surface properties and in vitro release profile in gradient pH. The release kinetics and mechanism were evaluated. Venlafaxine-Dowex® resinates were encapsulated using O/W solvent evaporation technique. Poly-ε-caprolactone, Poly(D, L-lactide-co-glycolide) ester, Poly(D, L-lactide) ester and Eudragit®RS100 were used as coating polymers alone and in combination. Drug-resinate microcapsules were evaluated for morphology, entrapment efficiency and in-vitro release profile. The selected formula was tested in rabbits using a randomized, single-dose, 2-way crossover study against Effexor-XR tablets under fasting condition. Results and Discussion: The equilibrium time was 30 min for Dowex®50WX4-400 and 90 min for Dowex®50WX8-100. The percentage drug loaded was 93.96 and 83.56% for both resins, respectively. Both drug-Dowex® resintes were efficient in sustaining venlafaxine release in comparison to the free drug (up to 8h.). Dowex®50WX4-400 based venlafaxine-resinate was selected for further encapsulation to optimize the release profile for once daily dosing and to lower the burst effect. The selected formula (coated with a mixture of Eudragit RS and PLGA in a ratio of 50/50) was chosen by applying a group of mathematical equations according to targeted values. It recorded the minimum burst effect, the maximum MDT (Mean dissolution time) and a Q24h (percentage drug released after 24 hours) between 95 and 100%. The 90% confidence intervals for the test/reference mean ratio of the log-transformed data of AUC0–24 and AUC0−∞ are within (0.8–1.25), which satisfies the bioequivalence criteria. Conclusion: The optimized formula could be a promising extended release form of the water soluble, short half lived venlafaxine. Being a multiple unit formulation, it lowers the probability of dose dumping and reduces the inter-subject variability in absorption.Keywords: biodegradable polymers, cation-exchange resin, microencapsulation, venlafaxine hcl
Procedia PDF Downloads 3941789 Rupture in the Paradigm of the International Policy of Illicit Drugs in the Field of Public Health and within the Framework of the World Health Organization, 2001 to 2016
Authors: Emy Nayana Pinto, Denise Bomtempo Birche De Carvalho
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In the present study, the harmful use of illicit drugs is seen as a public health problem and as one of the expressions of the social question, since its consequences fall mainly on the poorer classes of the population. This perspective is a counterpoint to the dominant paradigm on illicit drug policy at the global level, whose centrality lies within the criminal justice arena. The 'drug problem' is internationally combated through fragmented approaches that focus its actions on banning and criminalizing users. In this sense, the research seeks to answer the following key questions: What are the influences of the prohibitionism in the recommendations of the United Nations (UN), the World Health Organization (WHO), and the formulation of drug policies in member countries? What are the actors that have been provoking the prospect of breaking with the prohibitionist paradigm? What is the WHO contribution to the rupture with the prohibitionist paradigm and the displacement of the drug problem in the field of public health? The general objective of this work is to seek evidence from the perspective of rupture with the prohibitionist paradigm in the field of drugs policies at the global and regional level, through analysis of documents of the World Health Organization (WHO), between the years of 2001 to 2016. The research was carried out in bibliographical and documentary sources. The bibliographic sources contributed to the approach with the object and the theoretical basis of the research. The documentary sources served to answer the research questions and evidence the existence of the perspective of change in drug policy. Twenty-two documents of the UN system were consulted, of which fifteen had the contribution of the World Health Organization (WHO). In addition to the documents that directly relate to the subject of the research, documents from various agencies, programs, and offices, such as the Joint United Nations Program on HIV/AIDS (UNAIDS) and the United Nations Office on Drugs and Crime (UNODC), which also has drugs as the central or transversal theme of its performance. The results showed that from the 2000s it was possible to find in the literature review and in the documentary analysis evidence of the critique of the prohibitionist paradigm parallel to the construction of a new perspective for drug policy at the global level and the displacement of criminal justice approaches for the scope of public health, with the adoption of alternative and pragmatic interventions based on human rights, scientific evidence and the reduction of social damages and health by the misuse of illicit drugs.Keywords: illicit drugs, international organizations, prohibitionism, public health, World Health Organization
Procedia PDF Downloads 1561788 PNIPAAm-MAA Nanoparticles as Delivery Vehicles for Curcumin Against MCF-7 Breast Cancer Cells
Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi
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Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery
Procedia PDF Downloads 3741787 The Impact of CYP2C9 Gene Polymorphisms on Warfarin Dosing
Authors: Weaam Aldeeban, Majd Aljamali, Lama A. Youssef
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Background & Objective: Warfarin is considered a problematic drug due to its narrow therapeutic window and wide inter-individual response variations, which are attributed to demographic, environmental, and genetic factors, particularly single nucleotide polymorphism (SNPs) in the genes encoding VKORC1 and CYP2C9 involved in warfarin's mechanism of action and metabolism, respectively. CYP2C9*2rs1799853 and CYP2C9*3rs1057910 alleles are linked to reduced enzyme activity, as carriers of either or both alleles are classified as moderate or slow metabolizers, and therefore exhibit higher sensitivity of warfarin compared with wild type (CYP2C9*1*1). Our study aimed to assess the frequency of *1, *2, and *3 alleles in the CYP2C9 gene in a cohort of Syrian patients receiving a maintenance dose of warfarin for different indications, the impact of genotypes on warfarin dosing, and the frequency of adverse effects (i.e., bleedings). Subjects & Methods: This retrospective cohort study encompassed 94 patients treated with warfarin. Patients’ genotypes were identified by sequencing the polymerase chain reaction (PCR) specific products of the gene encoding CYP2C9, and the effects on warfarin therapeutic outcomes were investigated. Results: Sequencing revealed that 43.6% of the study population has the *2 and/or *3 SNPs. The mean weekly maintenance dose of warfarin was 37.42 ± 15.5 mg for patients with the wild-type allele (CYP2C9*1*1), whereas patients with one or both variants (*2 and/or *3) demanded a significantly lower dose (28.59 ±11.58 mg) of warfarin, (P= 0.015). A higher percentage (40.7%) of patients with allele *2 and/or *3 experienced hemorrhagic accidents compared with only 17.9% of patients with the wild type *1*1, (P = 0.04). Conclusions: Our study proves an association between *2 and *3 genotypes and higher sensitivity to warfarin and a tendency to bleed, which necessitates lowering the dose. These findings emphasize the significance of CYP2C9 genotyping prior to commencing warfarin therapy in order to achieve optimal and faster dose control and to ensure effectiveness and safety.Keywords: warfarin, CYP2C9, polymorphisms, Syrian, hemorrhage
Procedia PDF Downloads 1461786 Associations of Gene Polymorphism of IL-17 a (C737T) with Its Level in Patients with Erysipelas Kazakh Population
Authors: Nazira B. Bekenova, Lydia A. Mukovozova, Andrej M. Grjibovski, Alma Z. Tokayeva, Yerbol M. Smail, Nurlan E. Aukenov
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Erysipelas is an infectious disease with socio-economic significance and prone to prolonged recurrent course (30%). Contribution of genetic factors, in particular the gene polymorphism of cytokines, can be essential in disease etiology and pathogenesis. Interleukin – 17 A are produced by T helpers of 17 type and plays a key role in development of local inflammation process. Local inflammatory process is a dominant in the clinic of erysipelas. Established that the skin and mucosas are primary areas of migration (homing) Th17-cell and their cytokines are stimulate the barrier function of the epithelium. We studied associations between gene polymorphism of IL-17A (C737T) rs 8193036 and IL-17A level in patients with erysipelas Kazakh population. Altogether, 90 cases with erysipelas and 90 healthy controls from an ethnic Kazakh population comprised the sample. Cases were identified at Clinical Infectious Diseases Hospital of Semey (Kazakhstan). The IL-17A (rs8193036) polymorphism was analyzed by a real time polymerase chain reaction. Plasma levels of IL-17 A were assessed by immuneenzyme analysis method using ‘Vector-Best’ test-system (Russia). Differences in levels of IL-17 A between CC, TT, CT groups were studied using Kruskal — Wallis test. Pairwise comparisons were performed using Mann-Whitney tests with Bonferroni correction (New significance level was set to 0.025). We found, that in patients with erysipelas with CC genotype the level of IL-17 A was higher (p= 0, 010) compared to the carriers of CT genotype. When compared the level of IL – 17 A between the patients with TT genotype and patients with CC genotype, also between the patients with CT genotype and patients with TT genotype statistically significant differences are not revealed (p = 0.374 and p = 0.043, respectively). Comparisons of IL-17 A plasma levels between the CC and CT genotypes, between the CC and TT genotypes, and between the TT and CT in healthy patients did not reveal significant differences (p = 0, 291). Therefore, we are determined the associations of gene polymorphism of IL-17 A (C737T) with its level in patients erysipelas carriers CC genotype.Keywords: erysipelas, interleukin – 17 A, Kazakh, polymorphism
Procedia PDF Downloads 4351785 Mathematical Modeling on Capturing of Magnetic Nanoparticles in an Implant Assisted Channel for Magnetic Drug Targeting
Authors: Shashi Sharma, V. K. Katiyar, Uaday Singh
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The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling
Procedia PDF Downloads 4621784 The Bloom of 3D Printing in the Health Care Industry
Authors: Mihika Shivkumar, Krishna Kumar, C. Perisamy
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3D printing is a method of manufacturing wherein materials, such as plastic or metal, are deposited in layers one on top of the other to produce a three dimensional object. 3D printing is most commonly associated with creating engineering prototypes. However, its applications in the field of human health care have been frequently disregarded. Medical applications for 3D printing are expanding rapidly and are envisaged to revolutionize health care. Medical applications for 3D printing, both present and its potential, can be categorized broadly, including: creation of customized prosthetics tissue and organ fabrication; creation of implants, and anatomical models and pharmaceutical research regarding drug dosage forms. This piece breaks down bioprinting in the healthcare sector. It focuses on the better subtle elements of every particular point, including how 3D printing functions in the present, its impediments, and future applications in the health care sector.Keywords: bio-printing, prototype, drug delivery, organ regeneration
Procedia PDF Downloads 2711783 Targeting Calcium Dysregulation for Treatment of Dementia in Alzheimer's Disease
Authors: Huafeng Wei
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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis
Procedia PDF Downloads 1821782 Inclusion Complexes of Some Imidazoline Drugs with Cucurbit[N]Uril (N=7,8): Preparation, Characterization and Theoretical Calculations
Authors: Fakhreldin O. Suliman, Alia H. Al-Battashi
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This work explored the interaction of three different imidazoline drugs, naphazoline nitrate (NPH), oxymetazoline hydrochloride (OXY) and xylometazoline hydrochloride (XYL) with two different synthesized cucurbit[n]urils CB[n], cucurbit[7]uril (CB[7]) and cucuribit[8]uril (CB[8]). Three binary inclusion complexes have been investigated in solution and in the solid state. The solid complexes were obtained by lyophilization, whereas the physical mixtures of guests and hosts at a stoichiometric ratio of 1:1 were obtained for each drug. 1HNMR, electrospray ionization mass spectrometry (ESI-MS), and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry was used to study the complexes prepared in aqueous media. The lyophilized solid complexes were characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). MS, FT-IR and PXRD experimental results established in this work reveal that NPH, OXY and XYL molecules form stable inclusion complexes with the two hosts. The TGA and DSC confirmed the enhancement of the thermal stability of each drug and the production of a thermally stable solid complex. The 1HNMR has shown that the protons of the guests faced shifting in ppm and broadening of their peaks upon the formation of inclusion complexes with the selected CB[n]. The aromatic protons of the guest exhibited the highest changes in the chemical shifts and shape of the NMR peaks, suggesting their inclusion into the cavity of the CB[n]. The diffusion coefficients (D), developed from the diffusion-controlled NMR Spectroscopy (DOSY) measurements, for the complexation of the selected imidazoline drugs with CB[7] and CB[8], were decreased in the presence of hosts compared to the free guests indicating the formation of the guest-host adduct. Furthermore, we conducted molecular dynamic simulations and quantum mechanics calculations on these complexes. The results of the theoretical study corroborate the experimental findings and have also shed light on the mechanism of inclusion of the guests into the two hosts. This study generates initial data for potential drug delivery or drug formulation systems for these three selected imidazoline drug compounds based on their inclusion into the CB[n] cavities.Keywords: cucurbit[n]urils, imidazoline, inclusion complexes, molecular dynamics, DFT calculations, mass spectrometry
Procedia PDF Downloads 681781 Coupled Exciton - Surface Plasmon Polariton Enhanced Photoresponse of Two-Dimensional Hydrogenated Honeycomb Silicon Boride
Authors: Farzaneh Shayeganfar, Ali Ramazani
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Exciton (strong electronic interaction of electron-hole) and hot carriers created by surface plasmon polaritons has been demonstrated in nanoscale optoelectronic devices, enhancing the photoresponse of the system. Herein, we employ a quantum framework to consider coupled exciton- hot carriers effects on photovoltaiv energy distribution, scattering process, polarizability and light emission of 2D-semicnductor. We use density functional theory (DFT) to design computationally a semi-functionalized 2D honeycomb silicon boride (SiB) monolayer with H atoms, suitable for photovoltaics. The dynamical stability, electronic and optical properties of SiB and semi-hydrogenated SiB structures were investigated utilizing the Tran-Blaha modified Becke-Johnson (TB-mBJ) potential. The calculated phonon dispersion shows that while an unhydrogenated SiB monolayer is dynamically unstable, surface semi-hydrogenation improves the stability of the structure and leads to a transition from metallic to semiconducting conductivity with a direct band gap of about 1.57 eV, appropriate for photovoltaic applications. The optical conductivity of this H-SiB structure, determined using the random phase approximation (RPA), shows that light adsorption should begin at the boundary of the visible range of light. Additionally, due to hydrogenation, the reflectivity spectrum declines sharply with respect to the unhydrogenated reflectivity spectrum in the IR and visible ranges of light. The energy band gap remains direct, increasing from 0.9 to 1.8 eV, upon increasing the strain from -6% (compressive) to +6% (tensile). Additionally, compressive and tensile strains lead, respectively, to red and blue shifts of optical the conductivity threshold around the visible range of light. Overall, this study suggests that H-SiB monolayers are suitable as two-dimensional solar cell materials.Keywords: surface plasmon, hot carrier, strain engineering, valley polariton
Procedia PDF Downloads 1091780 Formulation of Famotidine Solid Lipid Nanoparticles (SLN): Preparation, Evaluation and Release Study
Authors: Rachmat Mauludin, Nurmazidah
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Background and purpose: Famotidine is an H2 receptor blocker. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%. To overcome these problems, Solid Lipid Nano particles (SLNs) as alternative delivery systems can be formulated. SLNs is a lipid-based drug delivery technology with 50-1000 nm particle size, where the drug incorporated into the bio compatible lipids and the lipid particles are stabilized using appropriate stabilizers. When the particle size is 200 nm or below, lipid containing famotidine can be absorbed through the lymphatic vessels to the subclavian vein, so first-pass metabolism can be avoided. Method: Famotidine SLNs with various compositions of stabilizer was prepared using a high-speed homogenization and sonication method. Then, the particle size distribution, zeta potential, entrapment efficiency, particle morphology and in vitro release profiles were evaluated. Optimization of sonication time also carried out. Result: Particle size of SLN by Particle Size Analyzer was in range 114.6 up to 455.267 nm. Ultrasonicated SLNs within 5 minutes generated smaller particle size than SLNs which was ultrasonicated for 10 and 15 minutes. Entrapment efficiency of SLNs were 74.17 up to 79.45%. Particle morphology of the SLNs was spherical and distributed individually. Release study of Famotidine revealed that in acid medium, 28.89 up to 80.55% of famotidine could be released after 2 hours. Nevertheless in basic medium, famotidine was released 40.5 up to 86.88% in the same period. Conclusion: The best formula was SLNs which stabilized by 4% Poloxamer 188 and 1 % Span 20, that had particle size 114.6 nm in diameter, 77.14% famotidine entrapped, and the particle morphology was spherical and distributed individually. SLNs with the best drug release profile was SLNs which stabilized by 4% Eudragit L 100-55 and 1% Tween 80 which had released 36.34 % in pH 1.2 solution, and 74.13% in pH 7.4 solution after 2 hours. The optimum sonication time was 5 minutes.Keywords: famotodine, SLN, high speed homogenization, particle size, release study
Procedia PDF Downloads 8601779 Magnetic Navigation of Nanoparticles inside a 3D Carotid Model
Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis
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Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.Keywords: artery, drug, nanoparticles, navigation
Procedia PDF Downloads 1071778 Dimensional-Controlled Functional Gold Nanoparticles and Zinc Oxide Nanorods for Solar Water Splitting
Authors: Kok Hong Tan, Hing Wah Lee, Jhih-Wei Chen, Chang Fu Dee, Chung-Lin Wu, Siang-Piao Chai, Wei Sea Chang
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Semiconductor photocatalyst is known as one of the key roles in developing clean and sustainable energy. However, most of the semiconductor only possesses photoactivity within the UV light region, and hence, decreases the overall photocatalyst efficiency. Generally, the overall effectiveness of the photocatalyst activity is determined by three critical steps: (i) light absorption efficiency and photoexcitation electron-hole pair generation, (ii) separation and migration of charge carriers to the surface of the photocatalyst, and (iii) surface reaction of the carriers with its environment. Much effort has been invested on optimizing hierarchical nanostructures of semiconductors for efficient photoactivity due to the fact that the visible light absorption capability and occurrence of the chemical reactions mostly depend on the dimension of photocatalysts. In this work, we incorporated zero-dimensional (0D) gold nanoparticles (AuNPs) and one dimensional (1D) Zinc Oxide (ZnO) nanorods (NRs) onto strontium titanate (STO) for efficient visible light absorption, charge transfer, and separation. We demonstrate that the electrical and optical properties of the photocatalyst can be tuned by controlling the dimensional structures of AuNPs and ZnO NRs. We found that smaller AuNPs sizes exhibited higher photoactivity because of Fermi level shifting toward the conductive band of STO, STO band gap narrowing and broadening of absorption spectrum to the visible light region. For ZnO NRs, it was found that the average ZnO NRs c-axis length must achieve of certain length to induce multiphoton absorption as a result of light reflection and trapping behavior in the free space between adjacent ZnO NRs hence broadening the absorption spectrum of ZnO from UV to visible light region. This work opens up a new way of broadening the absorption spectrum by incorporating controllable nanostructures of semiconductors, which is important in optimizing the solar water splitting process.Keywords: gold nanoparticles, photoelectrochemical, PEC, semiconductor photocatalyst, zinc oxide nanorods
Procedia PDF Downloads 1611777 Systematic Formulation Development and Evaluation of Self-Nanoemulsifying Systems of Rosuvastatin Employing QbD Approach and Chemometric Techniques
Authors: Sarwar Beg, Gajanand Sharma, O. P. Katare, Bhupinder Singh
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The current studies entail development of self-nano emulsifying drug delivery systems (SNEDDS) of rosuvastatin, employing rational QbD-based approach for enhancing its oral bioavailability. SNEDDS were prepared using the blend of lipidic and emulsifying excipients, i.e., Peceol, Tween 80, and Transcutol HP. The prepared formulations evaluated for in vitro drug release, ex vivo permeation, in situ perfusion studies and in vivo pharmacokinetic studies in rats, which demonstrated 3-4 fold improvement in biopharmaceutical performance of the developed formulations. Cytotoxicity studies using MTT assay and histopathological studies in intestinal cells revealed the lack of cytotoxicity and thereby safety and efficacy of the developed formulations.Keywords: SNEDDS, bioavailability, solubility, Quality by Design (QbD)
Procedia PDF Downloads 5051776 Investigating the Essentiality of Oxazolidinones in Resistance-Proof Drug Combinations in Mycobacterium tuberculosis Selected under in vitro Conditions
Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry
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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.Keywords: oxazolidinones, mutations, resistance, tuberculosis
Procedia PDF Downloads 1621775 Akt: Isoform-Specific Regulation of Cellular Signaling in Cancer
Authors: Bhumika Wadhwa, Fayaz Malik
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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition
Procedia PDF Downloads 2561774 The Impact of Intelligent Control Systems on Biomedical Engineering and Research
Authors: Melkamu Tadesse Getachew
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Intelligent control systems have revolutionized biomedical engineering, advancing research and enhancing medical practice. This review paper examines the impact of intelligent control on various aspects of biomedical engineering. It analyzes how these systems enhance precision and accuracy in biomedical instrumentation, improving diagnostics, monitoring, and treatment. Integration challenges are addressed, and potential solutions are proposed. The paper also investigates the optimization of drug delivery systems through intelligent control. It explores how intelligent systems contribute to precise dosing, targeted drug release, and personalized medicine. Challenges related to controlled drug release and patient variability are discussed, along with potential avenues for overcoming them. The comparison of algorithms used in intelligent control systems in biomedical control is also reviewed. The implications of intelligent control in computational and systems biology are explored, showcasing how these systems enable enhanced analysis and prediction of complex biological processes. Challenges such as interpretability, human-machine interaction, and machine reliability are examined, along with potential solutions. Intelligent control in biomedical engineering also plays a crucial role in risk management during surgical operations. This section demonstrates how intelligent systems improve patient safety and surgical outcomes when integrated into surgical robots, augmented reality, and preoperative planning. The challenges associated with these implementations and potential solutions are discussed in detail. In summary, this review paper comprehensively explores the widespread impact of intelligent control on biomedical engineering, showing the future of human health issues promising. It discusses application areas, challenges, and potential solutions, highlighting the transformative potential of these systems in advancing research and improving medical practice.Keywords: Intelligent control systems, biomedical instrumentation, drug delivery systems, robotic surgical instruments, Computational monitoring and modeling
Procedia PDF Downloads 441773 Pediatric Drug Resistance Tuberculosis Pattern, Side Effect Profile and Treatment Outcome: North India Experience
Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant
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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment
Procedia PDF Downloads 661772 Standardization of a Methodology for Quantification of Antimicrobials Used for the Treatment of Multi-Resistant Bacteria Using Two Types of Biosensors and Production of Anti-Antimicrobial Antibodies
Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.
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Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring
Procedia PDF Downloads 821771 Antidiabetic and Admet Pharmacokinetic Properties of Grewia Lasiocarpa E. Mey. Ex Harv. Stem Bark Extracts: An in Vitro and in Silico Study
Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.
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Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET
Procedia PDF Downloads 1041770 In vitro Disaggregation and Dissolution of Four IR Lamotrigine Solid Dosage Forms
Authors: Ilaria Manca, Ilaria Manca, Francesca Pettinau, Ignazia Mocci, Elisabetta M. Usai, Barbara Pittau
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Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to test and compare various solid forms of immediate release (IR) lamotrigine products, at different strenghts, in order to study their disaggregation and dissolution behavior. IR products are designed to release their active substance promptly after administration. Concentration of hydrochloric acid in gastric juice is about 0.1-0.001 M, so FDA (Food and Drug Administration) recommends, for lamotrigine regular tablets, dissolution tests in HCl 0.1 M.Toinvestigate the pH dependency of drug release in the entire gastrointestinal tract, we worked at two additional media with different pH values (4.5 and 6.8), that reflect conditions in it. To afford acceptable dissolution rates, tablets must disintegrate. Disaggregation of constituent particles increases the surface area and substantially increases the dissolution rate. For this reason availability of an active substance from tablets depends on its ability to disintegrate fast in dissolution media. pH of gastrointestinal fluid affects drug absorption by conditioning its solubility and dissolution, but also tablet disintegration may be influenced by it. To obtain information about the quantitative relationship between different mixture components, Nuclear Magnetic Resonance (NMR) spectroscopy was used. We also investigate tablet hardness. The investigation carried out confirms pH 1.2 as the ideal environment for the immediate availability of the active substance.Keywords: dissolution, disaggregation, Lamotrigine, bioequivalence
Procedia PDF Downloads 4531769 Combating Malaria: A Drug Discovery Approach Using Thiazole Derivatives Against Prolific Parasite Enzyme PfPKG
Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta
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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium
Procedia PDF Downloads 981768 Stability and Rheology of Sodium Diclofenac-Loaded and Unloaded Palm Kernel Oil Esters Nanoemulsion Systems
Authors: Malahat Rezaee, Mahiran Basri, Raja Noor Zaliha Raja Abdul Rahman, Abu Bakar Salleh
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Sodium diclofenac is one of the most commonly used drugs of nonsteroidal anti-inflammatory drugs (NSAIDs). It is especially effective in the controlling the severe conditions of inflammation and pain, musculoskeletal disorders, arthritis, and dysmenorrhea. Formulation as nanoemulsions is one of the nanoscience approaches that have been progressively considered in pharmaceutical science for transdermal delivery of drug. Nanoemulsions are a type of emulsion with particle sizes ranging from 20 nm to 200 nm. An emulsion is formed by the dispersion of one liquid, usually the oil phase in another immiscible liquid, water phase that is stabilized using surfactant. Palm kernel oil esters (PKOEs), in comparison to other oils; contain higher amounts of shorter chain esters, which suitable to be applied in micro and nanoemulsion systems as a carrier for actives, with excellent wetting behavior without the oily feeling. This research was aimed to study the effect of O/S ratio on stability and rheological behavior of sodium diclofenac loaded and unloaded palm kernel oil esters nanoemulsion systems. The effect of different O/S ratio of 0.25, 0.50, 0.75, 1.00 and 1.25 on stability of the drug-loaded and unloaded nanoemulsion formulations was evaluated by centrifugation, freeze-thaw cycle and storage stability tests. Lecithin and cremophor EL were used as surfactant. The stability of the prepared nanoemulsion formulations was assessed based on the change in zeta potential and droplet size as a function of time. Instability mechanisms including coalescence and Ostwald ripening for the nanoemulsion system were discussed. In comparison between drug-loaded and unloaded nanoemulsion formulations, drug-loaded formulations represented smaller particle size and higher stability. In addition, the O/S ratio of 0.5 was found to be the best ratio of oil and surfactant for production of a nanoemulsion with the highest stability. The effect of O/S ratio on rheological properties of drug-loaded and unloaded nanoemulsion systems was studied by plotting the flow curves of shear stress (τ) and viscosity (η) as a function of shear rate (γ). The data were fitted to the Power Law model. The results showed that all nanoemulsion formulations exhibited non-Newtonian flow behaviour by displaying shear thinning behaviour. Viscosity and yield stress were also evaluated. The nanoemulsion formulation with the O/S ratio of 0.5 represented higher viscosity and K values. In addition, the sodium diclofenac loaded formulations had more viscosity and higher yield stress than drug-unloaded formulations.Keywords: nanoemulsions, palm kernel oil esters, sodium diclofenac, rheoligy, stability
Procedia PDF Downloads 4231767 Antihyperlipidemic Activity of Butea Monosperma in Triton WR 1339 Induced Hyperlipidemic Rats
Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar
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The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339
Procedia PDF Downloads 3181766 Development of selective human matrix metalloproteinases-9 (hMMP-9) inhibitors as potent diabetic wound healing agents
Authors: Geetakshi Arora, Danish Malhotra
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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents
Procedia PDF Downloads 1261765 Novel Aminoglycosides to Target Resistant Pathogens
Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya
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Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.Keywords: bacterial resistance, aminoglycosides, screening, drugs
Procedia PDF Downloads 3701764 Increase of the Nanofiber Degradation Rate Using PCL-PEO and PCL-PVP as a Shell in the Electrospun Core-Shell Nanofibers Using the Needleless Blades
Authors: Matej Buzgo, Erico Himawan, Ksenija JašIna, Aiva Simaite
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Electrospinning is a versatile and efficient technology for producing nanofibers for biomedical applications. One of the most common polymers used for the preparation of nanofibers for regenerative medicine and drug delivery applications is polycaprolactone (PCL). PCL is a biocompatible and bioabsorbable material that can be used to stimulate the regeneration of various tissues. It is also a common material used for the development of drug delivery systems by blending the polymer with small active molecules. However, for many drug delivery applications, e.g. cancer immunotherapy, PCL biodegradation rate that may exceed 9 months is too long, and faster nanofiber dissolution is needed. In this paper, we investigate the dissolution and small molecule release rates of PCL blends with two hydrophilic polymers: polyethylene oxide (PEO) or polyvinylpyrrolidone (PVP). We show that adding hydrophilic polymer to the PCL reduces the water contact angle, increases the dissolution rate, and strengthens the interactions between the hydrophilic drug and polymer matrix that further sustain its release. Finally using this method, we were also able to increase the nanofiber degradation rate when PCL-PEO and PCL-PVP were used as a shell in the electrospun core-shell nanofibers and spread up the release of active proteins from their core. Electrospinning can be used for the preparation of the core-shell nanofibers, where active ingredients are encapsulated in the core and their release rate is regulated by the shell. However, such fibers are usually prepared by coaxial electrospinning that is an extremely low-throughput technique. An alternative is emulsion electrospinning that could be upscaled using needleless blades. In this work, we investigate the possibility of using emulsion electrospinning for encapsulation and sustained release of the growth factors for the development of the organotypic skin models. The core-shell nanofibers were prepared using the optimized formulation and the release rate of proteins from the fibers was investigated for 2 weeks – typical cell culture conditions.Keywords: electrospinning, polycaprolactone (PCL), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP)
Procedia PDF Downloads 2731763 Antibacterial Activity of Melaleuca Cajuputi Oil against Resistant Strain Bacteria
Authors: R. M. Noah, N. M. Nasir, M. R. Jais, M. S. S. Wahab, M. H. Abdullah, A. S. S. Raj
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Infectious diseases are getting more difficult to treat due to the resistant strains of bacteria. Current generations of antibiotics are most likely ineffective against multi-drug resistant strains bacteria. Thus, there is an urgent need in search of natural antibiotics in particular from medicinal plants. One of the common medicinal plants, Melaleuca cajuputi, has been reported to possess antibacterial properties. The study was conducted to evaluate and justify the presence of antibacterial activity of Melaleuca cajuputi essential oil (EO) against the multi-drug resistant bacteria. Clinical isolates obtained from the teaching hospital were re-assessed to confirm the exact identity of the bacteria to be tested, namely methicillin-resistant staphylococcus aureus (MRSA), carbapenem-resistant enterobacteriaceae (CRE), and extended-spectrum beta-lactamases producer (ESBLs). A well diffusion method was done to observe the inhibition zones of the essential oil against the bacteria. Minimum inhibitory concentration (MIC) was determined using the microdilution method in 96-well flat microplate. The absorbance was measured using a microplate reader. Minimum bactericidal concentration (MBC) was performed using the agar medium method. The zones of inhibition produced by the EO against MRSA, CRE, and ESBL were comparable to that of generic antibiotics used, gentamicin and augmentin. The MIC and MBC results highlighted the antimicrobial efficacy of the EO. The outcome of this study indicated that the EO of Melaleuca cajuputi had antibacterial activity on the multi-drug resistant bacteria. This finding was eventually substantiated by electron microscopy work.Keywords: melaleuca cajuputi, antibacterial, resistant bacteria, essential oil
Procedia PDF Downloads 1221762 Feasibility Study of Plant Design with Biomass Direct Chemical Looping Combustion for Power Generation
Authors: Reza Tirsadi Librawan, Tara Vergita Rakhma
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The increasing demand for energy and concern of global warming are intertwined issues of critical importance. With the pressing needs of clean, efficient and cost-effective energy conversion processes, an alternative clean energy source is needed. Biomass is one of the preferable options because it is clean and renewable. The efficiency for biomass conversion is constrained by the relatively low energy density and high moisture content from biomass. This study based on bio-based resources presents the Biomass Direct Chemical Looping Combustion Process (BDCLC), an alternative process that has a potential to convert biomass in thermal cracking to produce electricity and CO2. The BDCLC process using iron-based oxygen carriers has been developed as a biomass conversion process with in-situ CO2 capture. The BDCLC system cycles oxygen carriers between two reactor, a reducer reactor and combustor reactor in order to convert coal for electric power generation. The reducer reactor features a unique design: a gas-solid counter-current moving bed configuration to achieve the reduction of Fe2O3 particles to a mixture of Fe and FeO while converting the coal into CO2 and steam. The combustor reactor is a fluidized bed that oxidizes the reduced particles back to Fe2O3 with air. The oxidation of iron is an exothermic reaction and the heat can be recovered for electricity generation. The plant design’s objective is to obtain 5 MW of electricity with the design of the reactor in 900 °C, 2 ATM for the reducer and 1200 °C, 16 ATM for the combustor. We conduct process simulation and analysis to illustrate the individual reactor performance and the overall mass and energy management scheme of BDCLC process that developed by Aspen Plus software. Process simulation is then performed based on the reactor performance data obtained in multistage model.Keywords: biomass, CO2 capture, direct chemical looping combustion, power generation
Procedia PDF Downloads 506