Search results for: drug prediction

Authors: Sijing Xiong, Ran Su, Lit-Hsin Loo, Daniele Zink

Abstract:

The kidney is a major target for toxic effects of drugs, industrial and environmental chemicals and other compounds. Typically, nephrotoxicity is detected late during drug development, and regulatory animal models could not solve this problem. Validated or accepted in silico or in vitro methods for the prediction of nephrotoxicity are not available. We have established the first and currently only pre-validated in vitro models for the accurate prediction of nephrotoxicity in humans and the first predictive platforms based on renal cells derived from human pluripotent stem cells. In order to further improve the efficiency of our predictive models, we recently developed a high content screening (HCS) platform. This platform employed automated imaging in combination with automated quantitative phenotypic profiling and machine learning methods. 129 image-based phenotypic features were analyzed with respect to their predictive performance in combination with 44 compounds with different chemical structures that included drugs, environmental and industrial chemicals and herbal and fungal compounds. The nephrotoxicity of these compounds in humans is well characterized. A combination of chromatin and cytoskeletal features resulted in high predictivity with respect to nephrotoxicity in humans. Test balanced accuracies of 82% or 89% were obtained with human primary or immortalized renal proximal tubular cells, respectively. Furthermore, our results revealed that a DNA damage response is commonly induced by different PTC-toxicants with diverse chemical structures and injury mechanisms. Together, the results show that the automated HCS platform allows efficient and accurate nephrotoxicity prediction for compounds with diverse chemical structures.

Keywords: high content screening, in vitro models, nephrotoxicity, toxicity prediction

Procedia PDF Downloads 287

Authors: Yuxiang Pan, Yong Qiu, Chenlei Gu, Ping Wang

Abstract:

In the past decade, three-dimensional (3D) tumor cell models have attracted increasing interest in the field of drug screening due to their great advantages in simulating more accurately the heterogeneous tumor behavior in vivo. Drug sensitivity testing based on 3D tumor cell models can provide more reliable in vivo efficacy prediction. The gold standard fluorescence staining is hard to achieve the real-time and label-free monitoring of the viability of 3D tumor cell models. In this study, micro-groove impedance sensor (MGIS) was specially developed for dynamic and non-invasive monitoring of 3D cell viability. 3D tumor cells were trapped in the micro-grooves with opposite gold electrodes for the in-situ impedance measurement. The change of live cell number would cause inversely proportional change to the impedance magnitude of the entire cell/matrigel to construct and reflect the proliferation and apoptosis of 3D cells. It was confirmed that 3D cell viability detected by the MGIS platform is highly consistent with the standard live/dead staining. Furthermore, the accuracy of MGIS platform was demonstrated quantitatively using 3D lung cancer model and sophisticated drug sensitivity testing. In addition, the parameters of micro-groove impedance chip processing and measurement experiments were optimized in details. The results demonstrated that the MGIS and 3D cell-based biosensor and would be a promising platform to improve the efficiency and accuracy of cell-based anti-cancer drug screening in vitro.

Keywords: micro-groove impedance sensor, 3D cell-based biosensors, 3D cell viability, micro-electromechanical systems

Procedia PDF Downloads 107

Authors: Wen Huei Chou, Te Lung Pan, Tsu Wen Yeh

Abstract:

New media have recently received increasing attention as a new communication form. The COVID-19 outbreak has pushed people’s lifestyles into the digital age, and the drug market has infiltrated formal e-commerce platforms. The self-media boom has fostered growth in online drug myths. To set the record straight, it is imperative to develop new media-based interventions. However, the usefulness of new media on this issue has not yet been fully examined. This study selected 13 articles on the development of new media-based interventions to prevent drug abuse from Airiti Library and Pub-Med as of October 3, 2021. The key conclusions are that (1) new media have a significantly positive influence on skills, self-efficacy, and behavior; (2) most interventions package traditional course learning into new media formats; and (3) new media can create a covert, interactive environment that cannot be replicated offline, which may merit attention in future research.

Keywords: drug abuse, interventions, new media, systematic review

Procedia PDF Downloads 117

Authors: Sarah E. Casey

Abstract:

Epilepsy is the most common neurological disorder in children and approximately one-third of children with epilepsy have seizures that are uncontrolled on anticonvulsants alone. Cannabidiol is shown to be an effective treatment at reducing the amount of breakthrough seizures experienced by children with drug resistant epilepsy. Improvements in quality of life and overall condition were noted during cannabidiol treatment. Adverse side effects were experienced and were generally mild to moderate in nature. Additional double-blind, controlled studies with a more diverse sample population and standardized dosing are needed to ensure the efficacy and safety of cannabidiol use in children with drug resistant epilepsy.

Keywords: cannabis, drug resistant epilepsy, children, epilepsy

Procedia PDF Downloads 191

Authors: Li-Yu Lee, Yu-Shuan Chen, Jun Sheng Wang, I-Ming Chu

Abstract:

Microneedle patch is a painless transdermal drug delivery method, It could solve some problems in traditional drug delivery such as digestive system causing drug metabolism and subcutaneous injection causing some side effects. Coating drug on or loading drug in microneedle can carry active ingredient through stratum corneum, also can control dose well when microneedle patch apply on localized topical area. We used hyaluronic acid to fabricate dissolvable microneedle patch and encapsulated minoxidil into microneedles. Minoxdil is a drug for exterior use that can be used to treat Androgenetic alopecia, but related commercial products have some shortcomings, for example, propylene glycol which is used to soften stratum corneum cause skin allergic reaction, comparing chemical promotion, microneedle patch provide physical way to make drugs through nature barrier of skin. In this research, we designed a two-step process to fabricate microneedle patch, that can effectively reduce drug waste, and gentle production process could maintain drug activity well. We also do in vitro test on cadaver to make sure patch has enough mechanical strength to penetrate stratum corneum. In the release test and animal test, we found microneedle patch has higher delivery efficiency than tradition way. In this study, we may determine that germinal MNs patch is a potential commodity.

Keywords: dissolving microneedles, androgenetic alopecia, minoxidil, transdermal drug delivery

Procedia PDF Downloads 249

Authors: Surajj Sarode, G. P. Vadnere, G. Vidya Sagar

Abstract:

Compression coating is one of the strategies for delivering drug to the colon based on Gastrointestinal PH and transit time concept. The main aim of these formulations to develop rapidly disintegrating Zaltoprofen core tablets compression-coated with a mixture of time-dependent hydrophilic swellable polymer HPMC K 15 and PH responsive soluble polymer Chitosan and Guar gum in different ratios. The effect of the proportion of HPMC, Chitosan and Guar gum in the coat on premature drug release in upper part (Stomach and small intestine) of GIT and the amount of drug release in colon target area was studied. The formulations are carried out by using Direct Compression method. Sodium starch Glycolate used for rapid disintegration. FTIR used for Drug-Polymer Interaction studies. The prepared tablets were evaluated for hardness, thickness, friability, in-vitro disintegration, in-Vitro dissolution and in-vitro kinetic study.

Keywords: zaltoprofen, chitosan, formulation, drug delivery

Procedia PDF Downloads 424

Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

Abstract:

Drug dosage forms consisting of multi-unit particle systems (MUPS) for modified drug release provide a promising route for overcoming the limitation of conventional tablets. Despite the conventional use of pellets as units for MUP systems, 3D printed polymers loaded with a drug seem like an interesting candidate due to the control over dosing that 3D printing mechanisms offer. Further, 3D printing offers high flexibility and control over the spatial structuring of a printed object. The final MUPS tablets include PVP and HPC as granulate with other excipients, enabling the compaction process of this mixture with 3D printed inclusions, also termed minitablets. In this study, we have developed the multi-step production process for MUPS tablets, including the 3D printing technology. The MUPS tablets with incorporated 3D printed minitablets are a complex system for drug delivery, providing modified drug release. Such structured tablets promise to reduce drug fluctuations in blood, risk of local toxicity, and increase bioavailability, resulting in an improved therapeutic effect due to the fast transfer into the small intestine, where particles are evenly distributed. Drug loaded 3D printed minitablets were compacted into the excipient mixture, influencing drug release through varying parameters, such as minitablets size, matrix composition, and compaction parameters. Further, the mechanical properties and morphology of the final MUPS tablets were analyzed as many properties, such as plasticity and elasticity, can significantly influence the dissolution profile of the drug.

Keywords: 3D printing, dissolution kinetics, drug delivery, hot-melt extrusion

Procedia PDF Downloads 67

Authors: Krutika K. Sawant, Anil Solanki

Abstract:

The present study deals with the preparation and optimization of ethyl cellulose-containing disopyramide phosphate loaded microspheres using solvent evaporation technique. A central composite design consisting of a two-level full factorial design superimposed on a star design was employed for optimizing the preparation microspheres. The drug:polymer ratio (X1) and speed of the stirrer (X2) were chosen as the independent variables. The cumulative release of the drug at a different time (2, 6, 10, 14, and 18 hr) was selected as the dependent variable. An optimum polynomial equation was generated for the prediction of the response variable at time 10 hr. Based on the results of multiple linear regression analysis and F statistics, it was concluded that sustained action can be obtained when X1 and X2 are kept at high levels. The X1X2 interaction was found to be statistically significant. The drug release pattern fitted the Higuchi model well. The data of a selected batch were subjected to an optimization study using Box-Behnken design, and an optimal formulation was fabricated. Good agreement was observed between the predicted and the observed dissolution profiles of the optimal formulation.

Keywords: disopyramide phosphate, ethyl cellulose, microspheres, controlled release, Box-Behnken design, factorial design

Procedia PDF Downloads 430

Authors: Nungki Rositaningsih, Emil Budianto

Abstract:

Starch has been widely used as an encapsulation material for drug delivery system. However, starch hydrogel is very easily degraded during metabolism in human stomach. Modification of this material is needed to improve the encapsulation process in drug delivery system, especially for gastrointestinal drug. In this research, three modified starch-based hydrogels are synthesized i.e. Crosslinked starch hydrogel, Semi- and Full- Interpenetrating Polymer Network (IPN) starch hydrogel using Poly(N-Vinyl-Pyrrolidone). Non-modified starch hydrogel was also synthesized as a control. All of those samples were compared as biomaterials, floating drug delivery, and their ability in loading drug test. Biomaterial characterizations were swelling test, stereomicroscopy observation, Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FTIR). Buoyancy test and stereomicroscopy scanning were done for floating drug delivery characterizations. Lastly, amoxicillin was used as test drug, and characterized with UV-Vis spectroscopy for loading drug observation. Preliminary observation showed that Full-IPN has the most dense and elastic texture, followed by Semi-IPN, Crosslinked, and Non-modified in the last position. Semi-IPN and Crosslinked starch hydrogel have the most ideal properties and will not be degraded easily during metabolism. Therefore, both hydrogels could be considered as promising candidates for encapsulation material. Further analysis and issues will be discussed in the paper.

Keywords: biomaterial, drug delivery system, interpenetrating polymer network, poly(N-vinyl-pyrrolidone), starch hydrogel

Procedia PDF Downloads 223

Authors: Asif Khaliq, Sayeeda A. Sayed

Abstract:

The drug information centers provide drug related information to the requesters that include physicians, pharmacist, nurses and other allied health care professionals. The International Pharmacist Federation (FIP) describes basic functions of a drug and poison information centers as drug evaluation, therapeutic counseling, pharmaceutical advice, research, pharmaco-vigilence and toxicology. Continuous advancement in the field of medicine has expanded the medical literature, which has increased demand of a drug and poison information center for the guidance, support and facilitation of physicians. The objective of the study is to determine the need of drug and poison information centers in public and private hospitals of Karachi, Pakistan. A cross sectional study was conducted during July 2013 to April 2014 using a self-administered, multi-itemed questionnaire. Non Probability Convenient sampling was used to select the study participants. A total of 307 physicians from public and private hospitals of Karachi participated in the study. The need for 24/7 Drug and poison information center was highlighted by 92 % of physicians and 67% physicians suggested opening a drug information center at the hospital. It was reported that 70% physicians take at least 15 minutes for searching the information about the drug while managing a case. Regarding the poisoning case management, 52% physicians complaint about the unavailability of medicines in hospitals; and mentioned the importance of medicines for safe and timely management of patients. Although 73% physicians attended continued medical education (CME) sessions, 92 % physicians insisted on the need of 24/7 Drug and poison information center. The scarcity of organized channel for obtaining the information about drug and poisons is one of the most crucial problems for healthcare workers in Pakistan. The drug and poison information center is an advisory body that assists health care professional and patients in provision of appropriate drug and hazardous substance information. Drug and poison information center is one of the integral needs for running an effective health care system. Provision of a 24 /7 drug information centers with specialized staff offer multiple benefits to the hospitals while reducing treatment delays, addressing awareness gaps of all stakeholders and ensuring provision of quality health care.

Keywords: drug and poison information centers, Pakistan, physicians, public and private hospitals

Procedia PDF Downloads 301

Authors: Mustafa Malki, Ewan R. Pearson

Abstract:

Tools utilized by health care practitioners to flag potential adverse drug reactions secondary to drug-drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To our best knowledge, there have been limited published studies on the impact of genetic variation on drug-drug interactions. Therefore, our aim in this project is the discovery of previously unrecognized, clinically important drug-drug-gene interactions (DDGIs) within the list of most commonly used drug combinations in the UK. The UKBB database was utilized to identify the top most frequently prescribed drug combinations in the UK with at least one route of interaction (over than 200 combinations were identified). We have recognised 37 common and unique interacting genes considering all of our drug combinations. Out of around 600 potential genetic variants found in these 37 genes, 100 variants have met the selection criteria (common variant with minor allele frequency ≥ 5%, independence, and has passed HWE test). The association between these variants and the use of each of our top drug combinations has been tested with a case-control analysis under the log-additive model. As the data is cross-sectional, drug intolerance has been identified from the genotype distribution as presented by the lower percentage of patients carrying the risky allele and on the drug combination compared to those free of these risk factors and vice versa with drug tolerance. In GoDARTs database, the same list of common drug combinations identified by the UKBB was utilized here with the same list of candidate genetic variants but with the addition of 14 new SNPs so that we have a total of 114 variants which have met the selection criteria in GoDARTs. From the list of the top 200 drug combinations, we have selected 28 combinations where the two drugs in each combination are known to be used chronically. For each of our 28 combinations, three drug response phenotypes have been identified (drug stop/switch, dose decrease, or dose increase of any of the two drugs during their interaction). The association between each of the three phenotypes belonging to each of our 28 drug combinations has been tested against our 114 candidate genetic variants. The results show replication of four findings between both databases : (1) Omeprazole +Amitriptyline +rs2246709 (A > G) variant in CYP3A4 gene (p-values and ORs with the UKBB and GoDARTs respectively = 0.048,0.037,0.92,and 0.52 (dose increase phenotype)) (2) Simvastatin + Ranitidine + rs9332197 (T > C) variant in CYP2C9 gene (0.024,0.032,0.81, and 5.75 (drug stop/switch phenotype)) (3) Atorvastatin + Doxazosin + rs9282564 (T > C) variant in ABCB1 gene (0.0015,0.0095,1.58,and 3.14 (drug stop/switch phenotype)) (4) Simvastatin + Nifedipine + rs2257401 (C > G) variant in CYP3A7 gene (0.025,0.019,0.77,and 0.30 (drug stop/switch phenotype)). In addition, some other non-replicated, but interesting, significant findings were detected. Our work also provides a great source of information for researchers interested in DD, DG, or DDG interactions studies as it has highlighted the top common drug combinations in the UK with recognizing 114 significant genetic variants related to drugs' pharmacokinetic.

Keywords: adverse drug reactions, common drug combinations, drug-drug-gene interactions, pharmacogenomics

Procedia PDF Downloads 121

Authors: Kamel Abd Elaziz Mohamed

Abstract:

Introduction: Drug related problems (DRPs) are of major concern, affecting patients of both sex. They impose considerable economic burden on the society and the health-care systems. Aim of the work: The aim of this work was to identify and categorize drug-related problems in adult intensive care unit. Patients and methods: The study was a prospective, observational study as eighty six patients were included. They were consecutively admitted to ICU through the emergency room or transferred from the general ward due to DRPs. Parameters included in the study as length of stay in ICU, need for cardiovascular support or mechanical ventilation, dialysis, as well as APACHE II score were recorded. Results: Drug related problems represent 3.6% of the total ICU admission. The median (range) of APACHE II score for 86 patients included in the study was 17 (10-23), and length of ICU stay was 2.4 (1.5-4.2) days. In 45 patients (52%), DRP was drug over dose (group 1), while other DRP was present in the other 41 patients (48%, group 11). Patients in group 1 were older (39 years versus 32 years in group 11), with significant impaired renal function. The need of inotropic drugs and mechanical ventilation as well as the length of stay (LOS) in ICU was significantly higher in group 1. There were no significant difference in GCS between both groups, however APACHE II score was significantly higher in group 1. Only four patients (4.6%) were admitted by suicidal attempt as well as three patients (3.4%) due to trauma drug-related admissions, all were in (group 1). Nineteen percent of the patients had drug related problem due to hypoglycaemic medication followed by tranquilizer (15%). Adverse drug effect followed by failure to receive medication were the most causes of drug problem in (group11).The total mortality rate was 4.6%, all of them were eventually non preventable. Conclusion: The critically ill patients admitted due to drug related problems represented a small proportion (3.6%) of admissions to the ICU. Hypoglycaemic medication was one of the most common causes of admission by drug related problems.

Keywords: drug related problems, ICU, cost, safety

Procedia PDF Downloads 314

Authors: Zohreh Bayat, Dariush Minai-Tehrani

Abstract:

Lipases constitute one of the most important groups of industrial enzymes that catalyze the hydrolysis of triacylglycerol to glycerol and fatty acids. Muscarinic antagonist relieves smooth muscle spasm of the gastrointestinal tract and effect on the cardiovascular system. In this research, the effect of a muscarinic antagonist on the lipase activity of Pseudomonas aeruginosa was studied. Lineweaver–Burk plot showed that the drug inhibited the enzyme by competitive inhibition. The IC50 value (60 uM) and Ki (30 uM) of the drug revealed the drug bound to the enzyme with high affinity. Determination of enzyme activity in various pH and temperature showed that the maximum activity of lipase was at pH 8 and 60°C both in presence and absence of the drug.

Keywords: bacteria, inhibition, kinetics, lipase

Procedia PDF Downloads 423

Authors: Ephrem Mebratu Dagnew, Mohammed Biset Ayalew, Gizework Alemnew Mekonnen, Alehegn Bishaw Geremew, Ousman Abubeker Abdela

Abstract:

Objective: To assess the prevalence of drug-related problems and associated factors among adult psychiatric inpatients. Method: Hospital-based multicenter cross-sectional observational study was conducted from April to July 2021 at five randomly selected hospitals in North-west Ethiopia. A total of 325 consecutively sampled patients participated in the study. Clinical pharmacists assessed the DRPs based on clinical judgment supported by updated evidence-based diseases guidelines. A Medscape drug-interactions checker was used to check drug-drug interactions. The results were summarized using descriptive statistics, including frequency, mean, and standard deviation. Odds ratio (OR) with 95% confidence interval were also computed for each variable for the corresponding P-value. The value of P ≤ 0.05 was considered statistically significant. Result : From the total of 325 study participants, more than half of them (52.9%) were females and the mean age ± (standard deviation) was 30.8±11.3 years. At least one drug-related problem was recorded from 60.9%, 95% CI (55.7-65.8) of study participants with a mean of 0.6±0.49 per patient. Need additional drug therapy was the most common DRP (22.8%), followed by non-adherence to medicine (20.6%) and adverse drug reactions (11%), respectively. Factors independently associated with drug-related problems were rural residence [AOR=1.96,95%CI:1.01-2.84, P-value=0.046], self-employed [AOR=6.0 ,95% CI: 1.0-36.9, P-value=0.035] and alcohol drinkers [AOR=6.40,95%CI:1.12-37.5, p-value=0.034]. Conclusion: The prevalence of drug-related problems among adult psychiatric patients admitted to psychiatric wards was high. Healthcare providers give more attention to tackling these problems. Being a rural residence, self-employed, and Alcohol drinkers were associated with drug-related problems.

Keywords: psychiatric patients, drug-relatedproblems, multicenter, Ethiopia

Procedia PDF Downloads 118

Authors: Judith Stein, Elfriede Friedmann

Abstract:

The injection of a drug into the vitreous body for the treatment of retinal diseases like wet aged-related macular degeneration (AMD) is the most common medical intervention worldwide. We develop mathematical models for drug transport in the vitreous body of a human eye to analyse the impact of different rheological models of the vitreous on drug distribution. In addition to the convection diffusion equation characterizing the drug spreading, we use porous media modeling for the healthy vitreous with a dense collagen network and include the steady permeating flow of the aqueous humor described by Darcy's law driven by a pressure drop. Additionally, the vitreous body in a healthy human eye behaves like a viscoelastic gel through the collagen fibers suspended in the network of hyaluronic acid and acts as a drug depot for the treatment of retinal diseases. In a completely liquefied vitreous, we couple the drug diffusion with the classical Navier-Stokes flow equations. We prove the global existence and uniqueness of the weak solution of the developed initial-boundary value problem describing the drug distribution in the healthy vitreous considering the permeating aqueous humor flow in the realistic three-dimensional setting. In particular, for the drug diffusion equation, results from the literature are extended from homogeneous Dirichlet boundary conditions to our mixed boundary conditions that describe the eye with the Galerkin's method using Cauchy-Schwarz inequality and trace theorem. Because there is only a small effective drug concentration range and higher concentrations may be toxic, the ability to model the drug transport could improve the therapy by considering patient individual differences and give a better understanding of the physiological and pathological processes in the vitreous.

Keywords: coupled PDE systems, drug diffusion, mixed boundary conditions, vitreous body

Procedia PDF Downloads 104

Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

Abstract:

Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

Procedia PDF Downloads 290

Authors: Suyeon Kwon, Ik Joong Kang, Wang Bingjie

Abstract:

Chitosan is a polymer that is usually produced from N-deacetylation of chitin. It is emerging as a promising biocompatible polymer that is harmless to humans. For the reason that many merits such as good adsorptive, biodegradability, many researches are being done on the chitosan for drug delivery system. Drug delivery system (DDS) has been developed for the control of drug. It makes the drug can be delivered effectively and safely into the targeted human body. The drug used in this work is hydrocortisone that is used in Rheumatism, skin diseases, allergy treatment. In this work, hydrocortisone was used to make allergic rhinitis medicine. Our study focuses on drug delivery through the nasal mucosa by using hydrocortisone impregnated chitosan nanoshells. This study has performed an investigation in order to establish the optimal conditions, changing concentration, quantity of hydrocortisone. DLS, SEM, TEM, FT-IR, UV spectrum were used to analyze the manufactured chitosan-hydrocortisone silver nanoshell and silver nanoshell, whose function as drug carriers. This study has performed an investigation on new drug carriers and delivery routes for hydrocortisone. Various methods of manufacturing chitosan-hydrocortisone nanoshells were attempted in order to establish the optimal condition. As a result, the average size of chitosan-hydrocortisone silver nanoshell is about 80 nm. So, chitosan-hydrocortisone silver nanoshell is suitable as drug carriers because optimal size of drug carrier in human body is less than 120 nm. UV spectrum of Chitosan-hydrocortisone silver nanoshell shows the characteristic peak of silver nanoshell at 420 nm. Likewise, the average size of chitosan-hydrocortisone silver nanoshell is about 100nm. It is also suitable for drug carrier in human body. Also, multi-layered silver shell over chitosan nanoshells induced the red-shift of absorption peak and increased the intensity of absorption peak. The resultant chitosan–silver nanocomposites (or nanoshells) exhibited the absorption peak around 430nm attributed to silvershell formation. i.e. the absorption peak was red-shifted by ca. 40 nm in reference to 390 nm of silver nanoshells.

Keywords: chitosan, drug delivery, hydrocortisone, rhinitis, nanoshell

Procedia PDF Downloads 238

Authors: Zhou Yang, Heli Sun, Jianbin Huang, Jizhong Zhao, Shaojie Qiao

Abstract:

Traffic prediction is essential in a multitude of ways in modern urban life. The researchers of earlier work in this domain carry out the investigation chiefly with two major focuses: (1) the accurate forecast of future values in multiple time series and (2) knowledge extraction from spatial-temporal correlations. However, two key considerations for traffic prediction are often missed: the completeness of raw data and the full context of the prediction timestamp. Concentrating on the two drawbacks of earlier work, we devise an approach that can address these issues in a two-phase framework. First, we utilize the raw trajectories to a greater extent through building a VLA table and data compression. We obtain the intra-trajectory features with graph-based encoding and the intertrajectory ones with a grid-based model and the technique of back projection that restore their surrounding high-resolution spatial-temporal environment. To the best of our knowledge, we are the first to study direct feature extraction from raw trajectories for traffic prediction and attempt the use of raw data with the least degree of reduction. In the prediction phase, we provide a broader context for the prediction timestamp by taking into account the information that are around it in the training dataset. Extensive experiments on several well-known datasets have verified the effectiveness of our solution that combines the strength of raw trajectory data and prediction context. In terms of performance, our approach surpasses several state-of-the-art methods for traffic prediction.

Keywords: traffic prediction, raw data utilization, context building, data reduction

Procedia PDF Downloads 98

Authors: Morteza Keshavarz

Abstract:

In this work, using density functional theory (DFT) thermodynamic stability and quantum molecular descriptors of cyclophoshphamide (an anticancer drug)-functionalized zigzag (8,0) CNT, armchair (4,4) CNT and nanocone complexes in water, for two attachment namely the sidewall and tip, is considered. Calculation of the total electronic energy (Et) and binding energy (Eb) of all complexes indicates that the most thermodynamic stability belongs to the sidewall-attachment of cyclophosphamide into functional nanocone. On the other hand, results from chemical hardness show that drug-functionalized zigzag (8,0) and armchair (4,4) complexes in the tip-attachment configuration possess the smallest and greatest chemical hardness, respectively. By computing the solvation energy, it is found that the solution of the drug and all complexes are spontaneous in water. Furthermore, chirality, type of nanovector (nanotube or nanocone), or attachment configuration have no effects on solvation energy of complexes.

Keywords: carbon nanotube, drug delivery, cyclophosphamide drug, density functional theory (DFT)

Procedia PDF Downloads 332

Authors: Mohammad Zavid Parvez, Manoranjan Paul

Abstract:

A seizure prediction method is proposed by extracting global features using phase correlation between adjacent epochs for detecting relative changes and local features using fluctuation/deviation within an epoch for determining fine changes of different EEG signals. A classifier and a regularization technique are applied for the reduction of false alarms and improvement of the overall prediction accuracy. The experiments show that the proposed method outperforms the state-of-the-art methods and provides high prediction accuracy (i.e., 97.70%) with low false alarm using EEG signals in different brain locations from a benchmark data set.

Keywords: Epilepsy, seizure, phase correlation, fluctuation, deviation.

Procedia PDF Downloads 442

Authors: S. Ataei, F. Sarrafzadeh Javadi, K. Gilani, E. Moazeni

Abstract:

Drug delivery systems using colloidal particulate carriers such as niosomes or liposomes have distinct advantages over conventional dosage forms because the particles can act as drug-containing reservoirs. These carriers play an increasingly important role in drug delivery. Niosomes are vesicular delivery systems which result from the self-assembly of hydrated surfactant. Niosomes are now widely studied as an attractive to liposomes because they alleviate the disadvantages associated with liposomes, such as chemical instability, variable purity of phospholipids and high cost. The encapsulation of drugs in niosomes can decrease drug toxicity, increase the stability of drug and increase the penetrability of drug in the location of application, and may reduce the dose and systemic side effect. Nowadays, Niosomes are used by the pharmaceutical industry in manufacturing skin medications, eye medication, in cosmetic formulas and these vesicular systems can be used to deliver aspiratory drugs. One way of improving dispersion in the water phase and solubility of the hydrophobic drug is to formulate in into niosomes. Itraconazole (ITZ) was chosen as a model hydrophobic drug. This drug is water insoluble (solubility ~ 1 ng/ml at neutral pH), is a broad-spectrum triazole antifungal agent and is used to treat various fungal disease. This study aims to investigate the capability of forming itraconazole niosomes with Spans, Tweens, Brijs as non-ionic surfactants. To this end, various formulations of niosomes have been studied with regard to parameters such as the degree of containment and particle size.

Keywords: physicochemical, non-ionic surfactant vesicles, itraconazole

Procedia PDF Downloads 436

Authors: Jeena R. S., Sukesh Kumar A.

Abstract:

Stroke is one of the major reasons of adult disability and morbidity in many of the developing countries like India. Early diagnosis of stroke is essential for timely prevention and cure. Various conventional statistical methods and computational intelligent models have been developed for predicting the risk and outcome of stroke. This research work focuses on a multilevel approach for predicting the occurrence of stroke based on various risk factors and invasive techniques like retinal imaging. This risk prediction model can aid in clinical decision making and help patients to have an improved and reliable risk prediction.

Keywords: prediction, retinal imaging, risk factors, stroke

Procedia PDF Downloads 272

Authors: Sunit Kumar Sahoo, Prakash Chandra Senapati

Abstract:

The main drawback to design drug delivery systems with BCS class II drugs is their low bioavailabilty due to their inherent low permeability characteristics. So the present investigation aspire to develop a self-nanoemulsifying drug delivery system (SNEDDS) of BCS class II anti HIV drug efavirenz (EFZ) using mixtures of non-ionic surfactant mixtures with the main objective to improve the oral bioavailability of said drug. Results obtained from solubility studies of EFZ in various expients utilized for construction of the pseudo ternary phase diagram containing surfactant mixtures. Surfactants in 1:1 combination are used with different co-surfactants in different ratio to delineate the area of monophasic region of the pseudo ternary phase diagram. The formulations which offered positive results in different thermodynamic stability studies were considered for percentage transmittance and turbidity analysis. The various characterization studies like the TEM analysis of post diluted SNEDDS formulations r confirmed the size in nanometric range (below 50 nm) and FT-IR studies confirmed the intactness of the drug the in the preconcentrate. The in vitro dissolution profile of SNEDDS showed that 80% drug was released within 30 min in case of optimized SNEDDS while it was approximately 18.3 % in the case of plain drug powder.. The Pharmacokinetic study using rat model revealed a 2.63 fold increase in AUC (0-∞) in comparison to plain EFZ suspension. The designed delivery system illustrated the confidence in creating a formulation of EFZ with enhanced bioavailability for better HIV treatment.

Keywords: efavirenz, self-nanoemulsifying, surfactant mixture, bioavailability

Procedia PDF Downloads 329

Authors: Mostafa Sefidgar, Kaamran Raahemifar, Hossein Bazmara, Madjid Soltani

Abstract:

The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, and drug extravasation from microvascular. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to show how capillary network structure induced by tumor affects drug delivery. The effect of heterogeneous capillary network induced by tumor on interstitial fluid flow and drug delivery is investigated by this multi scale method. The sprouting angiogenesis model is used for generating capillary network induced by tumor. Fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network and fluid flow in normal and tumor tissues. The Starling’s law is used for closing this system of equations and coupling the intravascular and extravascular flows. Finally, convection-diffusion-reaction equation is used to simulate drug delivery. The dynamic approach which changes the capillary network structure based on signals sent by hemodynamic and metabolic stimuli is used in this study for more realistic assumption. The study indicates that drug delivery to solid tumors depends on the tumor induced capillary network structure. The dynamic approach generates the irregular capillary network around the tumor and predicts a higher interstitial pressure in the tumor region. This elevated interstitial pressure with irregular capillary network leads to a heterogeneous distribution of drug in the tumor region similar to in vivo observations. The investigation indicates that the drug transport properties have a significant role against the physiological barrier of drug delivery to a solid tumor.

Keywords: solid tumor, physiological barriers to drug delivery, angiogenesis, microvascular network, solute transport

Procedia PDF Downloads 284

Authors: Adinarayana Gorajana, Venkata Srikanth Meka, Sanjay Garg, Lim Sue May

Abstract:

This study was designed to evaluate and enhance the solubility of poorly soluble drug, docetaxel through solid dispersion (SD) technique prepared using freeze drying method. Docetaxel solid dispersions were formulated with Soluplus in different weight ratios. Freeze drying method was used to prepare the solid dispersions. Solubility of the solid dispersions were evaluated respectively and the optimized of drug-solubilizers ratio systems were characterized with different analytical methods like Differential scanning calorimeter (DSC), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) to confirm the formation of complexes between drug and solubilizers. The solubility data revealed an overall improvement in solubility for all SD formulations. The ternary combination 1:5:2 gave the highest increase in solubility that is approximately 3 folds from the pure drug, suggesting the optimum drug-solubilizers ratio system. This data corresponds with the DSC and SEM analyses, which demonstrates presence of drug in amorphous state and the dispersion in the solubilizers in molecular level. The solubility of the poorly soluble drug, docetaxel was enhanced through preparation of solid dispersion formulations employing freeze drying method. Solid dispersion with multiple carrier system shows better solubility compared to single carrier system.

Keywords: docetaxel, freeze drying, soluplus, solid dispersion technique

Procedia PDF Downloads 480

Authors: Muhammad Awais Shafique, Eiji Hato, Hideki Yaginuma

Abstract:

Recently GPS data is used in a lot of studies to automatically reconstruct travel patterns for trip survey. The aim is to minimize the use of questionnaire surveys and travel diaries so as to reduce their negative effects. In this paper data acquired from GPS and accelerometer embedded in smart phones is utilized to predict the mode of transportation used by the phone carrier. For prediction, Support Vector Machine (SVM) and Adaptive boosting (AdaBoost) are employed. Moreover a unique method to improve the prediction results from these algorithms is also proposed. Results suggest that the prediction accuracy of AdaBoost after improvement is relatively better than the rest.

Keywords: accelerometer, AdaBoost, GPS, mode prediction, support vector machine

Procedia PDF Downloads 327

Authors: Lakshmi Sirisha Kotikalapudi

Abstract:

Atenolol, the widely used antihypertensive drug is ionisable and degrades in the acidic environment of the GIT lessening the bioavailability. Transdermal route may be selected as an alternative to enhance the bioavailability. Half-life of the drug is 6-7 hours suggesting the requirement of prolonged release of the drug. The present work of transdermal niosomal gel aims to extend release of the drug and increase the bioavailability. Ethanol injection method was used for the preparation of niosomes using span-60 and cholesterol at different molar ratios following central composite design. The prepared niosomes were characterized for size, zeta-potential, entrapment efficiency, drug content and in-vitro drug release. Optimized formulation was selected by statistically analyzing the results obtained using the software Stat-Ease Design Expert. The optimized formulation also showed high drug retention inside the vesicles over a period of three months at a temperature of 4 °C indicating stability. Niosomes separated as a pellet were dried and incorporated into the hydrogel prepared using chitosan a natural polymer as a gelling agent. The effect of various chemical permeation enhancers was also studied over the gel formulations. The prepared formulations were characterized for viscosity, pH, drug release using Franz diffusion cells, and skin irritation test as well as in-vivo pharmacological activities. Atenolol niosomal gel preparations showed the prolonged release of the drug and pronounced antihypertensive activity indicating the suitability of niosomal gel for topical and systemic delivery of atenolol.

Keywords: atenolol, chitosan, niosomes, transdermal

Procedia PDF Downloads 248

Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah

Abstract:

Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.

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

Procedia PDF Downloads 263

Authors: Asho Ali

Abstract:

Tuberculosis is a disease of grave concern which infects one-third of the global population. The high incidence of tuberculosis is further compounded by the increasing emergence of drug resistant strains including multi drug resistant (MDR). Global incidence MDR-TB is ~4%. Molecular epidemiological studies, based on the assumption that patients infected with clustered strains are epidemiologically linked, have helped understand the transmission dynamics of disease. It has also helped to investigate the basis of variation in Mycobacterium tuberculosis (MTB) strains, differences in transmission, and severity of disease or drug resistance mechanisms from across the globe. This has helped in developing strategies for the treatment and prevention of the disease including MDR.

Keywords: Mycobcaterium tuberculosis, molecular epidemiology, drug resistance, disease

Procedia PDF Downloads 369

Authors: Carl van Walraven, Meltem Tuna

Abstract:

Background: Network meta-analysis (NMA) quantifies the relative efficacy of 3 or more interventions from studies containing a subgroup of interventions. This study applied the analytical approach of NMA to quantify the relative accuracy of prediction models with distinct inclusion criteria that are evaluated on a common population (‘concurrent external validation’). Methods: We simulated binary events in 5000 patients using a known risk function. We biased the risk function and modified its precision by pre-specified amounts to create 15 prediction models with varying accuracy and distinct patient applicability. Prediction model accuracy was measured using the Scaled Brier Score (SBS). Overall prediction model accuracy was measured using fixed-effects methods that accounted for model applicability patterns. Prediction model accuracy was summarized as the Network Relative Model Accuracy (NeRMA) Score which ranges from -∞ through 0 (accuracy of random guessing) to 1 (accuracy of most accurate model in concurrent external validation). Results: The unbiased prediction model had the highest SBS. The NeRMA score correctly ranked all simulated prediction models by the extent of bias from the known risk function. A SAS macro and R-function was created to implement the NeRMA Score. Conclusions: The NeRMA Score makes it possible to quantify the accuracy of binomial prediction models having distinct inclusion criteria in a concurrent external validation.

Keywords: prediction model accuracy, scaled brier score, fixed effects methods, concurrent external validation

Procedia PDF Downloads 184