Search results for: self nanoemulsifying drug delivery system
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 19782

Search results for: self nanoemulsifying drug delivery system

19242 Improving the Aqueous Solubility of Taxol through Altering XLOGP3

Authors: Arianna Zhu, Thomas Bakupog

Abstract:

Taxol (generic name paclitaxel) is an antineoplastic drug used to treat breast, lung, and ovarian cancer. It performs exceptionally well against a wide variety of tumors, including B16 melanoma, L1210 and P388 leukemias, MX-1 mammary tumors, and CX-1 colon tumor xenografts. However, despite taxol’s efficacy in antitumor activity, its aqueous solubility is extremely poor, decreasing its bioavailability and making it difficult for the body to absorb. The objective of this study is to improve the solubility of taxol, thus increasing the bioavailability of the drug in preventing cancer. By modifying the structure of taxol, four novel taxol derivatives were created with improved solubilities. Two of the derivatives were given an additional hydrogen donor and acceptor and thus showed a pronounced positive change in solubility. The results of this work solve the issue of taxol’s inadequate solubility and show potential in increasing the absorption of the drug.

Keywords: Taxol, Solubility, improving bioavailability, logP

Procedia PDF Downloads 42
19241 Fabrication and Characterization of Transdermal Spray Using Film Forming Polymer

Authors: Paresh Patel, Harshit Patel

Abstract:

Superficial fungal skin infection is among the most common skin disease. The drug administration through skin has received attention due to several advantages: Avoidance of significant pre-systemic metabolism, drug levels within the therapeutic window, drugs with short biological half-lives, decreased side effects, the non-invasive character, and very high acceptance.

Keywords: transdermal spray, ketoconazole, Eudragit® RLPO, therapeutic window

Procedia PDF Downloads 376
19240 Nano-emulsion/Nano-suspension as Precursors for Oral Dissolvable Film to Enhance Bioavalabilty for Poor-water Solubility Drugs

Authors: Yuan Yang, Mickey Lam

Abstract:

Oral dissolvable films have been considered as a unique alternative approach to conventional oral dosage forms. The films could be administrated via the gastrointestinal tract as conventional dosages or through sublingual/buccal mucosa membranes, which could enhance drug bioavailability by avoiding the first-pass effect and improving permeability due to high blood flow and lymphatic circulation. This work has described a state-of-art technic using nano-emulsion/nano-suspension as a precursor for the film to enhance the bioavailability of BCS class II drugs. The drug molecules are consequentially processed through the emulsification, gelation, and film-casting processes. The gelation process is critical to stabilizing the nano-emulsion for the film-casting as well as controlling the drug release process. Furthermore, the size of the nanoparticle on the film has a strong correlation with the size of the micelles in the precursor and the condition of the gelation process. It has been discovered that nanoparticle from 200 nm to 300 nm has shown the highest permeability for sublingual administration. In one example shown in work, the bioavailability of a low solubilize drug has been increased from 10% to 24% via sublingual administration of the film. The increasing of the bioavailability was thought to be associated with the enhancement of the diffusion process of the drug in the saliva layer above the mucosa membrane and the fact that the presents of the emulsifier help lose the rigid junction of the mucosa cells.

Keywords: oral dissolvable film, nano-suspension, nano-emulsion, bioavailability

Procedia PDF Downloads 150
19239 Potential Impact of Sodium Salicylate Nanoemulsion on Expression of Nephrin in Nephrotoxic Experimental Rat

Authors: Nadia A. Mohamed, Zakaria El-Khayat, Wagdy K. B. Khalil, Mehrez E. El-Naggar

Abstract:

Drug nephrotoxicity is still a problem for patients who have taken drugs for elongated periods or permanently. Ultrasound-assisted sol−gel method was used to prepare hollow structured poroussilica nanoemulsion loaded with sodium salicylate as a model drug. The work was extended to achieve the target of the current work via investigating the protective role of this nanoemulsion model as anti-inflammatory drug or ginger for its antioxidant effect against cisplatin-induced nephrotoxicity in male albino rats. The results clarify that the nanoemulsion model was synthesized using ultrasonic assisted with small size and well stabilization as proved by TEM and DLS analysis. Additionally, blood urea nitrogen (BUN), Serum creatinine (SC) and Urinary total protein (UTP) were increased, and the level of creatinine clearance (Crcl) was decreased. All those were met with disorders in oxidative stress and downregulation in the expression of the nephrin gene. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with silica nanoparticles loaded sodium salicylate (Si-Sc-NPs), ginger or both. Conclusions oil/water nanoemulsion of (Si-Sc NPs) and ginger showed a protective and promising preventive strategy against nephrotoxicity due to their antioxidant and anti-inflammatory effects, and that offers a new approach in attenuating drug induced nephrotoxicity.

Keywords: sodium salicylate nanoencapsulation, nephrin mRNA, drug nephrotoxicity, cisplatin, experimental rats

Procedia PDF Downloads 184
19238 Correlation between Fetal Umbilical Cord pH and the Day, the Time and the Team Hand over Times: An Analysis of 6929 Deliveries of the Ulm University Hospital

Authors: Sabine Pau, Sophia Volz, Emanuel Bauer, Amelie De Gregorio, Frank Reister, Wolfgang Janni, Florian Ebner

Abstract:

Purpose: The umbilical cord pH is a well evaluated contributor for prediction of neonatal outcome. This study correlates nenonatal umbilical cord pH with the weekday of delivery, the time of birth as well as the staff hand over times (midwifes and doctors). Material and Methods: This retrospective study included all deliveries of a 20 year period (1994-2014) at our primary obstetric center. All deliveries with a newborn cord pH under 7,20 were included in this analysis (6929 of 48974 deliveries (14,4%)). Further subgroups were formed according to the pH (< 7,05; 7,05 – 7,09; 7,10 – 7,14; 7,15 – 7,19). The data were then separated in day- and night time (8am-8pm/8pm-8am) for a first analysis. Finally, handover times were defined at 6 am – 6.30 am, 2 pm -2.30 pm, 10 pm- 10.30 pm (midwives) and for the doctors 8-8.30 am, 4 – 4.30 pm (Monday- Thursday); 2 pm -2.30 pm (Friday) and 9 am – 9.30 am (weekend). Routinely a shift consists of at least three doctors as well as three midwives. Results: During the last 20 years, 6929 neonates were born with an umbilical cord ph < 7,20 ( < 7,05 : 7,1%; 7,05 – 7,09 : 10,9%; 7,10 – 7,14 : 30,2%; 7,15 – 7,19:51,8%). There was no significant difference between either night/day delivery (p = 0.408), delivery on different weekdays (p = 0.253), delivery between Monday to Thursday, Friday and the weekend (p = 0.496 ) or delivery during the handover times of the doctors as well as the midwives (p = 0.221). Even the standard deviation showed no differences between the groups. Conclusion: Despite an increased workload over the last 20 years, the standard of care remains high even during the handover times and night shifts. This applies for midwives and doctors. As the neonatal outcome depends on various factors, further studies are necessary to take more factors influencing the fetal outcome into consideration. In order to maintain this high standard of care, an adaption of work-load and changing conditions is necessary.

Keywords: delivery, fetal umbilical cord pH, day time, hand over times

Procedia PDF Downloads 290
19237 A New Cytoprotective Drug on the Basis of Cytisine: Phase I Clinical Trial Results

Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

Abstract:

Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

Procedia PDF Downloads 343
19236 DeepLig: A de-novo Computational Drug Design Approach to Generate Multi-Targeted Drugs

Authors: Anika Chebrolu

Abstract:

Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

Procedia PDF Downloads 65
19235 Double-Spear 1-H2-1 Oncolytic-Immunotherapy for Refractory and Relapsing High-Risk Human Neuroblastoma and Glioma

Authors: Lian Zeng

Abstract:

Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

Procedia PDF Downloads 82
19234 Current Methods for Drug Property Prediction in the Real World

Authors: Jacob Green, Cecilia Cabrera, Maximilian Jakobs, Andrea Dimitracopoulos, Mark van der Wilk, Ryan Greenhalgh

Abstract:

Predicting drug properties is key in drug discovery to enable de-risking of assets before expensive clinical trials and to find highly active compounds faster. Interest from the machine learning community has led to the release of a variety of benchmark datasets and proposed methods. However, it remains unclear for practitioners which method or approach is most suitable, as different papers benchmark on different datasets and methods, leading to varying conclusions that are not easily compared. Our large-scale empirical study links together numerous earlier works on different datasets and methods, thus offering a comprehensive overview of the existing property classes, datasets, and their interactions with different methods. We emphasise the importance of uncertainty quantification and the time and, therefore, cost of applying these methods in the drug development decision-making cycle. To the best of the author's knowledge, it has been observed that the optimal approach varies depending on the dataset and that engineered features with classical machine learning methods often outperform deep learning. Specifically, QSAR datasets are typically best analysed with classical methods such as Gaussian Processes, while ADMET datasets are sometimes better described by Trees or deep learning methods such as Graph Neural Networks or language models. Our work highlights that practitioners do not yet have a straightforward, black-box procedure to rely on and sets a precedent for creating practitioner-relevant benchmarks. Deep learning approaches must be proven on these benchmarks to become the practical method of choice in drug property prediction.

Keywords: activity (QSAR), ADMET, classical methods, drug property prediction, empirical study, machine learning

Procedia PDF Downloads 53
19233 Is Presence of Psychotic Features Themselves Carry a Risk for Metabolic Syndrome?

Authors: Rady A., Elsheshai A., Elsawy M., Nagui R.

Abstract:

Background and Aim: Metabolic syndrome affect around 20% of general population , authors have incriminated antipsychotics as serious risk factor that may provoke such derangement. The aim of our study is to assess metabolic syndrome in patients presenting psychotic features (delusions and hallucinations) whether schizophrenia or mood disorder and compare results in terms of drug naïf, on medication and healthy control. Subjects and Methods: The study recruited 40 schizophrenic patients, half of them drug naïf and the other half on antipsychotics, 40 patients with mood disorder with psychotic features, half of them drug naïf and the other half on medication, 20 healthy control. Exclusion criteria were put in order to exclude patients having already endocrine or metabolic disorders that my interfere with results obtain to minimize confusion bias. Metabolic syndrome assessed by measuring parameters including weight, body mass index, waist circumference, triglyceride level, HDL, fasting glucose, fasting insulin and insulin resistance Results: No difference was found when comparing drug naïf to those on medication in both schizophrenic and psychotic mood disorder arms, schizophrenic patients whether on medication or drug naïf should difference with control group for fasting glucose, schizophrenic patients on medication also showed difference in insulin resistance compared to control group. On the other hand, patients with psychotic mood disorder whether drug naïf or on medication showed difference from control group for fasting insulin level. Those on medication also differed from control for insulin resistance Conclusion: Our study didn’t reveal difference in metabolic syndrome among patients with psychotic features whether on medication or drug naïf. Only patients with Psychotic features on medication showed insulin resistance. Schizophrenic patients drug naïf or on medication tend to show higher fasting glucose while psychotic mood disorder whether drug naïf or on medication tend to show higher fasting insulin. This study suggest that presence of psychotic features themselves regardless being on medication or not carries a risk for insulin resistance and metabolic syndrome. Limitation: This study is limited by number of participants and larger numbers in future studies should be included in order to extrapolate results. Cohort longitudinal studies are needed in order to evaluate such hypothesis.

Keywords: schizophrenia, metabolic syndrome, psychosis, insulin, resistance

Procedia PDF Downloads 516
19232 Factors Influencing Antipsychotic Drug Usage and Substitution among Nigerian Schizophrenic Patients

Authors: Ubaka Chukwuemeka Michael, Ukwe Chinwe Victoria

Abstract:

Background: The use of antipsychotic monotherapy remains the standard for schizophrenic disorders so also a prescription switch from older typical to newer atypical classes of antipsychotics on the basis of better efficacy and tolerability. However, surveys on the quality of antipsychotic drug use and substitution in developing countries are very scarce. This study was intended to evaluate quality and factors that drive the prescription and substitution of antipsychotic drugs among schizophrenic patients visiting a regional psychiatric hospital. Methods: Case files of patients visiting a federal government funded Neuropsychiatric Hospital between July 2012 and July 2014 were systematically retrieved. Patient demographic characteristics, clinical details and drug management data were collected and subjected to descriptive and inferential data analysis to determine quality and predictors of utilization. Results: Of the 600 case files used, there were more male patients (55.3%) with an overall mean age of 33.7±14.4 years. Typical antipsychotic agents accounted for over 85% of prescriptions, with majority of the patients receiving more than 2 drugs in at least a visit (80.9%). Fluphenazine (25.2%) and Haloperidol (18.8%) were mostly given as antipsychotics for treatment initiation while Olazenpine (23.0%) and Benzhexol (18.3%) were the most currently prescribed antipsychotics. Nearly half (42%, 252/600) of these patients were switched from one class to another, with 34.5% (207/600) of them switched from typical to atypical drug classes. No demographic or clinical factors influenced drug substitutions but a younger age and being married influenced being prescribed a polypharmacy regimen (more than 2 drugs) and an injectable antipsychotic agent. Conclusion: The prevalence of antipsychotic polypharmacy and use of typical agents among these patients was high. However, only age and marital status affected the quality of antipsychotic prescriptions among these patients.

Keywords: antipsychotics, drug substitution, pharmacoepidemiology, polypharmacy

Procedia PDF Downloads 450
19231 Instructional Resources Development in Open and Distance Learning: Prospects and Challenges of Media Integration in Nigeria

Authors: Felix E. Gbenoba, Opeyemi Dahunsi

Abstract:

Self-instructional materials are at the heart of instructional delivery in Open and Distance Learning (ODL). The success of any ODL institution depends on the availability of instructional materials in quality and quantity. An ODL study material is expected to fully play the teacher plays in the face-to-face learning environment. In Nigeria, efforts to deliver ODL learning materials have been peculiarly challenging. Although researchers are unrelenting in hewing out ways to make ODL delivery in Africa generally and Nigeria in particular, meet the learners’ needs and acceptable global practices, the prospects of integrating instructional media into distance learning courses are largely unexplored. In the present study, we critically examine the prospects of integration of instructional media into ODL courses for pedagogic and other benefits it portends for delivery via the distance learning mode. Although efforts to integrate media in ODL have been recorded before now, the reality has not matched the expectation so far in Nigeria. This does not mean that the existing instructional materials have not produced any significant positive results in improving the overall learning (and teaching) experience in its institutions; it implies that increased integration as suggested here will further improve the experience as well as bring up the new challenges. Obstacles and problems of instructional materials and media development that could have affected the open educational resource initiatives are well established. The first aspect of this paper recalls the revolutionary strides that ODL brought to delivery of education in Nigeria particularly. The other aspect is on what instructional media are, their role, prospects and challenges for ODL in Nigeria; these are examined vis a vis the challenges of development, production and distribution of print instructional materials as the major format of instructional delivery at Nigeria’s only single mode ODL institution, NOUN. In the third aspect, we justify the need and benefits of integrating instructional media into the courses and make recommendations.

Keywords: instructional delivery, instructional media, ODL, media integration, Nigeria, self-instructional materials

Procedia PDF Downloads 366
19230 Preparation, Solid State Characterization of Etraverine Co-Crystals with Improved Solubility for the Treatment of Human Immunodeficiency Virus

Authors: B. S. Muddukrishna, Karthik Aithal, Aravind Pai

Abstract:

Introduction: Preparation of binary cocrystals of Etraverine (ETR) by using Tartaric Acid (TAR) as a conformer was the main focus of this study. Etravirine is a Class IV drug, as per the BCS classification system. Methods: Cocrystals were prepared by slow evaporation technique. A mixture of total 500mg of ETR: TAR was weighed in molar ratios of 1:1 (371.72mg of ETR and 128.27mg of TAR). Saturated solution of Etravirine was prepared in Acetone: Methanol (50:50) mixture in which tartaric acid is dissolved by sonication and then this solution was stirred using a magnetic stirrer until the solvent got evaporated. Shimadzu FTIR – 8300 system was used to acquire the FTIR spectra of the cocrystals prepared. Shimadzu thermal analyzer was used to achieve DSC measurements. X-ray diffractometer was used to obtain the X-ray powder diffraction pattern. Shake flask method was used to determine the equilibrium dynamic solubility of pure, physical mixture and cocrystals of ETR. USP buffer (pH 6.8) containing 1% of Tween 80 was used as the medium. The pure, physical mixture and the optimized cocrystal of ETR were accurately weighed sufficient to maintain the sink condition and were filled in hard gelatine capsules (size 4). Electrolab-Tablet Dissolution tester using basket apparatus at a rotational speed of 50 rpm and USP phosphate buffer (900 mL, pH = 6.8, 37 ˚C) + 1% Tween80 as a media, was used to carry out dissolution. Shimadzu LC-10 series chromatographic system was used to perform the analysis with PDA detector. An Hypersil BDS C18 (150mm ×4.6 mm ×5 µm) column was used for separation with mobile phase comprising of a mixture of ace¬tonitrile and phosphate buffer 20mM, pH 3.2 in the ratio 60:40 v/v. The flow rate was 1.0mL/min and column temperature was set to 30°C. The detection was carried out at 304 nm for ETR. Results and discussions: The cocrystals were subjected to various solid state characterization and the results confirmed the formation of cocrystals. The C=O stretching vibration (1741cm-1) in tartaric acid was disappeared in the cocrystal and the peak broadening of primary amine indicates hydrogen bond formation. The difference in the melting point of cocrystals when compared to pure Etravirine (265 °C) indicates interaction between the drug and the coformer which proves that first ordered transformation i.e. melting endotherm has disappeared. The difference in 2θ values of pure drug and cocrystals indicates the interaction between the drug and the coformer. Dynamic solubility and dissolution studies were also conducted by shake flask method and USP apparatus one respectively and 3.6 fold increase in the dynamic solubility were observed and in-vitro dissolution study shows four fold increase in the solubility for the ETR: TAR (1:1) cocrystals. The ETR: TAR (1:1) cocrystals shows improved solubility and dissolution as compared to the pure drug which was clearly showed by solid state characterization and dissolution studies.

Keywords: dynamic solubility, Etraverine, in vitro dissolution, slurry method

Procedia PDF Downloads 322
19229 Digital Revolution a Veritable Infrastructure for Technological Development

Authors: Osakwe Jude Odiakaosa

Abstract:

Today’s digital society is characterized by e-education or e-learning, e-commerce, and so on. All these have been propelled by digital revolution. Digital technology such as computer technology, Global Positioning System (GPS) and Geographic Information System (GIS) has been having a tremendous impact on the field of technology. This development has positively affected the scope, methods, speed of data acquisition, data management and the rate of delivery of the results (map and other map products) of data processing. This paper tries to address the impact of revolution brought by digital technology.

Keywords: digital revolution, internet, technology, data management

Procedia PDF Downloads 422
19228 Spatial Analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) Patients in Lagos, Nigeria

Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

Abstract:

The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

Procedia PDF Downloads 132
19227 The Spread of Drugs in Higher Education

Authors: Wantana Amatariyakul, Chumnong Amatariyakul

Abstract:

The research aims to examine the spread of drugs in higher education, especially amphetamine which is rapidly increasing in Thai society, its causes and effects, including the sociological perspective, in order to explain, prevent, control, and solve the problems. The students who participated in this research are regular students of Rajamangala University of Technology Isan, Khon Kaen Campus. The data were collected using questionnaires, group discussions, and in-depth interviews. The quantity data were analyzed using frequency, percentage, mean and standard deviation and using content analysis to analyzed quality data. The result of the study showed that the students had the results of examination on level of knowledge and understanding on drug abuse projected that the majority of sample group attained their knowledge on drug abuse respectively. Despite their uncertainty, the majority of samples presumed that amphetamine, marijuana and grathom (Mitragyna Speciosa Korth) would most likely be abused. The reason for first drug abuse is because they want to try and their friends convince them, as well as, they want to relax or solve the problems in life, respectively. The bad effects appearing to the drug addicts shows that their health deteriorates or worsens, as well as, they not only lose their money but also face with worse mental states. The reasons that respondents tried to avoid using drugs or refused drugs offered by friends were: not wanting to disappoint or upset their family members, fear of rejection by family members, afraid of being arrested by the police, afraid of losing their educational opportunity and ruining their future respectively. Students therefore defended themselves against drug addiction by refusing to try all drugs. Besides this, the knowledge about the danger and the harm of drugs persuaded them to stay away from drugs.

Keywords: drugs, higher education, drug addiction, spread of drugs

Procedia PDF Downloads 300
19226 Screening for Non-hallucinogenic Neuroplastogens as Drug Candidates for the Treatment of Anxiety, Depression, and Posttraumatic Stress Disorder

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

Abstract:

With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

Procedia PDF Downloads 105
19225 The Effect of Drug Prevention Programme Based On Cognitive-Behavioral Therapy (CBT) and Multidimensional Self Concept Module Towards Resiliency and Aggression Among At-Risk Youth in Malaysia

Authors: Mohammad Aziz Shah Mohamed Arip, Aslina Ahmad, Fauziah Mohd Sa'ad, Samsiah Mohd Jais, Syed Sofian Syed Salim

Abstract:

This experimental study evaluates the effect of using Cognitive-Behavioral Therapy (CBT) and Multidimensional Self-Concept Model (MSCM) in a drug prevention programme to increase resiliency and reduce aggression among at-risk youth in Malaysia. A number of 60 (N=60) university students who were at-risk of taking drugs were involved in this study. Participants were identified with self-rating scales, Adolescent Resilience Attitude Scale (ARAS) and Aggression Questionnaire. Based on the mean score of these instruments, the participants were divided into the treatment group, and the control group. Data were analyzed using t-test. The finding showed that the mean score of resiliency was increased in the treatment group compared to the control group. It also shows that the mean score of aggression was reduced in the treatment group compared to the control group. Drug Prevention Programme was found to help in enhancing resiliency and reducing aggression among participants in the treatment group compared to the controlled group. Implications were given regarding the preventive actions on drug abuse among youth in Malaysia.

Keywords: drug prevention programme, cognitive-behavioral therapy (CBT), multidimensional self concept model (MSCM), resiliency, aggression, at-risk youth

Procedia PDF Downloads 702
19224 Associations and Interactions of Delivery Mode and Antibiotic Exposure with Infant Cortisol Level: A Correlational Study

Authors: Samarpreet Singh, Gerald Giesbrecht

Abstract:

Both c-section and antibiotic exposure are linked to gut microbiota imbalance in infants. Such disturbance is associated with the Hypothalamic-Pituitary-Adrenal (HPA) axis function. However, the literature only has contradicting evidence for the association between c-sections and the HPA axis. Therefore, this study aims to test if the mode of delivery and antibiotics exposure is associated with the HPA axis. Also, whether exposure to both interacts with the HPA-axis. It was hypothesized that associations and interactions would be observed. Secondary data analysis was used for this co-relational study. Data for the mode of delivery and antibiotics exposure variables were documented from hospital records or self-questionnaires. In addition, cortisol levels (Area under the curve with respect to increasing (AUCi) and Area under the curve with respect to ground (AUCg)) were based on saliva collected from three months old during the infant’s visit to the lab and after drawing blood. One-way and between-subject ANOVA analyses were run on data. No significant association between delivery mode and infant cortisol level was found, AUCi and AUCg, p > .05. Only the infant’s AUCg was found to be significantly higher if there were antibiotics exposure at delivery (p = .001) or their mothers were exposed during pregnancy (p < .05). Infants born by c-section and exposed to antibiotics at three months had higher AUCi than those born vaginally, p < .02. These results imply that antibiotic exposure before three months is associated with an infant’s stress response. The association might increase if antibiotic exposure occurs three months after a c-section birth. However, more robust and causal evidence in future studies is needed, given a variable group’s statistically weak sample size. Nevertheless, the results of this study still highlight the unintended consequences of antibiotic exposure during delivery and pregnancy.

Keywords: HPA-axis, antibiotics, c-section, gut-microbiota, development, stress

Procedia PDF Downloads 48
19223 Need for a Tailor Made HIV Prevention Services to the Migrants Community: Evidence from Implementing Migrant Service Delivery System (MSDS) among Migrant Workers, National AIDS Control Program, and India

Authors: Debasish Chowdhury, Sunil Mekale, Sarvanamurthy Sakthivel, Sukhvinder Kaur, Rambabu Khambampati, Ashok Agarwal

Abstract:

Introduction: The migrant intervention in India was initiated during the National AIDS Control Program (NACP) Phase-2 (2002-2007). HIV Sentinel surveillance Studies (HSS) conducted in 2012-13 indicated higher HIV prevalence among migrants (0.99%) compared to general populations (0.35%). Migrants continue to bear a heightened risk of HIV infection which results from the condition and structure of the migration process. USAID PHFI-PIPPSE project in collaboration with the National AIDS Control Organization (NACO) developed a unique system called Migrant Service Delivery System (MSDS) to capture migrants profile with respect to their risk profile and to provide tailor made services to them. Description: MSDS is a web-based system, designed and implemented to increase service uptake among migrants through evidence based planning. 110 destination migrants Targeted Intervention (TI) from 11 states were selected for study with varied target populations in terms of occupations; to understand occupation related risk behaviors among the migrants. Occupation wise registration data of high risk vulnerable migrants were analyzed through MSDS for the period April 2014–June 2016. Analysis was made on specific indicators among these occupational groups to understand the risk behavior and their vulnerability to HIV and STIs. Findings: Out of total HIV positive migrant’s workers (N= 847) enrolled in MSDS HIV rate is found to be highest among Auto-Rickshaw (18.66%) followed by Daily wage laborers (14.46%), Loom workers (10.73%), Industrial workers (10.04%) and Construction worker 7.93%. With 45.14% positivity, industrial workers are found to be most vulnerable to Sexually Transmitted Infections (STIs) (N=10057) among all occupational categories followed by loom workers (16.28%), Skilled worker (Furniture, Jeweler)-7.14%, daily wage laborers (5.45%). Conclusion: MSDS is an effective tool to assess migrants’ risk and their vulnerability to HIV for designing evidence informed program. This system calls for a replication across all destination TIs by NACO for differential strategies for different occupation groups to ensure better yield through scientific planning of intervention among high risk and high vulnerable migrants.

Keywords: migrants, migrant service delivery system, risk, vulnerability

Procedia PDF Downloads 250
19222 Racism in Drug Policies: A Report on United States Legislation

Authors: Frederick Monyepao

Abstract:

Crack cocaine first appeared on the scene in the form of cocaine freebasing in the late 1970s. Stockbrokers, investment bankers, rock stars, Hollywood elites, and a few pro athletes were regular users of the substance. As criminogenic factors associated with substance abuse began to surface, congress passed new legislation. The laws led to the increase of health coverage insurances and the expansion of hospitals. By the mid-1980s, crack use spread into America's inner cities among impoverished African Americans and Latinos. While substance abuse increased among minority communities, legislation pertaining to substance abuse evolved. The prison industry also expanded the number of cells available. A qualitative approach was taken, drawing from a range secondary sources for contextual analysis. This paper traces out the continued marginalisation and racist undertones towards minorities as perpetuated by certain drug policies. It was discovered that the new legislation on crack was instrumental in the largest incarcerations the United States ever faced. Drug offenders increased in prisons eightfold from 1986 to 2000. The paper concludes that American drug control policies are consistently irrational and ineffective when measured by levels of substance use and abuse. On the contrary, these policies have been successful as agents of social control in maintaining the stratification patterns of racial/ethnic minorities and women. To move beyond prohibition, radical law and policy reform may require a change in narratives on substance use.

Keywords: crack, drug policy, minorities, racism, substance abuse

Procedia PDF Downloads 262
19221 Neuropsychological Deficits in Drug-Resistant Epilepsy

Authors: Timea Harmath-Tánczos

Abstract:

Drug-resistant epilepsy (DRE) is defined as the persistence of seizures despite at least two syndrome-adapted antiseizure drugs (ASD) used at efficacious daily doses. About a third of patients with epilepsy suffer from drug resistance. Cognitive assessment has a crucial role in the diagnosis and clinical management of epilepsy. Previous studies have addressed the clinical targets and indications for measuring neuropsychological functions; best to our knowledge, no studies have examined it in a Hungarian therapy-resistant population. To fill this gap, we investigated the Hungarian diagnostic protocol between 18 and 65 years of age. This study aimed to describe and analyze neuropsychological functions in patients with drug-resistant epilepsy and identify factors associated with neuropsychology deficits. We perform a prospective case-control study comparing neuropsychological performances in 50 adult patients and 50 healthy individuals between March 2023 and July 2023. Neuropsychological functions were examined in both patients and controls using a full set of specific tests (general performance level, motor functions, attention, executive facts., verbal and visual memory, language, and visual-spatial functions). Potential risk factors for neuropsychological deficit were assessed in the patient group using a multivariate analysis. The two groups did not differ in age, sex, dominant hand and level of education. Compared with the control group, patients with drug-resistant epilepsy showed worse performance on motor functions and visuospatial memory, sustained attention, inhibition and verbal memory. Neuropsychological deficits could therefore be systematically detected in patients with drug-resistant epilepsy in order to provide neuropsychological therapy and improve quality of life. The analysis of the classical and complex indices of the special neuropsychological tasks presented in the presentation can help in the investigation of normal and disrupted memory and executive functions in the DRE.

Keywords: drug-resistant epilepsy, Hungarian diagnostic protocol, memory, executive functions, cognitive neuropsychology

Procedia PDF Downloads 54
19220 Library Screening and Evaluation of Mycobacterium tuberculosis Ketol-Acid Reductoisomerase Inhibitors

Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

Abstract:

Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

Procedia PDF Downloads 103
19219 Correlates of Multiplicity of Risk Behavior among Injecting Drug Users in Three High HIV Prevalence States of India

Authors: Santosh Sharma

Abstract:

Background: Drug abuse, needle sharing, and risky sexual behaviour are often compounded to increase the risk of HIV transmission. Injecting Drug Users are at the duel risk of needle sharing and risky sexual Behaviour, becoming more vulnerable to STI and HIV. Thus, studying the interface of injecting drug use and risky sexual behaviour is important to curb the pace of HIV epidemic among IDUs. The aim of this study is to determine the factor associated with HIV among injecting drug users in three states of India. Materials and methods: This paper analyzes covariates of multiplicity of risk behavior among injecting drug users. Findings are based on data from Integrated Behavioral and Biological Assessment (IBBA) round 2, 2010. IBBA collects the information of IDUs from the six districts. IDUs were selected on the criteria of those who were 18 years or older, who injected addictive substances/drugs for non-medical purposes at least once in past six month. A total of 1,979 in round 2 were interviewed in the IBBA. The study employs quantitative techniques using standard statistical tools to achieve the above objectives. All results presented in this paper are unweighted univariate measures. Results: Among IDUs, average duration of injecting drugs is 5.2 years. Mean duration between first drug use to first injecting drugs among younger IDUs, belongs to 18-24 years is 2.6 years Needle cleaning practices is common with above two-fifths reporting its every time cleaning. Needle sharing is quite prevalent especially among younger IDUs. Further, IDUs practicing needle sharing exhibit pervasive multi-partner behavior. Condom use with commercial partners is almost 81 %, whereas with intimate partner it is 39 %. Coexistence of needle sharing and unprotected sex enhances STI prevalence (6.8 %), which is further pronounced among divorced/separated/widowed (9.4 %). Conclusion: Working towards risk reduction for IDUs must deal with multiplicity of risk. Interventions should deal with covariates of risk, addressing youth, and risky sexual behavior.

Keywords: IDUs, HIV, STI, behaviour

Procedia PDF Downloads 258
19218 Supplier Risk Management: A Multivariate Statistical Modelling and Portfolio Optimization Based Approach for Supplier Delivery Performance Development

Authors: Jiahui Yang, John Quigley, Lesley Walls

Abstract:

In this paper, the authors develop a stochastic model regarding the investment in supplier delivery performance development from a buyer’s perspective. The authors propose a multivariate model through a Multinomial-Dirichlet distribution within an Empirical Bayesian inference framework, representing both the epistemic and aleatory uncertainties in deliveries. A closed form solution is obtained and the lower and upper bound for both optimal investment level and expected profit under uncertainty are derived. The theoretical properties provide decision makers with useful insights regarding supplier delivery performance improvement problems where multiple delivery statuses are involved. The authors also extend the model from a single supplier investment into a supplier portfolio, using a Lagrangian method to obtain a theoretical expression for an optimal investment level and overall expected profit. The model enables a buyer to know how the marginal expected profit/investment level of each supplier changes with respect to the budget and which supplier should be invested in when additional budget is available. An application of this model is illustrated in a simulation study. Overall, the main contribution of this study is to provide an optimal investment decision making framework for supplier development, taking into account multiple delivery statuses as well as multiple projects.

Keywords: decision making, empirical bayesian, portfolio optimization, supplier development, supply chain management

Procedia PDF Downloads 270
19217 Mesenchymal Stem Cells (MSC)-Derived Exosomes Could Alleviate Neuronal Damage and Neuroinflammation in Alzheimer’s Disease (AD) as Potential Therapy-Carrier Dual Roles

Authors: Huan Peng, Chenye Zeng, Zhao Wang

Abstract:

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

Procedia PDF Downloads 32
19216 Upconversion Nanomaterials for Applications in Life Sciences and Medicine

Authors: Yong Zhang

Abstract:

Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

Procedia PDF Downloads 139
19215 Secured Cancer Care and Cloud Services in Internet of Things /Wireless Sensor Network Based Medical Systems

Authors: Adeniyi Onasanya, Maher Elshakankiri

Abstract:

In recent years, the Internet of Things (IoT) has constituted a driving force of modern technological advancement, and it has become increasingly common as its impacts are seen in a variety of application domains, including healthcare. IoT is characterized by the interconnectivity of smart sensors, objects, devices, data, and applications. With the unprecedented use of IoT in industrial, commercial and domestic, it becomes very imperative to harness the benefits and functionalities associated with the IoT technology in (re)assessing the provision and positioning of healthcare to ensure efficient and improved healthcare delivery. In this research, we are focusing on two important services in healthcare systems, which are cancer care services and business analytics/cloud services. These services incorporate the implementation of an IoT that provides solution and framework for analyzing health data gathered from IoT through various sensor networks and other smart devices in order to improve healthcare delivery and to help health care providers in their decision-making process for enhanced and efficient cancer treatment. In addition, we discuss the wireless sensor network (WSN), WSN routing and data transmission in the healthcare environment. Finally, some operational challenges and security issues with IoT-based healthcare system are discussed.

Keywords: IoT, smart health care system, business analytics, (wireless) sensor network, cancer care services, cloud services

Procedia PDF Downloads 154
19214 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 64
19213 Using Group Concept Mapping to Identify a Pharmacy-Based Trigger Tool to Detect Adverse Drug Events

Authors: Rodchares Hanrinth, Theerapong Srisil, Peeraya Sriphong, Pawich Paktipat

Abstract:

The trigger tool is the low-cost, low-tech method to detect adverse events through clues called triggers. The Institute for Healthcare Improvement (IHI) has developed the Global Trigger Tool for measuring and preventing adverse events. However, this tool is not specific for detecting adverse drug events. The pharmacy-based trigger tool is needed to detect adverse drug events (ADEs). Group concept mapping is an effective method for conceptualizing various ideas from diverse stakeholders. This technique was used to identify a pharmacy-based trigger to detect adverse drug events (ADEs). The aim of this study was to involve the pharmacists in conceptualizing, developing, and prioritizing a feasible trigger tool to detect adverse drug events in a provincial hospital, the northeastern part of Thailand. The study was conducted during the 6-month period between April 1 and September 30, 2017. Study participants involved 20 pharmacists (17 hospital pharmacists and 3 pharmacy lecturers) engaging in three concept mapping workshops. In this meeting, the concept mapping technique created by Trochim, a highly constructed qualitative group technic for idea generating and sharing, was used to produce and construct participants' views on what triggers were potential to detect ADEs. During the workshops, participants (n = 20) were asked to individually rate the feasibility and potentiality of each trigger and to group them into relevant categories to enable multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the trigger list, cluster list, point map, point rating map, cluster map, and cluster rating map. The three workshops together resulted in 21 different triggers that were structured in a framework forming 5 clusters: drug allergy, drugs induced diseases, dosage adjustment in renal diseases, potassium concerning, and drug overdose. The first cluster is drug allergy such as the doctor’s orders for dexamethasone injection combined with chlorpheniramine injection. Later, the diagnosis of drug-induced hepatitis in a patient taking anti-tuberculosis drugs is one trigger in the ‘drugs induced diseases’ cluster. Then, for the third cluster, the doctor’s orders for enalapril combined with ibuprofen in a patient with chronic kidney disease is the example of a trigger. The doctor’s orders for digoxin in a patient with hypokalemia is a trigger in a cluster. Finally, the doctor’s orders for naloxone with narcotic overdose was classified as a trigger in a cluster. This study generated triggers that are similar to some of IHI Global trigger tool, especially in the medication module such as drug allergy and drug overdose. However, there are some specific aspects of this tool, including drug-induced diseases, dosage adjustment in renal diseases, and potassium concerning which do not contain in any trigger tools. The pharmacy-based trigger tool is suitable for pharmacists in hospitals to detect potential adverse drug events using clues of triggers.

Keywords: adverse drug events, concept mapping, hospital, pharmacy-based trigger tool

Procedia PDF Downloads 143