Search results for: antigen delivery

Authors: Papon Thamvasupong, Kwanchanok Viravaidya-Pasuwat

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Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO₄) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.

Keywords: controlled release, drug delivery system, glucosamine, pluronic, thermoreversible hydrogel

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Authors: Anurag Sharma, Dinesh Kumar, Rahul Malhotra, Manoj Kumar

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Fiber based access networks can deliver performance that can support the increasing demands for high speed connections. One of the new technologies that have emerged in recent years is Passive Optical Networks. This paper is targeted to show the simultaneous delivery of triple play service (data, voice and video). The comparative investigation and suitability of various data rates is presented. It is demonstrated that as we increase the data rate, number of users to be accommodated decreases due to increase in bit error rate.

Keywords: BER, PON, TDMPON, GPON, CWDM, OLT, ONT

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Authors: Aaron Samuels, Ahmad Badeghiesh, Haitham Baghlaf, Michael H. Dahan

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Importance: Cervical cancer is the fourth most common cancer among women globally and a significant cause of cancer-related deaths. Understanding the impact of cervical cancer diagnosed during pregnancy on maternal, delivery, and neonatal outcomes is crucial for improving clinical management and outcomes for affected women and their children. Objective: The goal is to determine the effects of cervical cancer diagnosed during pregnancy on maternal, delivery, and neonatal outcomes using a population-based American database. Design: This study is a retrospective analysis of the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database. The study period spans between 2004-2014, and the analysis was conducted in 2023. Setting: The study used the HCUP-NIS database, which includes data from hospital stays across the United States, covering 48 states and the District of Columbia. Participants: The study included all women who delivered a child or had a maternal death from 2004-2014, with pregnancies at 24 weeks or above. The population was comprised of 9,096,788 pregnant women, including 222 diagnosed with cervical cancer prior to delivery. Exposures: The exposure was a diagnosis of cervical cancer during pregnancy, identified using International Classification of Diseases 9th Revision codes 180.0, 180.1, 180.8, and 180.9. Main Outcomes and Measures: Primary outcomes included maternal, delivery, and neonatal complications including preterm delivery, cesarean section, hysterectomy, blood transfusion, deep venous thrombosis, pulmonary embolism, congenital anomalies, intrauterine fetal demise, and small-for-gestational-age neonates. Logistic regression analyses were conducted to evaluate the association between cervical cancer diagnosis and these outcomes, adjusting for potential confounding factors. Results: Women with cervical cancer were older (25.2% ≥35 years vs. 14.7%, p=0.001, respectively); more likely to have Medicare insurance (1.4% vs. 0.6%, p=0.005, respectively); use illicit drugs (4.1% vs. 1.4%, p=0.001, respectively); smoke tobacco during pregnancy (14.9% vs. 4.9%, p=0.001, respectively); and have chronic hypertension (3.6% vs. 1.8%, p=0.046, respectively). These women also had higher rates of preterm delivery (OR = 4.73, 95% CI (3.53-6.36), p=0.001); cesarean section (OR = 5.40, 95% CI (4.00-7.30), p=0.001); hysterectomy (OR = 390.23, 95% CI (286.43-531.65), p=0.001); blood transfusions (OR = 19.23, 95% CI (13.57-27.25), p=0.001); deep venous thrombosis (OR = 9.42, 95% CI (1.32-67.20), p=0.025); and pulmonary embolism (OR = 20.22, 95% CI (2.83-144.48), p=0.003). Neonatal outcomes, including congenital anomalies, intrauterine fetal demise, and small-for-gestational-age neonates, were comparable between groups. Conclusions and Relevance: Cervical cancer during pregnancy is associated with significant maternal and delivery risks; however, neonatal outcomes are largely unaffected. These findings highlight the need for a multidisciplinary approach to managing pregnant cervical cancer patients involving oncological, obstetrical, and neonatal care specialists.

Keywords: cervical cancer, maternal outcomes, neonatal outcomes, delivery outcomes

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Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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Authors: Susmita Roy, Madhavan Nallani

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

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

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Authors: Manal M. Kame, Hanan G. El-Baz, Zeinab A.Demerdash, Engy M. Abd El-Moneem, Mohamed A. Hendawy, Ibrahim R. Bayoumi

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There is a constant need to improve the performance of current diagnostic assays of schistosomiasis as well as develop innovative testing strategies to meet new testing challenges. This study aims at increasing the diagnostic efficiency of monoclonal antibody (MAb)-based antigen detection assays through gold nanoparticles conjugated with specific anti-Schistosoma mansoni monoclonal antibodies. In this study, several hybidoma cell lines secreting MAbs against adult worm tegumental Schistosoma antigen (AWTA) were produced at Immunology Department of Theodor Bilharz Research Institute and preserved in liquid nitrogen. One MAb (6D/6F) was chosen for this study due to its high reactivity to schistosome antigens with highest optical density (OD) values. Gold nanoparticles (AuNPs) were functionalized and conjugated with MAb (6D/6F). The study was conducted on serum samples of 116 subjects: 71 patients with S. mansoni eggs in their stool samples group (gp 1), 25 with other parasites (gp2) and 20 negative healthy controls (gp3). Patients in gp1 were further subdivided according to egg count in their stool samples into Light infection {≤ 50 egg per gram(epg) (n= 17)}, moderate {51-100 epg (n= 33)} and severe infection {>100 epg(n= 21)}. Sandwich ELISA was performed using (AuNPs -MAb) for detection of circulating schistosomal antigen (CSA) levels in serum samples of all groups and the results were compared with that after using MAb/ sandwich ELISA system. Results Gold- MAb/ ELISA system reached a lower detection limit of 10 ng/ml compared to 85 ng/ml on using MAb/ ELISA and the optimal concentrations of AuNPs -MAb were found to be 12 folds less than that of MAb/ ELISA system for detection of CSA. The sensitivity and specificity of sandwich ELISA for detection of CSA levels using AuNPs -MAb were 100% & 97.8 % respectively compared to 87.3% &93.38% respectively on using MAb/ ELISA system. It was found that CSA was detected in 9 out of 71 S.mansoni infected patients on using AuNPs - MAb/ ELISA system and was not detected by MAb/ ELISA system. All those patients (9) was found to have an egg count below 50 epg feces (patients with light infections). ROC curve analyses revealed that sandwich ELISA using gold-MAb was an excellent diagnostic investigator that could differentiate Schistosoma patients from healthy controls, on the other hand it revealed that sandwich ELISA using MAb was not accurate enough as it could not recognize nine out of 71 patients with light infections. Conclusion Our data demonstrated that: Loading gold nanoparticles with MAb (6D/6F) increases the sensitivity and specificity of sandwich ELISA for detection of CSA, thus active (early) and light infections could be easily detected. Moreover this binding will decrease the amount of MAb consumed in the assay and lower the coast. The significant positive correlation that was detected between ova count (intensity of infection) and OD reading in sandwich ELISA using gold- MAb enables its use to detect the severity of infections and follow up patients after treatment for monitoring of cure.

Keywords: Schistosomiasis, nanoparticles, gold, monoclonal antibodies, ELISA

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Authors: Alok Nahata

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Introduction: Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Methodology: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/kg p.o.). Major Findings: GL extracts attenuated the increase in the prostate/body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P < 0.01). Ethanolic extract (20 and 50 mg/kg p.o.) also exhibited significant activity (P < 0.01). The urine output also improved significantly (P < 0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies suggested improvement in prostatic histoarchitecture in extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.

Keywords: benign prostatic hyperplasia, Ganoderma lucidum, prostate-specific antigen, 5α-reductase, testosterone

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Authors: Helen K. Buteme, Rebecca Axelsson-Robertson, Moses L. Joloba, Henry W. Boom, Gunilla Kallenius, Markus Maeurer

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Background: The Ugandan population is heavily affected by infectious diseases and Human leukocyte antigen (HLA) diversity plays a crucial role in the host-pathogen interaction and affects the rates of disease acquisition and outcome. The identification of HLA class 1 alleles and determining which alleles are associated with tuberculosis (TB) outcomes would help in screening individuals in TB endemic areas for susceptibility to TB and to predict resistance or progression to TB which would inevitably lead to better clinical management of TB. Aims: To be able to determine the HLA class 1 phenotype distribution in a Ugandan TB cohort and to establish the relationship between these phenotypes and active and latent TB. Methods: Blood samples were drawn from 32 HIV negative individuals with active TB and 45 HIV negative individuals with latent MTB infection. DNA was extracted from the blood samples and the DNA samples HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. Results: HLA-A*02, A*01, A*74, A*30, B*15, B*58, C*07, C*03 and C*04 were the dominant phenotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the individuals with LTBI with only HLA-A*03 allele showing a statistically significant difference (p=0.0136). However, after FDR computation the corresponding q-value is above the expected proportion of false discoveries (q-value 0.2176). Key findings: We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results also suggest that there may be a positive association between the HLA-A*03 allele and TB implying that individuals with the HLA-A*03 allele are at a higher risk of developing active TB.

Keywords: HLA, phenotype, tuberculosis, Uganda

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Authors: V. Sathya Narayanan, P. Sidharth, V. R. Sanal Kumar

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The success of any retail business is predisposed by its swift response and its knack in understanding the constraints and the requirements of customers. In this paper a conceptual design model of an automated customer-friendly supermarket has been proposed. In this model a 10-sided, space benefited, regular polygon shaped gravity shelves have been designed for goods storage and effective customer-specific algorithms have been built-in for quick automatic delivery of the randomly listed goods. The algorithm is developed with two main objectives, viz., delivery time and priority. For meeting these objectives the randomly listed items are reorganized according to the critical-path of the robotic arm specific to the identified shop and its layout and the items are categorized according to the demand, shape, size, similarity and nature of the product for an efficient pick-up, packing and delivery process. We conjectured that the proposed automated supermarket model reduces business operating costs with much customer satisfaction warranting a win-win situation.

Keywords: automated supermarket, electronic shopping, polygon-shaped rack, shortest path algorithm for shopping

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Authors: Kgabo H. Badimo, Sheryl Buckley

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Knowledge is increasingly recognised in this, the knowledge era, as a strategic resource, by public sector organisations, in view of the public sector reform initiatives. People and knowledge play a vital role in attaining improved organisational performance and high service quality. Many government departments in the public sector have started to realise the importance of knowledge management in streamlining their operations and processes. This study focused on knowledge management in the public healthcare service organisations, where the concept of service provider competitiveness pales to insignificance, considering the huge challenges emanating from the healthcare and public sector reforms. Many government departments are faced with challenges of improving organisational performance and service delivery, improving accountability, making informed decisions, capturing the knowledge of the aging workforce, and enhancing partnerships with stakeholders. The purpose of this paper is to examine the knowledge management practices of the Gauteng Department of Health in South Africa, in order to understand how knowledge management practices influence improvement in organisational performance and healthcare service delivery. This issue is explored through a review of literature on dominant views on knowledge management and healthcare service delivery, as well as results of interviews with, and questionnaire responses from, the general staff of the Gauteng Department of Health. Web-based questionnaires, face-to-face interviews and organisational documents were used to collect data. The data were analysed using both the quantitative and qualitative methods. The central question investigated was: To what extent can the conditions required for successful knowledge management be observed, in order to improve organisational performance and healthcare service delivery in the Gauteng Department of Health. The findings showed that the elements of knowledge management capabilities investigated in this study, namely knowledge creation, knowledge sharing and knowledge application, have a positive, significant relationship with all measures of organisational performance and healthcare service delivery. These findings thus indicate that by employing knowledge management principles, the Gauteng Department of Health could improve its ability to achieve its operational goals and objectives, and solve organisational and healthcare challenges, thereby improving organisational.

Keywords: knowledge management, Healthcare Service Delivery, public healthcare, public sector

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Authors: Manju Kanu, Subrata Sinha, Surabhi Johari

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Viral proteins of Ebola viruses belong to one of the best studied viruses; however no effective prevention against EBOV has been developed. Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with Ebola virus as a model system. Hence great challenge in the field of ebola virus research is to design universal vaccine. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertypes Human Leukocyte Antigen (HLA) alleles. MUSCLE and MOTIF tools were used to find out most conserved peptide sequences of viral proteins. Immunoinformatics tools were used for prediction of immunogenic peptides of viral proteins in zaire strains of Ebola virus. Putative epitopes for viral proteins (VP) were predicted from conserved peptide sequences of VP. Three tools NetCTL 1.2, BIMAS and Syfpeithi were used to predict the Class I putative epitopes while three tools, ProPred, IEDB-SMM-align and NetMHCII 2.2 were used to predict the Class II putative epitopes. B cell epitopes were predicted by BCPREDS 1.0. Immunogenic peptides were identified and selected manually by putative epitopes predicted from online tools individually for both MHC classes. Finally sequences of predicted peptides for both MHC classes were looked for common region which was selected as common immunogenic peptide. The immunogenic peptides were found for viral proteins of Ebola virus: epitopes FLESGAVKY, SSLAKHGEY. These predicted peptides could be promising candidates to be used as target for vaccine design.

Keywords: epitope, b cell, immunogenicity, ebola

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Authors: Dale Dzemydiene, Aurelija Burinskiene, Arunas Miliauskas, Kristina Ciziuniene

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Data flow and the purpose of reporting the data are different and dependent on business needs. Different parameters are reported and transferred regularly during freight delivery. This business practices form the dataset constructed for each time point and contain all required information for freight moving decisions. As a significant amount of these data is used for various purposes, an integrating methodological approach must be developed to respond to the indicated problem. The proposed methodology contains several steps: (1) collecting context data sets and data validation; (2) multi-objective analysis for optimizing freight transfer services. For data validation, the study involves Grubbs outliers analysis, particularly for data cleaning and the identification of statistical significance of data reporting event cases. The Grubbs test is often used as it measures one external value at a time exceeding the boundaries of standard normal distribution. In the study area, the test was not widely applied by authors, except when the Grubbs test for outlier detection was used to identify outsiders in fuel consumption data. In the study, the authors applied the method with a confidence level of 99%. For the multi-objective analysis, the authors would like to select the forms of construction of the genetic algorithms, which have more possibilities to extract the best solution. For freight delivery management, the schemas of genetic algorithms' structure are used as a more effective technique. Due to that, the adaptable genetic algorithm is applied for the description of choosing process of the effective transportation corridor. In this study, the multi-objective genetic algorithm methods are used to optimize the data evaluation and select the appropriate transport corridor. The authors suggest a methodology for the multi-objective analysis, which evaluates collected context data sets and uses this evaluation to determine a delivery corridor for freight transfer service in the multi-modal transportation network. In the multi-objective analysis, authors include safety components, the number of accidents a year, and freight delivery time in the multi-modal transportation network. The proposed methodology has practical value in the management of multi-modal transportation processes.

Keywords: multi-objective, analysis, data flow, freight delivery, methodology

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Authors: Paul J Yazaki, Michael Bouvet, John Shively

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Surgery for solid gastrointestinal (GI) cancers such as pancreatic, colorectal, and gastric adenocarcinoma remains the mainstay of curative therapy. Complete resection of the primary tumor with negative margins (R0 resection), its draining lymph nodes, and distant metastases offers the optimal surgical benefit. Real-time fluorescence guided surgery (FGS) promises to improve GI cancer outcomes and is rapidly advancing with tumor-specific antibody conjugated fluorophores that can be imaged using near infrared (NIR) technology. Carcinoembryonic Antigen (CEA) is a non-internalizing tumor antigen validated as a surface tumor marker expressed in >95% of colorectal, 80% of gastric, and 60% of pancreatic adenocarcinomas. Our humanized anti-CEA hT84.66-M5A (M5A) monoclonal antibody (mAb)was conjugated with the NHS-IRDye800CW fluorophore and shown it can rapidly and effectively NIRoptical imageorthotopically implanted human colon and pancreatic cancer in mouse models. A limitation observed is that these NIR-800 dye conjugated mAbs have a rapid clearance from the blood, leading to a narrow timeframe for FGS and requiring high doses for effective optical imaging. We developed a novel antibody-fluorophore conjugate by incorporating a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity which effectively extended the agent’s blood circulation half-life leading to increased tumor sensitivity and lowered normal hepatic uptake. We hypothesized that our unique anti-CEA linked to the fluorophore, IR800 by PEGylated sidewinder, M5A-SW-IR800 will become the next generation optical imaging agent, safe, effective, and widely applicable for intraoperative image guided surgery in CEA expressing GI cancers.

Keywords: optical imaging, anti-CEA, cancer, fluorescence-guided surgery

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: Pradakshina Sharma, Jagriti Narang

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Due to the critical significance in the early identification of infectious diseases, electrochemical sensors have garnered considerable interest. Here, we develop a detection platform for the chikungunya virus by rationally implementing the extremely high charge-transfer efficiency of a ternary nanocomposite of graphene oxide, silver, and gold (G/Ag/Au) (CHIKV). Because paper is an inexpensive substrate and can be produced in large quantities, the use of electrochemical paper analytical device (EPAD) origami further enhances the sensor's appealing qualities. A cost-effective platform for point-of-care diagnostics is provided by paper-based testing. These types of sensors are referred to as eco-designed analytical tools due to their efficient production, usage of the eco-friendly substrate, and potential to reduce waste management after measuring by incinerating the sensor. In this research, the paper's foldability property has been used to develop and create 3D multifaceted biosensors that can specifically detect the CHIKVX-ray diffraction, scanning electron microscopy, UV-vis spectroscopy, and transmission electron microscopy (TEM) were used to characterize the produced nanoparticles. In this work, aptamers are used since they are thought to be a unique and sensitive tool for use in rapid diagnostic methods. Cyclic voltammetry (CV) and linear sweep voltammetry (LSV), which were both validated with a potentiostat, were used to measure the analytical response of the biosensor. The target CHIKV antigen was hybridized with using the aptamer-modified electrode as a signal modulation platform, and its presence was determined by a decline in the current produced by its interaction with an anionic mediator, Methylene Blue (MB). Additionally, a detection limit of 1ng/ml and a broad linear range of 1ng/ml-10µg/ml for the CHIKV antigen were reported.

Keywords: biosensors, ePAD, arboviral infections, point of care

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

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The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.

Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles

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Authors: Joanna Maj, Awais Hussain, Lyndsey Vu, Catherine Roxas

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Background: Bone injuries in babies are common conditions that arise during delivery. Fractures of the clavicle, humerus, femur, and skull are the most common neonatal bone injuries sustained from labor and delivery. During operative deliveries, zealous tractions, ineffective delivery techniques, improper uterine incision, and inadequate relaxation of the uterus can lead to bone fractures in the newborn. Neonatal anatomy is unique. Just as children are not mini-adults, newborns are not mini children. A newborn’s anatomy and physiology are significantly different from a pediatric patient's. In this paper, we describe common orthopedic trauma in newborn babies. We provide a comprehensive overview of the different types of bone injuries in newborns. We hypothesize that the rate of bone fractures sustained at birth is higher in cases of operative deliveries. Methods: Relevant literature was selected by using the PubMed database. Search terms included orthopedic conditions in newborns, neonatal anatomy, and bone fractures in neonates during operative deliveries. Inclusion criteria included age, gender, race, type of bone injury and progression of bone injury. Exclusion criteria were limited in the medical history of cases reviewed and comorbidities. Results: This review finds that a clavicle fracture is the most common type of neonatal orthopedic injury sustained at birth in both operative and non-operative deliveries. We confirm the hypothesis that infants born via operative deliveries have a significantly higher rate of bone fractures than non-cesarean section deliveries. Conclusion: Newborn babies born via operative deliveries have a higher rate of bone fractures of the clavicle, humerus, and femur. A clavicle bone fracture in newborns is most common during emergency operative deliveries in new mothers. We conclude that infants born via an operative delivery sustained more bone injuries than infants born via non-cesarean section deliveries.

Keywords: clavicle fracture, humerus fracture, neonates, newborn orthopedics, orthopedic surgery, pediatrics, orthopedic trauma, orthopedic trauma during delivery, cesarean section, obstetrics, neonatal anatomy, neonatal fractures, operative deliveries, labor and delivery, bone injuries in neonates

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Authors: R. Venkatesan, A. Sabari

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Developments of social networking internet scenario are recommended for the requirements of scalable, authentic, secure group communication model like multicasting. Multicasting is an inter network service that offers efficient delivery of data from a source to multiple destinations. Even though multicast has been very successful at providing an efficient and best-effort data delivery service for huge groups, it verified complex process to expand other features to multicast in a scalable way. Separately, the requirement for secure electronic information had become gradually more apparent. Since multicast applications are deployed for mainstream purpose the need to secure multicast communications will become significant.

Keywords: multicasting, scalability, security, social network

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Authors: Anh Vo Van Ha, Yun Zhao, Luat Cong Nguyen, Tan Khac Chu, Phung Hoang Nguyen, Minh Ngoc Pham, Colin W. Binns, Andy H. Lee

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This study aims to study longitudinal changes in blood pressure (BP) during the 1-year postpartum period and to evaluate the influence of parity, maternal age at delivery, prepregnancy BMI, gestational weight gain, gestational age at delivery and postpartum maternal weight. A prospective longitudinal cohort study of 883 singleton Vietnamese women was conducted in Hanoi, Haiphong, and Ho Chi Minh City, Vietnam during 2015-2017. Women diagnosed with gestational diabetes mellitus at 24-28 weeks of gestation, pre-eclampsia, and hypoglycemia was excluded from analysis. BP was repeatedly measured at discharge, 6 and 12 months postpartum using automatic blood pressure monitors. Linear mixed model with repeated measures was used to describe changes occurring during pregnancy to 1-year postpartum. Parity, self-reported prepregnancy BMI, gestational weight gain, maternal age and gestational age at delivery will be treated as time-invariant variables and measured maternal weight will be treated as a time-varying variable in models. Women with higher measured postpartum weight had higher mean systolic blood pressure (SBP), 0.20 mmHg, 95% CI [0.12, 0.28]. Similarly, women with higher measured postpartum weight had higher mean diastolic blood pressure (DBP), 0.15 mmHg, 95% CI [0.08, 0.23]. These differences were both statistically significant, P < 0.001. There were no differences in SBP and DBP depending on parity, maternal age at delivery, prepregnancy BMI, gestational weight gain and gestational age at delivery. Compared with discharge measurement, SBP was significantly higher in 6 months postpartum, 6.91 mmHg, 95% CI [6.22, 7.59], and 12 months postpartum, 6.39 mmHg, 95% CI [5.64, 7.15]. Similarly, DBP was also significantly higher in 6 and months postpartum than at discharge, 10.46 mmHg 95% CI [9.75, 11.17], and 11.33 mmHg 95% CI [10.54, 12.12]. In conclusion, BP measured repeatedly during the postpartum period (6 and 12 months postpartum) showed a statistically significant increase, compared with after discharge from the hospital. Maternal weight was a significant predictor of postpartum blood pressure over the 1-year postpartum period.

Keywords: blood pressure, maternal weight, postpartum, Vietnam

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Authors: Mewa Singh

Abstract:

Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

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Authors: S. T. Kumbhar, M. S. Bhatia, R. C. Khairate

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An effective nanodrug delivery system was developed by using chitosan for increased encapsulation efficiency and retarded release of curcumin. Potential ionotropic gelation method was used for the development of chitosan nanoparticles with TPP as cross-linker. The characterization was done for analysis of size, structure, surface morphology, and thermal behavior of synthesized chitosan nanoparticles. The encapsulation efficiency was more than 80%, with improved drug loading capacity. The in-vitro drug release study showed that curcumin release rate was decreased significantly. These chitosan nanoparticles could be a suitable platform for co-delivery of curcumin and anticancer agent for enhanced cytotoxic effect on tumor cells.

Keywords: Curcumin, chitosan, nanoparticles, anticancer activity

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Authors: Ashish Kumar Jain, Deepak Mishra

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The objective of the present investigation was to prepare and evaluate a vesicular dual drug delivery system for effective management of mucosal ulcer. Inner encapsulating and Double liposomes were prepared by glass bead and reverse phase evaporation method respectively. The formulation consisted of inner liposomes bearing Ranitidine Bismuth Citrate (RBC) and outer liposomes encapsulating Amoxicillin trihydrate (AMOX). The optimized inner liposomes and double liposomes were extensively characterized for vesicle size, morphology, zeta potential, vesicles count, entrapment efficiency and in vitro drug release. In vitro, the double liposomes demonstrated a sustained release of AMOX and RBC viz 91.4±1.8% and 77.2±2.1% respectively at the end of 72 hr. Furthermore binding specificity and targeting propensity toward H. pylori (SKP-56) was confirmed by agglutination and in situ adherence assay. Reduction of the absolute alcohol induced ulcerogenic index from 3.01 ± 0.25 to 0.31 ± 0.09 and 100% H. pylori clearance rate was observed. These results suggested that double liposomes are potential vector for the development of dual drug delivery for effective treatment of H. pylori-associated peptic ulcer.

Keywords: double liposomes, H. pylori targeting, PE liposomes, glass-beads method, peptic ulcers

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Authors: Gyati Shilakari Asthana, Abhay Asthana

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Purpose: The therapeutic potential of oligonucleotide (ODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study is focused to design low molecular weight chitosan nanoconstructs to meet the requirements of safe and effectual delivery of ODNs. LMW-chitosan is a biodegradable, water soluble, biocompatible polymer and is useful as a non-viral vector for gene delivery due to its better stability in water. Methods: LMW chitosan ODN nanoparticles (CHODN NPs) were formulated by self assembled method using various N/P ratios (moles ratio of amine groups of CH to phosphate moieties of ODNs; 0.5:1, 1:1, 3:1, 5:1 and 7:1) of CH to ODN. The developed CHODN NPs were evaluated with respect to gel retardation assay, particle size, zeta potential and cytotoxicity and transfection efficiency. Results: Complete complexation of CH/ODN was achieved at the charge ratio of 0.5:1 or above and CHODN NPs displayed resistance against DNase I. On increasing the N/P ratio of CH/ODN, particle size of the NPs decreased whereas zeta potential (ZV) value increased. No significant toxicity was observed at all CH concentrations. The transfection efficiency was increased on increasing N/P ratio from 1:1 to 3:1, whereas it was decreased with further increment in N/P ratio upto 7:1. Maximum transfection of CHODN NPs with both the cell lines (Raw 267.4 cells and Hela cells) was achieved at N/P ratio of 3:1. The results suggest that transfection efficiency of CHODN NPs is dependent on N/P ratio. Conclusion: Thus the present study states that LMW chitosan nanoparticulate carriers would be acceptable choice to improve transfection efficiency in vitro as well as in vivo delivery of oligonucleotide.

Keywords: LMW-chitosan, chitosan nanoparticles, biocompatibility, cytotoxicity study, transfection efficiency, oligonucleotide

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Authors: Abdullahi Bn Umar

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Over the years curriculum planners and researchers in education have continued to seek for ways to improve teaching and learning by way of varying approaches to curriculum and instruction in line with dynamic nature of knowledge. In this regards various innovative strategies to teaching and learning have been adopted to match with the technological advancement in education particularly in the aspect of instructional delivery through Information Communication Technology (ICT) as a tools. This paper reviews some innovative strategies and how they impact on learner’s achievement and educational development in Nigeria. The paper concludes by recommending innovative approach appropriate for use in Nigerian context.

Keywords: innovation, instructional delivery, virtual laboratory, educational design

Procedia PDF Downloads 483

Authors: Ainoa Guinart, Maria Korpidou, Daniel Doellerer, Cornelia Palivan, Ben L. Feringa

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Stimuli responsive systems arise from the need to meet unsolved needs of current molecular drugs. Our study presents the design of a delivery system with high spatiotemporal control and tuneable release profiles. We study the incorporation of a hydrophobic synthetic molecular motor into PDMS-b-PMOXA block copolymer vesicles to create a self-assembled system. We prove their successful incorporation and selective activation by low powered visible light (λ 430 nm, 6.9 mW). We trigger the release of a fluorescent dye with high release efficiencies over sequential cycles (up to 75%) with the ability to turn on and off the release behaviour on demand by light irradiation. Low concentrations of photo-responsive units are proven to trigger release down to 1 mol% of molecular motor. Finally, we test our system in relevant physiological conditions using a lung cancer cell line and the encapsulation of an approved drug. Similar levels of cell viability are observed compared to the free-given drugshowing the potential of our platform to deliver functional drugs on demand with the same efficiency and lower toxicity.

Keywords: molecular motor, polymer, drug delivery, light-responsive, cancer, selfassembly

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Authors: Alesandro Romero, Inaki Maulida Hakim

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This research was conducted in an automotive company in Indonesia to overcome the problem of high logistics cost. The problem causes high of additional truck delivery. From the breakdown of the problem, chosen one route, which has the highest gap value, namely for RE-04. Research methodology will be started from calculating the ideal condition, making simulation, calculating the ideal logistic cost, and proposing an improvement. From the calculation of the ideal condition, box arrangement was done on the truck; the average efficiency was 97,4 % with three trucks delivery per day. Route simulation making uses Tecnomatix Plant Simulation software as a visualization for the company about how the system is occurred on route RE-04 in ideal condition. Furthermore, from the calculation of logistics cost of the ideal condition, it brings savings of Rp53.011.800,00 in a month. The last step is proposing improvements on the area of route RE-04. The route arrangement is done by Saving Method and sequence of each supplier with the Nearest Neighbor. The results of the proposed improvements are three new route groups, where was expected to decrease logistics cost Rp3.966.559,40 per day, and increase the average of the truck efficiency 8,78% per day.

Keywords: efficiency, logistic cost, milkrun, saving methode, simulation

Procedia PDF Downloads 446

Authors: Chia-Ching Tsai

Abstract:

In service delivery, interpersonal interaction is the key to customer satisfaction, and apparently, the factor of human is critical in service delivery. Besides, customers quite care about the consequences of co-recovery. Thus, this research focuses on service failure caused by other customers and uses a 2x2 factorial design to investigate the impact of consequence and level of service co-recovery on post-recovery satisfaction and repurchase intent. 150 undergraduates were recruited as participants, and assigned to one of the four cells randomly. Every participant was requested to read the scenario and then rated the post-recovery satisfaction and repurchase intent. The results show that under the condition of failed co-recovery, level of co-recovery has no effect on post-recovery satisfaction, while under the condition of successful co-recovery, high-level co-recovery causes significantly higher post-recovery satisfaction than low-level co-recovery. Moreover, post-recovery satisfaction has significantly positive impact on repurchase intent. In the system of service delivery, customers interact with other customers frequently. Therefore, comparing with the literature, this research focuses on the service failure caused by other customers. This research also supplies a better understanding of customers’ view on consequences of different levels of co-recovery, which is helpful for the practitioners to make use of co-recovery.

Keywords: service failure, service co-recovery, consequence of co-recovery, level of co-recovery, post-recovery satisfaction, repurchase intent

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Authors: Nizar Jawad Hadi, Sajad Abd Alabbas

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Because of their ability to encapsulate and release drugs in a controlled manner, microspheres fabricated from polymer emulsions using microfluidic devices have shown promise for drug delivery applications. In this study, the effects of velocity, density, viscosity, and surface tension, as well as channel diameter, on microsphere generation were investigated using Fluent Ansys software. The software was programmed with the physical properties of the polymer emulsion such as density, viscosity and surface tension. Simulation will then be performed to predict fluid flow and microsphere production and improve the design of drug delivery applications based on changes in these parameters. The effects of capillary and Weber numbers are also studied. The results of the study showed that the size of the microspheres can be controlled by adjusting the speed and diameter of the channel. Narrower microspheres resulted from narrower channel widths and higher flow rates, which could improve drug delivery efficiency, while smaller microspheres resulted from lower interfacial surface tension. The viscosity and density of the polymer emulsion significantly affected the size of the microspheres, ith higher viscosities and densities producing smaller microspheres. The loading and drug release properties of the microspheres created with the microfluidic technique were also predicted. The results showed that the microspheres can efficiently encapsulate drugs and release them in a controlled manner over a period of time. This is due to the high surface area to volume ratio of the microspheres, which allows for efficient drug diffusion. The ability to tune the manufacturing process using factors such as speed, density, viscosity, channel diameter, and surface tension offers a potential opportunity to design drug delivery systems with greater efficiency and fewer side effects.

Keywords: polymer emulsion, microspheres, numerical simulation, microfluidic device

Procedia PDF Downloads 66

Authors: Filipa Vasconcelos

Abstract:

The administration of endoplasmic reticulum amino peptidases (ERAP1 or ERAP2) inhibitors can be used for therapeutic approaches against cancer and auto-immune diseases. However, one of the main shortcomings of drug delivery systems (DDS) is associated with the drug off-target distribution, which can lead to an increase in its side effects on the patient’s body. To overcome such limitations, the encapsulation of four representative compounds of ERAP inhibitors into Polycaprolactone (PCL), Polyvinyl-alcohol (PVA), crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes is proposed as a safe and controlled drug release system. The use of electrospun fibrous meshes as a DDS allows efficient solvent evaporation giving limited time to the encapsulated drug to recrystallize, continuous delivery of the drug while the fibers degrade, prevention of initial burst release (sustained release), tunable dosages, and the encapsulation of other agents. This is possible due to the fibers' small diameters and resemblance to the extracellular matrix (confirmed by scanning electron microscopy results), high specific surface area, and good mechanical strength/stability. Furthermore, release studies conducted on PCL, PVA, crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes with each of the ERAP compounds encapsulated demonstrated that they were capable of releasing >60%, 50%, 40%, and 45% of the total ERAP concentration, respectively. Fibrous meshes with ERAP_E compound encapsulated achieved higher released concentrations (75.65%, 62.41%, 56.05%, and 65.39%, respectively). Toxicity studies of fibrous meshes with encapsulated compounds are currently being accessed in vitro, as well as pharmacokinetics and dynamics studies. The last step includes the implantation of the drug-loaded fibrous meshes in vivo.

Keywords: drug delivery, electrospinning, ERAP inhibitors, liposomes

Procedia PDF Downloads 106

Authors: Shan Li, Qiuwen Ma

Abstract:

Integrated project delivery (IPD) is a project delivery method distinguished by a shared risk/rewards mechanism and multiparty agreement. IPD has drawn increasingly attention from construction industry because of its efficiency of solving adversarial problems and reliability to deliver high-performing buildings. However, some evidence showed that some project participants obtained less profit from IPD projects than the typical projects. They attributed it to the unfair IPD sharing mechanism, which resulted in additional time and cost of negotiation on the sharing fractions among project participants. The study is aimed to investigate the reward distribution by constructing a principal-agent model. Based on cooperative game theory, it is examined how to distribute the shared project rewards between client and non-client parties, and identify the sharing fractions among non-client parties. It is found that at least half of the project savings should be allocated to the non-client parties to motivate them to create more project value. Second, the client should raise his sharing fractions when the integration among project participants is efficient. In addition, the client should allocate higher sharing fractions to the non-client party who is more able. This study can help the IPD project participants make fair and motivated sharing mechanisms.

Keywords: cooperative game theory, IPD, principal agent model, sharing mechanism

Procedia PDF Downloads 293