Search results for: colon delivery system
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 18619

Search results for: colon delivery system

18319 Motivational Strategies and Job Satisfaction as Correlates of Library Service Delivery in Selected Tertiary Institutions in Southwest Nigeria

Authors: Esther Kelechi Soyele

Abstract:

Job satisfaction is the expression of an organisation's fulfillment of work output. In order to achieve effective job satisfaction, the motivation of employees is very essential in stimulating their obligation towards their work. The study examined the motivational strategies, job satisfaction as a correlation of library service delivery in some selected tertiary institutions in southwest Nigeria. The study adopted a descriptive survey research design. A simple random sampling method was employed to select 200 library staff consisting of both library professionals and para-professionals. Two hundred (200) questionnaires were given out, but only one hundred and twenty-nine 129 (96% response rate) were used for the study. Both simple percentage and one and two way ANOVA was used for data analysis. Findings revealed that 60.4% of the respondents were males while 39.6% were female; most of the respondents’ relatively belong to the age group of 31-40 and 41-50, 93.3% were within the age range of 21-50 years, and 43.2 % were M.Sc degree holders. The result revealed a (p < 0.05) significant relationship between work motivational strategies and library service delivery. The results also revealed that motivational development program strategies and job satisfaction have (p < 0.05) a positive significant relationship with library service delivery. It was concluded that work motivation strategies are essential for job satisfaction which is very important in any organization in the attainment of its goals and objectives and helps in maintaining a high standard. The study recommended that more incentive plans that will enhance job satisfaction should be put in place to encourage employees to be more active in carrying out their job effectively.

Keywords: job satisfaction, library, library services, motivational strategies

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18318 Engaging Citizen, Sustaining Service Delivery of Rural Water Supply in Indonesia

Authors: Rahmi Yetri Kasri, Paulus Wirutomo

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Citizen engagement approach has become increasingly important in the rural water sector. However, the question remains as to what exactly is meant by citizen engagement and how this approach can lead to sustainable service delivery. To understand citizen engagement, this paper argues that we need to understand basic elements of social life that consist of social structure, process, and culture within the realm of community’s living environment. Extracting from empirical data from Pamsimas villages in rural West Java, Indonesia, this paper will identify basic elements of social life and environment that influence and form the engagement of citizen and government in delivering and sustaining rural water supply services in Indonesia. Pamsimas or the Water Supply and Sanitation for Low Income Communities project is the biggest rural water program in Indonesia, implemented since 1993 in more than 27,000 villages. The sustainability of this sector is explored through a rural water supply service delivery life-cycle, starts with capital investment, operational and maintenance, asset expansion or renewal, strategic planning for future services and matching cost with financing. Using mixed-method data collection in case study research, this paper argues that increased citizen engagement contributes to a more sustainable rural water service delivery.

Keywords: citizen engagement, rural water supply, sustainability, Indonesia

Procedia PDF Downloads 244
18317 Strategy in Practice: Strategy Development, Strategic Error and Project Delivery

Authors: Nipun Agarwal, David Paul, Fareed Un Din

Abstract:

Strategy development and implementation is the key to an organization’s success in today’s competitive marketplace. Many organizations develop excellent strategy but are unable to implement this strategy in order to succeed. The difference between strategic goals and its implementation is called strategic error. Strategic error occurs when an organization does not have structures in place to implement their strategy. Strategy implementation happens through projects and having a project management method that provides certainty and agility will help an organization become more competitive in implementing strategy. Numerous project management methods exist in theory and practice. However, projects mainly used the Waterfall method in the past that provides certainty in terms of budget, delivery date and resourcing. It is common practice now to utilise Agile based methods. However, Agile based methods do not provide specific deadlines and budgets. But provide agility in product design and project delivery, which is useful to companies. Both Waterfall and Agile methods in some forms are the opposites of each other. Executive management prefer agility in delivery projects as the competitive landscape changes frequently. However, they also appreciate certainty in the projects being able to quantify budgets, deadlines and resources that is harder for an Agile based method to provide. This paper attempts to develop a hybrid project management method that attempts to merge these Waterfall and Agile methods to provide the positives from both these approaches.

Keywords: strategy, project management, strategy implementation, agile

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18316 An Enhanced AODV Routing Protocol for Wireless Sensor and Actuator Networks

Authors: Apidet Booranawong, Wiklom Teerapabkajorndet

Abstract:

An enhanced ad-hoc on-demand distance vector routing (E-AODV) protocol for control system applications in wireless sensor and actuator networks (WSANs) is proposed. Our routing algorithm is designed by considering both wireless network communication and the control system aspects. Control system error and network delay are the main selection criteria in our routing protocol. The control and communication performance is evaluated on multi-hop IEEE 802.15.4 networks for building-temperature control systems. The Gilbert-Elliott error model is employed to simulate packet loss in wireless networks. The simulation results demonstrate that the E-AODV routing approach can significantly improve the communication performance better than an original AODV routing under various packet loss rates. However, the control performance result by our approach is not much improved compared with the AODV routing solution.

Keywords: WSANs, building temperature control, AODV routing protocol, control system error, settling time, delay, delivery ratio

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18315 Application of Gold Nanorods in Cancer Photothermaltherapy

Authors: Mehrnaz Mostafavi

Abstract:

Lung cancer is one of the most harmful forms of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities such as surgical resection, radiation, and chemotherapy remains far from satisfactory. Systemic drug delivery is rarely successful because only a limited amount of the chemotherapeutic drug targets lung tumor sites, even when administered at a high dose. Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest.Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for lung cancer. Photothermal therapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation was investigated.Four types of small (<100nm), NIR absorbing gold nanoparticles (nanospheres, nanorods) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into lung cancer cell lines was measured using light scattering microscopy.Small gold nanorods had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 10°C and decrease in cell viability of up to 80% were obtained.

Keywords: photothermal, therapy, cancer, gold nanorods

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18314 Formulation and Evaluation of Curcumin-Zn (II) Microparticulate Drug Delivery System for Antimalarial Activity

Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

Abstract:

Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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18313 Hydrogel Hybridizing Temperature-Cured Dissolvable Gelatin Microspheres as Non-Anchorage Dependent Cell Carriers for Tissue Engineering Applications

Authors: Dong-An Wang

Abstract:

All kinds of microspheres have been extensively employed as carriers for drug, gene and therapeutic cell delivery. Most therapeutic cell delivery microspheres rely on a two-step methodology: fabrication of microspheres and subsequent seeding of cells onto them. In this study, we have developed a novel one-step cell encapsulation technique using a convenient and instant water-in-oil single emulsion approach to form cell-encapsulated gelatin microspheres. This technology is adopted for hyaline cartilage tissue engineering, in which autologous chondrocytes are used as therapeutic cells. Cell viability was maintained throughout and after the microsphere formation (75-100 µm diameters) process that avoids involvement of any covalent bonding reactions or exposure to any further chemicals. Further encapsulation of cell-laden microspheres in alginate gels were performed under 4°C via a prompt process. Upon the formation of alginate constructs, they were immediately relocated into CO2 incubator where the temperature was maintained at 37°C; under this temperature, the cell-laden gelatin microspheres dissolved within hours to yield similarly sized cavities and the chondrocytes were therefore suspended within the cavities inside the alginate gel bulk. Hence, the gelatin cell-laden microspheres served two roles: as cell delivery vehicles which can be removable through temperature curing, and as porogens within an alginate hydrogel construct to provide living space for cell growth and tissue development as well as better permeability for mutual diffusions. These cell-laden microspheres, namely “temperature-cured dissolvable gelatin microsphere based cell carriers” (tDGMCs), were further encapsulated in a chondrocyte-laden alginate scaffold system and analyzed by WST-1, gene expression analyses, biochemical assays, histology and immunochemistry stains. The positive results consistently demonstrated the promise of tDGMC technology in delivering these non-anchorage dependent cells (chondrocytes). It can be further conveniently translated into delivery of other non-anchorage dependent cell species, including stem cells, progenitors or iPS cells, for regeneration of tissues in internal organs, such as engineered hepatogenesis or pancreatic regeneration.

Keywords: biomaterials, tissue engineering, microsphere, hydrogel, porogen, anchorage dependence

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18312 Screening of Lactic Acid Bacteria Isolated from Traditional Fermented Products: Potential Probiotic Bacteria with Antimicrobial and Cytotoxic Activities

Authors: Genesis Julyus T. Agcaoili, Esperanza C. Cabrera

Abstract:

Thirty (30) isolates of lactic acid bacteria (LAB) from traditionally-prepared fermented products specifically fermented soy-bean paste, fermented mustard and fermented rice-fish mixture were studied for their in vitro antimicrobial and cytotoxic activities. Seventeen (17) isolates were identified as Lactobacillus plantarum, while 13 isolates were identified as Enterococcus spp using 16s rDNA sequences. Disc diffusion method was used to determine the antibacterial activity of LAB against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), while the modified agar overlay method was used to determine the antifungal activity of LAB isolates on the yeast Candida albicans, and the dermatophytes Microsporum gypseum, Trichophyton rubrum and Epidermophyton floccosum. The filter-sterilized LAB supernatants were evaluated for their cytotoxicity to mammalian colon cancer cell lines (HT-29 and HCT116) and normal human dermal fibrolasts (HDFn) using resazurin assay (PrestoBlueTM). Colchicine was the positive control. No antimicrobial activity was observed against the bacterial test organisms and the yeast Candida albicans. On the other hand, all of the tested LAB strains were fungicidal for all the test dermatophytes. Cytotoxicity index profiles of the supernatants of the 15 randomly picked LABs and negative control (brain heart infussion broth) suggest nontoxicity to the cells when compared to colchicine, whereas all LAB supernatants were found to be cytotoxic to HT-29 and HCT116 colon cancer cell lines. Results provide strong support for the role of the lactic acid bacteria studied in antimicrobial treatment and anticancer therapy.

Keywords: antimicrobial, fermented products, fungicidal activity, lactic acid bacteria, probiotics

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18311 Depressive-Like Behavior in a Murine Model of Colorectal Cancer Associated with Altered Cytokine Levels in Stress-Related Brain Regions

Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

Abstract:

Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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18310 Rapid Nanoparticle Formulation Development and Screening Using NanoFabTxTM Platform

Authors: Zhen Ye, Maryam Zaroudi, Elizabeth Aisenbrey, Nicolynn E. Davis, Peng Gao

Abstract:

Nanoparticles have been used as drug delivery systems in the treatment of life-threatening diseases for decades, but traditional formulation development methods are time consuming and labor intensive. Millipore Sigma has developed a platform¬¬– NanoFabTxTM¬¬– for rapid and reproducible formulation development and screening to ensure consistentnanoparticle characteristics. Reproducible and precise control of the development process for a range of nanoparticle formulations accelerates the introduction of novel formulations to the clinic.

Keywords: Bio platform, Formulation development, NanoFabTxTM, Drug delivery

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18309 Diselenide-Linked Redox Stimuli-Responsive Methoxy Poly(Ethylene Glycol)-b-Poly(Lactide-Co-Glycolide) Micelles for the Delivery of Doxorubicin in Cancer Cells

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

Abstract:

The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

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18308 Effect of an Oral Dose of M. elsdenii NCIMB 41125 on Lower Digestive Tract, Bacteria Count and Rumen Fermentation in Holstein Calves

Authors: M. C. Muya, L. J. Erasmus

Abstract:

Twenty four new born male Holstein calves were divided into two treatments groups and used to evaluate the effects of M. elsdenii NCIMB 41125. The first groups were dosed with 50 ml containing 108 CFU/mL of M. elsdenii NCIMB 41125 (Me) and the control calves were not dosed. Within each of the two treatments groups, calves were divided into three treatment groups (Not dosed: 7 d, 14 d and 21 d vs dosed Me 7 d, Me14 and Me21 d (treatments), each groups contained 4 calves within which two calves were euthanized at 24 h and two calves at 72 h. Calves entered the trial until euthanize at whether 24 or 72 H after dosing time. After receiving colostrum for 3 consecutive days after birth, calves were fed whole milk and had free access to a commercial calf starter pellet and fresh water. Fecal grab samples were taken from each calf in duplicate +24 h or +72 h relative to dosing. Immediately after euthanizing, the digestive tract was harvested, and duplicate rumen and colon digesta samples collected for VFA’s determination and DNA extraction for bacteria count using 16s RNA PCR probe technique. Independent two t-test was performed to compare mean volatile fatty acids. Mixed-effects linear regressions were performed to establish relationships between: 1) M. elsdenii and Me, and between VFA’s and Me using SAS (2009). M. elsdenii NCIMB 41125 was detected in the faeces, colon and rumen of dosed calves at both +24H and +72H and ranged from 1.6 x 106 to 4.9 x 109 cfu/ml, indicating its potential to colonize in the digestive tract of calves. There was a strong positive relationship (R²=0.96; P < 0.0001) between M. elsdenii NCIMB 41125 and M. elsdenii population (cfu/ml) in the rumen, suggesting that the increase in M. elsdenii was due to increased M. elsdenii NCIMB 41125. An increase in butyrate was observed from +24 h to +72 h when calves were dosed on both d 7 and 14. Results showed that Me presented a positive relationship with butyrate (P < 0.001, R² = 0.43) and a concomitant negative relationship with acetate (P = 0.017, R² = -0.33). These results suggest that dosing pre-weaned dairy calves with M. elsdenii NCIMB 41125 has the potential to alter ruminal VFA production through increasing proportions of butyrate at the expense of propionate.

Keywords: calves, megasphaera elsdenii, rumen fermentation, bacteria

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18307 Changing Patterns of Colorectal Cancer in Hail Region

Authors: Laila Salah Seada, Ashraf Ibrahim, Fawaz Al Rashid, Ihab Abdo, Hassan Kasim, Waleed Al Mansi, Saud Al Shabli

Abstract:

Background and Objectives: Colorectal carcinoma is increasing among both men and women worldwide. It has a multifactorial etiology including genetic factors, environmental factors and inflammatory conditions of the digestive tract. A clinicopathologic assessment of colorectal carcinoma in Hail region is done, considering any changing patterns in two 5-year periods from 2005-2009 (A) and from 2012 to 2017 (B). All data had been retrieved from histopathology files of King Khalid Hospital, Hail. Results: During period (A), 75 cases were diagnosed as colorectal carcinoma. Male patients comprised 56/75 (74.7%) of the study, with a mean age of 58.4 (36-97), while females were 19/75 (25.3%) with a mean age of 50.3(30-85) and the difference was significant (p = 0.05). M:F ratio was 2.9:1. Most common histological type was adenocarcioma in 68/75 (90.7%) patients mostly well differentiated in 44/68 (64.7%). Mucinous neoplasms comprised only 7/75 (9.3%) of cases and tended to have a higher stage (p = 0.04). During period (B), 115 cases were diagnosed with an increase of 53.3% in number of cases than period (A). Male to female ratio also decreased to 1.35:1, females being 44.83% more affected. Adenocarcinoma remained the prevalent type (93.9%), while mucinous type was still rare (5.2%). No distal metastases found at time of presentation. Localization of tumors was rectosigmoid in group (A) in 41.4%, which increased to 56.6% in group (B), with an increase of 15.2%. Iliocecal location also decreased from 8% to 3.5%, being 56.25% less. Other proximal areas of the colon were decreased by 25.75%, from 53.9% in group (A) to 40% in group (B). Conclusion: Colorectal carcinoma in Hail region has increased by 53.3% in the past 5 years, with more females being diagnosed. Localization has also shifted distally by 15.2%. These findings are different from Western world patterns which experienced a decrease in incidence and proximal shift of the colon cancer localization. This might be due to better diagnostic tools, population awareness of the disease, as well as changing of life style and/or food habits in the region.

Keywords: colorectal cancer, Hail Region, changing pattern, distal shift

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18306 Investigation of Delivery of Triple Play Service in GE-PON Fiber to the Home Network

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

Abstract:

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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18305 TopClosure® of Large Abdominal Wall Defect Instead of Staged Hernia Repair as Part of Damage Control Laparotomy

Authors: Andriy Fedorenko

Abstract:

Background Early closure of the open abdomen is a priority after damage control laparotomy to prevent retraction of fascial layers and prevent hernia formation that requires definitive repair at a later stage. This substantially reduces the complications associated with ventral hernia formation for up to a year after initial surgery. TopClosure® is an innovative method that employs stress-relaxation and mechanical creep for skin stretching. Its use enables the primary closure of large abdominal wall defects and mitigates large ventral hernia formation. Materials and Methods A 7-year-old girl presented with severe blast injury. She underwent initial laparotomy in a facility within the conflict zone and was transferred in a state of septic shock to our facility for further care. Her abdominal injuries included liver lacerations, multiple perforations of the transverse colon and ileum, and a 8x16cm oblique abdominal wall defect. Further damage control laparotomy was performed with primary suture of the colon and ileum and temporary closure of the abdomen using a Bagota bag. Twelve hours later, negative pressure wound therapy (NPWT) was applied to the abdominal wound after relook laparotomy. Five days later, TopClosure® was applied to the lower part of the wound incorporating NPWT to the upper wound. Results The patient suffered leak from the colonic suture line and required relaparotomy. TopClosure® abdominal closure was achieved after every laparotomy. Conclusion TopClosure® utilizes the viscoelastic properties of the skin achieving full closure of the abdominal wall (including the fascia and skin),eliminating the need for prolonged NPWT, skin graft, and delayed ventral hernia repair surgery.

Keywords: topclosure, abdominal wall defect, hernia, damage control

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18304 The Differences and Similarities between the Ship Waste Tracking Regulations of Turkey and Particular European Union Member Countries

Authors: Kaan Koyuncu, Umut Celen Arican, Sevilay Can

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In the maritime industry, there have been regulations to prevent pollution, and the first attempt to offer a legal basis was Marpol Convention which was held in 1973 in order to provide a framework for the disposal of ship wastes. Based on this convention, ports are obliged to build waste receiving facilities. European Union regulations make several member countries to follow these directions, In Turkey, under Blue Card System, the quantity and types of wastes, the delivery time, the capacity of the receiving facilities, and other required information can be monitored online. Therefore, yachts and other boats with the bilge, sewage, and waste which illegally discharge into the sea, can be blocked. This system is an outcome of the law adopted from European Union regulations. In this study, the present systems in Turkey which occurred in 2010 after the integration of the system, which has been put in the force in 2000 in Europe will be analyzed and interpreted to provide a useful comparison, a practical guide, and a roadmap for potential improvements.

Keywords: Europe-Turkey, blue card, marine environment, ship waste tracking system

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18303 Assessment of Drug Delivery Systems from Molecular Dynamic Perspective

Authors: M. Rahimnejad, B. Vahidi, B. Ebrahimi Hoseinzadeh, F. Yazdian, P. Motamed Fath, R. Jamjah

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In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.

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

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18302 Adherence to Dietary Approaches to Stop Hypertension-Style Diet and Risk of Mortality from Cancer: A Systematic Review and Meta-Analysis of Cohort Studies

Authors: Roohallah Fallah-Moshkani, Mohammad Ali Mohsenpour, Reza Ghiasvand, Hossein Khosravi-Boroujeni, Seyed Mehdi Ahmadi, Paula Brauer, Amin Salehi-Abargouei

Abstract:

Purpose: Several investigations have proposed the protective association between dietary approaches to stop hypertension (DASH) style diet and risk of cancers; however, they have led to inconsistent results. The present study aimed to systematically review the prospective cohort studies conducted in this regard and, if possible, to quantify the overall effect of using meta-analysis. Methods: PubMed, EMBASE, Scopus, and Google Scholar were searched for cohort studies published up to December 2017. Relative risks (RRs) which were reported for fully adjusted models and their confidence intervals were extracted for meta-analysis. Random effects model was incorporated to combine the RRs. Results: Sixteen studies were eligible to be included in the systematic review from which 8 reports were conducted on the effect of DASH on the risk of mortality from all cancer types, four on the risk of colorectal cancer, and three on the risk of colon and rectal cancer. Four studies examined the association with other cancers (breast, hepatic, endometrial, and lung cancer). Meta-analysis showed that high concordance with DASH significantly decreases the risk of all cancer types (RR=0.83, 95% confidence interval (95%CI):0.80-0.85); furthermore participants who highly adhered to the DASH had lower risk of developing colorectal (RR=0.79, 95%CI: 0.75-0.83), colon (RR=0.81, 95%CI: 0.74-0.87) and rectal (RR=0.79, 95%CI: 0.63-0.98) cancer compared to those with the lowest adherence. Conclusions: DASH-style diet should be suggested as a healthy approach to protect from cancer in the community. Prospective studies exploring the effect on other cancer types and from regions other than the United States are highly recommended.

Keywords: cancer, DASH-style diet, dietary patterns, meta-analysis, systematic review

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18301 Synthesis and Characterization of pH-Responsive Nanocarriers Based on POEOMA-b-PDPA Block Copolymers for RNA Delivery

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

Abstract:

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

Procedia PDF Downloads 238
18300 Optimizing a Hybrid Inventory System with Random Demand and Lead Time

Authors: Benga Ebouele, Thomas Tengen

Abstract:

Implementing either periodic or continuous inventory review model within most manufacturing-companies-supply chains as a management tool may incur higher costs. These high costs affect the system flexibility which in turn affects the level of service required to satisfy customers. However, these effects are not clearly understood because the parameters of both inventory review policies (protection demand interval, order quantity, etc.) are not designed to be fully utilized under different and uncertain conditions such as poor manufacturing, supplies and delivery performance. Coming up with a hybrid model which may combine in some sense the feature of both continuous and a periodic inventory review models should be useful. Therefore, there is a need to build and evaluate such hybrid model on the annual total cost, stock out probability and system’s flexibility in order to search for the most cost effective inventory review model. This work also seeks to find the optimal sets of parameters of inventory management under stochastic condition so as to optimise each policy independently. The results reveal that a continuous inventory system always incurs lesser cost than a periodic (R, S) inventory system, but this difference tends to decrease as time goes by. Although the hybrid inventory is the only one that can yield lesser cost over time, it is not always desirable but also natural to use it in order to help the system to meet high performance specification.

Keywords: demand and lead time randomness, hybrid Inventory model, optimization, supply chain

Procedia PDF Downloads 291
18299 Targeting Basic Leucine Zipper Transcription Factor ATF-Like Mediated Immune Cells Regulation to Reduce Crohn’s Disease Fistula Incidence

Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

Abstract:

Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

Procedia PDF Downloads 121
18298 Surface Functionalized Biodegradable Polymersome for Targeted Drug Delivery

Authors: Susmita Roy, Madhavan Nallani

Abstract:

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

Procedia PDF Downloads 135
18297 Target Drug Delivery of Pamidronate Nanoparticles for Enhancing Osteoblastic Activity in Osteoporosis

Authors: Purnima Rawat, Divya Vohora, Sarika Gupta, Farhan J. Ahmad, Sushama Talegaonkar

Abstract:

Nanoparticles (NPs) that target bone tissue were developed using PLGA–mPEG (poly(lactic-co-glycolic-acid)–polyethylene glycol) diblock copolymers by using pamidronate as a bone-targeting moieties. These NPs are expected to enable the transport of hydrophilic drugs. The NP was prepared by in situ polymerization method, and their in- vitro characteristics were evaluated using dynamic light scattering, transmission electron microscopy (TEM) and in phosphate-buffered solution. The bone targeting potential of the NP was also evaluated on in-vitro pre-osteoblast MCT3E1 cell line using ALP activity, degree of mineralization and RT-PCR assay. The average particle size of the NP was 101.6 ± 3.7nm, zeta potential values were negative (-25±0.34mV) of the formulations and the entrapment efficiency was 93± 3.1 % obtained. The moiety of the PLGA–mPEG–pamidronate NPs exhibited the best apatite mineral binding ability in-vitro MCT3E1 pre-osteoblast cell line. Our results suggested that the developed nanoparticles may use as a delivery system for Pamidronate in bone repair and regeneration, warranting further evaluation of the treatment of bone disease.

Keywords: nanoparticle, pamidronate, in-situ polymerization, osteoblast

Procedia PDF Downloads 461
18296 Design and Implementation of Remote Application Virtualization in Cloud Environments

Authors: Shuen-Tai Wang, Ying-Chuan Chen, Hsi-Ya Chang

Abstract:

Cloud computing is a paradigm of computing that shifts the way computing has been done in the past. The users can use cloud resources such as application software or storage space from the cloud without needing to own them. This paper is focused on solutions that are anticipated to introduce IaaS idea to build cloud base services and enable the individual remote user's applications in cloud environments, which appear as if they are running on the end user's local computer. The available features of application delivery solution have been developed based on our previous research on the virtualization technology to offer applications independent of location so that the users can work online, offline, anywhere, with appropriate device and at any time. This proposed effort has the potential to positively provide an efficient, resilience and elastic environment for cloud service. Users no longer need to burden the system managers and drastically reduces the overall cost of hardware and software licenses. Moreover, this flexible remote application virtualization service represents the next significant step to the mobile workplace, and it lets users access their applications remotely through cloud services anywhere. This is also made possible by the low administrative costs as well as relatively inexpensive end-user terminals and reduced energy expenses.

Keywords: cloud computing, IaaS, virtualization, application delivery

Procedia PDF Downloads 256
18295 Material Supply Mechanisms for Contemporary Assembly Systems

Authors: Rajiv Kumar Srivastava

Abstract:

Manufacturing of complex products such as automobiles and computers requires a very large number of parts and sub-assemblies. The design of mechanisms for delivery of these materials to the point of assembly is an important manufacturing system and supply chain challenge. Different approaches to this problem have been evolved for assembly lines designed to make large volumes of standardized products. However, contemporary assembly systems are required to concurrently produce a variety of products using approaches such as mixed model production, and at times even mass customization. In this paper we examine the material supply approaches for variety production in moderate to large volumes. The conventional approach for material delivery to high volume assembly lines is to supply and stock materials line-side. However for certain materials, especially when the same or similar items are used along the line, it is more convenient to supply materials in kits. Kitting becomes more preferable when lines concurrently produce multiple products in mixed model mode, since space requirements could increase as product/ part variety increases. At times such kits may travel along with the product, while in some situations it may be better to have delivery and station-specific kits rather than product-based kits. Further, in some mass customization situations it may even be better to have a single delivery and assembly station, to which an entire kit is delivered for fitment, rather than a normal assembly line. Finally, in low-moderate volume assembly such as in engineered machinery, it may be logistically more economical to gather materials in an order-specific kit prior to launching final assembly. We have studied material supply mechanisms to support assembly systems as observed in case studies of firms with different combinations of volume and variety/ customization. It is found that the appropriate approach tends to be a hybrid between direct line supply and different kitting modes, with the best mix being a function of the manufacturing and supply chain environment, as well as space and handling considerations. In our continuing work we are studying these scenarios further, through the use of descriptive models and progressing towards prescriptive models to help achieve the optimal approach, capturing the trade-offs between inventory, material handling, space, and efficient line supply.

Keywords: assembly systems, kitting, material supply, variety production

Procedia PDF Downloads 202
18294 Formulation and Evaluation of Silver Nanoparticles as Drug Carrier for Cancer Therapy

Authors: Abdelhadi Adam Salih Denei

Abstract:

Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

Procedia PDF Downloads 37
18293 Optimisation of Intermodal Transport Chain of Supermarkets on Isle of Wight, UK

Authors: Jingya Liu, Yue Wu, Jiabin Luo

Abstract:

This work investigates an intermodal transportation system for delivering goods from a Regional Distribution Centre to supermarkets on the Isle of Wight (IOW) via the port of Southampton or Portsmouth in the UK. We consider this integrated logistics chain as a 3-echelon transportation system. In such a system, there are two types of transport methods used to deliver goods across the Solent Channel: one is accompanied transport, which is used by most supermarkets on the IOW, such as Spar, Lidl and Co-operative food; the other is unaccompanied transport, which is used by Aldi. Five transport scenarios are studied based on different transport modes and ferry routes. The aim is to determine an optimal delivery plan for supermarkets of different business scales on IOW, in order to minimise the total running cost, fuel consumptions and carbon emissions. The problem is modelled as a vehicle routing problem with time windows and solved by genetic algorithm. The computing results suggested that accompanied transport is more cost efficient for small and medium business-scale supermarket chains on IOW, while unaccompanied transport has the potential to improve the efficiency and effectiveness of large business scale supermarket chains.

Keywords: genetic algorithm, intermodal transport system, Isle of Wight, optimization, supermarket

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18292 Surfactant-Free O/W-Emulsion as Drug Delivery System

Authors: M. Kumpugdee-Vollrath, J.-P. Krause, S. Bürk

Abstract:

Most of the drugs used for pharmaceutical purposes are poorly water-soluble drugs. About 40% of all newly discovered drugs are lipophilic and the numbers of lipophilic drugs seem to increase more and more. Drug delivery systems such as nanoparticles, micelles or liposomes are applied to improve their solubility and thus their bioavailability. Besides various techniques of solubilization, oil-in-water emulsions are often used to incorporate lipophilic drugs into the oil phase. To stabilize emulsions surface active substances (surfactants) are generally used. An alternative method to avoid the application of surfactants was of great interest. One possibility is to develop O/W-emulsion without any addition of surface active agents or the so called “surfactant-free emulsion or SFE”. The aim of this study was to develop and characterize SFE as a drug carrier by varying the production conditions. Lidocaine base was used as a model drug. The injection method was developed. Effects of ultrasound as well as of temperature on the properties of the emulsion were studied. Particle sizes and release were determined. The long-term stability up to 30 days was performed. The results showed that the surfactant-free O/W emulsions with pharmaceutical oil as drug carrier can be produced.

Keywords: emulsion, lidocaine, Miglyol, size, surfactant, light scattering, release, injection, ultrasound, stability

Procedia PDF Downloads 466
18291 The Conceptual Design Model of an Automated Supermarket

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

Procedia PDF Downloads 381
18290 Targeted Delivery of Docetaxel Drug Using Cetuximab Conjugated Vitamin E TPGS Micelles Increases the Anti-Tumor Efficacy and Inhibit Migration of MDA-MB-231 Triple Negative Breast Cancer

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

Abstract:

Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

Procedia PDF Downloads 256