Search results for: intracellular delivery

Authors: Victor Arokia Doss, Kuberapandian Dharaniyambigai, K. Julia Rose Mary

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Advanced Glycation End (AGE) products are the end products due to the reaction between excess reducing sugar present in diabetes and free amino group in protein lipids and nucleic acids. Thus, non-enzymic glycation of molecules such as hemoglobin, collagen, and other structurally and functionally important proteins add to the pathogenic complications such as diabetic retinopathy, neuropathy, nephropathy, vascular changes, atherosclerosis, Alzheimer's disease, rheumatoid arthritis, and chronic heart failure. The most common non-cross linking AGE, carboxymethyl lysine (CML) is formed by the oxidative breakdown of fructosyllysine, which is a product of glucose and lysine. CML is formed in a wide variety of tissues and is an index to assess the extent of glycoxidative damage. Thus we have constructed a mathematical and computational model that predicts the effect of temperature differences in vivo, on the formation of CML, which is now being considered as an important intracellular milieu. This hybrid model that had been tested for its parameter fitting and its sensitivity with available experimental data paves the way for designing novel laboratory experiments that would throw more light on the pathological formation of AGE adducts and in the pathophysiology of diabetic complications.

Keywords: advanced glycation end-products, CML, mathematical model, computational model

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Authors: Mazouzi Nourdjihane, K. Boutemak, A. Haddad, Y. Chegreouche

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In the last decades, biodegradable polymers have been considered as one of the most popular options for the delivery of drugs and various conventional doses. The film forming system (FFS) can be used in topical, transdermal, ophthalmic, oral and gastric applications. Recently this system has focused on improving drug delivery, which can promote drug release. In this context, the aim of this study is to create polymeric film-forming systems for the stomach and to evaluate and test their gastroprotective effects, comparing the effects of changes in composition on film characteristics. It uses a plant-derived polyphenol extract extracted from fennel to demonstrate anti-inflammatory activity in the film. The films are made from hydroxypropyl methylcellulose polymer and different types of plastic, glycerol and polyethylene glycol. The ffs properties show that MgO-glycerol-reinforced hydroxypropylmethylcellulose (HPMC-MgO-Gly) is better than that based on MgO-PEG-reinforced hydroxypropylmethylcellulose (HPMC-MgO-PEG). It is durable, has a faster drying time and allows for maximum recovery. Water vapor strength and blowing speed and other additions show another advantage of HPMC-MgO-Gly compared to HPMC-MgO-PEG, indicating good adhesion between the support (top) and film production. In this study, the gastroprotective effect of fennel phenol extract was found, showing that this plant material has a gastroprotective effect on ulcers and that the film can absorb the active substance.

Keywords: film formin system, hydroxypropyl methylcellulose, magnesium oxide, in vivo

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

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The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

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Authors: Joanne Joyce-McCoach

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Short courses are an integral part of the higher education sector, providing a pathway into tertiary qualifications. Recently, the Australian government has implemented a range of initiatives to support the development of short courses and micro-credentials designed to upskill the labor market and meet the needs of the healthcare workforce. While short courses have been an ongoing component of Australian nursing continuing professional development, there is an immediate need for more education opportunities as a response to the workforce shortages. However, despite the support for short courses, there are identified challenges for learners undertaking these courses online. As a result of restrictions to face-to-face classes and limited access to health services caused by the pandemic, education providers have had to transition to an online delivery requiring the redesign of skills acquisition. This paper will outline the transition of an immunisation short course to a fully online format, including the redesign of classes, content and assessment. Concurrently the enrolments for the immunisation short course substantially increased in direct response to the demand for nurse immunisers. In addition to providing a description of the curriculum changes implemented, an analysis of learners’ feedback on their experience of the new format will be discussed. Furthermore, it will explore the principles identified in the transition process for improving the short course design and learning activities. Finally, it will propose recommendations to integrate into the delivery of online short courses and to meet the learners' needs.

Keywords: nurse, immunisation, short course, micro-credential, continuing professional development, online design

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Authors: Emily Purdom, Rachel Robinson

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As the number of students worldwide requiring speech-language therapy, occupational therapy and mental health services during their school day increases, innovation is becoming progressively more important to meet the demand. Telepractice can be used to reach a greater number of students requiring specialized therapy while maintaining the highest quality of care. It can be provided in a way that is not only effective but ultimately more convenient for student, teacher and therapist without the added burden of travel. Teletherapy eradicates many hurdles to traditional on-site service delivery and helps to solve the pervasive shortage of certified professionals. Because location is no longer a barrier to specialized education plans for students with disabilities when teletherapy is conducted, there are many advantages that can be deployed. Increased frequency of engagement is possible along with students receiving specialized care from a clinician that may not be in their direct area. Educational teams, including parents, can work together more easily and engage in face-to-face, student-centered collaboration through videoconference. Practical strategies will be provided for connecting students with qualified therapists without the typical in-person dynamic. In most cases, better therapy outcomes are going to be achieved when treatment is most convenient for the student and educator. This workshop will promote discussion in the field of education to increase advocacy for remote service delivery. It will serve as a resource for those wanting to expand their knowledge of options for students with special needs afforded through innovation.

Keywords: education technology, innovation, student support services, telepractice

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Authors: Jeffrey Ansloos

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International trauma education in low and emerging economies requires innovative methods for capacity building in existing social service infrastructures. This study details the findings of a program evaluation used to assess the learning outcomes and community impact of an international trauma-focused graduate degree program in Guyana. Through a collaborative partnership between Lesley University, the Government of Guyana, and UNICEF, a 2-year low-residency masters degree graduate program in trauma-focused assessment, intervention, and treatment was piloted with a cohort of Guyanese mental health professionals. Through an analytical review of the program development, as well as qualitative data analysis of participant interviews and focus-groups, this study will address the efficacy of the programming in terms of preparedness of professionals to understand, evaluate and implement trauma-informed practices across various child, youth, and family mental health service settings. Strengths and limitations of this international trauma-education delivery model will be discussed with particular emphasis on the role of capacity-building interventions, community-based participatory curriculum development, innovative technological delivery platforms, and interdisciplinary education. Implications for further research and subsequent program development will be discussed.

Keywords: mental health promotion, global health promotion, trauma education, innovations in education, child, youth, mental health education

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Authors: B. Tiseo, V. Quaranta, G. Bruno, G. Sisinni

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There is an increasing demand of nano-satellite development among universities, small companies, and emerging countries. Low-cost and fast-delivery are the main advantages of such class of satellites achieved by the extensive use of commercial-off-the-shelf components. On the other side, the loss of reliability and the poor success rate are limiting the use of nano-satellite to educational and technology demonstration and not to the commercial purpose. Standardization of nano-satellite environmental testing by tailoring the existing test standard for medium/large satellites is then a crucial step for their market growth. Thus, it is fundamental to find the right trade-off between the improvement of reliability and the need to keep their low-cost/fast-delivery advantages. This is particularly even more essential for satellites of CubeSat family. Such miniaturized and standardized satellites have 10 cm cubic form and mass no more than 1.33 kilograms per 1 unit (1U). For this class of nano-satellites, the qualification process is mandatory to reduce the risk of failure during a space mission. This paper reports the description and results of the space qualification test campaign performed on Endurosat’s CubeSat nano-satellite and modules. Mechanical and environmental tests have been carried out step by step: from the testing of the single subsystem up to the assembled CubeSat nano-satellite. Functional tests have been performed during all the test campaign to verify the functionalities of the systems. The test duration and levels have been selected by tailoring the European Space Agency standard ECSS-E-ST-10-03C and GEVS: GSFC-STD-7000A.

Keywords: CubeSat, nano-satellite, shock, testing, vibration

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Authors: Paul Hernandez-Herrera, Fernando Montoya, Juan Manuel Rendon, Alberto Darszon, Gabriel Corkidi

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Intracellular calcium ([Ca2+]i) regulates sperm motility. The analysis of [Ca2+]i has been traditionally achieved in two dimensions while the real movement of the cell takes place in three spatial dimensions. Due to optical limitations (high speed cell movement and low light emission) important data concerning the three dimensional movement of these flagellated cells had been neglected. Visualizing [Ca2+]i in 3D is not a simple matter since it requires complex fluorescence microscopy techniques where the resulting images have very low intensity and consequently low SNR (Signal to Noise Ratio). In 4D sequences, this problem is magnified since the flagellum oscillates (for human sperm) at least at an average frequency of 15 Hz. In this paper, a novel approach to extract the flagellum’s center-line in 4D stacks is presented. For this purpose, an iterative algorithm based on the fast-marching method is proposed to extract the flagellum’s center-line. Quantitative and qualitative results are presented in a 4D stack to demonstrate the ability of the proposed algorithm to trace the flagellum’s center-line. The method reached a precision and recall of 0.96 as compared with a semi-manual method.

Keywords: flagellum, minimal path, segmentation, sperm

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Authors: S. Yesmin, N. F.Rahman, R. Akther, T. Begum, T. Tahmid, T. Chowdury, S. Afrin, J. D. Hamadani

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Abstract: Maternal depression is one of the risk factors of developmental delay in young children in low-income countries. Maternal depressions during pregnancy are rarely reported in Bangladesh. Objectives: The purpose of the present study was to examine the efficacy of a community based psychosocial intervention on women with mild to moderate depressive illness during the perinatal period and on their children from birth to 12 months on mothers’ mental status and their infants’ growth and development. Methodology: The study followed a prospective longitudinal approach with a randomized controlled design. Total 250 pregnant women aged between 15 and 40 years were enrolled in their third trimester of pregnancy of which 125 women were in the intervention group and 125 in the control group. Women in the intervention group received the “Thinking Healthy (CBT based) program” at their home setting, from their last month of pregnancy till 10 months after delivery. Their children received psychosocial stimulation from birth till 12 months. The following instruments were applied to get the outcome information- Bangla version of Edinburgh Postnatal Depression Scale (BEPDS), Prenatal Attachment Inventory (PAI), Maternal Attachment Inventory (MAI), Bayley Scale of Infant Development-Third version (Bayley–III) and Family Care Indicator (FCI). In addition, sever morbidity; breastfeeding, immunization, socio-economic and demographic information were collected. Data were collected at three time points viz. baseline, midline (6 months after delivery) and endline (12 months after delivery). Results: There was no significant difference between any of the socioeconomic and demographic variables at baseline. A very preliminary analysis of the data shows an intervention effect on Socioemotional behaviour of children at endline (p<0.001), motor development at midline (p=0.016) and at endline (p=0.065), language development at midline (p=0.004) and at endline (p=0.023), cognitive development at midline (p=0.008) and at endline (p=0.002), and quality of psychosocial stimulation at midline (p=0.023) and at endline (p=0.010). EPDS at baseline was not different between the groups (p=0.419), but there was a significant improvement at midline (p=0.027) and at endline (p=0.024) between the groups following the intervention. Conclusion: Psychosocial intervention is found effective in reducing women’s low and moderate depressive illness to cope with mental health problem and improving development of young children in Bangladesh.

Keywords: mental health, maternal depression, infant development, CBT, EPDS

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Authors: Piacentini Diego, Della Rovere Federica, Fattorini Laura, Lanni Francesca, Cittadini Martina, Altamura Maria Maddalena, Falasca Giuseppina

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Plants have evolved sophisticated mechanisms to cope with environmental cues. Changes in intracellular content and distribution of phytohormones, such as the auxin indole-3-acetic acid (IAA), have been involved in morphogenic adaptation to environmental stresses. In addition to phytohormones, plants can rely on a plethora of small signal molecules able to promptly sense and transduce the stress signals, resulting in morpho/physiological responses thanks also to their capacity to modulate the levels/distribution/reception of most hormones. Among these signaling molecules, nitrogen monoxide (nitric oxide – NO) is a critical component in several plant acclimation strategies to both biotic and abiotic stresses. Depending on its levels, NO increases plant adaptation by enhancing the enzymatic or non-enzymatic antioxidant systems or by acting as a direct scavenger of reactive oxygen/nitrogen (ROS/RNS) species produced during the stress. In addition, exogenous applications of NO-specific donor compounds showed the involvement of the signal molecule in auxin metabolism, transport, and signaling, under both physiological and stress conditions. However, the complex mechanisms underlying NO action in interacting with phytohormones, such as auxins, during metal stress responses are still poorly understood and need to be better investigated. Emphasis must be placed on the response of the root system since it is the first plant organ system to be exposed to metal soil pollution. The monocot Oryza sativa L. (rice) has been chosen given its importance as a stable food for some 4 billion people worldwide. In addition, increasing evidence has shown that rice is often grown in contaminated paddy soils with high levels of heavy metal cadmium (Cd) and metalloid arsenic (As). The facility through which these metals are taken up by rice roots and transported to the aerial organs up to the edible caryopses makes rice one of the most relevant sources of these pollutants for humans. This study aimed to evaluate if NO has a mitigatory activity in the roots of rice seedlings against Cd or As toxicity and to understand if this activity requires interactions with auxin. Our results show that exogenous treatments with the NO-donor SNP alleviate the stress induced by Cd, but not by As, in in-vitro-grown rice seedlings through increased intracellular root NO levels. The damages induced by the pollutants include root growth inhibition, root histological alterations and ROS (H2O2, O2●ˉ), and RNS (ONOOˉ) production. Also, SNP treatments mitigate both the root increase in root IAA levels and the IAA alteration in distribution monitored by the OsDR5::GUS system due to the toxic metal exposure. Notably, the SNP-induced mitigation of the IAA homeostasis altered by the pollutants does not involve changes in the expression of OsYUCCA1 and ASA2 IAA-biosynthetic genes. Taken together, the results highlight a mitigating role of NO in the rice root system, which is pollutant-specific, and involves the interaction of the signal molecule with both IAA and brassinosteroids at different (i.e., transport, levels, distribution) and multiple levels (i.e., transcriptional/post-translational levels). The research is supported by Progetti Ateneo Sapienza University of Rome, grant number: RG120172B773D1FF

Keywords: arsenic, auxin, cadmium, nitric oxide, rice, root system

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Authors: Zhiyong Li, Hiroshi Katayama

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Since 1990s, e-commerce and internet business have been grown gradually over the word and customers tend to express their demand attributes in terms of specification requirement on parts, component, product structure etc. This paper deals with designing effective decoupling points for build to order systems under e-commerce environment, which can be realized through tradeoff relation analysis between two major criteria, customer order lead time and value of work in progress. These KPIs are critical for successful BTO business, namely time-based service effectiveness on coping with customer requirements for the first issue and cost effective ness with risk aversive operations for the second issue. Approach of this paper consists of investigation of successful business standing for BTO scheme, manufacturing model development of this scheme, quantitative evaluation of proposed models by calculation of two KPI values under various decoupling point distributions and discussion of the results brought by pattern of decoupling point distribution, where some cases provide the pareto optimum performances. To extract the relevant trade-off relation between considered KPIs among 2-dimensional resultant performance, useful logic developed by former research work, i.e. Katayama and Fonseca, is applied. Obtained characteristics are evaluated as effective information for managing BTO manufacturing businesses.

Keywords: build-to-order (BTO), decoupling point, e-commerce, order-to-delivery lead time (ODLT), work in progress (WIP)

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Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

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The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

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Authors: P. Vanichkobchinda

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The Logistics Transportation techniques, Open Vehicle Routing (OVR) is an approach toward transportation cost reduction, especially for long distance pickup and delivery nodes. The outstanding characteristic of OVR is that the route starting node and ending node are not necessary the same as in typical vehicle routing problems. This advantage enables the routing to flow continuously and the vehicle does not always return to its home base. This research aims to develop a heuristic for the open vehicle routing problem with pickup and delivery under time window and loading capacity constraints to minimize the total distance. The proposed heuristic is developed based on the Insertion method, which is a simple method and suitable for the rapid calculation that allows insertion of the new additional transportation requirements along the original paths. According to the heuristic analysis, cost comparisons between the proposed heuristic and companies are using method, nearest neighbor method show that the insertion heuristic. Moreover, the proposed heuristic gave superior solutions in all types of test problems. In conclusion, the proposed heuristic can effectively and efficiently solve the open vehicle routing. The research indicates that the improvement of new transport's calculation and the open vehicle routing with "Insertion Heuristic" represent a better outcome with 34.3 percent in average. in cost savings. Moreover, the proposed heuristic gave superior solutions in all types of test problems. In conclusion, the proposed heuristic can effectively and efficiently solve the open vehicle routing.

Keywords: business competitiveness, cost reduction, SMEs, logistics transportation, VRP

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Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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Authors: Rita Ghosh, Joykrishna Dey

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PEG-based amphiphiles are of tremendous importance for its widespread applications in pharmaceutics, household purposes, and drug delivery. Previously, a number of single PEG-tailed amphiphiles having significant applications have been reported from our group. Therefore, it was of immense interest to explore the properties and application potential of PEG-based double tailed amphiphiles. Herein, for the first time, two novel double PEG-tailed amphiphiles having different PEG chain lengths have been developed. The self-assembly behavior of the newly developed amphiphiles in aqueous buffer (pH 7.0) was thoroughly investigated at 25 oC by a number of techniques including, 1H-NMR, and steady-state and time-dependent fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy, and isothermal titration calorimetry. Despite having two polar PEG chains both molecules were found to have strong tendency to self-assemble in aqueous buffered solution above a very low concentration. Surprisingly, the amphiphiles were shown to form stable vesicles spontaneously at room temperature without any external stimuli. The results of calorimetric measurements showed that the vesicle formation is driven by the hydrophobic effect (positive entropy change) of the system, which is associated with the helix-to-random coil transition of the PEG chain. The spectroscopic data confirmed that the bilayer membrane of the vesicles is constituted by the PEG chains of the amphiphilic molecule. Interestingly, the vesicles were also found to exhibit structural transitions upon addition of salts in solution. These properties of the vesicles enable them as potential candidate for drug delivery.

Keywords: double-tailed amphiphiles, fluorescence, microscopy, PEG, vesicles

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Authors: Yong Zhang

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

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

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Authors: Kyou Hee Shim, Hwa Sung Shin

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When a thrombolysis agent is administered to treat ischemic stroke, excessive reactive oxygen species are generated due to a sudden provision of oxygen and occurs secondary damage cell necrosis. Thus, it is necessary to administrate adjuvant as well as thrombolysis agent to protect and reduce damaged tissue. As cerebral blood vessels have specific structure called blood-brain barrier (BBB), it is not easy to transfer substances from blood to tissue. Therefore, development of a drug carrier is required to increase drug delivery efficiency to brain tissue. In this study, cyanobacterial pigment from the blue-green algae known for having neuroprotective effect as well as antioxidant effect was nasally administrated for bypassing BBB. In order to deliver cyanobacterial pigment efficiently, the nano-sized liposome was used as a carrier. Liposomes were coated with a positive charge of chitosan since negative residues are present at the nasal mucosa the first gateway of nasal administration. Characteristics of liposome including morphology, size and zeta potential were analyzed by transmission electron microscope (TEM) and zeta analyzer. As a result of cytotoxic test, the liposomes were not harmful. Also, being administered a drug to the ischemic stroke animal model, we could confirm that the pharmacological effect of the pigment delivered by chitosan coated liposome was enhanced compared to that of non-coated liposome. Consequently, chitosan coated liposome could be considered as an optimized drug delivery system for the treatment of acute ischemic stroke.

Keywords: ischemic stroke, cyanobacterial pigment, liposome, chitosan, nasal administration

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Authors: Ali Bayram, Burak Uz, Ilhan Dolasik, Remzi Yiğiter

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The GABARAP (GABAA-receptor-associated protein) family consists of GABARAP, GABARAPL1 (GABARAP-like 1) and GABARAPL2 (GABARAP-like 2). GABARAPL1, like GABARAP, was described to interact with both GABAA receptor and tubulin, and to be involved in intracellular GABAA receptor trafficking and promoting tubulin polymerization. In addition, GABARAPL1 is thought to be involved in various physiological (autophagosome closure, regulation of circadian rhythms) and/or pathological mechanisms (cancer, neurodegeneration). Alzheimer’s disease (AD) is a progressive neuro degenerative disorder characterized with impaired cognitive functions. Disruption of the GABAergic neuro transmission as well as cholinergic and glutamatergic interactions, may also be involved in the pathogenesis of AD. GABARAPL1 presents a regulated tissue expression and is the most expressed gene among the GABARAP family members in the central nervous system. We, herein, conducted a study to investigate the GABARAPL1 mRNA expression levels in patients with AD. 50 patients with AD and 49 control patients were enrolled to the present study. Messenger RNA expression levels of GABARAPL1 were detected by real-time polymerase chain reaction. GABARAPL1 mRNA expression in AD / control patients was 0,495 (95% confidence interval: 0,404-0,607), p= 0,00000002646. Reduced activity of GABARAPL1 gene might play a role, at least partly, in the pathophysiology of AD.

Keywords: Alzheimer’s disease, GABARAPL1, mRNA expression, RT-PCR

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Authors: Saradiya Mukherjee

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Background: Indian Muslims, compared to their counterparts in other religions, generally do not fare well on many yardsticks related to socio-economic progress and the same is true with maternal health care utilization. Due to low age at marriage a major percentage of child birth is ascribed to young (15-24 years) Muslim mothers in, which pose serious concerns on the maternal health care of Young Married Muslim women (YMMW). A thorough search of past literature on Muslim women’s health and health care reveals that studies in India have mainly focused on religious differences in fertility levels and contraceptive use while the research on the determinants of maternal health care utilization among Muslim women are lacking in India. Data and Methods: Retrieving data from the National Family Health Survey -3 (2005-06) this study attempts to assess the level of utilization and factors effecting three key maternal health indicators (full ANC, safe delivery and PNC) among YMMW (15-24 years) in India. The key socio-economic and demographic variables taken as independent or predictor variables in the study was guided by existing literature particularly for India. Bi-variate analysis and chi square test was applied and variables which were found to be significant were further included in binary logistic regression. Results: The findings of the study reveal abysmally low levels of utilization for all three indicators i.e. full ANC, safe delivery and PNC of maternal health care included in the study. Mother’s education, mass media exposure, women’s autonomy, birth order, economic status wanted status of child and region of residence were found to be significant variables effecting maternal health care utilization among YMMW. Multivariate analysis reveals that no mass media exposure, lower autonomy, education, poor economic background, higher birth order and unintended pregnancy are some of the reasons behind low maternal health care utilization. Conclusion: Considering the low level of safe maternal health care utilization and its proximate determinants among YMMW the study suggests educating Muslim girls, promoting family planning use, involving media and collaboration between religious leader and health care system could be some important policy level interventions to address the unmet need of maternity services among YMMW.

Keywords: young Muslim women, religion, socio-economic condition, antenatal care, delivery, post natal care

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Authors: Anurag Gaur Nidhi

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Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. This improves efficacy of the while reducing side effects. In the present work, we investigate the effect of magnetic field, flow rate and particle concentration on the capturing of magnetic particles transported in a stent implanted fluidic channel. Iron oxide magnetic nanoparticles (Fe3O4) nanoparticles were synthesized via co-precipitation method. The synthesized Fe3O4 nanoparticles were added in the de-ionized (DI) water to prepare the Fe3O4 magnetic particle suspended fluid. This fluid is transported in a cylindrical tube of diameter 8 mm with help of a peristaltic pump at different flow rate (25-40 ml/min). A ferromagnetic coil of SS 430 has been implanted inside the cylindrical tube to enhance the capturing of magnetic nanoparticles under magnetic field. The capturing of magnetic nanoparticles was observed at different magnetic magnetic field, flow rate and particle concentration. It is observed that capture efficiency increases from 47-67 % at magnetic field 2-5kG, respectively at particle concentration 0.6 mg/ml and at flow rate 30 ml/min. However, the capture efficiency decreases from 65 to 44 % by increasing the flow rate from 25 to 40 ml/min, respectively. Furthermore, it is observed that capture efficiency increases from 51 to 67 % by increasing the particle concentration from 0.3 to 0.6 mg/ml, respectively.

Keywords: capture efficiency, implant assisted-Magnetic drug targeting (IA-MDT), magnetic nanoparticles, In-vitro study

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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

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

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Authors: Janika Vien K. Valsorable, Filma C. Calalo

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Climate change is one of the most damaging and serious environmental threats worldwide being faced today. While almost everyone highly depends and puts their trust on what technology, innovations, and initiatives from hard-core science can do to cope with the changing climate, there are still people who find hope on indigenous knowledge systems. The study aimed to analyze the traditional farming practices of the Dumagats in Tanay, Rizal and how these relate to their adaptation and mitigation of climate change. The analysis is based on interviews with 17 members of the Dumagat tribe specifically residing in Barangay Cuyambay, San Andres, and Mamuyao, and supported by Key Informant Interview and Focus Group Discussion as well as document reviews. Results of the study showed that the Dumagats adopt indigenous knowledge systems and their high sensitivity and resilience to climate change aid them in their farming system and activities. These traditional farming practices are exemplified from land preparation to planting, fertilizer application, weed and pest management, harvesting and post-harvest activities. Owing to their dependence upon, and close relationship with the environment and its resources, the Dumagats have learned to interpret and react to the impacts of climate change in creative ways, drawing on their traditional knowledge to cope with the impending changes. With the increasing trend at all levels of government to service the needs of rural communities, there is the need for the extension to contextualize advisory service delivery for indigenous communities.

Keywords: climate change, Dumagat tribe, indigenous knowledge systems, traditional farming practices

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Authors: Samaneh Farokhirad, Fatemeh Ahmadpoor

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Biological membranes are constantly in contact with various filamentous soft nanostructures that either reside on their surface or are being transported between the cell and its environment. In particular, viral infections are determined by the interaction of viruses (such as filovirus) with cell membranes, membrane protein organization (such as cytoskeletal proteins and actin filament bundles) has been proposed to influence the mechanical properties of lipid membranes, and the adhesion of filamentous nanoparticles influence their delivery yield into target cells or tissues. The goal of this research is to integrate the rapidly increasing but still fragmented experimental observations on the adhesion and self-assembly of nanofilaments (including filoviruses, actin filaments, as well as natural and synthetic nanofilaments) on cell membranes into a general, rigorous, and unified knowledge framework. The global outbreak of the coronavirus disease in 2020, which has persisted for over three years, highlights the crucial role that nanofilamentbased delivery systems play in human health. This work will unravel the role of a unique property of all cell membranes, namely flexoelectricity, and the significance of nanofilaments’ flexibility in the adhesion and self-assembly of nanofilaments on cell membranes. This will be achieved utilizing a set of continuum mechanics, statistical mechanics, and molecular dynamics and Monte Carlo simulations. The findings will help address the societal needs to understand biophysical principles that govern the attachment of filoviruses and flexible nanofilaments onto the living cells and provide guidance on the development of nanofilament-based vaccines for a range of diseases, including infectious diseases and cancer.

Keywords: virus nanofilaments, cell mechanics, computational biophysics, statistical mechanics

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Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

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Autophagy has recently been linked with cancer cell survival post drug insult contributing to acquisition of resistance. However, the molecular signaling governing autophagic survival response is poorly explored. In our study, in osteosarcoma (OS) cells cisplatin shock was found to activate both MAPK and autophagy signaling. An activation of JNK and autophagy acted as pro-survival strategy, while ERK1/2 triggered apoptotic signals upon cisplatin stress. An increased sensitivity of the cells to cisplatin was obtained with simultaneous inhibition of both autophagy and JNK pathway. Furthermore, we observed that the autophagic stimulation upon drug stress regulates other developmentally active signaling pathways like the Hippo pathway in OS cells. Cisplatin resistant cells were thereafter developed by repetitive drug exposure followed by clonal selection. Basal levels of autophagy were found to be high in resistant cells to. However, the signaling mechanism leading to autophagic up-regulation and its regulatory effect differed in OS cells upon attaining drug resistance. Our results provide valuable clues to regulatory dynamics of autophagy that can be considered for development of improved therapeutic strategy against resistant type cancers.

Keywords: JNK, autophagy, drug resistance, cancer

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Authors: Truong H. Le, Ngoc M. To, Quang N. Tran, Luu T. Cao, Chi V. Le

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Introduction: In Vietnam, the current monitoring and treatment for ordinary diabetic patient mostly based on glucose monitoring with HbA1c test for every three months (recommended goal is HbA1c < 6.5%~7%). For diabetes in pregnant women or Gestational diabetes mellitus (GDM), glycemic control until the time of delivery is extremly important because it could reduce significantly medical implications for both the mother and the child. Besides, GDM requires continuos glucose monitoring at least every two weeks and therefore an alternative marker of glycemia for short-term control is considering a potential tool for the healthcare providers. There are published studies have indicated that the glycosylated serum protein is a better indicator than glycosylated hemoglobin in GDM monitoring. Based on the actual practice in Vietnam, this study was designed to evaluate the role of serum fructosamine as a monitoring tool in GDM treament and its correlations with fasting blood glucose (G0), 2-hour postprandial glucose (G2) and glycosylated hemoglobin (HbA1c). Methods: A cohort study on pregnant women diagnosed with GDM by the 75-gram oralglucose tolerance test was conducted at Endocrinology Department, Cho Ray hospital, Vietnam from June 2014 to March 2015. Cho Ray hospital is the final destination for GDM patient in the southern of Vietnam, the study population has many sources from other pronvinces and therefore researchers belive that this demographic characteristic can help to provide the study result as a reflection for the whole area. In this study, diabetic patients received a continuos glucose monitoring method which consists of bi-weekly on-site visit every 2 weeks with glycosylated serum protein test, fasting blood glucose test and 2-hour postprandial glucose test; HbA1c test for every 3 months; and nutritious consultance for daily diet program. The subjects still received routine treatment at the hospital, with tight follow-up from their healthcare providers. Researchers recorded bi-weekly health conditions, serum fructosamine level and delivery outcome from the pregnant women, using Stata 13 programme for the analysis. Results: A total of 500 pregnant women was enrolled and follow-up in this study. Serum fructosamine level was found to have a light correlation with G0 ( r=0.3458, p < 0.001) and HbA1c ( r=0.3544, p < 0.001), and moderately correlated with G2 ( r=0.4379, p < 0.001). During study timeline, the delivery outcome of 287 women were recorded with the average age of 38.5 ± 1.5 weeks, 9% of them have macrosomia, 2.8% have premature birth before week 35th and 9.8% have premature birth before week 37th; 64.8% of cesarean section and none of them have perinatal or neonatal mortality. The study provides a reference interval of serum fructosamine for GDM patient was 112.9 ± 20.7 μmol/dL. Conclusion: The present results suggests that serum fructosamine is as effective as HbA1c as a reflection of blood glucose control in GDM patient, with a positive result in delivery outcome (0% perinatal or neonatal mortality). The reference value of serum fructosamine measurement provided a potential monitoring utility in GDM treatment for hospitals in Vietnam. Healthcare providers in Cho Ray hospital is considering to conduct more studies to test this reference as a target value in their GDM treatment and monitoring.

Keywords: gestational diabetes mellitus, monitoring tool, serum fructosamine, Vietnam

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Authors: Jamshed Ahmad, Abdul Wahid Khan, Javed Ali Khan

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Managing software quality requirements change management is a difficult task in the field of software engineering. Avoiding incoming changes result in user dissatisfaction while accommodating to many requirement changes may delay product delivery. Poor requirements management is solely considered the primary cause of the software failure. It becomes more challenging in global software outsourcing. Addressing success factors in quality requirement change management is desired today due to the frequent change requests from the end-users. In this research study, success factors are recognized and scrutinized with the help of a systematic literature review (SLR). In total, 16 success factors were identified, which significantly impacted software quality requirement change management. The findings show that Proper Requirement Change Management, Rapid Delivery, Quality Software Product, Access to Market, Project Management, Skills and Methodologies, Low Cost/Effort Estimation, Clear Plan and Road Map, Agile Processes, Low Labor Cost, User Satisfaction, Communication/Close Coordination, Proper Scheduling and Time Constraints, Frequent Technological Changes, Robust Model, Geographical distribution/Cultural differences are the key factors that influence software quality requirement change. The recognized success factors and validated with the help of various research methods, i.e., case studies, interviews, surveys and experiments. These factors are then scrutinized in continents, database, company size and period of time. Based on these findings, requirement change will be implemented in a better way.

Keywords: global software development, requirement engineering, systematic literature review, success factors

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Authors: Florin G. Borcan, Ramona C. Albulescu, Adela Chirita-Emandi

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pH-responsive drug delivery systems are gaining more importance because these systems deliver the drug at a specific time in regards to pathophysiological necessity, resulting in improved patient therapeutic efficacy and compliance. Polyurethane materials are well-known for industrial applications (elastomers and foams used in different insulations and automotive), but they are versatile biocompatible materials with many applications in medicine, as artificial skin for the premature neonate, membrane in the hybrid artificial pancreas, prosthetic heart valves, etc. This study aimed to obtain the physico-chemical characterization of a drug delivery system based on polyurethane microparticles. The synthesis is based on a polyaddition reaction between an aqueous phase (mixture of polyethylene-glycol M=200, 1,4-butanediol and Tween® 20) and an organic phase (lysin-diisocyanate in acetone) combined with simultaneous emulsification. Different active agents (omeprazole, amoxicillin, metoclopramide) were used to verify the release profile of the macromolecular particles in different pH mediums. Zetasizer measurements were performed using an instrument based on two modules: a Vasco size analyzer and a Wallis Zeta potential analyzer (Cordouan Technol., France) in samples that were kept in various solutions with different pH and the maximum absorbance in UV-Vis spectra were collected on a UVi Line 9,400 Spectrophotometer (SI Analytics, Germany). The results of this investigation have revealed that these particles are proper for a prolonged release in gastric medium where they can assure an almost constant concentration of the active agents for 1-2 weeks, while they can be disassembled faster in a medium with neutral pHs, such as the intestinal fluid.

Keywords: lysin-diisocyanate, nanostructures, polyurethane, Zetasizer

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Authors: Pascal Roubides

Abstract:

The presentation proposed herein describes a research case study of a hybrid application of the competency-based education model best exemplified by Western Governor’s University, within the general temporal confines of an accelerated (8-week) term of a College Algebra course at the author’s institution. A competency-based model was applied to an accelerated online College Algebra course, built as an Open Educational Resources (OER) course, seeking quantifiable evidence of any differences in the academic achievement of students enrolled in the competency-based course and the academic achievement of the current delivery of the same course. Competency-based learning has been gaining in support in recent times and the author’s institution has also been involved in its own efforts to design and develop courses based on this approach. However, it is unknown whether there had been any research conducted to quantify evidence of the effect of this approach against traditional approaches prior to the author’s case study. The research question sought to answer in this experimental quantitative study was whether the online College Algebra curriculum at the author’s institution delivered via an OER-based competency-based model can produce statistically significant improvement in retention and success rates against the current delivery of the same course. Results obtained in this study showed that there is no statistical difference in the retention rate of the two groups. However, there was a statistically significant difference found between the rates of successful completion of students in the experimental group versus those in the control group.

Keywords: competency-based learning, online mathematics, online math education, online courses

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