Search results for: chimeric drug delivery vehicles

Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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Authors: Neelam Rashid, Muhammad Zafar, Mushtaq Ahmad, Khafsa Malik, Syed Nasar Shah

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The present study was conducted to study the role of medicinal plants used to cure different ailments in Azad Kashmir. Various ethno medicinal surveys were carried out during 2016 to enlist the uses of plants against various ailments by rural communities of the area. Information was obtained from 60 local people including 45 males (10 traditional health practitioners) and 15 females by semi structured interviews and group discussions. 65 plant species belonging to 45 families were reported. The dominant plant habit was herbaceous (56%) while decoction was the most common method of utilization (40%). The most cited turmoil was the gastrointestinal disorders. The data obtained were analyzed using ethno medicinal indices such as FL, UV, ICF, FC, and RFC. Results revealed that various species had numerous uses in curing of diseases. So conservation of biodiversity of these medicinal plants and traditional knowledge can play important role in improving the local health conditions of rural people and modern drug discovery and development.

Keywords: medicinal plants, ailments, drug, health, traditional

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Authors: Alexis John de Britto

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Studies were performed to select the superior genotypes based on intra-specific variations, caused by phytogeographical, climatic and edaphic parameters of three anti cancer drug yielding mangrove plants such as Acanthus ilicifolius L., Calophyllum inophyllum L. and Excoecaria agallocha L. using ISSR (Inter Simple Sequence Repeats) markers and phytochemical analysis such as preliminary phytochemical tests, TLC, HPTLC, HPLC and antioxidant tests. The plants were collected from five different geographical locations of the East Coast of south India. Genetic heterozygosity, Nei’s gene diversity, Shannon’s information index and Percentage of polymorphism between the populations were calculated using POPGENE software. Cluster analysis was performed using UPGMA algorithm. AMOVA and correlations between genetic diversity and soil factors were analyzed. Combining the molecular and phytochemical variations superior genotypes were selected. Conservation constraints and methods of efficient exploitation of the species are discussed.

Keywords: anti-cancer drug yielding plants, DNA fingerprinting, phytochemical analysis, selection of superior genotypes

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

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

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

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Authors: Jiahui Song, Ravindra P. Joshi

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The use of high-intensity, short-duration electric pulses is a promising development with many biomedical applications. The uses include irreversible electroporation for killing abnormal cells, reversible poration for drug and gene delivery, neuromuscular manipulation, and the shrinkage of tumors, etc. High intensity, short-duration electric pulses result in the creation of high-density, nanometer-sized pores in the cellular membrane. This electroporation amounts to localized modulation of the transverse membrane conductance, and effectively provides a voltage shunt. The electrically controlled changes in the trans-membrane conductivity could be used to affect neural traffic and action potential propagation. A rat was taken as the representative example in this research. The simulation study shows the pathway from the sensorimotor cortex down to the spinal motoneurons, and effector muscles could be reversibly blocked by using high-intensity, short-duration electrical pulses. Also, actual experimental observations were compared against simulation predictions.

Keywords: action potential, electroporation, high-intensity, short-duration

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Authors: Judith Mwakalonge, Geophrey Mbatta, Cuthbert Ruseruka, Gurcan Comert, Saidi Siuhi

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Recent advancements in technology have fostered the development of Electric Vehicles (EVs) that provides relief from transportation dependence on natural fossil fuels as sources of energy. It is estimated that more than 50% of petroleum is used for transportation, which accounts for 28% of annual energy use. Vehicles make up about 82% of all transportation energy use. It is also estimated that about 22% of global Carbon dioxide (CO2) emissions are produced by the transportation sector, therefore, it raises environmental concerns. Governments worldwide, including the United States, are investing in developing EVs to resolve the issues related to the use of natural fossil fuels, such as air pollution due to emissions. For instance, the Bipartisan Infrastructure Law (BIL) that was signed by President Biden on November 15th, 2021, sets aside about $5 billion to be apportioned to all 50 states, the District of Columbia, and Puerto Rico for the development of EV chargers. These chargers should be placed in a way that maximizes their utility. This study aims at studying the charging behaviors of Electric Vehicle (EV) users to establish factors to be considered in the selection of charging locations. The study will focus on social-economic and land use data by studying the relationship between charging time and charging locations. Local factors affecting the charging time and the chargers’ utility will be investigated.

Keywords: electric vehicles, EV charging stations, social economic factors, charging networks

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Authors: Henry Hexmoor, Kailash Yelasani

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We present vehicular platooning as a special case of crowd-sensing framework where sharing sensory information among a crowd is used for their collective benefit. After offering an abstract policy that governs processes involving a vehicular platoon, we review several common scenarios and components surrounding vehicular platooning. We then present a simulated prototype that illustrates efficiency of road usage and vehicle travel time derived from platooning. We have argued that one of the paramount benefits of platooning that is overlooked elsewhere, is the substantial computational savings (i.e., economizing benefits) in acquisition and processing of sensory data among vehicles sharing the road. The most capable vehicle can share data gathered from its sensors with nearby vehicles grouped into a platoon.

Keywords: cloud network, collaboration, internet of things, social network

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Authors: Pei-Chun Chen, Chi-Ting Tseng, Lih-Chi Chen, Kai-Hsiang Yang

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Introduction: The pharmacist is responsible for encouraging adverse drug reaction (ADR) reporting. In a local center in Northern Taiwan, promotion and rewarding of ADR reporting have continued for over six years but failed to bring significant changes. This study aims to find a solution to increase ADR reporting. Research question or hypothesis: We hypothesized that under-reporting is due to the inconvenience of the reporting system. Reports were made conventionally through printed sheets. We proposed that reports made per month will increase if they were computerized. Study design: An ADR reporting platform was established in April 2015, before which was defined as the first stage of this study (January-March, 2015) and after which the second stage. The third stage commenced in November, 2015, after adding a reporting module to physicians prescription system. ADRs could be reported simultaneously when documenting drug allergies. Methods: ADR report rates during the three stages of the study were compared. Effects of the information platform on reporting were also analyzed. Results: During the first stage, the number of ADR reports averaged 6 per month. In the second stage, the number of reports per month averaged 1.86. Introducing the information platform had little effect on the monthly number of ADR reports. The average number of reports each month during the third stage of the study was 11±3.06, with 70.43% made electronically. Reports per month increased significantly after installing the reporting module in November, 2015 (P<0.001, t-test). In the first two stages, 29.03% of ADR reports were made by physicians, as compared to 70.42% of cases in the third stage of the study. Increased physician reporting possibly account for these differences. Conclusion: Adding a reporting module to the prescription system significantly increased ADR reporting. Improved accessibility is likely the cause. The addition of similar modules to computer systems of other healthcare professions may be considered to encourage spontaneous ADR reporting.

Keywords: adverse drug reactions, adverse drug reaction reporting systems, regional hospital, prescription system

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Authors: Ashwani Kumar

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GPS plays an important role in everyday life for safe and convenient transportation. While pedestrians use hand held devices to know their position in a city, vehicles in intelligent transport systems use relatively sophisticated GPS receivers for estimating their current position. However, in urban areas where the GPS satellites are occluded by tall buildings, trees and reflections of GPS signals from nearby vehicles, GPS position estimation becomes poor. In this work, an exhaustive GPS data is collected at a single point in urban area under different times of day and under dynamic environmental conditions. The data is analyzed and statistical refinement methods are used to obtain optimal position estimate among all the measured positions. The results obtained are compared with publically available datasets and obtained position estimation refinement results are promising.

Keywords: global positioning system, statistical approach, intelligent transport systems, least squares estimation

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Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

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A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

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Authors: Shiri Elisheva Decktor, Sharon Hornstein

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Highway merges and unmarked junctions are key components in any urban road network, which can act as bottlenecks and create traffic disruption. Inefficient highway merges may trigger traffic instabilities such as stop-and-go waves, pose safety conditions and lead to longer journey times. These phenomena occur spontaneously if the average vehicle density exceeds a certain critical value. This study focuses on modeling the traffic using a microscopic traffic flow model. A hybrid traffic model, which combines human-driven and controlled vehicles is assumed. The controlled vehicles obey different driving policies when approaching the merge, or in the vicinity of other vehicles. We developed a co-simulation model in SUMO (Simulation of Urban Mobility), in which the human-driven cars are modeled using the IDM model, and the controlled cars are modeled using a dedicated controller. The scenario chosen for this study is a closed track with one merge and one exit, which could be later implemented using a scaled infrastructure on our lab setup. This will enable us to benchmark the results of this study obtained in simulation, to comparable results in similar conditions in the lab. The metrics chosen for the comparison of the performance of our algorithm on the overall traffic conditions include the average speed, wait time near the merge, and throughput after the merge, measured under different travel demand conditions (low, medium, and heavy traffic).

Keywords: highway merges, traffic modeling, SUMO, driving policy

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Authors: Ahmed El-Fiqi, Hae-Won Kim

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Incorporation of therapeutic elements such as Sr, Cu and Co into bioglass structure and their release as ions is considered as one of the promising approaches to enhance cellular responses, e.g., osteogenesis and angiogenesis. Here, cobalt as angiogenesis promoter has been incorporated (at 0, 1 and 4 mol%) into sol-gel derived calcium silicate mesoporous bioglass nanoparticles. The composition and structure of cobalt-free (CFN) and cobalt-doped (CDN) mesoporous bioglass nanoparticles have been analyzed by X-ray fluorescence (XRF), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier-Transform Infra-red spectroscopy (FT-IR). The physicochemical properties of CFN and CDN have been investigated using high-resolution transmission electron microscopy (HR-TEM), Selected area electron diffraction (SAED), and Energy-dispersive X-ray (EDX). Furthermore, the textural properties, including specific surface area, pore-volume, and pore size, have been analyzed from N²⁻sorption analyses. Surface charges of CFN and CDN were also determined from surface zeta potential measurements. The release of ions, including Co²⁺, Ca²⁺, and SiO₄⁴⁻ has been analyzed using inductively coupled plasma atomic emission spectrometry (ICP-AES). Loading and release of diclofenac as an anti-inflammatory drug model were explored in vitro using Ultraviolet-visible spectroscopy (UV-Vis). XRD results ensured the amorphous state of CFN and CDN whereas, XRF further confirmed that their chemical compositions are very close to the designed compositions. HR-TEM analyses unveiled nanoparticles with spherical morphologies, highly mesoporous textures, and sizes in the range of 90 - 100 nm. Moreover, N²⁻ sorption analyses revealed that the nanoparticles have pores with sizes of 3.2 - 2.6 nm, pore volumes of 0.41 - 0.35 cc/g and highly surface areas in the range of 716 - 830 m²/g. High-resolution XPS analysis of Co 2p core level provided structural information about Co atomic environment and it confirmed the electronic state of Co in the glass matrix. ICP-AES analysis showed the release of therapeutic doses of Co²⁺ ions from 4% CDN up to 100 ppm within 14 days. Finally, diclofenac loading and release have ensured the drug/ion co-delivery capability of 4% CDN.

Keywords: mesoporous bioactive glass, nanoparticles, cobalt ions, release

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Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

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Authors: Mostafa Ghasemi, Andrew Urquhart

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In this study, fluorescent carbon dots (CDs) were synthesized in a green way using a one-step hydrothermal method. Carbon dots are carbon-based nanomaterials with a size of less than 10 nm, unique structure, and excellent properties such as low toxicity, good biocompatibility, tunable fluorescence, excellent photostability, and easy functionalization. These properties make them a good candidate to use in different fields such as biological sensing, photocatalysis, photodynamic, and drug delivery. Fourier transformed infrared (FTIR) spectra approved OH/NH groups on the surface of the as-synthesized CDs, and UV-vis spectra showed excellent fluorescence quenching effect of Fe (III) ion on the as-synthesized CDs with high selectivity detection compared with other metal ions. The probe showed a linear response concentration range (0–2.0 mM) to Fe (III) ion, and the limit of detection was calculated to be about 0.50 μM. In addition, CDs also showed good sensitivity to the pH value in the range from 2 to 14, indicating great potential as a pH sensor.

Keywords: carbon dots, fluorescence, pH sensing, metal ions sensor

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Authors: Maninderjeet K. Grewal, Sakshi Bhatnor, Renu Chadha

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The composition of pharmaceutical entities and the molecular interactions can be altered to optimize drug properties such as solubility and bioavailability by the crystal engineering technique. The present work has emphasized on the preparation, characterization, and biopharmaceutical evaluation of co-crystal of BCS Class II anti-osteoarthritis drug, Oxaprozin (OXA) with aspartic acid (ASPA) as co-former. The co-crystals were prepared through the mechanochemical solvent drop grinding method. Characterization of the prepared co-crystal (OXA-ASPA) was done by using analytical tools such as differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD). DSC thermogram of OXA-ASPA cocrystal showed a single sharp melting endotherm at 235 ºC, which was between the melting peaks of the drug and the counter molecules suggesting the formation of a new phase which is a co-crystal that was further confirmed by using other analytical techniques. FT-IR analysis of OXA-ASPA cocrystal showed a shift in a hydroxyl, carbonyl, and amine peaks as compared to pure drugs indicating all these functional groups are participating in cocrystal formation. The appearance of new peaks in the PXRD pattern of cocrystals in comparison to individual components showed that a new crystalline entity has been formed. The Crystal structure of cocrystal was determined using material studio software (Biovia) from PXRD. The equilibrium solubility study of OXA-ASPA showed improvement in solubility as compared to pure drug. Therefore, it was envisioned to prepare the co-crystal of oxaprozin with a suitable conformer to modulate its physiochemical properties and consequently, the biopharmaceutical parameters.

Keywords: cocrystals, coformer, oxaprozin, solubility

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

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

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

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Eda Cagli, Irem Erel Goktepe

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Externally triggered and effective release of therapeutics from polymer nanoplatforms is one of the key issues in cancer treatment. In this study, we aim to prepare polymer multilayer films which are stable at physiological conditions (little or no drug release) but release drug molecules at acidic pH and via application of AC magnetic field. First, novel stimuli responsive diblock copolymers composed of pH- and temperature-responsive blocks were synthesized. Then, block copolymer micelles with pH-responsive core and temperature responsive coronae will be obtained via pH-induced self-assembly of these block copolymers in aqueous environment. A model anticancer drug, e.g. Doxorubicin will be loaded in the micellar cores. Second, superparamagnetic nanoparticles will be synthesized. Magnetic nanoparticles and drug loaded block copolymer micelles will be used as building blocks to construct the multilayers. To mimic the acidic nature of the tumor tissues, Doxorubicin release from the micellar cores will be induced at acidic conditions. Moreover, Doxorubicin release from the multilayers will be facilitated via magnetothermal trigger. Application of AC magnetic field will induce the heating of magnetic nanoparticles resulting in an increase in the temperature of the polymer platform. This increase in temperature is expected to trigger conformational changes on the temperature-responsive micelle coronae and facilitate the release of Doxorubicin from the surface. Such polymer platform may find use in biomedical applications.

Keywords: layer-by-layer films, magnetothermal trigger, smart polymers, stimuli responsive

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Authors: M. Kosacka, I. Kudelska

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Vehicle is one of the most influential and complex product worldwide, which affects people’s life, state of the environment and condition of the economy (all aspects of sustainable development concept) during each stage of lifecycle. With the increase of vehicles’ number, there is growing potential for management of End of Life Vehicle (ELV), which is hazardous waste. From one point of view, the ELV should be managed to ensure risk elimination, but from another point, it should be treated as a source of valuable materials and spare parts. In order to obtain materials and spare parts, there are established recycling networks, which are an example of sustainable policy realization at the national level. The basic object in the polish recycling network is dismantling facility. The output material streams in dismantling stations include waste, which very often generate costs and spare parts, that have the biggest potential for revenues creation. Both outputs are stored into warehouses, according to the law. In accordance to the revenue creation and sustainability potential, it has been placed a strong emphasis on storage process. We present the concept of storage method, which takes into account the specific of the dismantling facility in order to support decision-making process with regard to the principles of sustainable development. The method was developed on the basis of case study of one of the greatest dismantling facility in Poland.

Keywords: dismantling, end of life vehicles, sustainability, storage

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Authors: Florin Leon

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This paper describes a simulator of traffic scenarios tailored to facilitate autonomous driving model training for urban environments. With the rising prominence of self-driving vehicles, the need for diverse datasets is very important. The proposed simulator provides a flexible framework that allows the generation of custom scenarios needed for the validation and enhancement of trajectory prediction algorithms. Its controlled yet dynamic environment addresses the challenges associated with real-world data acquisition and ensures adaptability to diverse driving scenarios. By providing an adaptable solution for scenario creation and algorithm testing, this tool proves to be a valuable resource for advancing autonomous driving technology that aims to ensure safe and efficient self-driving vehicles.

Keywords: autonomous driving, car simulator, machine learning, model training, urban simulation environment

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Authors: Aneena Suresh, C. S. Sidharth

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Drug related problems (DRPs) are common in chronic kidney disease (CKD) patients and end stage patients undergoing hemodialysis. To treat the co-morbid conditions of the patients, more complex therapeutic regimen is required, and it leads to development of DRPs. So, this calls for frequent monitoring of the patients. Due to the busy work schedules, physicians are unable to deliver optimal care to these patients. Addition of a clinical pharmacist in the team will improve the standard of care offered to CKD patients by minimizing DRPs. In India, the role of clinical pharmacists in the improving the health outcomes in CKD patients is poorly recognized. Therefore, this study is conducted to put an insight on the role of clinical pharmacist in improving Drug Related Problems in patients with chronic kidney disease, thereby helping them to achieve desired therapeutic outcomes in the patients. A prospective interventional study was conducted for a year in a 620 bedded tertiary care hospital in India. Data was collected using an unstructured questionnaire, medication charts, etc. DRPs were categorized using Hepler and Strand classification. Relationships between the age, weight, GFR, average no of medication taken, average no of comorbidities, and average length of hospital days with the DRPs were identified using Mann Whitney U test. The study population primarily constituted of patients above the age of 50 years with a mean age of 59.91±13.59. Our study showed that 25% of the population presented with DRPs. On an average, CKD patients are prescribed at least 8 medications for the treatment in our study. This explains the high incidence of drug interactions in patients suffering from CKD (45.65%). The least common DRPs in our study were found to be sub therapeutic dose (2%) and adverse drug reactions (2%). Out of this, 60 % of the DRPs were addressed successfully. In our study, there is an association between the DRPs with the average number of medications prescribed, the average number of comorbidities, and the length of the hospital days with p value of 0.022, 0.004, and 0.000, respectively. In the current study, 86% of the proposed interventions were accepted, and 41 % were implemented by the physician, and only 14% were rejected. Hence, it is evident that clinical pharmacist interventions will contribute significantly to diminish the DRPs in CKD patients, thereby decreasing the economic burden of healthcare costs and improving patient’s quality of life.

Keywords: chronic kidney disease, clinical pharmacist, drug related problem, intervention

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

Abstract:

Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Ikram Elsiddig, Yacouba Djamila, Amna Hamad

Abstract:

Abstract—The worldwide increasing of using herbs in form of medicine with or without prescription medications potentiates the interactions between herbal products and conventional medicines; due to more research for herb-drug interactions are needed. for a long time hyperglycemia had been treated with several medicinal plants. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol and high blood pressure. The purpose of this study is to determine the interaction effect between A. sativum bulb extracts and metformin drug used in diabetes treatment. The in vitro and in vivo evaluation were conducted by glucose reuptake using isolated rats hemidiaphgrams tissue and by estimate glucose tolerance in glucose-loaded wistar albino rats. The results showed that, petroleum ether, chloroform and ethyl acetate extracts were found to have activity of glucose uptake in isolated rats hemidiaphgrams of 24.11 mg/g, 19.07 mg/g and 15.66 mg/g compared to metformin drug of 17 mg/g. These activity were reducded to 17.8 mg/g, 13.59 mg/g and 14.46 mg/g after combination with metformin, metformin itself reduced to 13.59 mg/g, 14.46 mg/g and 12.71 mg/g in comination with chloroform and ethyl acetate. These decrease in activity could be due to herbal–drug interaction between the extracts of A. sativum bulb and metformin drug. The interaction between A. sativum extract and metformin was also shown by in vivo study on the induced hyperglycemic rats. The glucose level after administered of 200 mg/kg was found to be increase with 47.2 % and 17.7% at first and second hour compared to the increase of blood glucose in the control group of 82.6% and76.7%.. At fourth hour the glucose level was became less than normal with 3.4% compared to control which continue to increase with 68.2%. Dose of 400 mg/kg at first hour showed increase in blood glucose of 31.5 %, at second and fourth hours the glucose level was became less than normal with decrease of 3.2 % and 30.4%. After combination the activity was found to be less than that of extract at both high and low dose, whereas, at first and second hour, the glucose level was found to be increase with 50.4% and 21.2%, at fourth hour the glucose level was became less than normal with 14%. Therefore A. sativum could be a potential source for anti-diabetic when it used alone, and it is significant important to use the garlic extract alone instead of combined with Metformin drug in diabetes- treatment.

Keywords: Antagonistic, Garlic, Metformin, Synergistic

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Authors: Orhun Vural, Oguz Bayat, Rustu Akay, Osman N. Ucan

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This study presents a new parallel approach clustering of GPS data. Evaluation has been made by comparing execution time of various clustering algorithms on GPS data. This paper aims to propose a parallel based on neighborhood K-means algorithm to make it faster. The proposed parallelization approach assumes that each GPS data represents a vehicle and to communicate between vehicles close to each other after vehicles are clustered. This parallelization approach has been examined on different sized continuously changing GPS data and compared with serial K-means algorithm and other serial clustering algorithms. The results demonstrated that proposed parallel K-means algorithm has been shown to work much faster than other clustering algorithms.

Keywords: parallel k-means algorithm, parallel clustering, clustering algorithms, clustering on flowing data

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Authors: Anil Ranjitbhai Patel, Clement John Shaji, Peter Liggesmeyer

Abstract:

Safety and security of autonomous vehicles (AVs) is a growing concern, first, due to the increased number of safety-critical functions taken over by automotive embedded systems; second, due to the increased exposure of the software-intensive systems to potential attackers; third, due to dynamic interaction in an uncertain and unknown environment at runtime which results in changed functional and non-functional properties of the system. Frequently occurring environmental uncertainties, random component failures, and compromise security of the AVs might result in hazardous events, sometimes even in an accident, if left undetected. Beyond these technical issues, we argue that the safety and security of AVs against accidental and deliberate faults are poorly understood and rarely implemented. One possible way to overcome this is through a well-known diversity approach. As an effective approach to increase safety and security, diversity has been widely used in the aviation, railway, and aerospace industries. Thus, the paper proposes fault-tolerance by diversity model takes into consideration the mitigation of accidental and deliberate faults by application of structure and variant redundancy. The model can be used to design the AVs with various types of diversity in hardware and software-based multi-version system. The paper evaluates the presented approach by employing an example from adaptive cruise control, followed by discussing the case study with initial findings.

Keywords: autonomous vehicles, diversity, fault-tolerance, adaptive cruise control, safety, security

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Authors: R. Venkatesan, A. Sabari

Abstract:

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

Keywords: multicasting, scalability, security, social network

Procedia PDF Downloads 284

Authors: Sunil Kumar

Abstract:

For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss.

Keywords: anticancer, antibiotic, lead molecule, natural product, synthetic analogues

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Authors: Natida Thongsima, Patompong Satapornpong

Abstract:

Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.

Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population

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Authors: Saad Roustom, Hajo Ribberink

Abstract:

In most cities in the world, traffic has increased strongly over the last decades, causing high levels of congestion and deteriorating inner-city air quality. This study analyzes the impact of connected and automated vehicles (CAVs) on traffic performance and greenhouse gas (GHG) emissions under different CAV penetration rates in mixed fleet environments of CAVs and driver-operated vehicles (DOVs) and under three different traffic demand levels. Utilizing meso-scale traffic simulations of the City of Ottawa, Canada, the research evaluates the traffic performance of three distinct CAV driving behaviors—Cautious, Normal, and Aggressive—at penetration rates of 25%, 50%, 75%, and 100%, across three different traffic demand levels. The study employs advanced correlation models to estimate GHG emissions. The results reveal that Aggressive and Normal CAVs generally reduce traffic congestion and GHG emissions, with their benefits being more pronounced at higher penetration rates (50% to 100%) and elevated traffic demand levels. On the other hand, Cautious CAVs exhibit an increase in both traffic congestion and GHG emissions. However, results also show deteriorated traffic flow conditions when introducing 25% penetration rates of any type of CAVs. Aggressive CAVs outperform all other driving at improving traffic flow conditions and reducing GHG emissions. The findings of this study highlight the crucial role CAVs can play in enhancing urban traffic performance and mitigating the adverse impact of transportation on the environment. This research advocates for the adoption of effective CAV-related policies by regulatory bodies to optimize traffic flow and reduce GHG emissions. By providing insights into the impact of CAVs, this study aims to inform strategic decision-making and stimulate the development of sustainable urban mobility solutions.

Keywords: connected and automated vehicles, congestion, GHG emissions, mixed fleet environment, traffic performance, traffic simulations

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Authors: Soad Ali Yehia, Mohamed Shafik El-Ridi, Mina Ibrahim Tadros, Nolwa Gamal El-Sherif

Abstract:

Fexofenadine hydrochloride (FXD) is a slightly soluble, bitter-tasting, drug having an oral bioavailability of 35%. The maximum plasma concentration is reached 2.6 hours (Tmax) post-dose. The current work aimed to develop taste-masked FXD orodispersible tablets (ODTs) to increase extent of drug absorption and reduce Tmax. Taste masking was achieved via solid dispersion (SD) with chitosan (CS) or sodium alginate (ALG). FT-IR, DSC and XRD were performed to identify physicochemical interactions and FXD crystallinity. Taste-masked FXD-ODTs were developed via addition of superdisintegrants (crosscarmelose sodium or sodium starch glycolate, 5% and 10%, w/w) or sublimable agents (camphor, menthol or thymol; 10% and 20%, w/w) to FXD-SDs. ODTs were evaluated for weight variation, drug-content, friability, wetting time, disintegration time and drug release. Camphor-based (20%, w/w) FXD-ODT (F12) was optimized (F23) by incorporation of a more hydrophilic lubricant, sodium stearyl fumarate (Pruv®). The topography of the latter formula was examined via scanning electron microscopy (SEM). The in vivo estimation of FXD pharmacokinetics, relative to Allegra® tablets, was evaluated in healthy human volunteers. Based on the gustatory sensation test in healthy volunteers, FXD:CS (1:1) and FXD:ALG (1:0.5) SDs were selected. Taste-masked FXD-ODTs had appropriate physicochemical properties and showed short wetting and disintegration times. Drug release profiles of F23 and phenylalanine-containing Allegra® ODT were similar (f2 = 96) showing a complete release in two minutes. SEM micrographs revealed pores following camphor sublimation. Compared to Allegra® tablets, pharmacokinetic studies in healthy volunteers proved F23 ability to increase extent of FXD absorption (14%) and reduce Tmax to 1.83 h.

Keywords: fexofenadine hydrochloride, taste masking, chitosan, orodispersible

Procedia PDF Downloads 337