Search results for: drug release model

Authors: Lin Tang, Xiaoxia Guo, Lingling Zhang

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Recent vaccine scandals overshadowed China’s accomplishment of public health, triggering discussions on the causes of vaccine incidents. Through legal interpretation of selected vaccine incidents and analysis of systemic vulnerabilities in vaccine circulation and lot release, a panoramic review of legislative progresses in the vaccine administration sheds the light on this debate. In essence, it is the combination of the lagging legal system and the absence of information technology infrastructure in the process of vaccine administration reform that has led to the recurrence of vaccine incidents. These findings have significant implications for further improvement of vaccine administration and China’s participation in global healthcare.

Keywords: legislation, lot release, public health, reform, vaccine administration, vaccine circulation

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Authors: Owonikoko Abayomi Dele

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Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

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Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

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Authors: Tadesse Melaku Abegaz

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Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.

Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence

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Authors: Jinfeng Zhang, Chun-Sing Lee

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Pure nanodrugs (PNDs) – nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for the next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile and controllable strategy for preparing PNDs via an anodized aluminium oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anti-cancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.

Keywords: drug delivery, pure nanodrugs, size control, template

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

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Elvitegravir is the mainstay of anti-HIV combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (Quercetin: QU) is a polyphenolic compound obtained from Argeria speciosa Linn (Family: Convolvulaceae), an anti-HIV candidate. In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination elvitegravir and Quercetin, in rat plasma. The method was linear over a range of 0.2–500 ng/ml. All validation parameters met the acceptance criteria according to regulatory guidelines. LC–MS/MS method for determination of Elvitegravir and Quercetin was developed and validated. Results show the potential of drug–drug interaction upon co-administration this marketed drugs and plant derived secondary metabolite.

Keywords: anti-HIV resistance, extraction, HPLC-ESI-MS-MS, validation

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Authors: Daniella Hirwa

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Attention Deficit Hyperactivity Disorder (ADHD) is associated with several risk-taking behaviors, including drug use and smoking. Such risk-taking behaviors are often a result of an attempt to self-manage symptoms associated with ADHD. The present review investigates the effects of nicotine on symptoms associated with ADHD. This systematic literature review was conducted for 2017-2024 using keywords associated with ADHD, smoking, and nicotine. The results indicate that individuals with ADHD start smoking earlier than those without ADHD, and it is believed that this prevalence and the higher rates of smoking are due to improvements in cognitive and executive function, attention, and impulsivity due to the effect that nicotine has on dopamine release. Longitudinal studies with larger sample sizes and comprehensive health history and cognitive testing are required to gain more insight into the ways that nicotine affects ADHD symptoms and the context by which smoking is used as a method of self-treatment to help aid the development of nicotine-based treatment options that do not pose the same health risks as smoking.

Keywords: ADHD, nicotine, risk-taking behaviors, smoking

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Authors: Hiba Hamdi, Thomas Corpetti, Laure Roupioz, Xavier Briottet

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Air temperatures are generally higher in cities than in their rural surroundings. The overheating of cities is a direct consequence of increasing urbanization, characterized by the artificial filling of soils, the release of anthropogenic heat, and the complexity of urban geometry. This phenomenon, referred to as urban heat island (UHI), is more prevalent during heat waves, which have increased in frequency and intensity in recent years. In the context of global warming and urban population growth, helping urban planners implement UHI mitigation and adaptation strategies is critical. In practice, the study of UHI requires air temperature information at the street canyon level, which is difficult to obtain. Many urban air temperature simulation models have been proposed (mostly based on physics or statistics), all of which require a variety of input parameters related to urban morphology, land use, material properties, or meteorological conditions. In this paper, we build and evaluate a neural network model based on Urban Weather Generator (UWG) model simulations and data from meteorological stations that simulate air temperature over Toulouse, France, on days favourable to UHI.

Keywords: air temperature, neural network model, urban heat island, urban weather generator

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Authors: Kiurski S. Jelena, Kecić S. Vesna, Oros B. Ivana, Ranogajec G. Jonjaua

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The paper represents the dependence of ammonia concentration on microclimate parameters and photocopying shop circulation. The concentration of ammonia was determined during 8-hours working time over five days including three sampling points of a photocopying shop in Novi Sad, Serbia. The obtained results pointed out that the room temperature possesses the highest impact on ammonia release. The obtained ammonia concentration was in the range of 1.53 to 0.42ppm and decreased with the temperature decreasing from 24.6 to 20.7 °C. As the detected concentrations were within the permissible levels of The Occupational Safety and Health Administration, The National Institute for Occupational Safety and The Health and Official Gazette of Republic of Serbia, in the range of 35 to 200ppm, there was no danger to the employee’s health in the photocopying shop.

Keywords: ammonia, emission, indoor environment, photocopying procedure

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Authors: Fulya Asena Uluç, Ehsan Tuzcuoğlu, Songül Bayraktar, Burak Koca, Alper Gürarslan

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Microplastics are contaminants that are widely distributed in the environment with a detrimental ecological effect. Besides this, recent research has proved the existence of microplastics in human blood and organs. Microplastics in the environment can be divided into two main categories: primary and secondary microplastics. Primary microplastics are plastics that are released into the environment as microscopic particles. On the other hand, secondary microplastics are the smaller particles that are shed as a result of the consumption of synthetic materials in textile products as well as other products. Textiles are the main source of microplastic contamination in aquatic ecosystems. Laundry of synthetic textiles (34.8%) accounts for an average annual discharge of 3.2 million tons of primary microplastics into the environment. Recently, microfiber shedding from laundry research has gained traction. However, no comprehensive study was conducted from the standpoint of rinsing parameters during laundry to analyze microfiber shedding. The purpose of the present study is to quantify microfiber shedding from fabric under different rinsing conditions and determine the effective rinsing parameters on microfiber release in a laundry environment. In this regard, a parametric study is carried out to investigate the key factors affecting the microfiber release from a front-load washing machine. These parameters are the amount of water used during the rinsing step and the spinning speed at the end of the washing cycle. Minitab statistical program is used to create a design of the experiment (DOE) and analyze the experimental results. Tests are repeated twice and besides the controlled parameters, other washing parameters are kept constant in the washing algorithm. At the end of each cycle, released microfibers are collected via a custom-made filtration system and weighted with precision balance. The results showed that by increasing the water amount during the rinsing step, the amount of microplastic released from the washing machine increased drastically. Also, the parametric study revealed that increasing the spinning speed results in an increase in the microfiber release from textiles.

Keywords: front load, laundry, microfiber, microfiber release, microfiber shedding, microplastic, pollution, rinsing parameters, sustainability, washing parameters, washing machine

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Zeynep R. Ege, Aydin Akan, Faik N. Oktar, Betul Karademir, Oguzhan Gunduz

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Early detection of cancer could save human life and quality in insidious cases by advanced biomedical imaging techniques. Designing targeted detection system is necessary in order to protect of healthy cells. Electrospun nanofibers are efficient and targetable nanocarriers which have important properties such as nanometric diameter, mechanical properties, elasticity, porosity and surface area to volume ratio. In the present study, indocyanine green (ICG) organic dye was stabilized and encapsulated in polymer matrix which polyethylene oxide (PEO) and chitosan (CHI) multilayer nanofibers via co-axial electrospinning method at one step. The co-axial electrospun nanofibers were characterized as morphological (SEM), molecular (FT-IR), and entrapment efficiency of Indocyanine Green (ICG) (confocal imaging). Controlled release profile of PEO/CHI/ICG nanofiber was also evaluated up to 40 hours.

Keywords: chitosan, coaxial electrospinning, controlled releasing, drug delivery, indocyanine green, polyethylene oxide

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Authors: Domenica Tambasco, Riina Bray, Sophia Jaworski, Gillian Grant, Celeste Corkery

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Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and reduced function. Management of symptoms include medications, physical treatments and mindfulness therapies. Myofascial Release is a modality that has been successfully applied in var-ious musculoskeletal conditions. However, to the author’s best knowledge, it is not yet recog-nized as a self-management therapy option in Fibromyalgia. In this study, we investigated whether Self-applied Myofascial Release (SMR) is associated with overall improved function and symptoms in Fibromyalgia. Methods: Eligible adult patients with a confirmed diagnosis of Fibromyalgia at Women’s College Hospital were recruited to SMR. Sessions ran for 1 hour once a week for 7 weeks, led by the same two Physiotherapists knowledgeable in this physical treat-ment modality. The main outcome measure was an overall impact score for function and symp-toms based on the validated assessment tool for Fibromyalgia, the Revised Fibromyalgia Impact Questionnaire (FIQR), measured pre and post-intervention. Both descriptive and analytical methods were applied and reported. Results: We analyzed results using a paired t-test to deter-mine if there was a statistically significant difference in mean FIQR scores between initial (pre-intervention) and final (post-intervention) scores. A clinically significant difference in FIQR was defined as a reduction in score by 10 or more points. Conclusions: Our pilot study showed that SMR appeared to be a safe and effective intervention for our Fibromyalgia participants and the overall impact on function and symptoms occurred in only 7 weeks. Further studies with larger sample sizes comparing SMR to other physical treatment modalities (such as stretching) in an RCT are recommended.

Keywords: fibromyalgia, myofascial release, physical therapy, FIQR

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Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

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Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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Authors: Javier Fernandez, Mayte Medina, Rafael Fernandez de Canete, Nuria Alcain, Juan Carlos Ramos-Diaz

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At present, the experimentation of anesthetic drugs on patients requires a regulation protocol, and the response of each patient to several doses of entry drug must be well known. Therefore, the development of pharmacological dose control systems is a promising field of research in anesthesiology. In this paper, it has been developed a non-linear compartmental the pharmacokinetic-pharmacodynamical model which describes the anesthesia depth effect in a sufficiently reliable way over a set of patients with the depth effect quantified by the Bi-Spectral Index. Afterwards, an Artificial Neural Network (ANN) predictive controller has been designed based on the depth of anesthesia model so as to keep the patient in the optimum condition while he undergoes surgical treatment. For the purpose of quantifying the efficiency of the neural predictive controller, a classical proportional-integral-derivative controller has also been developed to compare both strategies. Results show the superior performance of predictive neural controller during BiSpectral Index reference tracking.

Keywords: anesthesia, bi-spectral index, neural network control, pharmacokinetic-pharmacodynamical model

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Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

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Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

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Authors: Minh-Phuong Ngoc Bui, Abdennour Abbas

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Microbial spoilage of food/drug has been a constant nuisance and an unavoidable problem throughout history that affects food/drug quality and safety in a variety of ways. A simple and rapid test of fungi and bacteria in food/drugs and environmental clinical samples is essential for proper management of contamination. A number of different techniques have been developed for detection and enumeration of foodborne microorganism including plate counting, enzyme-linked immunosorbent assay (ELISA), polymer chain reaction (PCR), nucleic acid sensor, electrical and microscopy methods. However, the significant drawbacks of these techniques are highly demand of operation skills and the time and cost involved. In this report, we introduce a rapid method for detection of bacteria and fungi in food/drug products using a specific interaction between a reducing agent (tris(2-carboxylethyl)phosphine (TCEP)) and the microbial surface proteins. The chemical reaction was transferred to a transduction system using gold nanoplates-enhanced chemiluminescence. We have optimized our nanoplates synthetic conditions, characterized the chemiluminescence parameters and optimized conditions for the microbial assay. The new detection method was applied for rapid detection of bacteria (E.coli sp. and Lactobacillus sp.) and fungi (Mucor sp.), with limit of detection as low as single digit cells per mL within 10 min using a portable luminometer. We expect our simple and rapid detection method to be a powerful alternative to the conventional plate counting and immunoassay methods for rapid screening of microorganisms in food/drug products.

Keywords: microorganism testing, gold nanoplates, chemiluminescence, reducing agents, luminol

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Authors: Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder, Anil Chandewar

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The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

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Authors: Erfan Rahimi, Hadi Bahari Far, Mojgan Shikhpour

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Background: Urinary tract infection is one of the most common nosocomial infections, especially among women. E. coli is one of the main causes of urinary tract infections and one of the most common antibiotics to fight this bacterium is ampicillin. As conventional antibiotics led to bacterial antibiotic resistance, modification of the pure drugs can address this issue. The aim of this study was to prepare nanofluids containing carbon nanotubes conjugated with ampicillin to improve drug performance and reduce antibiotic resistance. Methods: Multi-walled carbon nanotubes (MWCNTs) were activated with thionyl chloride by reflux system and nanofluids containing antibiotics were prepared by ultrasonic method. The properties of the prepared nano-drug were investigated by general element analysis, infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and transmission electron microscopy. After the treatment of the desired strain with nanofluid, microbial studies were performed to evaluate the antibacterial effects and molecular studies were carried out to measure the expression of the resistance gene AcrAB. Result: We have shown that the antimicrobial effect of ampicillin-functionalized MWCNTs at low concentrations performed better than that of the conventional drug in both resistant and ATCC strains. Also, a decrease in antibiotic resistance of bacteria treated with ampicillin-functionalized MWCNTs compared to the pure drug was observed. Also, ampicillin-functionalized MWCNTs downregulated the expression of AcrAB in treated bacteria. Conclusion: Because carbon nanotubes are capable of destroying the bacterial wall, which provides antibiotic resistance features in bacteria, their usage in the form of nanofluids can make lower dosages (about three times less) than that of the pure drug more effective. Additionally, the expression of the bacterial resistance gene AcrAB decreased, thereby reducing antibiotic resistance and improving drug performance against bacteria.

Keywords: urinary tract infection, antibiotic resistance, carbon nanotube, nanofluid

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Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

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Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

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Authors: Nadjet Mekaouche, Hanane Zitouni, Fatma Boudia, Habiba Fetati, A. Saleh, A. Lardjam, H. Geniaux, A. Coubret, H. Toumi

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Medicines have undeniably played a major role in prolonging shelf life and improving quality. The absolute efficacy of the drug remains a lever for innovation, its benefit/risk balance is not always assured and it does not always have the expected effects. Prior to marketing, knowledge about adverse drug reactions is incomplete. Once on the market, phase IV drug studies begin. For years, the drug was prescribed with less care to a large number of very heterogeneous patients and often in combination with other drugs. It is at this point that previously unknown adverse effects may appear, hence the need for the implementation of a pharmacovigilance system. Pharmacovigilance represents all methods for detecting, evaluating, informing and preventing the risks of adverse drug reactions. The most severe adverse events occur frequently in hospital and that a significant proportion of adverse events result in hospitalizations. In addition, the consequences of hospital adverse events in terms of length of stay, mortality and costs are considerable. It, therefore, appears necessary to develop ‘hospital pharmacovigilance’ aimed at reducing the incidence of adverse reactions in hospitals. The most widely used monitoring method in pharmacovigilance is spontaneous notification. However, underreporting of adverse drug reactions is common in many countries and is a major obstacle to pharmacovigilance assessment. It is in this context that this study aims to describe the experience of the pharmacovigilance service at the University Hospital of Oran (EHUO). This is a retrospective study extending from 2011 to 2017, carried out on archived records of declarations collected at the level of the EHUO Pharmacovigilance Department. Reporting was collected by two methods: ‘spontaneous notification’ and ‘active pharmacovigilance’ targeting certain clinical services. We counted 217 statements. It involved 56% female patients and 46% male patients. Age ranged from 5 to 78 years with an average of 46 years. The most common adverse reaction was drug toxidermy. For the drugs in question, they were essentially according to the ATC classification of anti-infectives followed by anticancer drugs. As regards the evolution of declarations by year, a low rate of notification was noted in 2011. That is why we decided to set up an active approach at the level of some services where a resident of reference attended the staffs every week. This has resulted in an increase in the number of reports. The declarations came essentially from the services where the active approach was installed. This highlights the need for ongoing communication between all relevant health actors to stimulate reporting and secure drug treatments.

Keywords: adverse drug reactions, hospital, pharmacovigilance, spontaneous notification

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Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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Authors: Shashank Tiwari

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The most common method of drug delivery is the oral solid dosage form, of which tablets and capsules are predominant. The tablet is more widely accepted and used compared to capsules for a number of reasons, such as cost/price, tamper resistance, ease of handling and packaging, ease of identification, and manufacturing efficiency. Over the past several years, the issue of tamper resistance has resulted in the conversion of most over-the-counter (OTC) drugs from capsules to predominantly all tablets.

Keywords: capsule, drug delivery, dosages, solid, tablet

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Authors: Eun Ju Park, Wendy Rusli, He Tao, Alexander M. Van Herk, Sanggu Kim

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Hollow micro-/nano- structured materials have proven to be promising in wide range of applications, such as catalysis, drug delivery and controlled release, biotechnology, and personal and consumer care. Hollow sphere structures can be obtained through various templating approaches; colloid templates, emulsion templates, multi-surfactant templates, and single crystal templates. Vesicles are generally the self-directed assemblies of amphiphilic molecules including cationic, anionic, and cationic surfactants in aqueous solutions. The directed silica capsule formations were performed at the surface of dioctadecyldimethylammoniumbromide(DODAB) bilayer vesicles as soft template. The size of DODAB bilayer vesicles could be tuned by extrusion of a preheated dispersion of DODAB. The synthesized hollow silica particles were characterized by conventional TEM, cryo-TEM and SEM to determine the morphology and structure of particles and dynamic light scattering (DLS) method to measure the particle size and particle size distribution.

Keywords: characterization, DODAB, hollow silica particle, synthesis, vesicle

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Authors: Poteet Frances, Glovinski Ira

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INTRODUCTION: The interoceptive nervous system continuously senses chemical and anatomical changes and helps you recognize, understand, and feel what’s going on inside your body so it is important for energy regulation, memory, affect, and sense of self. A newborn needs predictable routines rather than confusion/chaos to make connections between internal experiences and emotions. AIM: Current legal protocols of removing babies from drug-addicted mothers impact the critical window of bonding. The newborn’s brain is social and the attachment process influences a child’s development which begins immediately after birth through nourishment, comfort, and protection. DESCRIPTION: Our project aims to educate drug-addicted mothers, and medical, nursing, and social work professionals on interoceptive concepts and practices to sustain the mother/newborn relationship. A mother’s interoceptive knowledge predicts children’s emotion regulation and social skills in middle childhood. CONCLUSION: When mothers develop an awareness of their inner bodily sensations, they can self-regulate and be emotionally available to co-regulate (support their newborn during distressing emotions and sensations). Our project has enhanced relationship preservation (mothers understand how their presence matters) and the overall mother/newborn connection.

Keywords: drug-addiction, interoception, legal, mothers, newborn, self-regulation

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Authors: Abdullah Eqal Al Mazrooei

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In this work, a new nonlinear model will be introduced. The model is in the state-space form. The nonlinearity of this model is in the state equation where the state vector is multiplied by its self. This technique makes our model generalizes many famous models as Lotka-Volterra model and Lorenz model which have many applications in the real life. We will apply our new model to estimate the wind speed by using a new nonlinear estimator which suitable to work with our model.

Keywords: nonlinear systems, state-space model, Kronecker product, nonlinear estimator

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Authors: Mohamed S. Selim, Nesreen A. Fatthallah, Shimaa A. Higazy, Zhifeng Hao, Ping Jing Mo

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As marine fouling-release (FR) surfaces, two new superhydrophobic nanocomposite series of polydimethylsiloxane (PDMS) loaded with reduced graphene oxide (RGO) and graphene oxide/boehmite nanorods (GO-γ-AlOOH) nanofillers were created. The self-cleaning and antifouling capabilities were modified by controlling the nanofillers' shapes and distribution in the silicone matrix. With an average diameter of 10-20 nm and a length of 200 nm, γ-AlOOH nanorods showed a single crystallinity. RGO was made using a hydrothermal process, whereas GO-γ-AlOOH nanocomposites were made using a chemical deposition method for use as fouling-release coating materials. These nanofillers were disseminated in the silicone matrix using the solution casting method to explore the synergetic effects of graphene-based materials on the surface, mechanical, and FR characteristics. Water contact angle (WCA), scanning electron, and atomic force microscopes were used to investigate the surface's hydrophobicity and antifouling capabilities (SEM and AFM). The roughness, superhydrophobicity, and surface mechanical characteristics of coatings all increased the homogeneity of the nanocomposite dispersion. To examine the antifouling effects of the coating systems, laboratory tests were conducted for 30 days using specified bacteria.PDMS/GO-γ-AlOOH nanorod composite demonstrated superior antibacterial efficacy against several bacterial strains than PDMS/RGO nanocomposite. The high surface area and stabilizing effects of the GO-γ-AlOOH hybrid nanofillers are to blame for this. The biodegradability percentage of the PDMS/GO-γ-AlOOH nanorod composite (3 wt.%) was the lowest (1.6%), while the microbial endurability percentages for gram-positive, gram-negative, and fungi were 86.42%, 97.94%, and 85.97%, respectively. The homogeneity of the GO-γ-AlOOH (3 wt.%) dispersion, which had a WCA of 151° and a rough surface, was the most profound superhydrophobic antifouling nanostructured coating.

Keywords: superhydrophobic nanocomposite, fouling release, nanofillers, surface coating

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Authors: Alya A. Arabi

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Bioisosteres are functional groups that can be interchangeably used without affecting the potency of the drug. Bioisosteres have similar pharmacological properties. Bioisosterism is useful for modifying the physicochemical properties of a drug while obeying the Lipinski’s rules. Bioisosteres are key in optimizing the pharmacokinetic and pharmacodynamics properties of a drug. Tetrazole and carboxylate anions are non-classic bioisosteres. Density functional theory was used to obtain the wavefunction of the molecules and the optimized geometries. The quantum theory of atoms in molecules (QTAIM) was used to uncover the similarity of the average electron density in tetrazole and carboxylate anions. This similarity between the bioisosteres capped by a methyl group was valid despite the fact that the groups have different volumes, charges, energies, or electron populations. The biochemical correspondence of tetrazole and carboxylic acid was also determined to be a result of the similarity of the topography of the electrostatic potential (ESP). The ESP demonstrates the pharmacological and biochemical resemblance for a matching “key-and-lock” interaction.

Keywords: bioisosteres, carboxylic acid, density functional theory, electrostatic potential, tetrazole

Procedia PDF Downloads 435

Authors: Vipin Saini, Manish Kumar, Shailendra Bhatt, A. Pandurangan

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The aim of the present study was to fabricate a thermo sensitive gel containing Chlorpheniramine maleate (CPM) loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan based nanoparticles were prepared by precipitation method followed by the addition of developed NPs within the Poloxamer 407 and carbopol 934P based mucoadhesive thermo-reversible gel. Developed formulations were evaluated for Particle size, PDI, % entrapment efficiency and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10±0.414 %) and highest drug permeation (90.92±0.531 %). The optimized formulation NP3 was then formulated into thermo reversible in situ gel. This intensifies the contact between nasal mucosa and the drug, increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimize on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the treatment of allergic rhinitis.

Keywords: chitosan, nanoparticles, in situ gel, chlorpheniramine maleate, poloxamer 407

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Authors: Xingyu Pan, Laure Tougne

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For recognizing coins, the graved release date is important information to identify precisely its monetary type. However, reading characters in coins meets much more obstacles than traditional character recognition tasks in the other fields, such as reading scanned documents or license plates. To address this challenging issue in a numismatic context, we propose a training-free approach dedicated to detection and recognition of the release date of the coin. In the first step, the date zone is detected by comparing histogram features; in the second step, a topology-based algorithm is introduced to recognize coin numbers with various font types represented by binary gradient map. Our method obtained a recognition rate of 92% on synthetic data and of 44% on real noised data.

Keywords: coin, detection, character recognition, topology

Procedia PDF Downloads 253