Search results for: drug release metronidazole
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2979

Search results for: drug release metronidazole

2619 Synthesis of New Anti-Tuberculosis Drugs

Authors: M. S. Deshpande, Snehal D. Bomble

Abstract:

Tuberculosis (TB) is a deadly contagious disease that is caused by a bacterium called Mycobacterium tuberculosis. More than sixty years ago, the introduction of the first anti-TB drugs for the treatment of TB (streptomycin (STR), p-aminosalcylic acid (PAS), isoniazid (INH), and then later ethambutol (EMB) and rifampicin (RIF)) gave optimism to the medical community, and it was believed that the disease would be completely eradicated soon. Worldwide, the number of TB cases has continued to increase, but the incidence rate has decreased since 2003. Recently, highly drug-resistant forms of TB have emerged worldwide. The prolonged use of classical drugs developed a growing resistance and these drugs have gradually become less effective and incapable to meet the challenges, especially those of multi drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB, and HIV-TB co-infections. There is an unmet medical need to discover newer synthetic molecules and new generation of potent drugs for the treatment of tuberculosis which will shorten the time of treatment, be potent and safe while effective facing resistant strains and non-replicative, latent forms, reduce adverse side effect and not interfere in the antiretroviral therapy. This paper attempts to bring out the review of anti-TB drugs, and presents a novel method of synthesizing new anti-tuberculosis drugs and potential compounds to overcome the bacterial resistance and combat the re-emergence of tuberculosis.

Keywords: tuberculosis, mycobacterium, multi-drug resistant (MDR)-TB, extensively drug resistant (XDR)-TB

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2618 Evaluation of the Microscopic-Observation Drug-Susceptibility Assay Drugs Concentration for Detection of Multidrug-Resistant Tuberculosis

Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

Abstract:

New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods. A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: isoniazid, MODS assay, MDR-TB, rifampin

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2617 Optimizing the Effectiveness of Docetaxel with Solid Lipid Nanoparticles: Formulation, Characterization, in Vitro and in Vivo Assessment

Authors: Navid Mosallaei, Mahmoud Reza Jaafari, Mohammad Yahya Hanafi-Bojd, Shiva Golmohammadzadeh, Bizhan Malaekeh-Nikouei

Abstract:

Background: Docetaxel (DTX), a potent anticancer drug derived from the European yew tree, is effective against various human cancers by inhibiting microtubule depolymerization. Solid lipid nanoparticles (SLNs) have gained attention as drug carriers for enhancing drug effectiveness and safety. SLNs, submicron-sized lipid-based particles, can passively target tumors through the "enhanced permeability and retention" (EPR) effect, providing stability, drug protection, and controlled release while being biocompatible. Methods: The SLN formulation included biodegradable lipids (Compritol and Precirol), hydrogenated soy phosphatidylcholine (H-SPC) as a lipophilic co-surfactant, and Poloxamer 188 as a non-ionic polymeric stabilizer. Two SLN preparation techniques, probe sonication and microemulsion, were assessed. Characterization encompassed SLNs' morphology, particle size, zeta potential, matrix, and encapsulation efficacy. In-vitro cytotoxicity and cellular uptake studies were conducted using mouse colorectal (C-26) and human malignant melanoma (A-375) cell lines, comparing SLN-DTX with Taxotere®. In-vivo studies evaluated tumor inhibitory efficacy and survival in mice with colorectal (C-26) tumors, comparing SLNDTX withTaxotere®. Results: SLN-DTX demonstrated stability, with an average size of 180 nm and a low polydispersity index (PDI) of 0.2 and encapsulation efficacy of 98.0 ± 0.1%. Differential scanning calorimetry (DSC) suggested amorphous encapsulation of DTX within SLNs. In vitro studies revealed that SLN-DTX exhibited nearly equivalent cytotoxicity to Taxotere®, depending on concentration and exposure time. Cellular uptake studies demonstrated superior intracellular DTX accumulation with SLN-DTX. In a C-26 mouse model, SLN-DTX at 10 mg/kg outperformed Taxotere® at 10 and 20 mg/kg, with no significant differences in body weight changes and a remarkably high survival rate of 60%. Conclusion: This study concludes that SLN-DTX, prepared using the probe sonication, offers stability and enhanced therapeutic effects. It displayed almost same in vitro cytotoxicity to Taxotere® but showed superior cellular uptake. In a mouse model, SLN-DTX effectively inhibited tumor growth, with 10 mg/kg outperforming even 20 mg/kg of Taxotere®, without adverse body weight changes and with higher survival rates. This suggests that SLN-DTX has the potential to reduce adverse effects while maintaining or enhancing docetaxel's therapeutic profile, making it a promising drug delivery strategy suitable for industrialization.

Keywords: docetaxel, Taxotere®, solid lipid nanoparticles, enhanced permeability and retention effect, drug delivery, cancer chemotherapy, cytotoxicity, cellular uptake, tumor inhibition

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2616 Tobephobia: Fear of Failure in Education Caused by School Violence and Drug Abuse

Authors: Prakash Singh

Abstract:

Schools throughout the world are facing increasing challenges in dealing with school violence and drug abuse by pupils. Therefore, the question of the fear of failure to meet the aims and objectives of education inevitably surfaces as it places increasing and challenging demands on educators and all other stakeholders to address this malaise. Multiple studies on the construct tobephobia (TBP) simply define TBP as the fear of failure in education. This study is a continuation of the exploratory studies on the manifestation of fear in education. The primary purpose of this study was to establish how TBP, caused by school violence and drug abuse affects teaching and learning in our schools. The qualitative research method was used for this study. Teachers admitted that they fear for their safety at school. Working in a fearful situation places a high rate of stress and anxiety on them. Tobephobic educators spend most of their time worrying about their fear of violence and drug abuse by pupils and are too frightened to carry out their normal duties. They prefer to stay in familiar surroundings for fear of being attacked by inebriated learners. This study, therefore, contributes to our understanding of the effects of TBP in our schools caused by school violence and drug abuse. Also, this study supplements the evidence accumulated over the past fifteen years that TBP is not a figment of someone’s imagination; it is a gruesome reality affecting the very foundation of our educational system globally to provide quality and equal education to all our learners in a harmonious, collegial school environment.

Keywords: tobephobia, tobephobic educators, fear of failure in education, school violence, drug abuse

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2615 Preparation of Essential Oil Capsule (Carum Copticum) In Chitosan Nanoparticles and Investigation of Its Biological Properties

Authors: Akbar Esmaeili, Azadeh Asgari

Abstract:

Essential oils’ unique and practical properties have been widely reported in recent years. Still, the sensitivity of critical oils to environmental factors and their poor solubility in aqueous solutions have limited their use in industries. Therefore, we encapsulated C. copticum essential oil in chitosan nanoparticles by emulsion-ionic gelation with sodium tripolyphosphate and sodium hexametaphosphate cross-linkers. The nanoparticles showed a round shape with an average size of 30-80 nm and a regular distribution. The release profile in the laboratory environment showed a burst in the initial release and then a stable release of C. copticum essential oil from chitosan nanoparticles at different pH. Antioxidant and antibacterial properties of C. copticum essential oil before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical and disc diffusion methods, respectively. The results showed that the encapsulation of C. copticum essential oil in chitosan nanoparticles could protect its quality and bioactive compounds and improve the properties of the crucial oil.

Keywords: essential oils, Carum copticum, biological activities, nanotechnology

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2614 Intensive Crosstalk between Autophagy and Intracellular Signaling Regulates Osteosarcoma Cell Survival Response under Cisplatin Stress

Authors: Jyothi Nagraj, Sudeshna Mukherjee, Rajdeep Chowdhury

Abstract:

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

Keywords: JNK, autophagy, drug resistance, cancer

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2613 A Preliminary Report of HBV Full Genome Sequencing Derived from Iranian Intravenous Drug Users

Authors: Maryam Vaezjalali, Koroush Rahimian, Maryam Asli, Tahmineh Kandelouei, Foad Davoodbeglou, Amir H. Kashi

Abstract:

Objectives: The present study was conducted to assess the HBV molecular profiles including genotypes, subgenotypes, subtypes & mutations in hepatitis B genes. Materials/Patients and Methods: This study was conducted on 229 intravenous drug users who referred to three Drop- in-Centers and a hospital in Tehran. HBV DNA was extracted from HBsAg positive serum samples and amplified by Nested PCR. HBV genotype, subgenotypes, subtype and genes mutation were determined by direct sequencing. Phylogenetic tree was constructed using neighbor- joining (NJ) method. Statistical analyses were carried out by SPSS 20. Results: HBV DNA was found in 3 HBsAg positive cases. Phylogenetic tree of derived HBV DNAs showed the existence of genotype D (subgenotype D1, subtype ayw2). Also immune escape mutations were determined in S gene. Conclusion: There were a few variations and genotypes and subtypes among infected intravenous drug users. This study showed the predominance of genotype D among intravenous drug users. Our study concurs with other reports from Iran, that all showing currently only genotype D is the only detectable genotype in Iran.

Keywords: drug users, genotype, HBV, phylogenetic tree

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2612 Detection of Some Drugs of Abuse from Fingerprints Using Liquid Chromatography-Mass Spectrometry

Authors: Ragaa T. Darwish, Maha A. Demellawy, Haidy M. Megahed, Doreen N. Younan, Wael S. Kholeif

Abstract:

The testing of drug abuse is authentic in order to affirm the misuse of drugs. Several analytical approaches have been developed for the detection of drugs of abuse in pharmaceutical and common biological samples, but few methodologies have been created to identify them from fingerprints. Liquid Chromatography-Mass Spectrometry (LC-MS) plays a major role in this field. The current study aimed at assessing the possibility of detection of some drugs of abuse (tramadol, clonazepam, and phenobarbital) from fingerprints using LC-MS in drug abusers. The aim was extended in order to assess the possibility of detection of the above-mentioned drugs in fingerprints of drug handlers till three days of handling the drugs. The study was conducted on randomly selected adult individuals who were either drug abusers seeking treatment at centers of drug dependence in Alexandria, Egypt or normal volunteers who were asked to handle the different studied drugs (drug handlers). An informed consent was obtained from all individuals. Participants were classified into 3 groups; control group that consisted of 50 normal individuals (neither abusing nor handling drugs), drug abuser group that consisted of 30 individuals who abused tramadol, clonazepam or phenobarbital (10 individuals for each drug) and drug handler group that consisted of 50 individuals who were touching either the powder of drugs of abuse: tramadol, clonazepam or phenobarbital (10 individuals for each drug) or the powder of the control substances which were of similar appearance (white powder) and that might be used in the adulteration of drugs of abuse: acetyl salicylic acid and acetaminophen (10 individuals for each drug). Samples were taken from the handler individuals for three consecutive days for the same individual. The diagnosis of drug abusers was based on the current Diagnostic and Statistical Manual of Mental disorders (DSM-V) and urine screening tests using immunoassay technique. Preliminary drug screening tests of urine samples were also done for drug handlers and the control groups to indicate the presence or absence of the studied drugs of abuse. Fingerprints of all participants were then taken on a filter paper previously soaked with methanol to be analyzed by LC-MS using SCIEX Triple Quad or QTRAP 5500 System. The concentration of drugs in each sample was calculated using the regression equations between concentration in ng/ml and peak area of each reference standard. All fingerprint samples from drug abusers showed positive results with LC-MS for the tested drugs, while all samples from the control individuals showed negative results. A significant difference was noted between the concentration of the drugs and the duration of abuse. Tramadol, clonazepam, and phenobarbital were also successfully detected from fingerprints of drug handlers till 3 days of handling the drugs. The mean concentration of the chosen drugs of abuse among the handlers group decreased when the days of samples intake increased.

Keywords: drugs of abuse, fingerprints, liquid chromatography–mass spectrometry, tramadol

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2611 Healthcare Workers' Attitudes Towards People Living With Hiv And Drug Users

Authors: Delband Yekta Moazami

Abstract:

Background: For proper care and treatment of HIV patients and drug users, the medical staff and physicians must have a correct and positive attitude and knowledge towards such patients. We aimed to assess the attitudes in a sample of health care workers (HCW) working in different hospitals and clinics and medical students in Georgia towards HIV infected people and drug users in Tbilisi. Method: We conducted a cross-sectional study to assess attitudes of health care workers towards people living with HIV and drug users in hospitals and clinics in Tbilisi. The study was carried out from 1st of May 2020 till 30th of September 2020. Data were collected using a self-administered structured online questionnaire. With this tool we evaluated four facets of attitudes: Discrimination, Acceptance of HIV/AIDS patients, Acceptance of drug users and Fear. All data were imported and analyzed with the software SPSS 22 for windows. Results: In total data was collected from168 respondents, that among them 107 (65%) were women and majority of the participants were medical doctors. Women had more acceptance attitudes rather than men towards drug abusers. We found significant differences regarding expressing negative attitudes among HCW who were more than 50 years old comparing with other age groups in all four aspects. Medical doctors expressed more acceptances towards people with HIV and drug users comparing two other groups. Also our study revealed that the group with working experience 21 years and more, showed more discriminatory attitudes comparing other groups. Conclusion: Based on our study findings, there are significant differences regarding respondent’s attitudes based on gender, medical specialty and working experience in health care system. People struggling with HIV and drug use need nonjudgmental and positive behaviors from health care workers and physicians in order to help them for harm reduction and receiving appropriate treatment.

Keywords: hiv, addiction, attitudes, healthcare workers

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2610 Human Metabolism of the Drug Candidate PBTZ169

Authors: Vadim Makarov, Stewart T.Cole

Abstract:

PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

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2609 Polymeric Microspheres for Bone Tissue Engineering

Authors: Yamina Boukari, Nashiru Billa, Andrew Morris, Stephen Doughty, Kevin Shakesheff

Abstract:

Poly (lactic-co-glycolic) acid (PLGA) is a synthetic polymer that can be used in bone tissue engineering with the aim of creating a scaffold in order to support the growth of cells. The formation of microspheres from this polymer is an attractive strategy that would allow for the development of an injectable system, hence avoiding invasive surgical procedures. The aim of this study was to develop a microsphere delivery system for use as an injectable scaffold in bone tissue engineering and evaluate various formulation parameters on its properties. Porous and lysozyme-containing PLGA microspheres were prepared using the double emulsion solvent evaporation method from various molecular weights (MW). Scaffolds were formed by sintering to contain 1 -3mg of lysozyme per gram of scaffold. The mechanical and physical properties of the scaffolds were assessed along with the release of lysozyme, which was used as a model protein. The MW of PLGA was found to have an influence on microsphere size during fabrication, with increased MW leading to an increased microsphere diameter. An inversely proportional relationship was displayed between PLGA MW and mechanical strength of formed scaffolds across loadings for low, intermediate and high MW respectively. Lysozyme release from both microspheres and formed scaffolds showed an initial burst release phase, with both microspheres and scaffolds fabricated using high MW PLGA showing the lowest protein release. Following the initial burst phase, the profiles for each MW followed a similar slow release over 30 days. Overall, the results of this study demonstrate that lysozyme can be successfully incorporated into porous PLGA scaffolds and released over 30 days in vitro, and that varying the MW of the PLGA can be used as a method of altering the physical properties of the resulting scaffolds.

Keywords: bone, microspheres, PLGA, tissue engineering

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2608 Development and Characterization of a Film Based on Hydroxypropyl Methyl Cellulose Incorporated by a Phenolic Extract of Fennel and Reinforced by Magnesium Oxide: In Vivo - in Vitro

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

Abstract:

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

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

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2607 Dry Needling Treatment in 38 Cases of Chronic Sleep Disturbance

Authors: P. Gao, Z. Q. Li, Y. G. Jin

Abstract:

In the past 10 years, computers and cellphones have become one of the most important factors in our lives, and one which has a tremendously negative impact on our muscles. Muscle tension may be one of the causes of sleep disturbance. Tension in the shoulders and neck can affect blood circulation to the muscles. This research uses a dry needling treatment to reduce muscle tension in order to determine if the strain in the head and shoulders can influence sleep duration. All 38 patients taking part in the testing suffered from tinnitus and have been experiencing disturbed sleep for at least one to five years. Even after undergoing drug therapy treatments and traditional acupuncture therapies, their sleep disturbances have not shown any improvement. After five to 10 dry needling treatments, 24 of the patients reported an improvement in their sleep duration. Five patients considered themselves to be completely recovered, while 12 patients experienced no improvement. This study investigated these pathogenic and therapeutic problems. The standard treatment for sleep disturbances is drug-based therapy; the results of most standard treatments are unfortunately negative. The result of this clinical research has demonstrated that: The possible cause of sleep disturbance for a lot of patients is the result of tensions in the neck and shoulder muscles. Blood circulation to those muscles is also influenced by the duration of sleep. Hypertonic neck and shoulder muscles are considered to impact sleeping patterns and lead to disturbed sleep. Poor posture, often adopted while speaking on the phone, is one of the main causes of hypertonic neck and shoulder muscle problems. The dry needling treatment specifically focuses on the release of muscle tension.

Keywords: dry needling, muscle tension, sleep duration, hypertonic muscles

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2606 The Interplay of Dietary Fibers and Intestinal Microbiota Affects Type 2 Diabetes by Generating Short-Chain Fatty Acids

Authors: Muhammad Mazhar, Yong Zhu, Likang Qin

Abstract:

Foods contain endogenous components known as dietary fibers, which are classified into soluble and insoluble forms. Dietary fibers are resistant to gut digestive enzymes, modulating anaerobic intestinal microbiota (AIM) and fabricating short-chain fatty acids (SCFAs). Acetate, butyrate, and propionate dominate in the gut, and different pathways, including Wood-Ljungdahl and acrylate pathways, generate these SCFAs. In pancreatic dysfunction, the release of insulin/glucagon is impaired, which leads to hyperglycemia. SCFAs enhance insulin sensitivity or secretion, beta-cell functions, leptin release, mitochondrial functions, and intestinal gluconeogenesis in human organs, which positively affect type 2 diabetes (T2D). Research models presented that SCFAs either enhance the release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) from L-cells (entero-endocrine) or promote the release of leptin hormone satiation in adipose tissues through G-protein receptors, i.e., GPR-41/GPR-43. Dietary fibers are the components of foods that influence AIM and produce SCFAs, which may be offering beneficial effects on T2D. This review addresses the effectiveness of SCFAs in modulating gut AIM in the fermentation of dietary fiber and their worth against T2D.

Keywords: dietary fibers, intestinal microbiota, short-chain fatty acids, fermentation, type 2 diabetes

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2605 In Silico Study of Antiviral Drugs Against Three Important Proteins of Sars-Cov-2 Using Molecular Docking Method

Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

Abstract:

Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

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2604 Effect of Anionic Lipid on Zeta Potential Values and Physical Stability of Liposomal Amikacin

Authors: Yulistiani, Muhammad Amin, Fasich

Abstract:

A surface charge of the nanoparticle is a very important consideration in pulmonal drug delivery system. The zeta potential (ZP) is related to the surface charge which can predict stability of nanoparticles as nebules of liposomal amikacin. Anionic lipid such as 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) is expected to contribute to the physical stability of liposomal amikacin and the optimal ZP value. Suitable ZP can improve drug release profiles at specific sites in alveoli as well as their stability in dosage form. This study aimed to analyze the effect of DPPG on ZP values and physical stability of liposomal amikacin. Liposomes were prepared by using the reserved phase evaporation method. Liposomes consisting of DPPG, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), cholesterol and amikacin were formulated in five different compositions 0/150/5/100, 10//150/5/100, 20/150/5/100, 30/150/5/100 and 40/150/5/100 (w/v) respectively. A chloroform/methanol mixture in the ratio of 1 : 1 (v/v) was used as solvent to dissolve lipids. These systems were adjusted in the phosphate buffer at pH 7.4. Nebules of liposomal amikacin were produced by using the vibrating nebulizer and then characterized by the X-ray diffraction, differential scanning calorimetry, particle size and zeta potential analyzer, and scanning electron microscope. Amikacin concentration from liposome leakage was determined by the immunoassay method. The study revealed that presence of DPPG could increase the ZP value. The addition of 10 mg DPPG in the composition resulted in increasing of ZP value to 3.70 mV (negatively charged). The optimum ZP value was reached at -28.780 ± 0.70 mV and particle size of nebules 461.70 ± 21.79 nm. Nebulizing process altered parameters such as particle size, conformation of lipid components and the amount of surface charges of nanoparticles which could influence the ZP value. These parameters might have profound effects on the application of nebules in the alveoli; however, negatively charge nanoparticles were unexpected to have a high ZP value in this system due to increased macrophage uptake and pulmonal clearance. Therefore, the ratio of liposome 20/150/5/100 (w/v) resulted in the most stable colloidal system and might be applicable to pulmonal drug delivery system.

Keywords: anionic lipid, dipalmitoylphosphatidylglycerol, liposomal amikacin, stability, zeta potential

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2603 Mobulid Ray Post-Release Mortality to Assess the Feasibility of Live-Release Management Measures

Authors: Sila K. Sari, Betty J.L. Laglbauer, Muhammad G. Salim, Irianies C. Gozali, Iqbal Herwata, Fahmi Fahmi, Selvia Oktaviyani, Isabel Ender, Sarah Lewis, Abraham Sianipar, Mark Erdmann

Abstract:

Taking strides towards the sustainable use of marine stocks requires science-based management of target fish populations and reduction of bycatch in non-selective fisheries. Among elasmobranchs, mobulid rays are faced with high extinction risk due to intrinsic vulnerability to fishing and their conservation has been recognized as a strong priority both in Indonesia and worldwide. Despite their common vulnerabilities to fishing pressure due to slow growth, late maturation and low fecundity, only manta rays, but not devil rays, are protected in Indonesian waters. However, both manta and devil rays are captured in non-selective fisheries, in particular drift gillnets, since their habitat overlaps with fishing grounds for primary target species (e.g. marlin, swordfish and bullet tuna off the coast of Muncar). For this reason, mobulid populations are being heavily impacted, and while national-level protections are crucial to help conservation, they may not suffice alone to insure populations sustainability. In order to assess the potential of applying live-release management measures to conserve mobulids captured as bycatch in drift gillnets, we deployed pop-up survival archival transmitters to assess post-release mortality in Indonesian mobulid rays. We also assessed which fishing practices, in particular, soak duration, affected post-release mortality in order to draw relevant conclusions for management.

Keywords: Mobulid, Devil ray, Manta ray, Bycatch

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2602 NanoCelle®: A Nano Delivery Platform to Enhance Medicine

Authors: Sean Hall

Abstract:

Nanosystems for drug delivery are not new; as medicines evolve, so too does the desire to deliver a more targeted, patient-compliant medicine. Though, historically the widespread use of nanosystems for drug delivery has been fouled by non-replicability, scalability, toxicity issues, and economics. Examples include steps of manufacture and thus cost to manufacture, toxicity for nanoparticle scaffolding, autoimmune response, and considerable technical expertise for small non-commercial yields. This, unfortunately, demonstrates the not-so-obvious chasm between science and drug formulation for regulatory approval. Regardless there is a general and global desire to improve the delivery of medicines, reduce potential side effect profiles, promote increased patient compliance, and increase and/or speed public access to medicine availability. In this paper, the author will discuss NanoCelle®, a nano-delivery platform that specifically addresses degradation and solubility issues that expands from fundamental micellar preparations. NanoCelle® has been deployed in several Australian listed medicines and is in use of several drug candidates across small molecules, with research endeavors now extending into large molecules. The author will discuss several research initiatives as they relate to NanoCelle® to demonstrate similarities seen in various drug substances; these examples will include both in vitro and in vivo work.

Keywords: NanoCelle®, micellar, degradation, solubility, toxicity

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2601 Sun Protection Factor (SPF) Determination of Sericin Cream and Niosomal Gel

Authors: Farzad Doostishoar, Abbas Pardakhty, Abdolreza Hassanzadeh, Sudeh salarpour, Elham Sharif

Abstract:

Background: Sericin is a protein extracted from silk and has antioxidant, antimicrobial, antineoplastic, wound healing and moisturizing properties. Different cosmetic formulation of sericin is available in different countries such as Japan and the other south-eastern Asian countries. We formulated and evaluated the sunscreen properties of topical formulations of sericin by an in vitro method. Method: Niosomes composed of sorbitan palmitate (Span 40), polysorbate 40 (Tween 40) and cholesterol (300 µmol, 3.5:3.5:3 molar ratio) were prepared by film hydration technique. Sericin was dissolved in normal saline and the lipid hydration was carried out at 60°C and the niosomes were incorporated in a Carbomer gel base. A W/O cream was also prepared and the release of sericin was evaluated by using Franz diffusion cell. Particle size analysis, sericin encapsulation efficiency measurement, morphological studies and stability evaluation were done in niosomal formulations. SPF was calculated by using Transpore tape in vitro method for both formulations. Results: Niosomes had high stability during 6 months storage at 4-8°C. The mean volume diameter of niosomes was less than 7 µm which is ideal for sustained release of drugs in topical formulations. The SPF of niosomal gel was 25 and higher than sericin cream with a diffusion based release pattern of active material. Conclusion: Sericin can be successfully entrapped in niosomes with sustained release pattern and relatively high SPF.

Keywords: sericin, niosomes, sun protection factor, cream, gel

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2600 Differential Expression of Arc in the Mesocorticolimbic System Is Involved in Drug and Natural Rewarding Behavior in Rats

Authors: Yuhua Wang, Mu Li, Jinggen Liu

Abstract:

Aim: To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning. Methods: Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously. Results: Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration. Conclusion: The VLS is likely to be critically involved in drug-seeking behavior. The NMDA and D1 receptor-dependent Arc expression is important in drug-seeking behavior.

Keywords: arc, mesocorticolimbic system, drug rewarding behavior, NMDA receptor

Procedia PDF Downloads 389
2599 Drug Therapy Problems and Associated Factors among Patients with Heart Failure in the Medical Ward of Arba Minch General Hospital, Ethiopia

Authors: Debalke Dale, Bezabh Geneta, Yohannes Amene, Yordanos Bergene, Mohammed Yimam

Abstract:

Background: A drug therapy problem (DTP) is an event or circumstance that involves drug therapies that actually or potentially interfere with the desired outcome and requires professional judgment to resolve. Heart failure is an emerging worldwide threat whose prevalence and health loss burden constantly increase, especially in the young and in low-to-middle-income countries. There is a lack of population-based incidence and prevalence of heart failure (HF) studies in sub-Saharan African countries, including Ethiopia. Objective: The aim of this study was designed to assess drug therapy problems and associated factors among patients with HF in the medical ward of Arba Minch General Hospital(AGH), Ethiopia, from June 5 to August 20, 2022. Methods: A retrospective cross-sectional study was conducted among 180 patients with HF who were admitted to the medical ward of AGH. Data were collected from patients' cards by using questionnaires. The data were categorized and analyzed by using SPSS version 25.0 software, and data were presented in tables and words based on the nature of the data. Result: Out of the total, 85 (57.6%) were females, and 113 (75.3%) patients were aged over fifty years. Of the 150 study participants, 86 (57.3%) patients had at least one DTP identified, and a total of 116 DTPs were identified, which is 0.77 DTPs per patient. The most common types of DTP were unnecessary drug therapy (32%), followed by the need for additional drug therapy (36%), and dose too low (15%). Patients who used polypharmacy were 5.86 (AOR) times more likely to develop DTPs than those who did not (95% CI = 1.625–16.536, P = 0.005), and patients with more co-morbid conditions developed 3.68 (AOR) times more DTPs than those who had fewer co-morbidities (95% CI = 1.28–10.5, P = 0.015). Conclusion: The results of this study indicated that drug therapy problems were common among medical ward patients with heart failure. These problems are adversely affecting the treatment outcomes of patients, so it requires the special attention of healthcare professionals to optimize them.

Keywords: heart failure, drug therapy problems, Arba Minch general hospital, Ethiopia

Procedia PDF Downloads 105
2598 Synthesis and Characterization of pH-Sensitive Graphene Quantum Dot-Loaded Metal-Organic Frameworks for Targeted Drug Delivery and Fluorescent Imaging

Authors: Sayed Maeen Badshah, Kuen-Song Lin, Abrar Hussain, Jamshid Hussain

Abstract:

Liver cancer is a significant global health issue, ranking fifth in incidence and second in mortality. Effective therapeutic strategies are urgently needed to combat this disease, particularly in regions with high prevalence. This study focuses on developing and characterizing fluorescent organometallic frameworks as distinct drug delivery carriers with potential applications in both the treatment and biological imaging of liver cancer. This work introduces two distinct organometallic frameworks: the cake-shaped GQD@NH₂-MIL-125 and the cross-shaped M8U6/FM8U6. The GQD@NH₂-MIL-125 framework is particularly noteworthy for its high fluorescence, making it an effective tool for biological imaging. X-ray diffraction (XRD) analysis revealed specific diffraction peaks at 6.81ᵒ (011), 9.76ᵒ (002), and 11.69ᵒ (121), with an additional significant peak at 26ᵒ (2θ), corresponding to the carbon material. Morphological analysis using Field Emission Scanning Electron Microscopy (FE-SEM), and Transmission Electron Microscopy (TEM) demonstrated that the framework has a front particle size of 680 nm and a side particle size of 55±5 nm. High-resolution TEM (HR-TEM) images confirmed the successful attachment of graphene quantum dots (GQDs) onto the NH2-MIL-125 framework. Fourier-Transform Infrared (FT-IR) spectroscopy identified crucial functional groups within the GQD@NH₂-MIL-125 structure, including O-Ti-O metal bonds within the 500 to 700 cm⁻¹ range, and N-H and C-N bonds at 1,646 cm⁻¹ and 1,164 cm⁻¹, respectively. BET isotherm analysis further revealed a specific surface area of 338.1 m²/g and an average pore size of 46.86 nm. This framework also demonstrated UV-active properties, as identified by UV-visible light spectra, and its photoluminescence (PL) spectra showed an emission peak around 430 nm when excited at 350 nm, indicating its potential as a fluorescent drug delivery carrier. In parallel, the cross-shaped M8U6/FM8U6 frameworks were synthesized and characterized using X-ray diffraction, which identified distinct peaks at 2θ = 7.4 (111), 8.5 (200), 9.2 (002), 10.8 (002), 12.1 (220), 16.7 (103), and 17.1 (400). FE-SEM, HR-TEM, and TEM analyses revealed particle sizes of 350±50 nm for M8U6 and 200±50 nm for FM8U6. These frameworks, synthesized from terephthalic acid (H₂BDC), displayed notable vibrational bonds, such as C=O at 1,650 cm⁻¹, Fe-O in MIL-88 at 520 cm⁻¹, and Zr-O in UIO-66 at 482 cm⁻¹. BET analysis showed specific surface areas of 740.1 m²/g with a pore size of 22.92 nm for M8U6 and 493.9 m²/g with a pore size of 35.44 nm for FM8U6. Extended X-ray Absorption Fine Structure (EXAFS) spectra confirmed the stability of Ti-O bonds in the frameworks, with bond lengths of 2.026 Å for MIL-125, 1.962 Å for NH₂-MIL-125, and 1.817 Å for GQD@NH₂-MIL-125. These findings highlight the potential of these organometallic frameworks for enhanced liver cancer therapy through precise drug delivery and imaging, representing a significant advancement in nanomaterial applications in biomedical science.

Keywords: liver cancer cells, metal organic frameworks, Doxorubicin (DOX), drug release.

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2597 The Safety Profile of Vilazodone: A Study on Post-Marketing Surveillance

Authors: Humraaz Kaja, Kofi Mensah, Frasia Oosthuizen

Abstract:

Background and Aim: Vilazodone was approved in 2011 as an antidepressant to treat the major depressive disorder. As a relatively new drug, it is not clear if all adverse effects have been identified. The aim of this study was to review the adverse effects reported to the WHO Programme for International Drug Monitoring (PIDM) in order to add to the knowledge about the safety profile and adverse effects caused by vilazodone. Method: Data on adverse effects reported for vilazodone was obtained from the database VigiAccess managed by PIDM. Data was extracted from VigiAccess using Excel® and analyzed using descriptive statistics. The data collected was compared to the patient information leaflet (PIL) of Viibryd® and the FDA documents to determine adverse drug reactions reported post-marketing. Results: A total of 9708 adverse events had been recorded on VigiAccess, of which 6054 were not recorded on the PIL and the FDA approval document. Most of the reports were received from the Americas and were for adult women aged 45-64 years (24%, n=1059). The highest number of adverse events reported were for psychiatric events (19%; n=1889), followed by gastro-intestinal effects (18%; n=1839). Specific psychiatric disorders recorded included anxiety (316), depression (208), hallucination (168) and agitation (142). The systematic review confirmed several psychiatric adverse effects associated with the use of vilazodone. The findings of this study suggested that these common psychiatric adverse effects associated with the use of vilazodone were not known during the time of FDA approval of the drug and is not currently recorded in the patient information leaflet (PIL). Conclusions: In summary, this study found several adverse drug reactions not recorded in documents emanating from clinical trials pre-marketing. This highlights the importance of continued post-marketing surveillance of a drug, as well as the need for further studies on the psychiatric adverse events associated with vilazodone in order to improve the safety profile.

Keywords: adverse drug reactions, pharmacovigilance, post-marketing surveillance, vilazodone

Procedia PDF Downloads 114
2596 Energy Production with Closed Methods

Authors: Bujar Ismaili, Bahti Ismajli, Venhar Ismaili, Skender Ramadani

Abstract:

In Kosovo, the problem with the electricity supply is huge and does not meet the demands of consumers. Older thermal power plants, which are regarded as big environmental polluters, produce most of the energy. Our experiment is based on the production of electricity using the closed method that does not affect environmental pollution by using waste as fuel that is considered to pollute the environment. The experiment was carried out in the village of Godanc, municipality of Shtime - Kosovo. In the experiment, a production line based on the production of electricity and central heating was designed at the same time. The results are the benefits of electricity as well as the release of temperature for heating with minimal expenses and with the release of 0% gases into the atmosphere. During this experiment, coal, plastic, waste from wood processing, and agricultural wastes were used as raw materials. The method utilized in the experiment allows for the release of gas through pipes and filters during the top-to-bottom combustion of the raw material in the boiler, followed by the method of gas filtration from waste wood processing (sawdust). During this process, the final product is obtained - gas, which passes through the carburetor, which enables the gas combustion process and puts into operation the internal combustion machine and the generator and produces electricity that does not release gases into the atmosphere. The obtained results show that the system provides energy stability without environmental pollution from toxic substances and waste, as well as with low production costs. From the final results, it follows that: in the case of using coal fuel, we have benefited from more electricity and higher temperature release, followed by plastic waste, which also gave good results. The results obtained during these experiments prove that the current problems of lack of electricity and heating can be met at a lower cost and have a clean environment and waste management.

Keywords: energy, heating, atmosphere, waste, gasification

Procedia PDF Downloads 235
2595 Effect of Nicotine on the Reinforcing Effects of Cocaine in a Nonhuman Primate Model of Drug Use

Authors: Mia I. Allen, Bernard N. Johnson, Gagan Deep, Yixin Su, Sangeeta Singth, Ashish Kumar, , Michael A. Nader

Abstract:

With no FDA-approved treatments for cocaine use disorders (CUD), research has focused on the behavioral and neuropharmacological effects of cocaine in animal models, with the goal of identifying novel interventions. While the majority of people with CUD also use tobacco/nicotine, the majority of preclinical cocaine research does not include the co-use of nicotine. The present study examined nicotine and cocaine co-use under several conditions of intravenous drug self-administration in monkeys. In Experiment 1, male rhesus monkeys (N=3) self-administered cocaine (0.001-0.1 mg/kg/injection) alone and cocaine+nicotine (0.01-0.03 mg/kg/injection) under a progressive-ratio schedule of reinforcement. When nicotine was added to cocaine, there was a significant leftward shift and significant increase in peak break point. In Experiment 2, socially housed female and male cynomolgus monkeys (N=14) self-administered cocaine under a concurrent drug-vs-food choice schedule. Combining nicotine significantly decreased cocaine choice ED50 values (i.e., shifted the cocaine dose-response curve to the left) in females but not in males. There was no evidence of social rank differences. In delay discounting studies, the co-use of nicotine and cocaine required significantly larger delays to the preferred drug reinforcer to reallocate choice compared with cocaine alone. Overall, these results suggest drug interactions of nicotine and cocaine co-use is not simply a function of potency but rather a fundamentally distinctive condition that should be utilized to better understand the neuropharmacology of CUD and the evaluation of potential treatments.

Keywords: polydrug use, animal models, nonhuman primates, behavioral pharmacology, drug self-administration

Procedia PDF Downloads 87
2594 Sol-Gel Coated Fabric for Controlled Release of Mosquito Repellent

Authors: Bhaskar M. Murai, Neeraj Banchor, Ishveen Chabbra, Madhusudhan Nadgir, S. Vidhya

Abstract:

Sol-gel technology combined with electronics and biochemistry helps to overcome the problems caused by mosquitoes by developing a portable, low-cost device which enables controlled release of trapped compound inside it. It is a wet-chemical technique which is used primarily for fabrication of silicate gel which is usually allowed to dry as per requirement. The outcome is solid rock hard material which is porous and has lots of applications in different fields. Taking porosity as a key factor, allethrin a naturally occurring synthetic compound with molecular mass 302.40 was entrapped inside the sol-gel matrix as a dopant. Allethrin is commonly used as an insecticide and is a key ingredient in commercially available mosquitoes repellent in Asian and subtropical countries. It has low toxicity for humans and birds, and are used in many household insecticides such as RAID as well as mosquito coils. They are however highly toxic to fish and bees. Insects subject to its exposure become paralyzed (nervous system effect) before dying. They are also used as an ultra-low volume spray for outdoor mosquito control. Therefore, there is a need for controlled release of allethrin in the environment. For controlled release of allethrin from sol-gel matrix, its (allethrin) we utilized temperature based controlled evaporation through porous sol-gel. Different types of fabric like cotton, Terri-cotton, polyester, surgical cap, knee-cap etc are studied and the best with maximum absorption capacity is selected to hold the sol-gel matrix with maximum quantity. For sol-gel coating 2 x 2cm cloth pieces are dipped in sol-gel solution for 10 minutes and by calculating the weight difference we concluded that Terri cotton is best suitable for our project. An electronic circuit with heating plate is developed in to test the controlled release of compound. An oscillatory circuit is used to produce the required heat.

Keywords: sol-gel, allethrin, TEOS, biochemistry

Procedia PDF Downloads 375
2593 Upon Poly(2-Hydroxyethyl Methacrylate-Co-3, 9-Divinyl-2, 4, 8, 10-Tetraoxaspiro (5.5) Undecane) as Polymer Matrix Ensuring Intramolecular Strategies for Further Coupling Applications

Authors: Aurica P. Chiriac, Vera Balan, Mihai Asandulesa, Elena Butnaru, Nita Tudorachi, Elena Stoleru, Loredana E. Nita, Iordana Neamtu, Alina Diaconu, Liliana Mititelu-Tartau

Abstract:

The interest for studying ‘smart’ materials is entirely justified and in this context were realized investigations on poly(2-hydroxyethylmethacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane), which is a macromolecular compound with sensibility at pH and temperature, gel formation capacity, binding properties, amphilicity, good oxidative and thermal stability. Physico-chemical characteristics in terms of the molecular weight, temperature-sensitive abilities and thermal stability, as well rheological, dielectric and spectroscopic properties were evaluated in correlation with further coupling capabilities. Differential scanning calorimetry investigation indicated Tg at 36.6 °C and a melting point at Tm=72.8°C, for the studied copolymer, and up to 200oC two exothermic processes (at 99.7°C and 148.8°C) were registered with losing weight of about 4 %, respective 19.27%, which indicate just processes of thermal decomposition (and not phenomena of thermal transition) owing to scission of the functional groups and breakage of the macromolecular chains. At the same time, the rheological studies (rotational tests) confirmed the non-Newtonian shear-thinning fluid behavior of the copolymer solution. The dielectric properties of the copolymer have been evaluated in order to investigate the relaxation processes and two relaxation processes under Tg value were registered and attributed to localized motions of polar groups from side chain macromolecules, or parts of them, without disturbing the main chains. According to literature and confirmed as well by our investigations, β-relaxation is assigned with the rotation of the ester side group and the γ-relaxation corresponds to the rotation of hydroxy- methyl side groups. The fluorescence spectroscopy confirmed the copolymer structure, the spiroacetal moiety getting an axial conformation, more stable, with lower energy, able for specific interactions with molecules from environment, phenomena underlined by different shapes of the emission spectra of the copolymer. Also, the copolymer was used as template for indomethacin incorporation as model drug, and the biocompatible character of the complex was confirmed. The release behavior of the bioactive compound was dependent by the copolymer matrix composition, the increasing of 3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane comonomer amount attenuating the drug release. At the same time, the in vivo studies did not show significant differences of leucocyte formula elements, GOT, GPT and LDH levels, nor immune parameters (OC, PC, and BC) between control mice group and groups treated just with copolymer samples, with or without drug, data attesting the biocompatibility of the polymer samples. The investigation of the physico-chemical characteristics of poly(2-hydrxyethyl methacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) in terms of temperature-sensitive abilities, rheological and dielectrical properties, are bringing useful information for further specific use of this polymeric compound.

Keywords: bioapplications, dielectric and spectroscopic properties, dual sensitivity at pH and temperature, smart materials

Procedia PDF Downloads 282
2592 Dual Drug Piperine-Paclitaxel Nanoparticles Inhibit Migration and Invasion in Human Breast Cancer Cells

Authors: Monika Verma, Renuka Sharma, B. R. Gulati, Namita Singh

Abstract:

In combination therapy, two chemotherapeutic agents work together in a collaborative action. It has appeared as one of the promising approaches to improve anti-cancer treatment efficacy. In the present investigation, piperine (P-NPS), paclitaxel (PTX NPS), and a combination of both, piperine-paclitaxel nanoparticle (Pip-PTX NPS), were made by the nanoprecipitation method and later characterized by PSA, DSC, SEM, TEM, and FTIR. All nanoparticles exhibited a monodispersed size distribution with a size of below 200 nm, zeta potential ranges from (-30-40mV) and a narrow polydispersity index (>0.3) of the drugs. The average encapsulation efficiency was found to be between 80 and 90%. In vitro release of drugs for nanoparticles was done spectrophotometrically. FTIR and DSC results confirmed the presence of the drug. The Pip-PTX NPS significantly inhibit cell proliferation as compared to the native drugs nanoparticles in the breast cancer cell line MCF-7. In addition, Pip-PTX NPS suppresses cells in colony formation and soft gel agar assay. Scratch migration and Transwell chamber invasion assays revealed that combined nanoparticles reduce the migration and invasion of breast cancer cells. Morphological studies showed that Pip-PTX NPS penetrates the cells and induces apoptosis, which was further confirmed by DNA fragmentation, SEM, and western blot analysis. Taken together, Pip-PTX NPS inhibits cell proliferation, anchorage dependent and anchorage independent cell growth, reduces migration and invasion, and induces apoptosis in cells. These findings support that combination therapy using Pip-PTX NPS represents a potential approach and could be helpful in the future for breast cancer therapy.

Keywords: piperine, paclitaxel, breast cancer, apoptosis

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2591 Immunoliposomes Conjugated with CD133 Antibody for Targeting Melanoma Cancer Stem Cells

Authors: Chuan Yin

Abstract:

Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

Procedia PDF Downloads 382
2590 Effect of Therapeutic Exercises with or without Positional Release Technique in Treatment of Chronic Mechanical Low Back Pain Patients a Randomized Controlled Trial

Authors: Ghada M. R. Koura, Mohamed N. Mohamed, Ahmed M. F. El Shiwi

Abstract:

Chronic mechanical Low back dysfunction (CMLBD) is the most common problem of the working-age population in modern industrial sociaty; it causes a substantial economic burden due to the wide use of medical services and absence from work. Aim of work: the aim of this study was to investigate the effect of positional release technique on patients with chronic mechanical low back pain. Materials and Methods: Thirty two patients from both sexes were diagnosed with CMLBP, aged 20 to 45 years and were divided randomly into two equal groups; sixteen patients each; group A (control group) received therapeutic exercises that include (Stretch and Strength exercises for back and abdominal muscles). Group B (experimental group) received therapeutic exercises with positional release technique; treatment was applied 3 days/week for 4 weeks. Pain was measured by Visual Analogue Scale, Lumbar range of motion was measured by Inclinometer and Functional disability was measured by Oswestry disability scale. Measurements were taken at two intervals pre-treatment and post-treatment. Results: Data obtained was analyzed via paired and unpaired t-Test. There were statistical differences between the 2 groups, where the experimental group showed greater improvement than control group. Conclusion: Positional release technique is considered as an effective treatment for reducing pain, functional disability and increasing lumbar range of motion in individuals with chronic mechanical low back pain.

Keywords: chronic mechanical low back pain, traditional physical therapy program, positional release technique, randomized controlled trial

Procedia PDF Downloads 594