Search results for: drug kinetics

Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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Authors: Meltem Haktaniyan, Eda Cagli, Irem Erel Goktepe

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Polymers that change their properties in response to different stimuli (e.g. light, temperature, pH, ionic strength or magnetic field) are called ‘smart’ or ‘stimuli-responsive polymers’. These polymers have been widely used in biomedical applications such as sensors, gene delivery, drug delivery or tissue engineering. Temperature-responsive polymers have been studied extensively for controlled drug delivery applications. As regard of pseudo-peptides, poly (2-alky-2-oxazoline)s are considered as good candidates for delivery systems due to their stealth behavior and nontoxicity. In order to build responsive multilayer films for controlled drug release applications from surface, Layer by layer technique (LBL) is a powerful technique with an advantage of nanometer scale control over spatial architecture and morphology. Multilayers can be constructed on surface where non-covalent interactions including electrostatic interactions, hydrogen bonding, and charge-transfer or hydrophobic-hydrophobic interactions. In the present study, hydrogen bounded multilayer films of poly (2-alky-2-oxazoline) s with tannic acid were prepared in order to use as a platform to release Doxorubicin (DOX) from surface with pH and thermal triggers. For this purpose, poly (2-isopropyl-2-oxazoline) (PIPOX) and poly (2-ethyl-2-oxazoline) (PETOX) were synthesized via cationic ring opening polymerization (CROP) with hydroxyl end groups. Two polymeric multilayer systems ((PETOX)/(DOX)-(TA) complexes and (PIPOX)/(DOX)-(TA) complexes) were designed to investigate of controlled release of Doxorubicin (DOX) from surface with pH and thermal triggers. The drug release profiles from the multilayer thin films with alterations of pH and temperature will been examined with UV-Vis Spectroscopy and Fluorescence Spectroscopy.

Keywords: temperature responsive polymers, h-bonded multilayer films, drug release, polyoxazoline

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery 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 ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that 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.

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

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Authors: Niharika Keot, Manabendra Sarma

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A thorough investigation of Ln3+ complexes with more than one inner-sphere water molecule is crucial for designing high relaxivity contrast agents (CAs) used in magnetic resonance imaging (MRI). This study accomplished a comparative stability analysis of two hexadentate (H3cbda and H3dpaa) and two heptadentate (H4peada and H3tpaa) ligands with Ln3+ ions. The higher stability of the hexadentate H3cbda and heptadentate H4peada ligands has been confirmed by the binding affinity and Gibbs free energy analysis in aqueous solution. In addition, energy decomposition analysis (EDA) reveals the higher binding affinity of the peada4− ligand than the cbda3− ligand towards Ln3+ ions due to the higher charge density of the peada4− ligand. Moreover, a mechanistic overview of water exchange kinetics has been carried out based on the strength of the metal–water bond. The strength of the metal–water bond follows the trend Gd–O47 (w) > Gd–O39 (w) > Gd–O36 (w) in the case of the tris-aquated [Gd(cbda)(H2O)3] and Gd–O43 (w) > Gd–O40 (w) for the bis-aquated [Gd(peada)(H2O)2]− complex, which was confirmed by bond length, electron density (ρ), and electron localization function (ELF) at the corresponding bond critical points. Our analysis also predicts that the activation energy barrier decreases with the decrease in bond strength; hence kex increases. The 17O and 1H hyperfine coupling constant values of all the coordinated water molecules were different, calculated by using the second-order Douglas–Kroll–Hess (DKH2) approach. Furthermore, the ionic nature of the bonding in the metal–ligand (M–L) bond was confirmed by the Quantum Theory of Atoms-In-Molecules (QTAIM) and ELF along with energy decomposition analysis (EDA). We hope that the results can be used as a basis for the design of highly efficient Gd(III)-based high relaxivity MRI contrast agents for medical applications.

Keywords: MRI contrast agents, lanthanide chemistry, thermodynamic stability, water exchange kinetics

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Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Polymeric disperse systems such as nanoparticles (NPs) are of high interest for numerous applications in contemporary medicine and nanobiotechnology to a considerable potential for treatment of many human diseases. The important technological advantages of NPs usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic(water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. At the next step of this research was carried out an evaluation of biocompability and bioavailability of the synthesized NPs using a stable human cell culture line – A549. It was established that the obtained NPs are not only biocompatible but they stimulate the cell growth.

Keywords: amino acids, biodegradable polymers, bioavailability, nanoparticles

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Authors: Sameena Malik, Ghosh Prakash, Sandeep Mudliar, Vishal Waindeskar, Atul Vaidya

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In this study, the biodegradability enhancement along with COD color and toxicity removal of pharmaceutical effluent by O₃, O₃/Fe²⁺, O₃/nZVI processes has been evaluated. The nZVI particles were synthesized and characterized by XRD and SEM analysis. Kinetic model was reasonably developed to select the ozone doses to be applied based on the ozonation kinetic and mass transfer coefficient values. Nano catalytic ozonation process (O₃/nZVI) effectively enhanced the biodegradability (BI=BOD₅/COD) of pharmaceutical effluent up to 0.63 from 0.18 of control with a COD, color and toxicity removal of 62.3%, 93%, and 75% respectively compared to O₃, O₃/Fe²⁺ pretreatment processes. From the GC-MS analysis, 8 foremost organic compounds were predominantly detected in the pharmaceutical effluent. The disappearance of the corresponding GC-MS spectral peaks during catalyzed ozonation process indicated the degradation of the effluent. The changes in the FTIR spectra confirms the transformation/destruction of the organic compounds present in the effluent to new compounds. Subsequent aerobic biodegradation of pretreated effluent resulted in biodegradation rate enhancement by 5.31, 2.97, and 1.22 times for O₃, O₃/Fe²⁺ and O₃/nZVI processes respectively.

Keywords: iron nanoparticles, pharmaceutical effluent, ozonation, kinetics, mass transfer

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

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

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

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Authors: Christi Jackson, Chuka Onaga

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

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

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Authors: Melike Sultan Karasu Asnaz, Ayse Ozdogan Dolcek

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Crop drying, which aims to reduce the moisture content to a certain level, is a method used to extend the shelf life and prevent it from spoiling. One of the oldest food preservation techniques is open sunor shade drying. Even though this technique is the most affordable of all drying methods, there are some drawbacks such as contamination by insects, environmental pollution, windborne dust, and direct expose to weather conditions such as wind, rain, hail. However, solar dryers that provide a hygienic and controllable environment to preserve food and extend its shelf life have been developed and used to dry agricultural products. Thus, foods can be dried quickly without being affected by weather variables, and quality products can be obtained. This research is mainly devoted to investigating the modelling of drying kinetics of cantaloupe in a forced convection solar dryer. Mathematical models for the drying process should be defined to simulate the drying behavior of the foodstuff, which will greatly contribute to the development of solar dryer designs. Thus, drying experiments were conducted and replicated five times, and various data such as temperature, relative humidity, solar irradiation, drying air speed, and weight were instantly monitored and recorded. Moisture content of sliced and pretreated cantaloupe were converted into moisture ratio and then fitted against drying time for constructing drying curves. Then, 10 quasi-theoretical and empirical drying models were applied to find the best drying curve equation according to the Levenberg-Marquardt nonlinear optimization method. The best fitted mathematical drying model was selected according to the highest coefficient of determination (R²), and the mean square of the deviations (χ^²) and root mean square error (RMSE) criterial. The best fitted model was utilized to simulate a thin layer solar drying of cantaloupe, and the simulation results were compared with the experimental data for validation purposes.

Keywords: solar dryer, mathematical modelling, drying kinetics, cantaloupe drying

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Authors: Malay K. Das, Bhanu P. Sahu

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Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailability of 10-90%. The aim of this study was to enhance the oral bioavailability of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA).These were characterized for particle size, ζ potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The effect of nanoprecipitation on oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption study in rats and compared to pure drug. The stable nanosuspension was obtained with average size range of the precipitated nanoparticles between 150-300 nm and was found to be homogenous showing a narrow polydispersity index of 0.3±0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. The in vivo studies on rats revealed a significant increase in the oral absorption of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and Cmax values of nanosuspension were approximately 1.38 and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06±0.02 % decrease in systolic blood pressure compared to 13.37±0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamics effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.

Keywords: furosemide, nanosuspension, bioavailability enhancement, nanoprecipitation, oral drug delivery

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Authors: Madhuresh Dwivedi, Navneet Singh Deora, Aastha Deswal, H. N. Mishra

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FT-NIR spectroscopy and electronic nose was used to study the kinetics of dough proofing. Spectroscopy was conducted with an optic probe in the diffuse reflectance mode. The dough leavening was carried out at different temperatures (25 and 35°C) and constant RH (80%). Spectra were collected in the range of wave numbers from 12,000 to 4,000 cm-1 directly on the samples, every 5 min during proofing, up to 2 hours. NIR spectra were corrected for scatter effect and second order derivatization was done to transform the spectra. Principal component analysis (PCA) was applied for the leavening process and process kinetics was calculated. PCA was performed on data set and loadings were calculated. For leavening, four absorption zones (8,950-8,850, 7,200-6,800, 5,250-5,150 and 4,700-4,250 cm-1) were involved in describing the process. Simultaneously electronic nose was also used for understanding the development of odour compounds during fermentation. The electronic nose was able to differential the sample on the basis of aroma generation at different time during fermentation. In order to rapidly differentiate samples based on odor, a Principal component analysis is performed and successfully demonstrated in this study. The result suggests that electronic nose and FT-NIR spectroscopy can be utilized for the online quality control of the fermentation process during leavening of bread dough.

Keywords: FT-NIR, dough, e-nose, proofing, principal component analysis

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

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

Keywords: cocrystals, coformer, oxaprozin, solubility

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Eda Cagli, Irem Erel Goktepe

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

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

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Authors: Aneena Suresh, C. S. Sidharth

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

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

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

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

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Ikram Elsiddig, Yacouba Djamila, Amna Hamad

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

Keywords: Antagonistic, Garlic, Metformin, Synergistic

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Authors: Reenu Yadav, Abhay Asthana, S. K. Yadav

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Purpose: The aim of the present work was to develop an oral gel for brushing with an antimicrobial activity which will cure/protect from various periodontal diseases such as periodontitis, gingivitis, and pyorrhea. Methods: Plant materials procured from local suppliers, extracted and standardized. Screening of antimicrobial activity was carried out with the help of disk diffusion method. The gel was formulated by dried extracts of Beautea monosperma and Cordia obliquus. Gels were evaluated on various parameters and standardization of the formulation was performed. The release of drugs was studied in pH 6.8 using a mastication device.Total phenolic and flavonoid contents were estimated by folin-Ciocalteu and aluminium chloride method, and stability studies were performed (40°C and RH 75% ± 5% for 90 days) to assess the effect of temperature and humidity on the concentration of phenolic and flavonoid contents. The results of accelerated stability conditions were compared with that of samples kept at controlled conditions (RT). The control samples were kept at room temperature (25°C, 35% RH for 180 days). Results: Results are encouraging; extracts possess significant antimicrobial activity at very low concentration (15µg/disc, 20µg/disc and 15 µg/ disc) on oral pathogenic bacteria. The formulation has optimal characteristics, as well as has a pleasant appearance, fragrance, texture, and taste, is highly acceptable by the volunteers. The diffusion coefficient values ranged from 0.6655 to 0.9164. Since the R values of korsmayer papas were close to 1, Drug release from formulation follows matrix diffusion kinetics. Hence, diffusion was the mechanism of the drug release. Formulation follows non-Fickian transport mechanism. Most Formulations released 50 % of their contents within 25-30 minutes. Results obtained from the accelerated stability studies are indicative of a slight reduction in flavonoids and phenolic contents with time on long time storage. When measured degradation under ambient conditions, degradation was significantly lower than in accelerated stability study. Conclusion: Plant extracts possess compounds with antimicrobial properties can be used as. Developed formulation will cure/protect from various periodontal diseases. Further development and evaluations oral gel including the isolated compounds on the commercial scale and their clinical and toxicological studies are the future challenges.

Keywords: herbal gel, dental care, ambient conditions, commercial scale

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Authors: Sunil Kumar

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

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

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Authors: Natida Thongsima, Patompong Satapornpong

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

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

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

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

Keywords: fexofenadine hydrochloride, taste masking, chitosan, orodispersible

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Authors: Christian Fercher, Jiaul Islam, Simon R. Corrie

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Fluorescence-based immunodiagnostics are an emerging field in biosensor development and exhibit several advantages over traditional detection methods. While various affinity biosensors have been developed to generate a fluorescence signal upon sensing varying concentrations of analytes, reagentless, reversible, and continuous monitoring of complex biological samples remains challenging. Here, we aimed to genetically engineer biosensors based on single-chain antibody fragments (scFv) that are site-specifically labeled with environmentally sensitive fluorescent unnatural amino acids (UAA). A rational design approach resulted in quantifiable analyte-dependent changes in peak fluorescence emission wavelength and enabled antigen detection in vitro. Incorporation of a polarity indicator within the topological neighborhood of the antigen-binding interface generated a titratable wavelength blueshift with nanomolar detection limits. In order to ensure continuous analyte monitoring, scFv candidates with fast binding and dissociation kinetics were selected from a genetic library employing a high-throughput phage display and affinity screening approach. Initial rankings were further refined towards rapid dissociation kinetics using bio-layer interferometry (BLI) and surface plasmon resonance (SPR). The most promising candidates were expressed, purified to homogeneity, and tested for their potential to detect biomarkers in a continuous microfluidic-based assay. Variations of dissociation kinetics within an order of magnitude were achieved without compromising the specificity of the antibody fragments. This approach is generally applicable to numerous antibody/antigen combinations and currently awaits integration in a wide range of assay platforms for one-step protein quantification.

Keywords: antibody engineering, biosensor, phage display, unnatural amino acids

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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Authors: Mahdi Akhbardeh

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St John's wort plant can help to treat depression disease through decreasing this disease symptom, due to having some similar features of Prozac (Fluoxetine Hcl) pill. People suffering from slight depression who have fear of using antidepressants side effects can use St John's wort drops under doctor observation. This method of treatment is proposed specially to those women who are spending menopause or depression resulted from this period. St John's wort plant have proposed traditional and plant medicine as newest researches in treating mood disorders compared to Prozac (Fluoxetine Hcl) drug in treating depression disease which is being administrated in clinic research center of Washington. Objective: the aim of this study is to find an alternative treatment method in people suffering from depression which are treated with Prozac (Fluoxetine Hcl). Almost 70 percent of treatment failures with Prozac (Fluoxetine Hcl) drug in patients suffering from slight to normal depression is due to intensive side effects including: decrease in blood pressure, reduce in sexual desire and 30 percent of it is due to this drug affectless in treatment procedure which leads to leaving treatment. Results of Hypercuim plant function are exactly similar to antidepressants. Increase in serotonin amount in brain synopsis terminal end causes increase in existence time of this material in this part. In fact these two drugs have similar function. Though side effects of Hypercuim plant(St John's wort) including headache and slight nausea tolerable. Results: St John's wort plant can be used lonely in slight to normal depressions in which patients are avoiding Prozac (Fluoxetine Hcl) drug due to it's side effects. In intensive depressions through which general patients don’t indicate positive response to drug, it is probably expected relative or even complete treatment through combining antidepressants drugs with this plant. This treatment method has been investigated and confirmed in clinical tests and researches.

Keywords: depression, St John's wort, Prozac, antidepressant

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Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

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Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

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Authors: Haile F. Darge, Hsieh C. Tsai

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

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

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Authors: Rosa L. Figueroa, Joselyn A. Hernández

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During the last couple of years, the Ministry of Health have been developing new health policies in order to regulate and improve in benefit of the patient the pharmaceutical system in our country. However, there are still some deficiencies in how medicines have been accessed, distributed, and sold. Therefore, it is necessary to empower the patient by offering new instances to improve access to drug information. This work introduces ‘the bioequivalent’ a medical drug search tool created to increase both diffusion and getting information about the therapeutic equivalence of medicines for the patient. The development of the search tool started with a study on the availability of sources of drug information accessible to the patient where advantages and disadvantages were analyzed. The information obtained was used to feed the functional design of the new tool. The design of the new tool shows an external interface that includes a header, body, sidebar and footer. The header has a menu containing ‘Home,’ ‘Who we are,’ and ‘Mission and vision.’ The Body contains the medical drug search tool, and the Sidebar is for the user logging in. It could be anonym, registered user, as well as, administrator. Anonym user could only use the tool. Registered users could add some information on existing medicines in the database; however, adding information will be restricted and limited to specific items and subject to administrator approval because the information added must be endorsed by the Chilean Public Health Institute. On the other hand, the administrator will have all the privileges, including creating or deleting drugs or information about them. The Bioequivalent was tested on different mobile devices, and no fails have been found. Moreover, a small survey was answered by ten people who tested the tool, and all of them agree that the tool was useful to get information about bioequivalent drugs, and they would recommend the tool to others. Nevertheless, an 80% of people who tested the tool says it was easy to use, and a 70% indicates that additional help is not required. These results are evidence that ‘the Bioequivalent’ may contribute to the knowledge about the therapeutic bioequivalence and bioequivalent drugs existing in Chile. As future work, the tool will be developed to make it available to the public for a first testing stage in a more massive scenario.

Keywords: collaborative database, bioequivalent drugs, search tool, web platform

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Authors: Caiyun Liu, A. Hernandez-Manas, N. Grimi, E. Vorobiev

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Drying is one of the most used methods for food preservation, which extend shelf life of food and makes their transportation, storage and packaging easier and more economic. The commonly dried method is hot air drying. However, its disadvantages are low energy efficiency and long drying times. Because of the high temperature during the hot air drying, the undesirable changes in pigments, vitamins and flavoring agents occur which result in degradation of the quality parameters of the product. Drying process can also cause shrinkage, case hardening, dark color, browning, loss of nutrients and others. Recently, new processes were developed in order to avoid these problems. For example, the application of pulsed electric field provokes cell membrane permeabilisation, which increases the drying kinetics and moisture diffusion coefficient. Microwave drying technology has also several advantages over conventional hot air drying, such as higher drying rates and thermal efficiency, shorter drying time, significantly improved product quality and nutritional value. Rehydration kinetics of dried product is a very important characteristic of dried products. Current research has indicated that the rehydration ratio and the coefficient of rehydration are dependent on the processing conditions of drying. The present study compares the efficiency of two processes (1: room temperature air drying, 2: microwave/air drying) in terms of drying rate, product quality and rehydration ratio. In this work, potato slices (≈2.2g) with a thickness of 2 mm and diameter of 33mm were placed in the microwave chamber and dried. Drying kinetics and drying rates of different methods were determined. The process parameters included inlet air velocity (1 m/s, 1.5 m/s, 2 m/s) and microwave power (50 W, 100 W, 200 W and 250 W) were studied. The evolution of temperature during microwave drying was measured. The drying power had a strong effect on drying rate, and the microwave-air drying resulted in 93% decrease in the drying time when the air velocity was 2 m/s and the power of microwave was 250 W. Based on Lewis model, drying rate constants (kDR) were determined. It was observed an increase from kDR=0.0002 s-1 to kDR=0.0032 s-1 of air velocity of 2 m/s and microwave/air (at 2m/s and 250W) respectively. The effective moisture diffusivity was calculated by using Fick's law. The results show an increase of effective moisture diffusivity from 7.52×10-11 to 2.64×10-9 m2.s-1 for air velocity of 2 m/s and microwave/air (at 2m/s and 250W) respectively. The temperature of the potato slices increased for higher microwaves power, but decreased for higher air velocity. The rehydration ratio, defined as the weight of the the sample after rehydration per the weight of dried sample, was determined at different water temperatures (25℃, 50℃, 75℃). The rehydration ratio increased with the water temperature and reached its maximum at the following conditions: 200 W for the microwave power, 2 m/s for the air velocity and 75°C for the water temperature. The present study shows the interest of microwave drying for the food preservation.

Keywords: drying, microwave, potato, rehydration

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were water, SBF and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

Procedia PDF Downloads 57