Search results for: biomedical drug

Authors: Emílie Kučerová, Tereza Veverková, Marina Morozovová, Eva Kudová, Jitka Viktorová

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The blood-brain barrier (BBB) is a key element regulating the transport of substances between the blood and the central nervous system (CNS). The BBB protects the CNS from potentially harmful substances and maintains a suitable environment for nervous activity in the CNS, but at the same time, it represents a significant obstacle to the entry of drugs into the CNS. Pharmacoresistant epilepsy is a form of epilepsy that cannot be suppressed using two (or more) appropriately chosen antiepileptic drugs. In many cases, pharmacoresistant epilepsy is characterized by an increased concentration of efflux pumps on the luminal sides of the endothelial cells that form the BBB and an increased number of drug-metabolizing enzymes in the BBB cells, thereby preventing the effective transport of antiepileptic drugs into the CNS. Currently, a number of scientific groups are focusing on the preparation and improvement of BBB models in vitro in order to study cell interactions or transport mechanisms. However, in pathological conditions such as pharmacoresistant epilepsy, there are changes in BBB structure, and current BBB models are insufficient for related research. Our goal is to develop a suitable BBB model for pharmacoresistant epilepsy in vitro and use it to test the transfer of potential antiepileptic drugs. This model is created by co-culturing immortalized human cerebral microvascular endothelial cells, human vascular pericytes and immortalized human astrocytes. The BBB in vitro is cultivated in the form of a 2D transwell model and the integrity of the barrier is verified by measuring transendothelial electrical resistance (TEER). From the current results, a contact cell arrangement with the cultivation of endothelial cells on the upper side of the insert and the co-cultivation of astrocytes and pericytes on the lower side of the insert is selected as the most promising for BBB model cultivation. The pharmacoresistance of the BBB model is achieved by long-term cultivation of endothelial cells in an increasing concentration of selected antiepileptic drugs, which should lead to increased production of efflux pumps and drug-metabolizing enzymes. The pharmacoresistant BBB model in vitro will be further used for the screening of substances that could act both as antiepileptics and at the same time as inhibitors of efflux pumps in endothelial cells. This project was supported by the Technology Agency of the Czech Republic (TACR), Personalized Medicine: Translational research towards biomedical applications, No. TN02000109 and by the Academy of Sciences of the Czech Republic (AS CR) – grant RVO 61388963.

Keywords: antiepileptic drugs, blood-brain barrier, efflux transporters, pharmacoresistance

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Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

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Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

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Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane

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There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.

Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes

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Authors: Sajjad Seifi Mofarah, S. K. Sadrnezhaad, Shokooh Moghadam, Javad Tavakoli

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In recent years a new method of combination treatment for cancer has been developed and studied that has led to significant advancements in the field of cancer therapy. Hyperthermia is a traditional therapy that, along with a creation of a medically approved level of heat with the help of an alternating magnetic AC current, results in the destruction of cancer cells by heat. This paper gives details regarding the production of the spherical nanocomposite PVA/γ-Fe2O3 in order to be used for medical purposes such as tumor treatment by hyperthermia. To reach a suitable and evenly distributed temperature, the nanocomposite with core-shell morphology and spherical form within a 100 to 200 nanometer size was created using phase separation emulsion, in which the magnetic nano-particles γ-Fe2O3 with an average particle size of 20 nano-meters and with different percentages of 0.2, 0.4, 0.5, and 0.6 were covered by polyvinyl alcohol. The main concern in hyperthermia and heat treatment is achieving desirable specific absorption rate (SAR) and one of the most critical factors in SAR is particle size. In this project all attempts has been done to reach minimal size and consequently maximum SAR. The morphological analysis of the spherical structure of the nanocomposite PVA/γ-Fe2O3 was achieved by SEM analyses and the study of the chemical bonds created was made possible by FTIR analysis. To investigate the manner of magnetic nanocomposite particle size distribution a DLS experiment was conducted. Moreover, to determine the magnetic behavior of the γ-Fe2O3 particle and the nanocomposite PVA/γ-Fe2O3 in different concentrations a VSM test was conducted. To sum up, creating magnetic nanocomposites with a spherical morphology that would be employed for drug loading opens doors to new approaches in developing nanocomposites that provide efficient heat and a controlled release of drug simultaneously inside the magnetic field, which are among their positive characteristics that could significantly improve the recovery process in patients.

Keywords: nanocomposite, hyperthermia, cancer therapy, drug releasing

Procedia PDF Downloads 289

Authors: Pedro J. Rolim-Neto, Leslie R. M. Ferraz, Fabiana L. A. Santos, Pablo A. Ferreira, Ricardo T. L. Maia-Jr., Magaly A. M. Lyra, Danilo A F. Fonte, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim

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Initially developed as an antimalarial agent, hydroxychloroquine (HCQ) sulfate is often used as a slow-acting antirheumatic drug in the treatment of disorders of connective tissue. The United States Pharmacopeia (USP) 37 provides a reversed-phase HPLC method for quantification of HCQ. However, this method was not reproducible, producing asymmetric peaks in a long analysis time. The asymmetry of the peak may cause an incorrect calculation of the concentration of the sample. Furthermore, the analysis time is unacceptable, especially regarding the routine of a pharmaceutical industry. The aiming of this study was to develop a fast, easy and efficient method for quantification of HCQ sulfate by High Performance Liquid Chromatography (HPLC) based on the Quality by Design (QbD) methodology. This method was optimized in terms of peak symmetry using the surface area graphic as the Design of Experiments (DoE) and the tailing factor (TF) as an indicator to the Design Space (DS). The reference method used was that described at USP 37 to the quantification of the drug. For the optimized method, was proposed a 33 factorial design, based on the QbD concepts. The DS was created with the TF (in a range between 0.98 and 1.2) in order to demonstrate the ideal analytical conditions. Changes were made in the composition of the USP mobile-phase (USP-MP): USP-MP: Methanol (90:10 v/v, 80:20 v/v and 70:30 v/v), in the flow (0.8, 1.0 and 1.2 mL) and in the oven temperature (30, 35, and 40ºC). The USP method allowed the quantification of drug in a long time (40-50 minutes). In addition, the method uses a high flow rate (1,5 mL.min-1) which increases the consumption of expensive solvents HPLC grade. The main problem observed was the TF value (1,8) that would be accepted if the drug was not a racemic mixture, since the co-elution of the isomers can become an unreliable peak integration. Therefore, the optimization was suggested in order to reduce the analysis time, aiming a better peak resolution and TF. For the optimization method, by the analysis of the surface-response plot it was possible to confirm the ideal setting analytical condition: 45 °C, 0,8 mL.min-1 and 80:20 USP-MP: Methanol. The optimized HPLC method enabled the quantification of HCQ sulfate, with a peak of high resolution, showing a TF value of 1,17. This promotes good co-elution of isomers of the HCQ, ensuring an accurate quantification of the raw material as racemic mixture. This method also proved to be 18 times faster, approximately, compared to the reference method, using a lower flow rate, reducing even more the consumption of the solvents and, consequently, the analysis cost. Thus, an analytical method for the quantification of HCQ sulfate was optimized using QbD methodology. This method proved to be faster and more efficient than the USP method, regarding the retention time and, especially, the peak resolution. The higher resolution in the chromatogram peaks supports the implementation of the method for quantification of the drug as racemic mixture, not requiring the separation of isomers.

Keywords: analytical method, hydroxychloroquine sulfate, quality by design, surface area graphic

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Authors: Kotchamon Yodkhum, Thawatchai Phaechamud

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Hydrophobic chitosan-based materials have been developed as controlled drug delivery system. This study was aimed to prepare and evaluate chitosan-aluminum monostearate composite dispersion (CLA) as fabricating liquid for construct a hydrophobic, controlled-release solid drug delivery matrix. This work was attempted to blend hydrophobic substance, aluminum monostearate (AMS), with chitosan in acidic aqueous medium without using any surfactants or grafting reaction, and high temperature during mixing that are normally performed when preparing hydrophobic chitosan system. Lactic acid solution (2%w/v) was employed as chitosan solvent. CLA dispersion was prepared by dispersing different amounts of AMS (1-20% w/w) in chitosan solution (4% w/w) with continuous agitation using magnetic stirrer for 24 h. Effect of AMS amount on physicochemical properties of the dispersion such as viscosity, rheology and particle size was evaluated. Morphology of chitosan-AMS complex (dispersant) was observed under inverted microscope and atomic force microscope. Stability of CLA dispersions was evaluated after preparation within 48 h. CLA dispersions containing AMS less than 5 % w/w exhibited rheological behavior as Newtonian while that containing higher AMS amount exhibited as pseudoplastic. Particle size of the dispersant was significantly smaller when AMS amount was increased up to 5% w/w and was not different between the higher AMS amount system. Morphology of the dispersant under inverted microscope displayed irregular shape and their size exhibited the same trend with particle size measurement. Observation of the dispersion stability revealed that phase separation occurred faster in the system containing higher AMS amount which indicated lower stability of the system. However, the dispersions were homogeneous and stable more than 12 hours after preparation that enough for fabrication process. The prepared dispersions had ability to be fabricated as a porous matrix via lyophilization technique.

Keywords: chitosan, aluminum monostearate, dispersion, controlled-release

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Authors: S. M. Arciniegas, D. Vargas, L. Gutierrez

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The aim of this study was to develop oral drug presentation of doxycycline hyclate that maintains longer therapeutic levels than conventional forms. A polymethacrylate and acrylic acid based matrix were used in different proportions to obtain controlled-release formulations; DOX1 (1:0.25:0.0035), DOX2 (1:2:0.0225) and DOX-C (without excipients). All were tested in vivo in healthy dogs and their serum concentrations vs. time profile was investigated after its oral administration in this species. DOX1 and DOX2 show therapeutic concentrations for 60 hours, while DOX-C only for 24 hours. The pharmacokinetics values tested were K½el, Cmax, Tmax, AUC, AUC∞, AUCt, AUMC, RT, Kel, Vdss, Clb and Frel. DOX1 does not differ significantly from DOX-C, but shows significant differences in all variables with DOX2 (p<0.05). In conclusion, DOX1 presents best pharmacokinetics for time-dependent drug and longer release time of 60 hours, thereby reducing the frequency of administration, the patient's stress, the occurrence of adverse effects and the cost of treatment.

Keywords: tetracyclines, long-acting, sustained-release, carbopol, eudragit, canine

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Authors: D. L. Tambe, S. Dighe Nachiket

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Objective: Depression is a common but serious illness and the phenothiazine derivatives shows prominent effect against the depression hence work was undertaken to validate this use scientifically. Material and Methods: Synthesis of phenothiazine derivatives are done by the substitution of various groups, but the basic scheme of synthesis is started with synthesis of 4-(Cyclohexylidene) Benzoic acid using PABA. After that with the further six step of synthesis of 3-(10H-phenothiazin-2-yl)-N, 5-diphenyl-4H-1, 2, 4-triazol-4-amine is done which is final product. Antidepressant activity of all the synthesized compounds was evaluated by despair swim test by using Sprague Dawley Rats. Standard drug imipramine was used as the control. In the despair swim test, all the synthesized derivatives showed antidepressant activity. Results: Among the all phenothiazine derivatives four compounds (6.6-7.2 (14H –phenyl ), 9.43 (1H OH), 8.50 (1H NH phenothiazine),6.85-8.21(14H phenyl), 8.50 (1H NH phenothiazine), 11.82 (1H – OH), 6.6-7.2 (8H –phenyl ), 9.43 (1H OH), 8.50 (1H NH phenothiazine), 4.2 (1H NH) and 6.85-8.21(8H phenyl), 8.50 (1H NH phenothiazine), 3.9 (1H NH) 11.82 (1H – OH) showed significant antidepressant activity comparing with control drug imipramine. Conclusion: Various Novel phenothiazine derivatives show more potent antidepressant activity and it plays more beneficial role in human health for the treatment of depression.

Keywords: antidepressant activities, despair swim test, phenothiazine, Sprague Dawley Rats

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Authors: Mosaab A. Omar, Mohammad Saleh Al-Aboody, Mohmed A. Rizk, Shimaa M. Elsayed, Ahmed ElSify, Naoaki Yokoyama, Ikuo Igarashi

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Enoxacin is a broad-spectrum 6-fluoronaphthyridinone antibacterial agent (fluoroquinolones) structurally related to nalidixic acid used mainly in the treatment of urinary tract infections and gonorrhea. Also, it has been shown recently that it may have cancer inhibiting effect. The primary antibabesial effect of Enoxacin is due to inhibition of DNA gyrase subunit A, and DNA topoisomerase. In the present study, enoxacin was tested as a potent inhibitor against the in vitro growth of bovine and equine Piroplasms. The in vitro growth of five Babesia species that were tested was significantly inhibited (P<0.05) by micromolar concentrations of enoxacin (IC50 values= 13.5, 7.2, 7.5, and 24.2 µM for Babesia bovis, Babesia bigemina, Babesia caballi, and Theileria equi, respectively). Enoxacin IC50 values for Babesia and Theileria parasites were satisfactory as the drug is a potent antibacterial drug with minimum side effects. Therefore, enoxacin might be used for the treatment of Babesiosis and Theileriosis especially in case of mixed infections with bacterial diseases or in the case of animal sensitivity against diminazin toxicity.

Keywords: enoxacin, Babesia, Theileria, IC50 and dimenazin

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Authors: Leila Asadollahi

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Dry powder inhalers (DPIs) have come a long way since their creation, starting with the Spinhaler Fisons in 1967. For optimal performance, it is important to consider the interplay between formulation, device, and patient. DPIs have shown great potential in treating systemic disorders, as evidenced by their success in clinical practices. Ongoing clinical trials and market availability of DPI products for systemic disease treatment are also examined. Furthermore, the current COVID-19 pandemic has sparked increased interest in dry powder inhalation as a potential avenue for vaccines and antiviral drugs, prompting further exploration of its applications. To achieve optimal treatment outcomes for respiratory diseases, a thorough understanding of the various types of DPIs currently available is crucial. These include single-dose, multiple-unit dose, and multi-dose DPIs. This informative article delves into the administration of drugs via inhalation, examining its diverse routes of administration. Additionally, it illuminates the exciting advancements in inhalation delivery systems and investigates the latest therapeutic approaches for the treatment of respiratory ailments. Additionally, the article discusses the historical development of DPIs and the need for improved designs to enhance efficacy and patient adherence. The potential of DPIs in treating systemic diseases is also examined. Overall, this review provides valuable insights into the advancements, challenges, and future prospects of inhalation drug delivery systems, highlighting the potential they hold for respiratory and systemic disorders. The review aims to provide valuable insights into the advancements, challenges, and future prospects of inhalation drug delivery systems, highlighting the potential they hold for respiratory and systemic disorders.

Keywords: dry powder inhalers (DPIs), respiratory diseases, systemic disorders, pulmonary drug delivery

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Authors: B. S. Muddukrishna, Karthik Aithal, Aravind Pai

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Introduction: Preparation of binary cocrystals of Etraverine (ETR) by using Tartaric Acid (TAR) as a conformer was the main focus of this study. Etravirine is a Class IV drug, as per the BCS classification system. Methods: Cocrystals were prepared by slow evaporation technique. A mixture of total 500mg of ETR: TAR was weighed in molar ratios of 1:1 (371.72mg of ETR and 128.27mg of TAR). Saturated solution of Etravirine was prepared in Acetone: Methanol (50:50) mixture in which tartaric acid is dissolved by sonication and then this solution was stirred using a magnetic stirrer until the solvent got evaporated. Shimadzu FTIR – 8300 system was used to acquire the FTIR spectra of the cocrystals prepared. Shimadzu thermal analyzer was used to achieve DSC measurements. X-ray diffractometer was used to obtain the X-ray powder diffraction pattern. Shake flask method was used to determine the equilibrium dynamic solubility of pure, physical mixture and cocrystals of ETR. USP buffer (pH 6.8) containing 1% of Tween 80 was used as the medium. The pure, physical mixture and the optimized cocrystal of ETR were accurately weighed sufficient to maintain the sink condition and were filled in hard gelatine capsules (size 4). Electrolab-Tablet Dissolution tester using basket apparatus at a rotational speed of 50 rpm and USP phosphate buffer (900 mL, pH = 6.8, 37 ˚C) + 1% Tween80 as a media, was used to carry out dissolution. Shimadzu LC-10 series chromatographic system was used to perform the analysis with PDA detector. An Hypersil BDS C18 (150mm ×4.6 mm ×5 µm) column was used for separation with mobile phase comprising of a mixture of ace¬tonitrile and phosphate buffer 20mM, pH 3.2 in the ratio 60:40 v/v. The flow rate was 1.0mL/min and column temperature was set to 30°C. The detection was carried out at 304 nm for ETR. Results and discussions: The cocrystals were subjected to various solid state characterization and the results confirmed the formation of cocrystals. The C=O stretching vibration (1741cm-1) in tartaric acid was disappeared in the cocrystal and the peak broadening of primary amine indicates hydrogen bond formation. The difference in the melting point of cocrystals when compared to pure Etravirine (265 °C) indicates interaction between the drug and the coformer which proves that first ordered transformation i.e. melting endotherm has disappeared. The difference in 2θ values of pure drug and cocrystals indicates the interaction between the drug and the coformer. Dynamic solubility and dissolution studies were also conducted by shake flask method and USP apparatus one respectively and 3.6 fold increase in the dynamic solubility were observed and in-vitro dissolution study shows four fold increase in the solubility for the ETR: TAR (1:1) cocrystals. The ETR: TAR (1:1) cocrystals shows improved solubility and dissolution as compared to the pure drug which was clearly showed by solid state characterization and dissolution studies.

Keywords: dynamic solubility, Etraverine, in vitro dissolution, slurry method

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Authors: Elham Ahmadi

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This study is conducted with the aim of investigating the effect of moderate physical activity (60% of maximal heart rate-MHR) on blood pressure in an elderly female with hypertension. Hypertension is considered a modifiable risk factor for cardiovascular disease through physical activity. The purpose and significance of this study were to investigate the role of exercise as an alternative therapy since some patients exhibit sensitivity/intolerance to some drugs. Initially, 65 hypertensive females (average age = 49.7 years) (systolic blood pressure, SBP >140 mmHg and/or diastolic blood pressure, DBP>85 mmHg) and 25 hypertensive females as a control group (average age = 50.3 years and systolic blood pressure, SBP >140 mmHg and/or diastolic blood pressure, DBP>85 mmHg) were selected. The subjects were divided based on their age, duration of disease, physical activity, and drug consumption. Then, blood pressure and heart rate (HR) were measured in all of the patients using a sphygmomanometer (pre-test). The exercise sessions consisted of warm-up, aerobic activity, and cooling down (total duration of 20 minutes for the first session up to 55 minutes in the last session). At the end of the 12th session (mid-test) and final session (24th session), blood pressure was measured for the last time (post-test). The control group was without any exercise during the study. The results were analyzed using a t-test. Our results indicated that moderate physical activity was effective in lowering blood pressure by 6.4/5.6–mm Hg for SBP and 2.4/4.3mm Hg for DBP in hypertensive patients, irrespective of age, duration of disease, and drug consumption ( P<.005). The control group indicates no changes in BP. Physical activity programs with moderate intensity (approximately at 60% MHR), three days per week, can be used not only as a preventive measure for diastolic hypertension (DBP>90 mmHg high blood pressure) but also as an alternative to drug therapy in the treatment of hypertension, as well.

Keywords: endurance exercise, elderly female, hypertension, physical activity

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Authors: Katarzyna Bialik-Wąs, Klaudia Pluta, Dagmara Malina, Małgorzata Miastkowska

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In recent years, biocompatible hydrogels have been used more and more in medical applications, especially as modern dressings and drug delivery systems. The main goal of this research was the characteristics of bio-hybrid hydrogel materials incorporated with the nanocarrier-drug system, which enable the release in a gradual and prolonged manner, up to 7 days. Therefore, the use of such a combination will provide protection against mechanical damage and adequate hydration. The proposed bio-hybrid hydrogels are characterized by: transparency, biocompatibility, good mechanical strength, and the dual release system, which allows for gradual delivery of the active substance, even up to 7 days. Bio-hybrid hydrogels based on sodium alginate (SA), poly(vinyl alcohol) (PVA), glycerine, and Aloe vera solution (AV) were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate as a crosslinking agent. Additionally, a nanocarrier-drug system was incorporated into SA/PVA/AV hydrogel matrix. Here, studies were focused on the release profiles of active substances from bio-hybrid hydrogels using the USP4 method (DZF II Flow-Through System, Erweka GmbH, Langen, Germany). The equipment incorporated seven in-line flow-through diffusion cells. The membrane was placed over support with an orifice of 1,5 cm in diameter (diffusional area, 1.766 cm²). All the cells were placed in a cell warmer connected with the Erweka heater DH 2000i and the Erweka piston pump HKP 720. The piston pump transports the receptor fluid via seven channels to the flow-through cells and automatically adapts the setting of the flow rate. All volumes were measured by gravimetric methods by filling the chambers with Milli-Q water and assuming a density of 1 g/ml. All the determinations were made in triplicate for each cell. The release study of the model active substance was carried out using a regenerated cellulose membrane Spectra/Por®Dialysis Membrane MWCO 6-8,000 Carl Roth® Company. These tests were conducted in buffer solutions – PBS at pH 7.4. A flow rate of receptor fluid of about 4 ml /1 min was selected. The experiments were carried out for 7 days at a temperature of 37°C. The released concentration of the model drug in the receptor solution was analyzed using UV-Vis spectroscopy (Perkin Elmer Company). Additionally, the following properties of the modified materials were studied: physicochemical, structural (FT-IR analysis), morphological (SEM analysis). Finally, the cytotoxicity tests using in vitro method were conducted. The obtained results exhibited that the dual release system allows for the gradual and prolonged delivery of the active substances, even up to 7 days.

Keywords: wound dressings, SA/PVA hydrogels, nanocarrier-drug system, USP4 method

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Authors: R. K. Purohit

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Ionizing radiation induces cellular damage through direct ionization of DNA and other cellular targets and indirectly via reactive oxygen species which may include effects from epigenetic changes. So there is a need of hour is to search for an ideal radioprotector which could minimize the deleterious and damaging effects caused by ionizing radiation. Radioprotectors are agents which reduce the radiation effects on cell when applied prior to exposure of radiation. The aim of this study was to access the efficacy of Emblica officinalis in reducing radiation and lead induced changes in mice liver. For the present experiment, healthy male Swiss albino mice (6-8 weeks) were selected and maintained under standard conditions of temperature and light. Fruit extract of Emblica was fed orally at the dose of 0.01 ml/animal/day. The animal were divided into seven groups according to the treatment i.e. lead acetate solution as drinking water (group-II) or exposed to 3.5 or 7.0 Gy gamma radiation (group-III) or combined treatment of radiation and lead acetate (group-IV). The animals of experimental groups were administered Emblica extract seven days prior to radiation or lead acetate treatment (group V, VI and VII) respectively. The animals from all the groups were sacrificed by cervical dislocation at each post-treatment intervals of 1, 2, 4, 7, 14 and 28 days. After sacrificing the animals pieces of liver were taken out and some of them were kept at -20°C for different biochemical parameters. The histopathological changes included cytoplasmic degranulation, vacuolation, hyperaemia, pycnotic and crenated nuclei. The changes observed in the control groups were compared with the respective experimental groups. An increase in the value of total proteins, glycogen, acid phosphtase, alkaline phosphatase activity and RNA was observed up to day-14 in the non drug treated group and day 7 in the Emblica treated groups, thereafter value declined up to day-28 without reaching to normal. The value of cholesterol and DNA showed a decreasing trend up to day -14 in non drug treated groups and day-7 in drug treated groups, thereafter value elevated up to day-28. The biochemical parameters were observed in the form of increase or decrease in the values. The changes were found dose dependent. After combined treatment of radiation and lead acetate synergistic effect were observed. The liver of Emblica treated animals exhibited less severe damage as compared to non-drug treated animals at all the corresponding intervals. An early and fast recovery was also noticed in Emblica pretreated animals. Thus, it appears that Emblica is potent enough to check lead and radiation induced heptic lesion in Swiss albino mice.

Keywords: radiation, lead , emblica, mice, liver

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: Amira M. Hassanein, Nehal A. Salahuddin, Atsunori Matsuda, Toshiaki Hattori, Mona N. Elfiky

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New insights into the design of highly sensitive, carbon-based electrochemical sensors are presented in this work. This was achieved by exploring the interesting properties of conductive (Mg/Al) layered double hydroxide- Dodecyl Sulphate/Polypyrrole nanocomposites which were synthesized by in-situ polymerization of pyrrole during the assembly of (Mg/Al) layered double hydroxide, and by employing the anionic surfactant Dodecyl sulphate as a modifier. The morphology and surface area of the nanocomposites changed with the percentage of Pyrrole. Under optimal conditions, the modified carbon paste electrode successfully achieved detection limits of 0.057 and 0.134 nmol.L-1 of Terazosin hydrochloride in pharmaceutical formulation and spiked human serum fluid, respectively. Moreover, the sensors are highly stable, reusable, and free from interference by other commonly present excipients in drug formulations.

Keywords: layered double hydroxide, polypyrrole, terazosin hydrochloride, square-wave adsorptive anodic stripping voltammetry

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Authors: Tresna Lestari, Tita Nofianti, Ade Yeni Aprilia, Lilis Tuslinah, Ruswanto Ruswanto

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Nanoparticle formulation is often used to improve drug absorptivity, thus increasing the sharpness of the action. Ginger torch flower extract was formulated into nanoparticle form using poloxamer 1, 3 and 5%. The nanoparticle was then characterized by its particle size, polydispersity index, zeta potential, entrapment efficiency and morphological form by SEM. The result shows that nanoparticle formulations have particle size 134.7-193.1 nm, polydispersity index less than 0.5 for all formulations, zeta potential -41.0 - (-24.3) mV and entrapment efficiency 89.93-97.99 against flavonoid content with a soft surface and spherical form of particles. Methanolic extract of ginger torch flower could enhance superoxide dismutase activity by 1,3183 U/mL in male rats. Nanoparticle formulation of ginger torch extract is expected to increase the capability of the drug to enhance superoxide dismutase activity.

Keywords: superoxide dismutase, ginger torch flower, nanoparticle, poloxamer

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Authors: Anoosh Eghdami

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Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

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Authors: Mohammed Ghazwani, Shyma Ali Alshahrani, Zahra Abdu Yousef, Taif Torki Asiri, Ghofran Abdur Rahman, Asma Ali Alshahrani, Umme Hani

Abstract:

Background and introduction: Piroxicam is a nonsteroidal anti-inflammatory drug characterized by low solubility-high permeability used to reduce pain, swelling, and joint stiffness from arthritis. Hydrotropes are a class of compounds that normally increase the aqueous solubility of insoluble solutes. Aim: The objective of the present research study was to formulate and optimize Piroxicam hydrotropic starch gel using sodium salicylate, sodium benzoate as hydrotropic salts, and potato starch for topical application. Materials and methods: The prepared Piroxicam hydrotropic starch gel was characterized for various physicochemical parameters like drug content estimation, pH, tube extrudability, and spreadability; all the prepared formulations were subjected to in-vitro diffusion studies for six hours in 100 ml phosphate buffer (pH 7.4) and determined gel strength. Results: All formulations were found to be white opaque in appearance and have good homogeneity. The pH of formulations was found to be between 6.9-7.9. Drug content ranged from 96.8%-99.4.5%. Spreadability plays an important role in patient compliance and helps in the uniform application of gel to the skin as gels should spread easily; F4 showed a spreadability of 2.4cm highest among all other formulations. In in vitro diffusion studies, extrudability and gel strength were good with F4 in comparison with other formulations; hence F4 was selected as the optimized formulation. Conclusion: Isolated potato starch was successfully employed to prepare the gel. Hydrotropic salt sodium salicylate increased the solubility of Piroxicam and resulted in a stable gel, whereas the gel prepared using sodium benzoate changed its color after one week of preparation from white to light yellowish. Hydrotropic potato starch gel proposed a suitable vehicle for the topical delivery of Piroxicam.

Keywords: Piroxicam, potato starch, hydrotropic salts, hydrotropic starch gel

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Authors: Sunil Kamboj, Vipin Saini, Suman Bala, Gaurav Sharma

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The main aim of the present research was to encapsulate mefenamic acid in niosomes and incorporate the prepared niosomes in the carbopol gel base for sustained therapeutic action. Mefenamic acid loaded niosomes were prepared by thin film hydration technique and evaluated for entrapment efficiency, vesicular size and zeta potential. The entrapment efficiency of the prepared niosomes was found to increase with decreasing the HLB values of surfactants and vesicle size was found to increase with increasing the cholesterol concentration. Niosomal vesicles with good entrapment efficiencies were incorporated in carbopol gel base to form the niosomal gel. The prepared niosomal gel was evaluated for pH, viscosity, spreadability, extrudability and skin permeation study across the rat skin.The results of permeation study revealed that the gel formulated with span 60 niosomes sustained the drug release for 12 h. Further the in vivo study showed the good inhibition of inflammation by the gel prepared with span 60 niosomes.

Keywords: mefenamic acid, niosomal gel, nonionic surfactants, sustained release

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Authors: Dmitry Nosik, Nickolay Nosik, Elli Kaplina, Olga Lobach, Marina Chataeva, Lev Rasnetsov

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Background and aims: Human Immunodeficiency Virus (HIV) infection is very often associated with Herpes Simplex Virus (HSV) infection but HIV patients are treated with a cocktail of antiretroviral drugs which are toxic. The use of an antiviral drug which will be active against both viruses like ferrovir found in our previous studies is rather actual. Earlier we had shown that Fullerene poly-amino capronic acid (FPACA) was active in case of monoinfection of HIV-1 or HSV-1. The aim of the study was to analyze the efficiency of FPACA against mixed infection of HIV and HSV. Methods: The peripheral blood lymphocytes, CEM, MT-4 cells were simultaneously infected with HIV-1 and HSV-1. FPACA was added 1 hour before infection. Cells viability was detected by MTT assay, virus antigens detected by ELISA, syncytium formation detected by microscopy. The different multiplicity of HIV-1/HSV-1 ratio was used. Results: The double viral HIV-1/HSV-1 infection was more cytopathic comparing with monoinfections. In mixed infection by the HIV-1/HSV-1 concentration of HIV-1 antigens and syncytium formations increased by 1,7 to 2,3 times in different cells in comparison with the culture infected with HIV-1 alone. The concentration of HSV-1 increased by 1,5-1,7 times, respectively. Administration of FPACA (1 microg/ml) protected cells: HIV-1/HSV-1 (1:1) – 80,1%; HIV-1/HSV-1 (1:4) – 57,2%; HIV-1/HSV-1 (1:8) – 46,3 %; HIV-1/HSV-1 (1:16) – 17,0%. Virus’s antigen levels were also reduced. Syncytium formation was totally inhibited in all cases of mixed infection. Conclusion: FPACA showed antiviral activity in case of mixed viral infection induced by Human Immunodeficiency Virus and Herpes Simplex Virus. The effect of viral inhibition increased with the multiplicity of HIV-1 in the inoculum. The mechanism of FPACA action is connected with the blocking of the virus particles adsorption to the cells and it could be suggested that it can have an antiviral activity against some other viruses too. Now FPACA could be considered as a potential drug for treatment of HIV disease complicated with opportunistic herpes viral infection.

Keywords: antiviral drug, human immunodeficiency virus (hiv), herpes simplex virus (hsv), mixed viral infection

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Authors: Mabruka S. Elashheb, Adullah Ali Bakush

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Schizophrenia is referred to as a disorder, not a disease, because there has not been any clear, reliable, and specific etiological factor. Even if schizophrenia is not a very frequent disease, it is among the most burdensome and costly illnesses worldwide. Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a comparison of a newer, atypical antipsychotic drug, Risperidone, and an older, conventional neuroleptic drug, Haloperidol, in terms of the effect on the usual kidney and liver functions and negative and positive symptoms in patients with schizophrenia and schizoaffective disorder after three and five weeks of their treatments. It is apparent from the comparative data of Haloperidol and Risperidone treatments in schizophrenic patients that Resperidone had superior improvement of negative and positive symptoms of patients, no harmful effect on liver and kidney functions and greater efficacy and faster recovery from schizophrenic symptoms in patients. On the basis of our findings of the present study, we concluded that treatment with Risperidone is superior to Haloperidol in reducing the risk of relapse among outpatients with schizophrenic disorders.

Keywords: schizophrenia, Haloperidol, Risperidone, positive and negative symptom

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Authors: Surajj Sarode, G. Vidya Sagar, G. P. Vadnere

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The purpose of the present study was to prolong the gastric residence time of Stavudine by developing gastric floating drug delivery system (GFDDS). Moreover, to study influence of different polymers on its release rate using gas-forming agents, like sodium bicarbonate, citric acid. Floating tablets were prepared by wet granulation method using PVP K-30 as a binder and the other polymers include Pullulan Gum, HPMC K100M, six different formulations with the varying concentrations of polymers were prepared and the tablets were evaluated in terms of their pre-compression parameters like bulk density, tapped density, Haunsner ratio, angle of repose, compressibility index, post compression physical characteristics, in vitro release, buoyancy, floating lag time (FLT), total floating time (TFT) and swelling index. All the formulations showed good floating lag time i.e. less than 3 mins. The batch containing combination of Pullulan Gum and HPMC 100M (i.e. F-6) showed total floating lag time more than 12 h., the highest swelling index among all the prepared batches. The drug release was found to follow zero order kinetics.

Keywords: Suavudine, floating, total floating time (TFT), gastric residence

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Authors: Sandeep Vasaikar, Lary Obi

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Rapid and discriminative genotyping methods are useful for determining the clonality of the isolates in nosocomial or household outbreaks. Multilocus sequence typing (MLST) is a nucleotide sequence-based approach for characterising bacterial isolates. The genetic diversity and the clinical relevance of the drug-resistant Klebsiella isolates from Mthatha are largely unknown. For this reason, prospective, experimental study of the molecular epidemiology of Klebsiella isolates from patients being treated in Mthatha over a three-year period was analysed. Methodology: PCR amplification and sequencing of the drug-resistance-associated genes, and multilocus sequence typing (MLST) using 7 housekeeping genes mdh, pgi, infB, FusAR, phoE, gapA and rpoB were conducted. A total of 32 isolates were analysed. Results: The percentages of multidrug-resistant (MDR), extensively drug-resistance (XDR) and pandrug-resistant (PDR) isolates were; MDR 65.6 % (21) and XDR and PDR with 0 % each. In this study, K. pneumoniae was 19/32 (59.4 %). MLST results showed 22 sequence types (STs) were identified, which were further separated by Maximum Parsimony into 10 clonal complexes and 12 singletons. The most dominant group was Klebsiella pneumoniae with 23/32 (71.8 %) isolates, Klebsiella oxytoca as a second group with 2/32 (6.25 %) isolates, and a single (3.1 %) K. varricola as a third group while 6 isolates were of unknown sequences. Conclusions/significance: A phylogenetic analysis of the concatenated sequences of the 7 housekeeping genes showed that strains of K. pneumoniae form a distinct lineage within the genus Klebsiella, with K. oxytoca and K. varricola its nearest phylogenetic neighbours. With the analysis of 7 genes were determined 1 K. variicola, which was mistakenly identified as K. pneumoniae by phenotypic methods. Two misidentifications of K. oxytoca were found when phenotypic methods were used. No significant differences were observed between ESBL blaCTX-M, blaTEM and blaSHV groups in the distribution of Sequence types (STs) or Clonal complexes (CCs).

Keywords: phylogenetic analysis, phylogeny, klebsiella phylogenetic, klebsiella

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Authors: Abonyi, Emmanuel Ebuka, Amina Jafaru O.

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Background: Illicit substance use among students is a phenomenon that has been widely studied, but it remains of interest due to its high prevalence and potential consequences. It is a major mental health concern among university students which may result in behavioral and academic problems, psychiatric disorders, and infectious diseases. Thus, this study was done to ascertain the prevalence and factors associated with the use of illicit drugs among these groups of people. Methods: A cross-sectional and descriptive survey was conducted among undergraduate students of the University of Lagos for the duration of three(3) months (August to October 2021). A total number of 938 undergraduate students were selected from seventeen faculties in the university. Pretested questionnaires were administered, completed, and returned. The data were analyzed using descriptive statistics and multivariate regression analysis. Results: From the data collected, it was observed that out of 938 undergraduate students of the University of Lagos that completed and returned the questionnaires, 56.3% were female and 43.7% were male. No gender differences were observed in the prevalence of use of any of the illicit substances. The result showed that the majority of the students that participated in the research were females(56.6%); it was observed that there were a total of 541 2nd-year students(57.7%) and 397 final-year students(42.3). Students between the age brackets of 20- 24 years had the highest frequency of 648(69.1%) of illicit drug use and students in none health-related disciplines. The result also showed that the majority of the students reported that they use Marijuana (31.7%), while lifetime use of LSD (6.3%), Heroin(4.8%), Cocaine (4.7%), and Ecstasy(4.5), Ketamine (3.4%). Besides, the use of alcohol was below average(44.1%). Additionally, Marijuana was among the ones that were mostly taken by students having a higher percentage and most of these respondents had experienced relationship problems with their family and intentions (50.9%). From the responses obtained, major reasons students indulge in illicit drug use were; curiosity to experiment, relief of stress after rigorous academic activities, social media influence, and peer pressure. Most Undergraduate students are in their most hyperactive stage in life, which makes them vulnerable to always want to explore practically every adventure. Hence, individual factors and social media influence are identified as major contributors to the prevalence of illicit drug use among undergraduate students at the University of Lagos, Nigeria. Conclusion: Control programs are most needed among the students. They should be comprehensive and focused on students' psycho-education about substances and their related negative consequences, plus the promotion of students' life skills, and integration into the family – and peer-based preventive interventions.

Keywords: illicit drugs, addiction, undergraduate students, prevalence, substances

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Authors: Parthasarathi Pramanik

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Body packing is a way of transfer drugs across the international border or any drug prohibited area. The drugs are usually hidden in body packets inside the anatomical body cavities like mouth, intestines, rectum, ear, vagina etc. Cocaine is a very common drug for body packing across the world. A 48 year old male was reported dead in his hotel after complaining of chest pain and vomiting. At autopsy, there were eighty-two white cylindrical body packs in the stomach, small and large intestines. Seals of few of the packets were opened. Toxicological examination revealed presence of cocaine in the stomach, liver, kidney and hair samples. Microscopically, presence of myocardial necrosis with interstitial oedema along with hypertrophy and fibrosis of the myocardial fibre suggested heart failure due to cocaine cardio toxicity. However, focal lymphocyte infiltration and perivascular fibrosis in the myocardium also indicated chronic cocaine toxicity of the deceased. After careful autopsy examination it was considered the victim was died due congestive heart failure secondary to acute and chronic cocaine poisoning.

Keywords: cardiac failure, cocaine, body packer, sudden death

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Authors: Farzaneh Ziaee, Mohammad Ziaee

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N-acetyl-L-cysteine (NAC) is a well-known mucolytic agent, and recently its efficacy has been examined for the prevention and remediation of several diseases such as lung infections caused by Coronavirus. Also, it is administrated as the main antidote in paracetamol overdose and is effective for the treatment of idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD). This medicine is used as an antioxidant to prevent diabetic kidney disease (nephropathy). In this study, a method for the acylation of amino acids is employed to manufacture this drug in a height yield. Regarding this patented path, NAC can be made in a single batch step at ambient pressure and temperature. Moreover, this study offers a technique to make peptide bonds which is of interest for pharmaceutical and medicinal industries. The separation process was undertaken using appropriate solvents to achieve an excellent purification level. The synthesized drug was characterized via proton nuclear magnetic resonance (1H NMR), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FT-IR), elemental analysis, and melting point.

Keywords: N-acetylcysteine, synthesis, mucolytic medication, lung anti-inflammatory, COVID-19, antioxidant, pharmaceutical supplement, characterization

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Authors: Vladimir Hovhannisyan, Chen Yuan Dong

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Recently nanoparticles (NPs) have been introduced in biomedicine as effective agents for cancer-targeted drug delivery and noninvasive tissue imaging. The most important requirements to these agents are their non-toxicity, biocompatibility and stability. In view of these criteria, the zeolite (ZL) nanoparticles (NPs) may be considered as perfect candidates for biomedical applications. ZLs are crystalline aluminosilicates consisting of oxygen-sharing SiO4 and AlO4 tetrahedral groups united by common vertices in three-dimensional framework and containing pores with diameters from 0.3 to 1.2 nm. Generally, the behavior and physical properties of ZLs are studied by SEM, X-ray spectroscopy, and AFM, whereas optical spectroscopic and microscopic approaches are not effective enough, because of strong scattering in common ZL bulk materials and powders. The light scattering can be reduced by using of ZL NPs. ZL NPs have large external surface area, high dispersibility in both aqueous and organic solutions, high photo- and thermal stability, and exceptional ability to adsorb various molecules and atoms in their nanopores. In this report, using multiphoton microscopy and nonlinear spectroscopy, we investigate nonlinear optical properties of clinoptilolite type of ZL micro- and nanoparticles with average diameters of 2200 nm and 240 nm, correspondingly. Multiphoton imaging is achieved using a laser scanning microscope system (LSM 510 META, Zeiss, Germany) coupled to a femtosecond titanium:sapphire laser (repetition rate- 80 MHz, pulse duration-120 fs, radiation wavelength- 720-820 nm) (Tsunami, Spectra-Physics, CA). Two Zeiss, Plan-Neofluar objectives (air immersion 20×∕NA 0.5 and water immersion 40×∕NA 1.2) are used for imaging. For the detection of the nonlinear response, we use two detection channels with 380-400 nm and 435-700 nm spectral bandwidths. We demonstrate that ZL micro- and nanoparticles can produce nonlinear optical response under the near-infrared femtosecond laser excitation. The interaction of hypericine, chlorin e6 and other dyes with ZL NPs and their photodynamic activity is investigated. Particularly, multiphoton imaging shows that individual ZL NPs particles adsorb Zn-tetraporphyrin molecules, but do not adsorb fluorescein molecules. In addition, nonlinear spectral properties of ZL NPs in native biotissues are studied. Nonlinear microscopy and spectroscopy may open new perspectives in the research and application of ZL NP in biomedicine, and the results may help to introduce novel approaches into the clinical environment.

Keywords: multiphoton microscopy, nanoparticles, nonlinear optics, zeolite

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Authors: Tambe Daniel Atem

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Background: Clinical Research is an organized research on human beings intended to provide adequate information on the drug use as a therapeutic agent on its safety and efficacy. The significance of the study is to educate the global health and life science graduates in Clinical Research in depth to perform better as it involves testing drugs on human beings. Objectives: to provide an overall understanding of the scientific approach to the evaluation of new and existing medical interventions and to apply ethical and regulatory principles appropriate to any individual research. Methodology: It is based on – Primary data analysis and Secondary data analysis. Primary data analysis: means the collection of data from journals, the internet, and other online sources. Secondary data analysis: a survey was conducted with a questionnaire to interview the Clinical Research Professionals to understand the need of training to perform clinical trials globally. The questionnaire consisted details of the professionals working with the expertise. It also included the areas of clinical research which needed intense training before entering into hardcore clinical research domain. Results: The Clinical Trials market worldwide worth over USD 26 billion and the industry has employed an estimated 2,10,000 people in the US and over 70,000 in the U.K, and they form one-third of the total research and development staff. There are more than 2,50,000 vacant positions globally with salary variations in the regions for a Clinical Research Coordinator. R&D cost on new drug development is estimated at US$ 70-85 billion. The cost of doing clinical trials for a new drug is US$ 200-250 million. Due to an increase trained Clinical Research Professionals India has emerged as a global hub for clinical research. The Global Clinical Trial outsourcing opportunity in India in the pharmaceutical industry increased to more than $2 billion in 2014 due to increased outsourcing from U.S and Europe to India. Conclusion: Assessment of training need is recommended for newer Clinical Research Professionals and trial sites, especially prior the conduct of larger confirmatory clinical trials.

Keywords: clinical research, clinical trials, clinical research professionals

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Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

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