9^th Annual European Pharma Congress June 26-28, 2017 Madrid, Spain

Hicham Khodr obtained his PhD in NMR studies of ligand-Ferritin interaction. He is an expert in NMR spectroscopy and programming. He had developed an autotitration system ( Methods in Enzymology 335:190-203 • February 2001) at King’s College London Pharmacy, UK. This system enable us to studies the physico chemical properties of many compounds that of agriculture and clinical uses. Furthermore, he worked with Prof Hider group at KCL, Pharmacy in the area of synthesis and characterisation of new candidates compounds as pro drug for the treatment of -thalassemia major. Hicham’s major target is to develop new candidate compounds (bidentate and tetradentate) for preventing the oxidative damage in red blood cell haemolysis as well as for the treatment of -thalassemia major.

The development of potent metal chelators has a great benefit in medicine, agriculture and industry. Surprisingly, the clinically use of defriprone (L1) in synergism with desferal (DFO) as potents metal chelators for the treatment of iron(III) overload in thalassemic patients, has additional clinical applications such as inhibiting prostate cancer proliferation at clinically relevant doses and plasma concentrations1. Furthermore, the bidentate ligand L1 and hexadentate ligand DFO exhibit a great effect by recovering the oxyhaemoglobin from the iron-mediated oxidative damage on oxy-haemoglobin in haemolysed red blood cells after five minutes of iron addition(data not published yet). In this work, physical and chemical properties (pKas and β) values of L1 and DFO were used to theoretically show the potential of DFO over L1 in complexing iron(III). These simulations might offer an insight into which compound recovers faster the oxidative damage from oxyhaemoglobin that occurs in blood haemolysate associated with an accumulation of iron(III). This study shows that 0.5mM DFO recover 95% of the oxidative damage of oxyhaemoglobin faster than that of 0.5mM L1. This was measured by monitoring the absorbance in the visible region between 500nm and 800nm of the oxyheamoglobin with varying concentrations of iron(III) from 50µM to 250µM in 50 increment steps at physiological pH using 50mM phosphate buffer in the presence and absence of L1 and DFO. The potential medical application of these compounds would be useful to prevent oxidative damage that occurs as a result of red blood cell haemolysis with the commensurate release of oxy-haemoglobin, that contributes to acute and chronic vascular disease, inflammation, thrombosis, and renal impairment

Maria Isabel Patiño is a Microbiologist and Bioanalist from the University of Antioquia. Her experience has been focused on scientific research, and, currently, she is a member of the Tissue Engineering and Cell Therapy Group. As a PhD student, with a student loan from COLCIECIAS (scholarship Program No.727 of 2015), she has been working on the development of a non-viral transfection system of human fibroblasts and keratinocytes, incorporated in an 3D skin model in order to over-express the antimicrobial peptide hCAP 18-LL 37 as a strategy for the treatment of skin wounds.

Skin wounds caused by burns have high global incidence (1). Autologous tissue recovery in these lesions is ineffective, due to affected area low vascularization and the susceptibility of the patients to infections caused by multiresistant microorganisms, resulting in a high mortality rate. Non-viral vectors continue to be an attractive alternative to viral vectors due to their safety, ease of preparation and scale-up. These systems could represent a strategy to treat or improve skin wounds by genetically modifying own patients cells (2). In this work we have developed a system of non-viral transfection of human keratinocytes and fibroblasts, consisting in a polymer/plasmid DNA complex (polyethyleneimine/CAMP modified Lenti-IRES bicistronic vector with tRFP), known as polyplexes in order to overexpress the antimicrobial peptide hCAP 18-LL37 (3)(4), which has been shown to exhibit a broad spectrum of antimicrobial activity as well as additional defensive roles such as regulating the inflammatory response and promoting re-epthelialization and wound closure (5). By measuring the amount of free pDNA, the formation and stability of the complexes were determined. Transfection efficiency in 2D cultures was evaluated by flow cytometry. Quantification of mRNA by RT-qPCR demonstrated the expression of the CAMP gene in transfected keratinocytes and fibroblasts, this suggests that the antimicrobial peptide hCAP18 / LL-37 is being expressed at higher levels than those of the same non-transfected cells. These are promising results for the use of polyplexes in the transfection of different cell types and stimulation of a gene of interest overexpression as the CAMP gene, with important antimicrobial and angiogenic effects on cutaneous wound healing.

Abdulaziz alhedethe a fully qualified pharmacist committed professional with a genuine interest in improving patients services and customer awareness focused on compliance. Self motivated and able to take the initiative , able to give specialized services to help Patients manage conditions. Able to guide customers on the selections of medicines brands, medical equipments and health care supplies

Bacterial resistance to antibiotic is posing a global health threat as many antibiotic no longer work against urinary and skin infections. Prevalence of substandard medicine in the developing countries can lead to further development of new strain with antibiotic resistance. Sierra Leone is one of such countries where multidrug resistant Shigella dysenteries serotype and tet (x)- containing clinical isolates are already detected. A mystery shopper has visited a local market in Sierra Leone and purchased 6 different brands of Amoxicillin capsules, which has been analysed using spectroscopic methods. The sample of Amoxicillin capsules have been purchased using convenience sampling approach at an undisclosed location in Sierra Leone. The 100 mg of sample was dissolved in D2O and 100 mg of sample was dissolved in CD3OD. The dissolved sample were vortexed for 30 seconds, followed by centrifugation. The supernatants were filtered when transferred in to NMR tubes. The 1D 1H and 1H2D COSY NMR spectra were acquired using JEOL ECA 600 MHZ at 298 K and were processed JEOL Delta software. The weighing of the content of the capsules has provided initial indication that some of the purchased medicine is substandard. Furthermore, preliminary NIR measurement have suggested that there is significant variation in the sample composition between manufactures. The pilot study of the quality of medicine in developing countries has indicated that substandard medicine is freely available on the market despite efforts by governments to improve their healthcare system. The poor quality medicine can harm patients directly via lack of effort or toxicity of additional components, but it can also contribute to the spread of bacterial resistance to antibiotics.

Dina S. El-Kafrawy is graduated 2003 from faculty of pharmacy, Alexandria university. She has her expertise in development and validation of new analytical methods for the determination of various drugs in their pure form and different dosage forms, also development of stability indicating analytical methods for many drugs and their simultaneous determination with their degradation products and related substances. She has got her master in pharmaceutical sciences 2007 and her PhD 2012.

This study deals with the development and validation of a comprehensive stability-indicating high performance liquid chromatography with diode array detection (HPLC-DAD) method for simultaneous determination of sertaconazole nitrate (SN), sorbic acid (SA) and methylparaben (MP). To the best of our knowledge, no published methods could be found in the scientific literature for analysis of this ternary mixture. Effective chromatographic separation was achieved using Venusil XBP CN column (4.6 × 250 mm) with gradient elution of the mobile phase composed of mixed phosphate buffer pH 2.5 and acetonitrile. The quantification of SN was based on measuring its peak areas at 225 nm, while the quantification of MP and SA was based on measuring their peak areas at 259 nm. SA, MP and SN peaks eluted at retention times of 4.76, 6.77 and 11.28 min, respectively. Analytical performance of the proposed HPLC procedure was thoroughly validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity ranges for SN, MP and SA were 1–200, 1–250 and 0.5–100 μg mL−1, respectively, with correlation coefficients >0.9999. The analytes were subjected to forced-degradation conditions of neutral, acidic and alkaline hydrolysis, oxidation, photo and thermal degradation. The proposed method proved to be stability-indicating by resolution of the analytes from their forced-degradation products. Moreover, specificity of the method was verified by resolution of the analytes from more than 15 pharmaceutical compounds of various medicinal categories. The validated HPLC method was successfully applied to the analysis of the cited compounds in their combined cream dosage form. The proposed method made use of DAD as a tool for peak identity and purity confirmation

Sahar Nasser received her bachelor degree in pharmacy from Qatar University, college of pharmacy (CCAPP accredited) in 2011. She began her pharmacy career in the National Center of Cancer Care and Research (NCCCR). She is also a clinical preceptor for undergraduate pharmacy students and got promoted to senior pharmacist in 2015. She is recently completing her post graduate year 1 (PGY1) pharmacy practice residency in Hamad medical corporation (in candidate status for accreditation by ASHP). Her early-career focus was on patient centered care practice and medication safety. Throughout her career, she participated in various educational activities directed to healthcare providers, students and patients. Her main research interest is in improving cancer patients’ outcomes and cancer epidemiology.

Background: Bone-targeting agents (BTA) like Zoledronic acid (ZA) and Denosumab (DE) are approved for prevention of skeletal-related events (SREs) in patients with Bone Metastases (BM) including hypercalcemia of malignancy (HCM). Hypocalcemia has been observed with both ZA and DE. However, Studies showed a higher incidence of hypocalcemia with Denosumab. International guidelines do not favor one BTA over the other. Due to the differences in patients’ characteristics and treatment related factors; hypocalcemia incidence might differ in varying Cancer settings. The primary objective: to identify the incidence of hypercalcemia and hypocalcemia in ZA and DE groups. Secondary objective: to identify the correlation between calcium supplement and calcium level control. Methods: An observational retrospective cohort study, conducted by reviewing patients’ electronic records, laboratory and medication reports from August 1st 2015 till July 31st 2016. Adult Cancer patients diagnosed with BM secondary to a solid tumor or Multiple Myelomas and receiving either ZA or DE were included. Other indications for BTA were excluded. BTA administration visits were collected, evaluated and analyzed. Results: A total of 271 patients (1367 visits) were included in our study. Over Incidence of hypocalcemia in DE group compared to ZA was (4.1% vs 3%, OR=0.72, CI 95% [0.43 – 1.19]). Hypercalcemia was reported in both groups (3.5% vs 5.3% respectively, CI 95% [0.97 – 2.4]). Breast cancer was the most common malignancy associated with hypocalcemia (70%) followed by (10%) in both prostate cancer and Multiple myelomas. Patients received calcium supplement were 23% less likely to develop hypocalcemia (RR= 0.77, CI 95% [0.48 – 1.23]). Conclusion: Despite hypocalcemia was common in DE group, it was not statistically significant. Adequate calcium intake substantially reduces the risk of hypocalcemia. Our results highlight the importance of preventing hyper and hypocalcemia upon BTAs initiation and during treatment by regular monitoring of calcium levels, and providing calcium supplements accordingly.

Third year medical student from the Universidad Nacional Autonoma de Mexico. I’ve been part of the investigation program from the Faculty of Medicine since 2014 and I was part of the Organization Committee of the International Contest of Medical Knowledge organized in the faculty since the same year. Also, I am technician in histophatology certified by the same university.

It is now widely accepted that compensatory mechanisms are involved during the early phase of Parkinson's disease (PD) to delay the expression of motor symptoms. Our objective was to determine the effects on motor behavior in a TiO2DA implant inserted in the caudate in a hemiparkinsonism rat model and its correlation with the in vivo binding of [11-C] raclopride to D2 dopamine receptors in its basal ganglia. Each rat underwent a PET study, before and after of treatment with microimplant. Material and methods. Male Wistar rats (250-300gr) were used divided into 4 groups: Sham, Lesioned (Lx), Lx+implant and Implant. Post-lesion for 21 days anxiety behavior and locomotor activity of the rats of each group through the open field test was evaluated. The test was made in an acrylic box (with transparent walls and floor), whose floor is divided with painted black lines forming’s squares and illuminated with floodlights. The test was recorded for five minutes; the following measurement parameters were assessed: total distance traveled and the number of crossed lines marked on the floor. The tests were recorded. In each group analysis of microPET was done, each rat underwent a PET study, before and after of treatment with microimplant. The implant induced an increase in the in vivo binding of [11C] raclopride in the striatum of hemiparkinsonian rats. This observation indicates that there is a higher amount of transporters bound to striatal dopamine; higher dopamine levels were found in the Lx+Imp group than in the Lx group as well as a larger number of dopaminergic neurons in striatum in the histological analysis. This observation indicates that the microimplant with dopamine produce an increase in extracellular levels of dopamine sufficiently to inhibit raclopride binding, this effect probably due to dopamine release from TiO2DA matrix implanted in caudate nucleus.

I am a MD and a PhD in Psychological Research and I have worked in the Faculty of Medicine UNAM in Mexico for more than 30 years. I am collaborating with the Physics Institute of the National Polytechnique Institute. My research is focused on the field of Parkinson disease (PD): Study of the nigrostriatal pathway degeneration, and involved mechanism caused by rotenone and 6-OHDA; stabilization of Dopamine and its use as treatment for PD; the study of the effects produced in vivo of a TiO2 amorphous matrix as a reservoir for dopamine in a PD model in rats; description of the cognitive implications of PD in patients; toxicity and biological implications of rotenone exposure in animal models.

The aim of this study was to evaluate the effect that applies an amorphous matrix with dopamine obtained by sol-gel method produces in the caudate nucleus of induced hemiparkinsonian rats. The estimation of this matrix with dopamine effects was evaluated by behavioral, histological and neurochemical tests. Material and method. We used 64 male Wistar rats about 250-300 g aleatory divided in 4 groups of 8 each one with free access to water and food. The groups that conformed each experimental block were: Control (C), Lesioned (Lx); Lesion + implant (Lx-IMP) and Implant (Imp). The behavioral evaluation was made on day 1, 21, 90, 180 and 360 of the experimental phase. It was made an evaluation of the exploratory behavior and induced twist. We exanimated the fine motor in the reach test, number of induced twist with APO and we determinate the DA levels by HPLC in the SN and NC. The results showed differences (p<0.05) between Lx group compare with control in the test made. Also we found statistically significant differences between Lx and Lx+Imp groups with reports of improvement in the implant group. These results suggest that the dopamine was released through the nanoporos that has the matrix with dopamine walls resulting in a frank rise in the number of squares walk in the open field test for the Lx+Imp group, less number of induced rotations, better performance in the reaching task and superior dopamine levels compare with Lx group. With these results we can conclude that a matrix with dopamine implanted in the NC of hemiparkinsonian rats causes a beneficial effect that we attributed to the released dopamine in the rats with hemiparkinsonism + implant caudate nucleus.

The purpouse of this project was to determine the effects of an implant TiO2DA inserted in the caudate nucleus in a rat model hemiparkinsonism induced on motor activity and its correlation with dopamine and serotonin levels. Material and methods. Male Wistar rats (250-300 g) were used, which were randomly divided into 4 groups: a) control b) injury (Lx); c) Lx+implant (Lx+I); d) Implant (I). For 21 days post-injury motor activity was evaluated 1. The exploration behavior;the test was recorded for five minutes, and were assessed global activity time, and inactivity time; 2. The rotational behavior was recorded for fifty minutes, through count of spins; 3. For the swimming forced test, was evaluated the activity and inactivity in the fishbowl and test was recorded. In each group, determinations levels dopamine was performed, by means of HPLC. Results. The exploratory behavior in the Lx group showed a decrement significative of activity exploratory regarding control group, for the other hand, Lx+I group enhanced the activity exploratory and movements in relationship to Lx group, showing similar behavior to the control group. The I group not showed significantly difference to control group. In the rotational behavior, the control group rats showed spins to the predominant side, Lx group increased the number of spins toward contralateral injury side with respect control group, Lx + I group revealed similar activity to control group and showed significant difference to Lx group. In the swimming force test the Lx + I group, increased significantly swimming behavior in relationship to Lx group. Implant group showed hyperactivity in swimming behavior. HPLC showed an increased level of DA in Striatum vs. Lx an Control group. The results obtained in our model suggest that the TiO2DA implant in the caudate nucleus of rats induces a beneficial effect that can be attributed to the dopamine released from the TiO2DA complexes into caudate nucleus.

Professor Valverde obtained his PhD. in Physics on 2003 at Institute of Physics, UNAM. His Postdoctoral stay was made in UCLA, USA for two years. His research is focused in electrical and optical properties from amorphous and nanostructured sol-gel materials. His field of research includes photoluminescence, drug delivery, photoconductivity and hydrogen production. Prof. Valverde has been published 58 papers international journals

Statement of the Problem: Parkinson´s disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra causing dopamine depletion in the striatum. The purpose of this research was to evaluate the temporal stability of dopamine encapsulated in a titanium dioxide (TiO2) matrix synthesized by sol-gel method under atmospheric conditions. The formation of the oxidation products from dopamine were analyzed by colour change of the microimplant, optical absorption and infrared spectroscopy. The evaluation in vivo on the locomotor activity in the open field test of hemiparkinson rat model was studied. Material y Methods: a) TiO2 precursor solution. A mixture of Tetrabutyl orthotitanate and diethanolamine which prevent the precipitation of oxides and stabilize the solutions was obtained with deionized water. Tetraethyleneglycol was added to the above solution under stirring. b) TiO2/DA solution. To 20 ml of TiO2 solution prepared in section (a), the Dopamine was added and the sol was stirred at room temperature under darkness. The states of dopamine oxidation were evaluated using infrared spectroscopy. Forty Winstar rats were divided into 4 groups: Sham, Lx (hemiparkinsonian), Lx + TiO2/DA matrix, and TiO2/DA matrix only. Induced rotation test and locomotor activity task were performed on days 0, 1, 21, 90 days after the insertion of the TiO2/DA in the caudate nucleus. Findings: Results show that the TiO2 matrix can protect the dopamine inhibiting its chemical instability and retarding its oxidation gradually. Less induced rotations and better performance in the locomotor activity during the 90 days of the experimental evaluation suggest that probably dopamine successfully stabilized and it was released from its reservoir in the striatum. Conclusion: Advantages of this treatment are its easy and fast elaboration, low cost and immediate benefits on the motor disturbances presented by the animals with hemiparkinsonismo.

Dr. Eman I. El-Kimary an Associate Professor of Pharmaceutical Analytical Chemistry and Quality Control at the Faculty of Pharmacy, Alexandria University, Egypt. Received BSc in Pharmacy in 2003, Master degree in Pharmaceutical Analysis in 2007 and PhD in Pharmaceutical Analysis in 2011 from Faculty of Pharmacy, Alexandria University. Currently teaching general and physical chemistry, analytical chemistry, instrumental analysis and pharmaceutical quality control to pharmacy students in Alexandria University. Having the practical experience in working with devices such as: High Performance Liquid Chromatography, Polarograph, Spectrofluorimeter, Spectrophotometer, High Performance Thin Layer Chromatography, FT-IR Spectrophotometer, Capillary electrophoresis. Attended about 22 scientific and professional workshops and training courses. Published about 18 research papers in peer reviewed scientific journals and about 8 abstracts in national and international conferences. Served as a reviewer for more than 5 journals specialized in analytical chemistry and its applications

Statement of the Problem: Large number of β-blockers’ marketed formulations contain racemic mixtures except for levobunolol and betaxolol. As the two enantiomers have different stereoselective mechanisms, they should be considered as different drugs. Taking into consideration the numerous side effects of these drugs and that the only pharmacologically active enantiomer is the levo one whereas the detxtro enantiomer is inactive or harmful in some cases, there is no doubt that reliable and rapid methods should be developed for monitoring the stereoselective synthesis or checking enantiometric purity. Methodology: The present work involves economic novel procedure for separation of the two (+) and (-) enantiomers of the drugs sotalol, carvedilol and betaxolol using β-cyclodextrin as chiral mobile phase additive. Chromatographic separation was performed on Fluka HPTLC silica gel plates 60 F254 (20 × 10 cm). The mobile phase used consists of acetonitrile-methanol-acetic acid-water (4:3:0.2:1 v/v) and containing 0.3 mM β-cyclodextrin. Detection of the spots was performed using iodine vapor or densitometrically at 245 nm for carvedilol or at 220 nm for both betaxolol and sotalol. Findings: Using the proposed method, linear calibration graphs were obtained for (-) and (+) enantiomers of betaxolol in the ranges 0.5-6.0 and 0.4-6.0 μg/band, respectively (r ˃ 0.998, n = 6) with good accuracy and precision (%Er and %RSD < 2.0%). Limits of detection of for (-) and (+) enantiomers were 0.15 and 0.13 µg/band, respectively. The sensitivity for the detection of sotalol and carvedilol racemates was 0.3 and 0.2 µg/band, respectively. Conclusion & Significance: The proposed method is selective and simple for separation of the enantiomers of carvedilol and sotalol and quantitation of both (-) and (+) betaxolol enantiomers in the bulk and in pharmaceutical preparation.

Burak Çelik graduated from Faculty of Pharmacy at Yeditepe University and completed his PhD at the age of 27 from Istanbul University, Department of Pharmaceutical Technology. He is currently working in Bezmialem Vakıf University, Faculty of Pharmacy as a research assistant.

Piribedil is a piperazin derivative drug used in the treatment of Parkinson’s disease. Orally administrated piribedil has low bioavailability (10%) accompanied with gastrointestinal and cognitive side effects. Buccal tablets are thin and flat tablets with 5-8 mm diameter which are applied to the oral mucosa in the mouth cavity. This route of administration increases bioavailability of drugs by eliminating the hepatic first pass effect and reduces side effect risks with controlled release by lowering the required dosage. In this study, buccal tablets were prepared by using three different polymers; carbopol (CP), hydroxypropyl methylcellulose (HPMC) and carboxymethyl cellulose (CMC) at three different concentrations to achieve controlled release. Physicochemical properties of powder and tablet formulations were investigated and dissolution studies were conducted. These tablets were also subjected to stability studies for 6 months at 40 ± 2 oC and 75% ± 5 relative humidity. Physical characterization results were satisfactory and met compendial limits for all formulations. Slowest drug release was observed with CP followed by HPMC and CMC respectively. Drug release kinetics displayed diffusion-polymer relaxation for CP and HPMC and diffusion-tablet erosion for CMC tablets. Piribedil was found to be compatible with other tablet ingredients and tablets retained physical properties after 6 months of stability studies. Buccal tablets containing piribedil designed for the first time may serve as a new alternative for the Parkinson’s disease treatment.

Ji Sook Han is a professor and is doing research on developing a bioactive compound from natural plants, especially seaweeds, and investigating its effect for the prevention and treatment of obesity and type 2 diabetes. The active compound containing in seaweeds may be a good anti-diabetic source by improving insulin secretary defect or insulin resistance. It may also be a potential anti-obesity source owing to its inhibitory effect on adipogenesis. She evaluates the effect and mechanism of a bioactive compound isolated from natural plant through in vitro and in vivo study.

Background: Adipocyte lipid accumulation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. Thus, this study investigated the anti-adipogenic effects of pheophorbide A isolated from Gelidium amansii in 3T3-L1 adipocytes. Methods: Upon differentiation of 3T3-L1 pre-adipocytes into adipocytes, they were treated with pheophorbide A (0–83 μM). Results: Pheophorbide A inhibited triglyceride accumulation and stimulated glycerol release in a dose-dependent manner in 3T3-L1 adipocytes. In addition, pheophorbide A significantly decreased leptin levels in 3T3-L1 adipocytes. Pheophorbide A inhibited adipogenesis via suppression of the expression of adipogenic transcriptional factors including peroxisome proliferator-activated receptor γ (PPARγ), CCATT/enhancer binding protein α (C/EBPα), sterol regulatory element binding protein 1c (SREBP1c), and fatty acid synthase (FAS). It also induced the expression of phosphorylation of AMP-activated protein kinase (AMPK). Conclusion: Pheophorbide A isolated from Gelidium amansii inhibit adipogenesis by down-regulating adipogenic transcription factors in 3T3-L1 adipocytes. These results suggest that pheophorbide A may be useful for the prevention or treatment of obesity owing to its inhibitory effect on adipogenesis.

Katerina O. Filatova has completed her master study in 2009 from VNMU Pyrogov b.n., Pharmaceutical Faculty. Currently she is studying doctoral program at the Technological Faculty at the TBU in Zlin, Czech Republic.

Conventional development in an understanding of the reasons of diseases with a deepening of knowledge in pharmacokinetic mechanisms allows to develop modern dosage forms for the effective, safe and reliable application of bioactive compounds at the targeted site of action within a desirable time and duration. Unfortunately, current excipients cannot meet all the requirements to the modern pharmaceutical formulations and mostly play a role of fillers. However, an active ingredient is just one part of the medicine administered to the patient and it is the formulation of the drug and an excipient that translates drug properties into clinical effect. It is shown that dosage forms engineered using the nano- and submicro-scaled excipients have an additional functionality and can control a pharmacological effect of a drug. Nanomaterials as active excipients not only improve pharmacokinetic of cargo molecules but also increase their solubility and permeability, which is of great importance because just nearly 25% of all pharmaceutically active compounds are recognized as highly soluble and permeable, while the rest of them has either/or low solubility and permeability or even both of them simultaneously with other disadvantages (very short or very long shelf-life, poor adsorption through GIT). In the sight of aforementioned a concept of therapeutic treatment is realized in a development of silica-based nanomaterials that maintain drug concentration in GIT at a desired value as long as possible, i.e. they are able to exert a control on the drug release rate and duration, for further pharmaceutical implementation as an active excipient in solid dosage forms. Silica-based submicro- and nanoparticles were prepared using a template sol-gel approach in the presence of cationic and nonionic surfactants. Methotrexate was loaded into silica-based mesoporous materials with different textural properties. An amount of the drug loaded and an in vitro release kinetics were revealed as a function of the pore size of the materials. A release of methotrexate from synthesized carriers in comparison with the release from the commercially available pharmaceutical form mimicking an oral administration were investigated. It was turned out that silica-based materials exhibit control release kinetic with the absence of a burst effect, while the later one is considerably worst in an adjustment of controllable in-vitro pharmacokinetic of a drug. Mesoporous materials with a wide range of size (25-1000 nm) and variable textural characteristics were obtained that allowed to adapt different synthetic routs for further use as the perspective reservoirs for carrying in pharmaceutical means. Further development of the pharmaceutical forms on the basis of silica-based nano- and submicro-materials will ensure that a drug will be available at the desired site within the required time and duration. Those materials can serve as substituents of current fillers in pharmaceutical formulations.

Valentin Karabelyov has completed his secondary education in 2013 from National High School of Maths and Science. Now he is studing in the Medical University of Sofia, Faculty of Pharmacy and he is a fourth year student of Faculty of Pharmacy. He works as an assistant in a pharmacy from 3 years ago. He is interested in the fields of LC-MS, Organic synthesis, Pharmacognosy, Pharmacology and Pharmacotherapy. Last year, Valentin participated in the European Chemistry Congress, where he presented a poster on the theme ,, Anticonvulsant activity of newly synthesized benzoylhydrazones with 2H-chromene and coumarin moieties in ICR mice.”

A series of coumarin-linked hydrazide–hydrazones 4a-e and 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-ones 5b-g were synthesized via an efficient one-pot protocol. All compounds demonstrated significant minimum inhibitory concentrations (MIC) ranging from 0.28 to 1.69 μM against reference M. tuberculosis H37Rv strain. The cytotoxicity against the human embryonic kidney cell line HEK-293 was also evaluated and the selectivity of the antiproliferative effects was thus assessed. All compounds displayed good SI values ranging from 33 to more than 645. In general, 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives 5b-g possessed potent antimycobacterial activity combined with low cytotoxicity what resulted into SI values higher than that of their open chain analogues 4a-e. The activity of the tested compounds may be attributed to the significant interactions with the inhibitor binding cavity of M. tuberculosis Enoyl-ACP reductase and\or related to ability of the tested compounds to penetrate mycobacterial cells. The above observations show that the novel hydrazide–hydrazones 4a-e and 2-aroyl-[1]benzopyrano[4,3-c]pyrazol-4(1H)-one derivatives 5b-g have potential as antimycobacterial agents. The results of the study can be utilized to further optimize and improve the potency and selectivity toward ENR enzyme by varying the basic skeleton and the substituents.