17^th Annual Congress on Pharmaceutics & Drug Delivery Systems September 20-22, 2018 Prague, Czech Republic | Panorama Hotel Prague | Milevská 7, 140 63 Praha

Biography:

Youhoon Chong has completed his PhD at the age of 33 years from University of Georgia and postdoctoral studies from The Scripps Research Institute. He is the chairman of the department of integrative bioscience & biotechnology, Konkuk University. He has published more than 140 papers in reputed journals.    

Abstract:

(-)-Epigallocatechin-3-gallate (EGCG) is known as a mitochondria-targeted molecule that can prevent mitochondrial deterioration and induce mitochondrial biogenesis by modulating key regulators of mitochondrial metabolism. In this study, we tackled whether derivatization of EGCG could result in enhancement of its effects on mitochondrial biogenesis. EGCG, EGCG peracetate (AcEGCG), and its 4″-O-alkyl substituted congeners prepared by previously reported procedures were biologically evaluated. Interestingly, EGCG and AcEGCG were only marginally effective in inducing mitochondrial biogenesis, while AcEGCG congeners with an alkyl group at the 4″-O position showed significantly increased biological activity compared to their parent compound. Among these series, compound 3f with a methyl-branched carbonate chain at the 4″-O position of the AcEGCG scaffold showed the most enhancement in inducing mitochondrial biogenesis. Hepa1-6 cells treated with 3f exhibited increases in both mitochondrial mass (1.5 times) and relative mtDNA content to nDNA (1.5 times). As a mitochondrial biogenesis enhancer, 3f also increased expression levels of regulators for mitochondrial function, including PGC-1α (4.0 fold), p-AMPK (2.5 fold), SIRT1 (4.2 fold), ERRα (1.8 fold), NRF-1 (1.6 fold), NRF-2 (1.7 fold), and mtTFA (2.0 folds). Investigation of oxidative phosphorylation by mitochondria in the presence of 3f revealed that 3f increased NAD⁺/NADH ratio, the amount of cytochrome c, ATP synthesis, and oxygen consumption in Hepa1-6 cells by 2.2, 1.4, 1.5, and 2.1 folds, respectively. Taken together, these results warrant extensive structure-activity relationship study for EGCG derivatives to develop novel mitochondrial biogenesis enhancers.

Biography:

Flavia Laffleur, is an assistant prfoessorand a senior researcher of Drug Delivery in the Department of Pharmacy at LFU Innsbruck, Austria. Flavia Laffleur published over 68 publications and gave oral presentations on several international conferences. From 2010 until 2013 she completed her doctoral thesis focused on smart drug delivery systems. Since 2013, she is a senior researcher at the Department of Pharmaceutical Technology in Innsbruck. Since 2017, Dr. Flavia Laffleur is a researcher at the MIT, in Boston, Massachusetts. She received several awards, including LesmüllerStiftung award and the Galenus Foundation Technology Award. Currently Dr. Laffleur´s research focusses on mucosal drug delivery as well as smart delivery systems to overcome biological barriers 

Abstract:

Predominantly, the majority of fungal infections (dermal and nail) are caused by dermatophytes, such as Trichophyton rubrum known as one of the most prominent . Among fungal infections, nail infections or onychomycosis exhibit the most difficulties and limitations in their treatment. Onychomycosis affects around 5-10% of the population in the world. Onychomycosis is a common infection of the nail caused by dermatophyte affecting mostly toenails in adults being associated with limited treatment options. In this study novel dosage forms were prepared and evaluated for their suitability in treatment of onychomycosis. Films were prepared comprising polymeric excipients such as chitosan, (hydroxypropyl)methyl cellulose, hydroxyethyl-cellulose, carboxymethylcellulose according to solvent evaporation method. Developed formulations were evaluated in terms of physical appearance, stability and adhesiveness. Furthermore skin and nail irritation studies were conducted. Five potential formulations (F1-F5) were designed while F1 and F4 exhibited the most promising results in terms of stability with 26 min and 40.67 min, respectively, and suitability in nail application. F1 as the most favorable dosage form revealed with 2.9438 kg/m/s in terms of adhesive force the most adhesive properties in contrast to the other preparations. All formulations were found to be non-skin irritating and safe to use. Taken together, these findings suggest novel designed films containing polymeric excipients as a fruitful platform for the treatment in onychomycosis. 

Biography:

HF is the director of Department of Plastic and Reconstructive Surgery, Hamamatsu University School of Medicine. He published some articles on drug delivery in the following journals.

1. Development of three-microneedle device for hypodermic drug delivery and clinical application.      Plast Reconstr Surg, 2012.

2. Application of a three-microneedle device for the delivery of local anesthetics. Patient Preference and Adherence, 2015.

Abstract:

Background: We have developed a new device with multiple fine needles fabricated with a bevel angle to release a drug broadly and homogeneously into the skin in a horizontal fashion and reported in the article. It led us to develop another type of multiple needles to release a drug in the epidermis or upper dermis.  The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity.

Methods: We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and developed a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses.

Results: The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge-shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination.

Conclusions: The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy.

Biography:

Yukihiro Akao has completed his PhD, United Graduate School of Drug Discovery and Medical Information Sciences

Abstract:

Despite considerable research on K-Ras inhibitors, none had been developed until now. We synthesized nuclease-resistant synthetic miR-143 (miR-143#12), which strongly silenced K-Ras, its effector signal molecules AKT and ERKs, and the K-Ras activator Sos1. We examined the anti-proliferative effect of miR-143#12 and the mechanism in human colon cancer DLD-1 cell (G13D) and other cell types harboring K-Ras mutations. Cell growth was markedly suppressed in a concentration-dependent manner by miR-143#12 (IC₅₀: 1.32 nM) with a decreased in the K-Ras mRNA level. Interestingly, this mRNA level was also down-regulated by either a PI3K/AKT or MEK inhibitor, which finding indicates a positive circuit of K-Ras mRNA expression. MiR-143#12 silenced cytoplasmic K-Ras mRNA expression and impaired the positive circuit by directly targeting AKT and ERK mRNAs. Combination treatment with miR-143#12 and a low-dose EGFR inhibitor induced a synergistic inhibition of growth with a marked inactivation of both PI3K/AKT and MAPK/ERK signaling pathways. However, silencing K-Ras by siR-KRas instead of miR-143#12 did not induce this synergism by the combined treatment with the EGFR inhibitor. Thus, miR-143#12 perturbed the K-Ras expression system and K-Ras activation by silencing SOS1 and resultantly, recovered the efficacy of the EGFR inhibitors. In vivo results also supported those of the in vitro experiments. The extremely potent miR-143#12 enabled us to well understand K-Ras networks and shut them down by combination treatment with this miRNA and EGFR inhibitor in K-Ras-driven colon cancer cells

Biography:

Hiba Natsheh is currently a PhD candidate under the supervision of Prof. Elka Touitou at the Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem. Prof. Touitou (elka.touitou@mail.huji.ac.il) is well recognized for her novel approaches for enhanced transmucosal drug delivery.

Abstract:

The nasal route for drug administration can be considered a safe, convenient and noninvasive alternative to the conventional oral and parenteral routes. However, by using classic carriers, the delivery to brain of hydrophilic molecules, peptides and proteins is poor. We have designed and investigated a new nasal carrier for enhanced drug delivery to brain, we call Phospholipid Magnesome. The system contains soft phospholipid vesicles, composed of phospholipid, water, propylene glycol and magnesium salt.  In addition, the carrier contains the mucoadhesive polymer, alginate. Electron microscopy, calorimetry and dynamic light scattering measurements show that the system is composed of soft multilamellar nanosized vesicles. The ability of the carrier's vesicles to entrap both lipophilic and hydrophilic molecules is evidenced by CLSM and ultracentrifugation studies. The mucoadhesivity test results of the Phospholipid Magnesome carrier following in vitro application on porcine nasal mucosa, indicate a prolonged contact time of the drug with the nasal membrane as compared to control. Effective delivery of various molecules to brain, Rohdamine 6G (R6G), Insulin and Epidermal Growth Factor (EGF) was demonstrated by two methods, Multiphoton Microscopy and Near Infrared (NIR) imaging. Moreover, results of a pharmacodynamic study measuring the antinociceptive effect of Oxytocin administrated nasally to an animal model indicate the efficiency of the Phospholipid Magnesome as compared to three control compositions. In an additional study in animals, nasal administration of Insulin, resulted in a strong and prolonged hypoglycemic effect for the drug incorporated in the new carrier but not for control systems. Histopathological analysis of nasal mucosa following sub-chronic administration indicates the local safety of the system.

In conclusion, the results of this investigation suggest that Phospholipid Magnesome nasal carrier is able to improve drug effect, probably by a combined mechanism, absorption enhancement and prolongation of mucosal contact

Biography:

Abstract:

Objective: The most important objective of this presentation is to attract attention that sometimes the prescription of drugs become abusive and the phenomenon is really very difficult to be controlled. 

Material and methods: The idea of this presentation appeared after many clinical observations from my medical practice, regarding a new phenomenon. The intention of the patients is to consult many doctors, from different specialties in a short period of time, for diverse health issues and because every physician prescribe his therapeutic scheme, in the end the patient accumulate many therapeutic schemes in same time and in conclusion a lot of drugs, many unnecessary. Interactions between these accumulations of drugs from different classes are indeed very difficult to monitor and quantify. The truth is that many unnecessary drugs appear in complexes therapeutic scheme, most of them difficult to can be stopped sudden. Often the patients came with severe allergic reactions, which after investigations remain of unknown etiology and in reality the interactions between different classes of medications represent the real cause of allergy.

Results and discussions: Because the patients consults many physicians in a short period of time, abusive therapeutics schemes appear in the medical practice and the phenomenon is really difficult to be controlled. More than that, sometimes the patient administers from his own initiative other drugs and don’t recognize and complicate more the situation.

Conclusion: The most important conclusion of this presentation is that the side effects between different classes of drugs represent a reality and the abusive therapeutic schemes with many unnecessary drugs must to be stopped.

Biography:

Hazal Ezgi Gültekin graduated from Gazi University Faculty of Pharmacy, at the age of 23. She is doing her PhD in the Department of Pharmaceutical Technology of Gazi University since 2014. Her area of interests are 3D printing, fused deposition modeling and hot melt extrusion. She has studies on the development of dosage forms by FDM 3DP technology. She participated various scientific conferences and meetings with her studies.

Abstract:

3D printing (3DP) is a layer-by-layer production process which is used to manufacture 3D objects utilizing computer aided design data. In pharmaceutical area, fabrication of personalized dosage forms is one of the important advantages of this technology. Fused deposition modeling (FDM) is a widely used 3DP technology. In FDM, an extruded polymer filament passes through a heated nozzle and after moltening it deposits onto a build plate to create a hard object. Pramipexole is a commonly used drug for the symptomatic treatment of Parkinson’s disease.The aim of this study was to prepare pramipexole loaded 3DP tablets.

    Firstly, drug loaded polymer filaments were prepared by hot melt extrusion (Filabot Filament Extruder). After that, by using these filaments 3DP tablets were printed via 3D printer (MakerBot^® Replicator_ 2X Experimental 3D Printer). In the present study, scanning electron microscope (SEM) images of the filaments and the 3DP tablets were taken, the physico-pharmaceutical properties (weight uniformity, dimensions and friability) of the 3DP tablets were evaluated and in vitro dissolution profiles of commercial tablets and 3DP tablets were compared.

    In conclusion, drug loaded 3DP tablets were successfully fabricated by FDM. This study demonstrates that fused deposition modeling 3D printing is an effective technology for the development of personalized dosage forms on the treatment of diseases.

Biography:

Gamze Rüzgar Özemre graduated from Ankara University in 2012. She is studying for her doctoral studies at Gazi University School of Pharmacy Department of Pharmaceutical Technology. Her areas of interest are nanotechnology and drug delivery systems. She has studies and poster presentations on these topics

Abstract:

Heparin and it’s derivates, as an anti-coagulant, are considered the drug of choice in  the treatment of deep vein thrombosis (DVT) and pulmonary embolism. Due to high molecular weight and high negative charge density, oral bioavailability of heparin is limited and insufficient to provide the desired clinical therapeutic effects.

The electrospinning technique, a straightforward procedure applied in the production of nanomaterials, requires a basic experimental setup composed by a high voltage source which provides high electrical field between the dip of a needle and a grounded target at few centimeters from ejection of charged jet.Electrospun nanofibers show great promise for developing many types of novel drug delivery systems (DDS) due to their special characteristics and the simple but useful and effective top-down fabricating process.

The aim of this study is the development and evaluation of efficacy of nanofibers to increase the oral bioavailability of low molecular weight heparin. Core-shell nanofibers were prepared using the co-axial electrospinning (NE- 300 Laboratory Scale Electrospinning Unit, Inovenso LTD, Turkey). Therefore low molecular weight heparin which is in the core of nanofibers were protected from degradation and absorbed through the intestine by using different cationic polymers which are insoluble in acidic pH in the shell of nanofibers.

Biography:

Emel Mataracı Kara has completed her PhD at the age of 30 years from Istanbul University and postdoctoral studies from Istanbul University Faculty of Pharmacy. She has published more than 15 papers in reputed journals.

Abstract:

Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as host's immune defense mechanisms. Because of the rising in multidrug resistance from infectious agents, there is a prompted interest for the development of new antimicrobial agents and new therapeutic strategies to combat the infections caused by the resistant bacterial biofilm infections.

Antimicrobial cationic peptides (AMPs) have attracted attention as alternative antibiotics due to their prospective potency, rapid action, and borad sprectrum of activities against Gram negative and positive bacteria viruses, fungi and parasites. AMPs can be found as major component of the innate immun systems of most living organisms, including insects, plants, microorganisms, and mammals, to protect against environmental microorganisms. In addition, they exhibit multiple mechanisms of action and, consequently, a low potential to induce the resistance, which allows the limited use of other antibiotics.

Therefore we investigated the in vitro pharmacokinetic activities of antimicrobial cationic peptides (indolicidin and nisin) alone or in combination with antibiotics (daptomycin, linezolid, teicoplanin, ciprofloxacin) against MRSA biofilms. With checkerboard technique, synergistic interactions against MRSA biofilms were frequent with almost all antibiotic-AMP combinations. The time kill curve studies demonstrated that synergistic interaction occured most frequently when using nisin+daptomycin/ciprofloxacin, indolicidin+teicoplanin. No antagonism was observed.

Consequently, use of a combination of antimicrobial agents can provide a synergistic effect and may help prevent or delay the emergence of resistance. AMPs seem to be good candidates for further investigations in the treatment of MRSA biofilms, alone or in combination with antibiotics.

Biography:

He is the professor at Al-Azhar University

Abstract:

Bifidobacterium represent one of the major genera of the intestinal tract of human and animals used as probiotics in dairy and nondairy foods for restore the intestinal microflora which confers a health benefit. The identification of Bifidobacterium by phenotypic features is commonly unreliable, time, money, and effort consuming. We sought to improve the Bifidobacterium identification method based on molecular level to identify probiotic bacteria in complex microbial communities. The application of 16S-23S rRNA oligonucleotide primers is the best and most reliable, rapid, and precise species and sub species identification approach. The ribosomal intergenic spacer region (ISR) located between the highly conserved 16S rRNA and 23S rRNA shows a high degree of variation in length and sequence and potential for intra species discrimination and providing the phylogenetic Relationship of the Genus Bifidobacterium spp. Results showed that one of the two primer sets Bflac2-Bflac5 species specific gives positive results differentiating between B. animalis ssp. Lactis isolated from breast fed infants milk of human and that isolated from feces of breast fed infant and detecting reference strain for B. animalis ssp. Lactis DSM10140. DNA sequences of the two strains were submitted to the Genbank NCBI under accession number (KT758845) named as B. animalis ssp. Lactis Egm1 (Egyptian milk) and accession number (KT758846) named as Egf1 Egyptian feces while the second primer give false positive result. Also, we aim to obtain patent protection under Intellectual property rights (IPRs) for B. animalis ssp.Lactis which was isolated from Egyptian resources to be used for a better and healthier food and dairy products

Biography:

Dr Nicolaes has completed his PhD at the age of 28 years from the Maastricht University and postdoctoral studies from Lund University (Sweden). He is a unit leader in the department of Biochemistry at the Cardiovascular Research Institute Maastricht, has an appointment at the Academic Medical Centre Amsterdam and is CSO for Matisse Pharmaceuticals BV, a start-up university spin-off. He has published more than 80 peer-reviewed papers in the fields of coagulation, atherosclerosis, inflammation and drug design.

Abstract:

Chronic inflammation of the arterial wall, as occurs in atherosclerosis, may lead to stroke or myocardial infarction. One of the interactions that are known to drive this inflammatory reaction in atherosclerosis is that between CD40 protein and its ligand CD40L. For CD40 to elicit intracellular signalling, it needs to recruit adaptor proteins called tumour necrosis factor receptor-associated factors (TRAFs). Interactions of CD40 with TRAF6 but not those with  TRAF2/3/5 are critically involved in atherosclerosis progression and plaque stabilization; which makes theCD40-TRAF6 interaction a downstream target for potential inhibition of inflammatory processes in atherosclerosis.

We have used a hierarchical protocol of structure-based virtual ligand screening (SBVLS) to discover small drug-like inhibitors of the CD40-TRAF6 interaction and combined in silico researches with in vitro cell-based assays and biophysical methods. Top hit molecules were administered to Apoe-/- mice models of initial and of established atherosclerosis. In both models hit molecules, named TRAF-STOPs reduced total plaque area and changed the plaque phenotype to a more stable phenotype. Intravital microscopy showed a reduction in leukocyte recruitment. We furthermore used rHDL nanoparticles loaded with one of the compounds to specifically target TRAF STOPs to macrophages, resulting in clear attenuation of atherosclerosis.

The compounds inhibited CD40-TRAF6 interaction by direct binding to TRAF6 C-domain and reduced progression of atherosclerosis by inhibition of chemokine-mediated leukocyte influx into the arterial wall, while the molecules did not impair classical immune pathways of CD40. Our results indicate possibilities of long-term therapeutic inhibition of CD40-TRAF6 interactions in atherosclerosis and possibly other inflammatory diseases.

Biography:

Gleb N. Zyuz`kov is a Scientist Secretary of Institute, Head of the laboratory of pathology and experimental therapy  (Goldberg Research Institute of Pharmacology and Regenerative Medicine), Tomsk National Research Medical Center. Ph.D (2003),  Doctor of Medicine (2006), Professor of Russian Academy of Sciences (2016). Author of 56 patents. International Award of Elsevier`s "SciVal/Scopus Award Russia» (2012). Dr. Zyuz′kov G.N. is: auditor of the Tomsk branch of «National society for regenerative medicine» (Russia), a member of «Russian scientific society of Pharmacology» and «Tomsk Professors Society».

Abstract:

Advances in the field of cellular technologies have led to the possibility of developing a new direction of targeted therapy in regenerative medicine - "Strategy of Pharmacological Regulation of Intracellular Signal Transduction in Regenerator-competent Cells". The role of NF-кB, IKK, PKC, PKB, PI3K, ERK ½, p38, adenylate cyclase, PKA, JAKs, STAT3, JNK, p53 in the realization of functioning progenitor elements of different classes and cells of tissue microenvironment was studied in vitro by means of cultural, immunological and other methods. On the models of posthypoxic encephalopathy, skin wound and cytostatic myelosuppression in experimental animals the therapeutic effects and mechanisms of action of modifiers of signal molecules activity were studied. The specificity of the involvement of a number of signaling molecules in the regulation of cell cycle and development of progenitor cells of various classes, as well as in the production of humoral factors by microenvironment cells was revealed. The neuroregenerative effects of JNK inhibitors associated with activation of neural stem cells of brain were shown on the model of encephalopathy. An algorithm and approaches for estimating the potential efficiency and many-sided selectivity of the modifiers of signaling molecules activity as targeted hemostimulators were developed. The effectiveness of various targeted pharmacological agents determined by the selective effect on different types of regenerative-competent cells was demonstrated on the models of cytostatic myelosuppression of various genesis. The perspective of using intracellular signaling molecules in regenerative-competent cells as targets of drugs for regenerative medicine was shown..

Biography:

Radostina Alexandrova Graduated with honors in Biochemistry and Microbiology, Sofia University “St. Kl. Ohridski” (SU); MSc and PhD in Virology, lecturer in SU and PhD School of BAS; > 160  publications, > 550 abstracts, 3 Book chapters;  Postdoctoral training in Slovakia, Hungary, Denmark; Leading researcher in 5 national and 10 bilateral projects; MC Member of  five COST Actions; Member of Union of Scientists in Bulgaria, Bulgarian Society of Anatomy, Secretary-Treasurer of the Immunological Society; Member of the Organizing/Scientific Committees of 45 scientific forums; Editor/Member of editorial boards of 2 national and 4 international journals; Editor of the proceeding books of two Workshops.

Abstract:

The aim of our study was to evaluate the cytotoxic activity of the following compounds: six complexes of Zn(II)/Au(I) and Zn(II)/Ag(I) with Salen, Salampy and Salampy and  eight complexes of Cu(II) and Co(II) with Schiff bases derived by a condensation reaction of  Ð¾-Vanillin with S-Tyrosine, L-Threonine, DL-Tryptophan or L-Serine.

            As model systems were used six permanent cell lines: MCF-7 and MDA-MB-231 (human breast cancer); HeLa (human cervical carcinoma); LACC-SF-Mc29 (chicken hepatoma); LSR-SF-SR (rat sarcoma) and Lep-3 (non-tumor human embryonic fibroblastoid cells).

The investigations were performed by MTT test, neutral red uptake cytotoxicity assay, crystal violet staining, double staining with propidium iodide and acridine orange, Comet assay, Annexin V – FITC test (in short-term experiments, 3-72h, with monolayer cultures) and colony-forming method (in long-term experiments, 30-40 days, with 3D cell colonies). The  compounds were examined in ROS generating systems, DPPH test was also performed.

Our results indicate that the complexes investigated decrease viability and proliferation of the treated cells in a time- and concentration-dependent manner. The most pronounced cytotoxic agents are Zn(II)/Au(I) complexes with Salen, Salampy and Saldmen (active in the concentration range 0.05 - 5 µg/ml), followed by Zn(II)/Ag(I) complexes of the same ligands (active in the concentration range 1-20 µg/ml). The CC₅₀ of Zn(II)/Au(I) and Zn(II)/Ag(I) complexes are lower than those of cisplatin. Cu(II) complexes are effective applied at concentrations of 10-200 µg/ml. Co(II) complexes show the lowest rate of cytotoxicity (active in a concentration range 50 - 400 µg/ml).   Cu(II) and Co(II)   complexes do not express antioxidant activity.

Biography:

Khedr Naglaa has completed his PhD at the age of 25 years from Andhra University and postdoctoral studies from Stanford University School of Medicine. He is the director of a premier Bio-Soft service organization. He has published more than 25 papers in reputed journals and has been serving as an editorial board member of repute. (Up to 100 words)     
 

Abstract:

Acute pancreatitis (AP) is a common inflammatory disease mediated by damage in acinar cells and subsequent pancreatic inflammation with infiltration of leukocytes. The pancreatic renin-angiotensin system may play an important role in the pathogenesis of AP. The present study aimed to investigate the possible role of captopril (CAP), an angiotensin-converting enzyme inhibitor, in attenuating L-arginine-induced AP in a rat model and to elucidate the underlying molecular mechanisms. Forty-eight adult male Wister rats were divided into 4 equal groups: control group (rats received vehicle orally for 10 days), AP group (3 g/kg L-arginine, single i.p.) on 10^th day of the experiment, CAP group (50 mg/kg captopril, orally, once daily) and MP group (30 mg/kg methylprednisolone, orally, once daily). CAP and MP were administered for 10 days prior to L-arginine injection. Then rats were sacrificed 24 h after L-arginine injection. Inflammatory biomarkers; pancreatic tumor necrosis factor-alpha (TNF-α) concentration, myeloperoxidase (MPO) activity and inducible nitric oxide synthase (iNOS) gene expression were determined. Oxidative stress biomarkers; nitric oxide (NO) and reduced glutathione (GSH) concentrations were assayed. In addition, serum α-amylase and lipase activities were measured and histopathological studies of the pancreas were done. CAP treatment significantly reduced TNF-α, MPO activity, NO and downregulated iNOS gene expression compared to AP group. CAP treatment significantly increaseed pancreatic GSH and ameliorated the histological changes of AP. Captopril treatment may have a protective role in AP rat model which is comparable to MP treatment.

Biography:

Rabindra Nath Das he is a professor at  The University of Burdwan, India.

Abstract:

Objectives: The report presents the effects of dobutamine dose on the cardiac parameters such as blood pressures (basal, systolic, diastolic & maximum),  heart rates (basal, peak & maximum), baseline cardiac ejection fraction, ejection fraction on dobutamine dose.  

Background: There is a little literature about the effects of dobutamine dose on the cardiac parameters.

Materials and Methods: The effects of dobutamine dose on the  cardiac parameters have been examined based on a real echocardiography stress data set, collected at University of California, Los Angeles on 558 patients with 31 explanatory variables/ factors. The distribution of the considered cardiac parameters is gamma with non-constant variance. So, they have been analyzed by joint generalized linear gamma  models.  

Results: The mean basal blood pressure (BBP) decreases as the double product of  maximum heart rate (MHR) & maximum blood pressure (MBP) at dobutamine dose (DPMAXDO) (P<0.001) increases, while the variance of BBP increases as the DPMAXDO (P<0.001) increases. The mean systolic blood pressure (SBP) increases as the dobutamine dose (DOSE) (P=0.032) increases, while the mean SBP increases as the DPMAXDO (P<0.001) decreases. The mean MBP increases as the DPMAXDO (P<0.001) increases. The mean baseline cardiac ejection fraction (BEF) decreases as the DOSE (P=0.025) increases. The mean ejection fraction on dobutamine dose (DOBEF) increases as the DOSE (P=0.011) increases, while the variance of DOBEF increases as the dobutamine dose at maximum double product (DOBDOSE) (P=0.001) decreases. The mean basal heart rate (BHR) increases as the DPMAXDO (P<0.001), or DOBDOSE (P=0.074) decreases. The mean peak heart rate (PHR), or maximum heart rate (MHR) increases as the DPMAXDO (P<0.001) increases, while the variance of PHR, (MHR) increases as the DOBDOSE (P<0.001) decreases (increases). On the other hand, dobutamine dose is associated with many cardiac parameters such as SBP, MBP, new myocardial infraction (new MI), history of MI (hxofMI)etc.              

Conclusions: Only the dobutamine dose effects are observed on SBP, MBP, DOBEF, newMI, histMI, etc, while the joint effects of dobutamine (DPMAXDO and DOBDOSE) are observed on each cardiac parameters. The results are new inputs in the dobutamine dose study literature.

Biography:

Ahmed Awd is currently working as professor in Department of Chemical Engineering in Egypt.

Abstract:

Lactobacillus represent one of the major genera of the intestinal tract of human and animals and are used, as probiotics, in dairy and non-dairy foods to restore the intestinal microflora which confer a health benefit. After an adaptation period for 7 days, the first group was fed on basal diet (80 g- for each rat group /day) and served as control I, while the second group was offered basal diet plus standardized buffalo's milk (40 ml. for each rat group / day) and served as control II. The other groups were fed on 80 grams of basal diet for each rat group / day and 40 ml. / day for each rat group, buffalo's milk plus one of the following Lactobacillus strains respectively L.casei strain AZ1, L.rhamnosus strain AZ1 and L.gasseri strain AZ1. Furthermore, supplementation of diets with fermented milk products cultured with L. casei KY123805 or L. rhamnosus KY123789 resulted in noticeable decreases in Total cholesterol, HDL- cholesterol and triglycerides levels at the end of the experiment (28 days) as compared to dry diet (control I). Species of lactobacilli occurring in intestinal tract deconjugate both taurocholic and glycocholic acids, such serum cholesterol levels when it is considered that deconjugated bile acids function more poorly in supporting adsorption of lipids from the intestinal tract than deconjugated ones, this could result in reduce adsorption of cholesterol from the intestines and thus influence its serum level. Therefore, the main target of the present investigation was to isolate and identify some local isolates belonging to genera Lactobacillus. Also, the isolated strains have been screened in order to define their characteristics that would be as probiotic strains or not. Furthermore, the long-term goal of this work is to registering patent protection for some Lactobacillus spp. isolated from local Egyptian resources to increase the additive values of the Egyptian microbial wealth and well use it in the industrial healthy dairy products and pharmaceutical.  

Biography:

Abstract:

The purpose of this review is to summarize the pertinent literature published in the present era regarding ulcerogenic effectors, and all available therapeutic concepts in this regard including; different physiological/pathological changes in response to H. pylori infection, nonsteroidal anti-inflammatory drugs (NSAID), bile acids, nitric oxide, copper complexes, acid pump inhibitors, histamine blockers, curcuminoids, cytokines and/or growth factors and finally probiotics. Because of the partial understanding of gastric ulcer pathogenesis three major hypotheses were strongly speculated and widely documented. Firstly, the hyperacidity hypothesis entailing the disturbance of the gastric acid, histamine, gastrin and somatostatin. Secondly, the eicosanoid imbalance hypothesis exploiting changes in the microcirculation through the vasoconstrictor eicosanoids such as TXA2 and vasodilator cytoprotectant eicosanoids such as PGE2. Thirdly, the infective hypothesis implementing H. pylori as the major pathogenic effectror for the gastroduodenal ulceration. In fact, all of the previous effectors could be involved and possibly employing inflammatory/antiinflammatory, oxidative stress and/or angiogenic disturbance.   

Biography:

Hye Jin Jung is an associate professor at the Department of Pharmaceutical Engineering & Biotechnology, Sun Moon University from 2014. She received her PhD in Bioscience and Biotechnology from Sejong University in 2006. She started her postdoctoral studies at Yonsei University in the area of chemical biology. In 2008, she was appointed as a research professor of Yonsei Biomolecule Research Initiative (YBRI). She was a senior fellow at the Institute for Refractory Cancer Research (IRCR), Samsung Medical Center from 2012 to 2014. She is currently working on discovering novel bioactive small molecules from natural products and deciphering their molecular action mechanisms.

Abstract:

Glioblastoma stem cells (GSCs) have been proposed as central drivers of tumor progression, treatment resistance and tumor recurrence. Although several molecular markers, such as Wnt, Hedgehog, Notch, TGF-β and EGFR, are known to be useful for targeted therapy in GSCs, exploring novel therapeutic targets and agents to eradicate GSCs can provide a promising treatment strategy that significantly improves glioblastoma patient survival and quality of life. We recently demonstrated that downregulation of mitochondrial ubiquinol−cytochrome c reductase binding protein (UQCRB) and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibits cancer stem cell-like properties in glioblastoma. The treatment with specific inhibitors and siRNAs against the molecular targets significantly inhibited not only the self-renewal capacity, such as cell growth and neurosphere formation, but also the metastasis-promoting ability, such as migration and invasion of GSCs. Notably, the inhibition of stem-like features of glioblastoma cells was associated with the downregulation of mitochondrial ROS/HIF-1a/c-Met and calmodulin/CaMKII/c-Met pathways, resulting in reduction of the expression levels of GSC markers, such as CD133, Nanog, Sox2 and Oct4. These findings suggest that UQCRB and CaMKII could be new therapeutic targets and thus their inhibitors might be utilized as lead compounds for eliminating cancer stem cells in glioblastoma.

Biography:

Professor Raid Alany is a registered New Zealand Pharmacist with a PhD from the University of Otago, Dunedin, New Zealand. He is the Inaugural Head of School of Life Sciences, Pharmacy and Chemistry at Kingston University London, UK; holds an honorary professorship at the University of Auckland, New Zealand. He is the Editor-in-Chief of Pharmaceutical Development and Technology (Taylor and Francis) and Immediate Past President of the New Zealand Chapter of the Controlled Release Society. Raid’s research is on ophthalmic drug delivery, lipid and surfactant-based systems, in-situ gels and animal health. He holds international patents that have been commercialized in New Zealand and Australia where he consults for animal health companies, regulatory bodies and IP-specialized law firms. His ResearchGate score is 35.72 and his h-index is 21 (google scholar).

Abstract:

Oxford dictionary defines research as ‘’the systematic investigation into and study of materials and sources in order to establish facts and reach new conclusions’’. Merriam-Webster dictionary defines research as ‘’studious inquiry or examination; especially: investigation or experimentation aimed at the discovery and interpretation of facts, revision of accepted theories or laws in the light of new facts, or practical application of such new or revised theories or laws’’.

Academic institutes worldwide consider research a key academic domain and would expect all their academic staff to conduct and engage in research unless they are on a non-traditional contract (teaching fellow, teaching practitioner, demonstrator, hourly paid lecturers etc.). Career progression and promotion in academic institutes involves a thorough and comprehensive review and critique of research outputs. The contribution of a particular academic staff member is assessed; the quality and quantity of journal articles published are scrutinized. Successful publication of scientific outputs is a demanding exercise especially when the target publication medium is a reputable and well established journal.

The aim of this keynote presentation is to shed light on the editorial process involved in reviewing and making editorial  decisions on scientific manuscripts submitted for publication in ‘’Pharmaceutical Development and Technology’’ ; a Taylor and Francis journal that has been in publication for 22 years and has an impact factor of 1.86. An overview of the various metrics used in ranking journals and individual scientific outputs will be covered. Tips on how to prepare a manuscript; to improve chances of success with manuscript submission for publication in leading journals will be given. 

Biography:

Young Bong Kim has received his Doctorate from Sogang University in Korea and trained at the NIAID/NIH and CWRU in United States. Since his appointment as a Professor at Konkuk University in 2003, he has been working on several vaccines against pathogenic viruses such as HIV, MERS-CoV and ZIKA virus.

Abstract:

Middle east respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been an emerging infectious disease in human. In 2015, the MERS-CoV outbreak has been occurred in the Republic of Korea. In order to aid prophylactic strategies and control of MERS-CoV outbreak in future, we have developed a MERS-CoV DNA vaccine using baculoviral delivery system. For enhancing cellular delivery, we constructed a non-replicating recombinant baculovirus coated with human endogenous retrovirus envelope (AcHERV). First, we constructed a recombinant baculovirus encoding each of S, S1, RBD genes under the control of the AcHERV system. We confirmed MERS-CoV S, S1 and RBD genes expression levels by western blot in Huh7 cell. To investigate the efficacy of vaccine, we immunized with each of recombinant baculoviruses in Balb/c mice. We found that all three recombinant baculoviruses delivering each of MERS-CoV S, S1 and RBD genes elicited high level of IgG, neutralizing antibody, and IFN-r. Of these three constructs, S1 showed the highest humoral and cellular immune response. In conclusions, AcHERV baculoviruse could be a potential prophylactic vaccine against MERS-CoV.

Biography:

Dr. Lalit Baregama has completed his Master in Organic Chemistry and PhD in Medicinal Chemistry from Mohan Lal Sukhadia University, Udaipur. He has 28 patents and 14 Research articles in his credit. He has worked with many reputed companies in India and abroad like Ranbaxy, Hikal, Vimta, Wuxiapptech and currently associated with Cadila Pharmaceutical Ahmedabad as a General Manager-International Business Development. He has contributed from Drug Discovery to commercialization of drugs and specialty chemicals. He has presented in about 18 international conferences worldwide as an invited speaker.

Abstract:

Pharmaceutical market is already crossed the USD one trillion mark and growing further. Business strategies are changing to meet the market demand where formulation development and drug delivery system plays an important role. All big pharmaceutical companies are changing the R&D execution strategy and outsourcing full/partly development to CRO/CDMO.

Outsourcing: current scenario

• Transformational shifts of Pharma industry
• Reshaping of development strategy
• Core sectors become the growth strategy
• Essential elements for successful partnership

• Strategic intent of outsourcing
• Nature of business, risk tolerance
• Mode of partnership: single transduction or long term

Advantages, Challenges and Limitations

• Partner selection: Location, opportunities, risk and cost
• Preference advantages
• Challenges and Limitations: competition, policies, pricing, EHS

Future perspective

Biography:

Syed Abid Hassan has completed his D. Pharma from RLSY college, Master of Science in Chemistry from VM University, Master of Business Administration (in International Business) from EILM- India. Mr. Abid is doing his Ph.D in Chemistry from SSSUTM from India.

Mr. Abid is Certified Lead Auditor for ISO13485 (Medical Device) from the following well recognized centres:

BSI (British Standard Institute) UK

IRCA (International Register of Certificated Auditors) UK

Abstract:

The Regulatory Affairs is one of the key department in an organization and for those who are involved with the regulation of healthcare and related products, including medical devices, pharmaceuticals, biologics and nutritional products. It helps to.

Regulatory submission team:

Regulator submission team taking care of the preparation and submission of dossiers in different countries as per the national regional requirements and template.

Regulatory compliance team:

Regulatory compliance team is responsible to see the regulatory compliance in the initial product evaluation, product development at research and development unit; plant regulatory compliance, impact analysis of changes (Variation), Change control system,  CAPP (Corrective action and preventive measure), cGxP (GDP, GLP, GMP) at Manufacturing unit, Post marketing surveillance/complain, Vendor qualification as per regulatory compliance.

Regulatory Affairs department is governed by the in-built SOPs and system, which is based on the cGDP.

Regulatory affairs department ensures that the company adheres to Regulatory requirements as per rules/regulations and laws imposed to protect public health.

Since Regulations are set and changed by the leading regulatory bodies such, as ICH, WHO, FDA and EMA etc., and consequently by local and regional regulatory bodies (SFDA, GCC, JFDA, NHRA, TFDA  etc.) too, we are operating in, hence the Compliance has been an unavoidable mandatory factor for adherence to laws, regulations in accordance with the guidelines. And failing to the compliance, results in delays, rejection of approval -- even refusal at initial submission sometimes. Not only this, violating of it may result to legal punishment, including from warning letter, federal penalties to the extent of locking the firm, as it has befallen few companies, we have come across.

Hence Pharma companies across the globe are compelled to alter their practices to conform to day-to-day changes in regulations and stringent laws, so as a result of evolvement these days a dedicated section/dept. called Plant Regulatory is in vogue to ensure the adequacy of the following major basic parts (comprises all the technical items/modules) of a dossier before application/compilation/submission:

• Different Task: Development of the Vendor for compliant of API and the relevant docs

Wherein in order to raise, meet, demonstrate and maintain the standard of the dossier, many manufacturers were/are developed by educating and guiding them through series of e_mails, telephonic discussions and video conferencing etc. to bring their standard to the level of compliance to the regulatory requirements to expedite registration, renewal or variation approval by avoiding and/or minimizing the queries. 

So, a holistic approach is required to ensure that the proper steps are taken to meet global regulatory compliance from the beginning to ensure the origination of correct documents for regulatory filling and to set the system to increase the productivity with high quality and expedition, because if any step is skipped/missed, and thus right practices are NOT implemented correctly on/in time, then reverse effort to meet regulations and policies later, is likely to add cost dearly, and even may fail sometime to repair/meet.

Biography:

Laura Sánchez García is a PhD student at the Universitat Autònoma de Barcelona. She is doing her research in the Nanobiotechnology group, which is working in the development of targeted protein-only nanoparticles against cancer stem cells. She has studied a degree in Microbiology and a masters in Applied Microbiology. She has published 13 papers in reputed journals and has received an EMBO Fellowship to perform a 3-month internship in Slovenia.

Abstract:

Nowadays, conventional cancer treatments present high systemic toxicity, leading to side effects on healthy tissues. For that reason, it is of great relevance to develop targeted drugs that can increase the local drug concentration, minimize toxic effects on off-target tissues and reduce the dose administered. Moreover, loading capacity and drug leakage from vehicles during circulation in blood is a major concern when developing nanoparticle-based cell-targeted cytotoxics. To circumvent this potential issue it would be convenient the engineering of drugs as self-delivered nanoscale entities, devoid of any heterologous carriers. In this context, we have engineered potent protein toxins, using the active fragments of the diphtheria toxin and the Pseudomonas aeruginosa exotoxin, as self-assembling, self-delivered therapeutic materials targeted to CXCR4⁺ cancer stem cells. CXCR4 receptor is overexpressed in a variety of human cancers and plays a critical role in metastatic process. For this reason, we have fused T22 to the toxic domains (T22-TOXIN-H6), as it is a CXCR4 ligand able to bind specifically and internalize into the target cells.

The systemic administration of both nanostructured drugs in a colorectal cancer xenograft mouse model promotes efficient and specific local destruction of target tumor tissues and a significant reduction of the tumor volume. This observation strongly supports the concept of intrinsically functional protein nanoparticles, which having a dual role as drug and carrier, are designed to be administered without the assistance of heterologous vehicles. The promising results obtained have allowed the development of a new patent (EP17169722) that has been licensed to NANOLIGENT SL.

Biography:

Gulay Yelken Demirel has a degree in Department of Chemistry from University of Gazi (Ankara, Turkey) followed by a master degree in Medicinal and Pharmaceutical Chemistry (faculty of pharmacy) from the same university and studied Executive Master of Business Administration at Istanbul University. Currently, She has an ongoing PhD in Medicinal and Pharmaceutical Chemistry(faculty of pharmacy) at Yeditepe University. She is also a Turkish Patent Attorney. She has eleven years experience in R&D department of generic pharmaceutical companies. She worked as formulation scientist at the Pharmaceutical Technology Department of Nobel Pharmaceuticals. Presently, She owns the R&D Project Group Executive position at Sanovel Pharmaceuticals. She has several published papers in the academic areas and over 100 patents&patent applications in the industrial areas on pharmaceutical dosage forms

Abstract:

Biography:

Syed Abid Hassan has completed his D. Pharma from RLSY college, Master of Science in Chemistry from VM University, Master of Business Administration (in International Business) from EILM- India. Mr. Abid is doing his Ph.D in Chemistry from SSSUTM from India.

Mr. Abid is Certified Lead Auditor for ISO13485 (Medical Device) from the following well recognized centres:

BSI (British Standard Institute) UK

IRCA (International Register of Certificated Auditors) UK

Abstract:

Medical device is an instrument, appliance, apparatus, implement, machine, software, calibrator, contrivance, implant, In-vitro reagent, or other similar or related article, along or in combination, including a component part, or accessory or other article which is intended for the following :

• Diagnosis, prevention, monitoring, treatment, mitigation, cure or alleviation of disease,
• Investigation, replacement, or modification of the anatomy or of a physiological process
• Supporting or sustaining life
• Providing information for medical or diagnostic purposes by means of In-vitro examination of specimens derived from the human body
• To affect the structure or any function of the body of man or other animals, and/but does NOT achieve any of its primary intended purposes through its chemical action (within or on the body)
• A medical device should not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but may be assisted in its function by such means.

Medical device Classification determinations should be based on a device’s potential to harm a patient, its intended use and also the technology it uses:

Manufacturers should document their justifications for assigning their devices to Class A, B, C or D

RAs should establish a device classification system consisting of four classes where Class A represents the lowest hazard, and Class D the highest hazard.

Principle of Medical Device Classification by GHTF through doc number GHTF/SG1/N77:2012 was developed and intended for use by RAs (Regulatory Authorities), CABs (Conformity & Assessment Bodies) and Industry.

21. Regulatory Authority (RA): A government body or other entity that exercises a legal right to control the use or sale of medical devices within its jurisdiction, and that may take enforcement action to ensure that medical products marketed within its jurisdiction comply with legal requirements.
21. Conformity Assessment Body (CAB): A body, other than a Regulatory Authority, engaged in determining whether the relevant requirements in technical regulations or standards are fulfilled.

The actual classification of each device depends on the claims made by the manufacturer for its intended use and the technologies. As an aid to interpreting the purpose of each rule, illustrative examples of medical devices that should conform to the rule have been provided in the table of previous slide. However, it must be emphasized that a manufacturer of the medical device should NOT rely on its appearing as an example, but should instead make an independent decision on classification taking account of its particular design and intended use:

21. Manufacturers of Class A devices should implement and maintain the basic elements of a QMS, but have the option of excluding design and development controls from it. The QMS is normally not subject to premarket on-site audit by the RA or CAB, except where assurance of sterility or of a measuring function is required.
21. Manufacturers of Class B devices should implement and maintain an effective QMS, but may have the option of excluding design and development controls from it.
21. Manufacturers of Class C and D devices should implement and maintain an effective QMS that includes design and development controls, and complies with GHTF SG3 guidance documents.
21. For Class B, C, and D devices, the RA or CAB needs to have confidence that the manufacturer has an appropriate and effective QMS in place.

Biography:

Pranav Shah has completed his Ph D at the age of 27 years from The Maharaja  Sayajirao University of Baroda, India. He is working as an Professor in Pharmaceutics at Maliba Pharmacy College, Gujarat, India. He has published 20 papers in reputed journals, 2 book chapters and 1 book. He has presented several papers in national and international conferences.          

Abstract:

   Rivaroxaban is a potent selective oral direct factor Xa inhibitor, Rivaroxaban belongs to BCS Class II. Liquisolid system involves dissolving water insoluble drugs in non-volatile solvents and then converting them into dry, nonadherent, free- flowing and compressible powder mixtures by blending with selected carriers and coating materials. Liquisolid compacts (LSC) of poorly water soluble drug Rivaroxaban were prepared to enhance its dissolution rate and bioavailability. Liquisolid tablets were prepared using Polyethylene Glycol (PEG-400) as the non-volatile solvent with selected carriers and coating materials. The prepared liquisolid (LS) systems were evaluated for the flow properties.The physico–chemical properties of liquisolid systems were evaluated by Infrared spectra analysis (IR), Differential scanning calorimetry (DSC) and X- ray diffraction (XRD) and Scanning electron microscopy(SEM). DSC studies revealed that there was no interaction between the drug and carrier. XRD studies demonstrated that there was a loss in crystallinity of pure drug present in LS system. SEM indicating that the drug existed in a solid dosage form, it is held within the powder substrate in a solubilized, almost molecularly dispersed state, which contributed to the enhanced drug dissolution properties. And it is  also complies with the results of XRD and DSC that the drug is in the liquisolid system. The liquisolid tablets were evaluated for Weight variation, Hardness, Drug content, Disintegration time and Dissolution rate. Liquisolid compact exhibited higher dissolution rate as compared to marketed tablet. This enhanced dissolution rate might be due to increased wetting properties and surface area of drug available for dissolution.

Biography:

My self Pradeep Kumar, Ph.D. Scholar at Amity Institute Of microbial Technology, Amity University Rajasthan under the supervision of Prof. (Dr.) G.K. Aseri. I have 12-month Experience of Work on Synthesis of dendrimer and its utilization in pharmaceutical application from the national institute of Immunology, JNU Campus, New Delhi

Abstract:

Leishmaniasis: a vector-borne disease has a worldwide existence. It presents mainly in four forms: visceral leishmaniasis, Cutaneous Leishmaniasis, Mucocutaneous Leishmaniasis and Post Kala-Azar Dermal leishmaniasis (PKDL).In India Visceral leishmaniasis is the most existence type of leishmaniasis. Visceral leishmaniasis is also known as Kala-Azar, Black Fever, Dumdum Fever, Bardwan Fever, Sarkari Bimari etc. Visceral Leishmaniasis is caused by protozoa species haemoflagellate leishmaniasis Donovan and transmitted by the bite of sand flies of Phlebotomus genus. Visceral leishmaniasis affects various age groups. Approximate 10k morbidity with 1k mortality occurs annually due to visceral leishmaniasis in India. Fast urbanization, poverty, improper sanitation, lack of knowledge about prevention and individual risk factors like HIV, malnutrition and genetic susceptibility is the major source of visceral leishmaniasis existence in India. Approximate 90% cases of Indian visceral leishmaniasis come from Bihar. Available treatment modalities have limitations like serious side effects, nonoral solubility, high cost and long hospitalization due to this a favorable treatment option for visceral leishmaniasis is still out of range of a common man. A dendrimer is a new generation of artificial polymeric macromolecules constructed in a step-by-step fashion using repetitive chemistry. Dendrimer has a number of applications in several pharmaceutical fields such as enhancing the solubility of the poorly soluble drug, enhancing the delivery of DNA, and as a carrier for the development of novel drug delivery systems. The present research emphasizes the development of a conjugate of Dendrimer with the nonoral soluble drug for the purpose of oral solubility enhancement and then use for the treatment of visceral leishmaniasis.