Scientific Program

Conference Series LLC Ltd invites all the participants across the globe to attend 19th Annual Congress on Pharmaceutics & Drug Delivery Systems Geneva, Switzerland.

Day 1 :

Keynote Forum

Yuxin Pei

Northwest A&F University, Yangling, Shaanxi 712100, China

Keynote: pH and H2O2 dual-responsive nanoparticles for monitoring intracellular protein Delivery

Time : 09:30-10:15

Euro Pharmaceutics 2020 International Conference Keynote Speaker Yuxin Pei photo
Biography:

Yuxin Pei did her PhD in 1998 in material science at China Textile University (Donghua University at present) in Shanghai. After a two-year postdoctoral training at Zhejiang University, she moved to Europe and worked as post-doctoral fellow at Lund University, Royal Institute of Technology, Technical University of Denmark, and Heidelberg University. Since 2010, she has been a full professor of chemistry at Northwest A&F University. Her current research interest is drug delivery systems and target.

 

Abstract:

Protein therapy holds enormous promise for cancer treatment due to its potential high potency. However, its clinical application is severely limited due to poor membrane permeability of proteins as well as lack of efficient delivery vehicles and methods of real-time protein-tracking. Here a pH and H2O2 dual-responsive NIRF (near-infrared fluorescence) turn-on protein delivery system incorporating an NIRF turn-on probe and protein into one single nanoparticle was rationally designed and fabricated based on tumor microenvironment for monitoring intracellular protein delivery. The nanoparticles can be taken up efficiently by A549 cells, where protein release and NIRF recovery happen simultaneously in response to low pH and excessive H2O2. More importantly, the delivery of protein via such a delivery system didn’t compromise on the activity of the protein. Thus, we provide a new approach to fabricate biocompatible and efficient stimuli-responsive turn-on systems for monitoring intracellular protein delivery. We believe that the strategy developed in this work may find broad applications in drug release monitoring and cancer cell imaging.

 

Protein therapy holds enormous promise for cancer treatment due to its potential high potency. However, its clinical application is severely limited due to poor membrane permeability of proteins as well as lack of efficient delivery vehicles and methods of real-time protein-tracking. Here a pH and H2O2 dual-responsive NIRF (near-infrared fluorescence) turn-on protein delivery system incorporating an NIRF turn-on probe and protein into one single nanoparticle was rationally designed and fabricated based on tumor microenvironment for monitoring intracellular protein delivery. The nanoparticles can be taken up efficiently by A549 cells, where protein release and NIRF recovery happen simultaneously in response to low pH and excessive H2O2. More importantly, the delivery of protein via such a delivery system didn’t compromise on the activity of the protein. Thus, we provide a new approach to fabricate biocompatible and efficient stimuli-responsive turn-on systems for monitoring intracellular protein delivery. We believe that the strategy developed in this work may find broad applications in drug release monitoring and cancer cell imaging.

 

 

Keynote Forum

Radostina Alexandrova

Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria

Keynote: Metal [Zn(II), Co(II), Ni(II)] complexes with kojic acid: do they help us to fight against cancer?

Time : 10:15-11:00

Euro Pharmaceutics 2020 International Conference Keynote Speaker Radostina Alexandrova photo
Biography:

Prof. Radostina Alexandrova has graduated with honors in Biochemistry and Microbiology, Sofia University “St. Kl. Ohridski” (SU) in 1991; MSc and PhD in Virology; Postdoctoral training in Slovakia, Hungary, Denmark, Iceland; lecturer in SU and PhD School of Bulgarian Academy of Sciences (BAS). She is a team-leader in the Department of Pathology, IEMPAM-BAS. She has published more than 150 papers in reputed journals and conference proceedings.

 

Abstract:

The aim of our study was to evaluate the influence of newly synthesized  complexes of Zn(II), Co(II) and Ni(II) with kojic acid on viability and proliferation of cultured human (HeLa cervical carcinoma), rat (sarcoma LSR-SF-SR) and avian (liver cancer LSCC-SF-Mc29) cancer cells. Short-term experiments (24-72 h, with monolayer cell cultures) by thiazolyl blue tetrazolium bromide (MTT) test, neutral red uptake assay (NR), crystal violet staining (CV), double staining with acridine orange and propidium iodide, AnnexinV/FITC method as well as long-term experiments (14 days, with 3D cancer cell colonies) by 3D-colony forming method were carried out to investigate the cytotoxic activity of the compounds. The results obtained revealed that the compounds examined decreased viability and inhibited 2D and 3D growth of the treated cells in a time- and concentration-dependent manner. Co(II) complex with kojic acid (CoKoj) was found to be the most promising cytotoxic agent in human HeLa and rat LSR-SF-SR cells whereas ZnKoj showed the highest effectivity in chicken LSCC-SF-Mc29 cells. NiKoj exhibited the lowest cytotoxicity. Cytopathological changes and apoptosis were observed in the cells cultivated in the presence of the compounds tested.

 

  • Pharmaceutical Technology
Location: Geneva

Session Introduction

Patricia Hegger

Sanofi Aventis Deutschland GmbH, Frankfurt, Germany

Title: Biopharmaceutical evaluation of a parenterally injected formulation
Biography:

Dr. Patricia Hegger has completed her PhD on “Hyaluronan Based ECM-Mimetics with Tunable Charge Densities – Physico-Chemical Properties and Biological Implications” from Max-Planck-Institute for medical research in 2017. Before starting her career in industry she took over an interim-groupleader position at the Max-Planck-Institute for medical research continuing her studies on hyaluronic acid. She is now a labhead in the biopharmacy group of the TIDES Drug Product department of Sanofi-Aventis Deutschland GmbH, a global pharmaceutical company.
 

Abstract:

The uptake of subcutaneous (s.c.) administered formulations into the systemic circulation is a function of numerous quite diverse processes like active pharmaceutical ingredient (API) dissolution from the formulation and disintegration to monomers (“liberation”), local metabolism and the permeation through the interstitium and endothelium into the blood vessels (“absorption”). The determination of these parameters prior to launch of the drug is the field of biopharmacy, with its three pillars: In silico, in vitro and in vivo assessment combined with in vivo - in vitro correlation.

For s.c. administered formulations however there is only a limited number of systematically applied biopharmaceutical in vitro - in silico tools for characterization of those processes. For example the first in vitro methods for biopharmaceutical evaluation was published in 2015, whereas comparable methods for orally administered small molecules are established since the 1960s. Taken into account, that around 70 % of the marketed drugs today are s.c. applied, this is a highly evolving field with the potential of improvement for (I) molecule selection, (II) formulation selection and optimization and (III) understanding as well as prediction of in vivo findings in animals and humans.

 

Biography:

Leena H. Saeed – a clinical pharmacist

Graduated from King Saud University 2009 with first honor degree.

Held Master Degree in Clinical pharmacy on 2013 also from King Saud University.

Currently working as clinical pharmacist at King Fahad Medical City. Riyadh, Saudi Arabia- covering neurology and neurosurgery

I'm interested in pharmacoeconomics – the use of drug formulations for cost minimization. also in pharamcogenetics.

 

Abstract:

Background:

In each hospital, there is a good number of patients who are candidates for the switch-over from intravenous (IV) to oral therapy.

The main hindrance that restricts intravenous to oral conversion is the idea that oral medications do not reach the same bioavailability as that of intravenous medications and that the same item must be used both intravenously and orally. Although several drugs commonly used in hospitalized patients are equally bioavailable intravenously and orally, Patients usually are not shifted to the oral medication when stable and taking oral medications or eating an oral diet

There are many advantages involved in earlier conversion from the intravenous to the oral therapy, including but not conclusive to less nursing time for medication administration, lower cost,  less intravenous catheters needed can lead to increased patient satisfaction and safety.

Objective:

Establishment of a pharmacist-led IV to oral switch over protocol in the national neuroscience institute (NNI) at King Fahad Medical City (KFMC), in an attempt to reduce the annual medication cost.

 

Method:

  1. Setting: the study was conducted in the NNI of KFMC in Riyadh Saudi Arabia.
  2. The study was prospective. We identified five targeted medications that are commonly prescribed in NNI (NHDU, NW1, Stroke) inpatient wards with almost identical oral and intravenous bioavailability (Table 1). 45 patients were recruited. Their files were reviewed by the pharmacist and recommendation to switch was communicated to physician either verbally or documented in the patient file. The total cost of the medications was compared between oral and intravenous forms according to the length of stay in the ward. Inclusion and exclusion criteria are mentioned (Table 2).
  3. Difference between oral and IV medication cost were compared using Mann-Whitney U test. All data entry and statistical analyses were performed using SPSS 22.0 software.

Results:

This study has been in place for 6 months. 71 recommendations were made. Of these recommendations, 11 (15.5%) were rejected and 60 (84.5%) were accepted and implemented, resulting in a cost savings of 10,652 SAR (P=0.001). When annualized, the expected savings is 21,304 SAR or nearly the monthly salary of 2 full-time pharmacists.

Conclusion

This study demonstrates successful implementation of a pharmacist-led switch-over strategy. Duration of IV treatment reduced dramatically and the annual savings significantly improved.

This program has been well accepted by physicians and pharmacists. It appears to be having a positive impact on physician awareness of using oral medications when appropriate.

This study may be used as a template for the introduction of further pharmacist-led early IV to oral switch-over initiatives.

 

Biography:

Ehab Rasmy Bendas is Professor of Pharmaceutics, Pharmaceutical technology and Pharmacy Practice at the Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University in Egypt. He got his Master degree & Ph.D. in Pharmaceutics from Faculty of Pharmacy, Cairo University. He was Post-doctoral research fellow at Oregon State University, USA. His research interests are focused on nanotechnology, drug delivery and pharmacokinetics.

 

Abstract:

In latest years, excipient development is become essential part of research in pharmaceutical drug delivery because it impacts the formulation development and drug delivery process. Repeated dose medication usually maximizes adverse effects, while sustained release systems did not offer a fast onset of action. The aim of this study is to formulate Etodolac to enable pulsatile and sustained drug release patterns, which was chronologically more suitable as an anti-inflammatory drug.

Eudragit  RSPO, Eudragit  RLPO, and Hydroxypropyl Methylcellulose  (HPMC K15M) were added in the sustained release layer and tried in different ratios. Croscarmellose sodium or sodium starch glycolate were used as superdisintegrants for the fast release layer offering the loading dose for rapid onset of drug action. Bilayer tablets were successively coated with Opadry II, HPMC K4M and HPMC E5 (1:40), and Surelease. All formulations complied with the Pharmacopeial standards for post-compression parameters. The coated bilayer tablet showed pulsatile and sustained release effects in rats. The licking time and swelling degree were tested and results demonstrated significant difference (P < 0.05) between the sustained anti-inflammatory action of formulation C1 compared to other groups.

Therefore the new chronological design could provide a consistent drug release over 24 h with good protection against associated symptoms of gastric release.

 

Biography:

Dóra Csicsák is a second year PhD student in the Department of Pharmaceutical Chemistry at Semmelweis University, Hungary. She graduated from Semmelweis University’s Faculty of Pharmacy in 2017. In her doctoral research, she investigates  the dissolution and permeabilty of polymorphous, amorphous, micro- and nanosized drugs. 

 

Abstract:

The study of polymorphism is important in drug research and development, since the different physico-chemical properties of the polymorphs may affect the stability, solubility, dissolution, and therefore the bioavailability of the substance.


In our work we investigated the pH-dependent equilibrium solubility of two carvedilol polymorphs according to a standard protocol, in the pH range of 3-11, using saturation shake-flask method and µDISS device.

Measurements were performed using two solutions: Britton-Robinson (B-R) with standard ionic strength, and B-R buffer where the ionic strength was modified with 0.15 M KCl. Solubility results were compared to the values ​​predicted by the Henderson-Hasselbalch equation.

In two different buffers (pH 6 and 6.5), in-situ UV probes were used to monitor the dissolution in real-time, so it was possible to obtain precise information on the time needed to achieve the equilibrium, and the rate of supersaturation.

At the end of the solubility measurements, the solid phase analysis of the samples was performed by X-ray powder diffraction and Raman spectroscopy.


Twofold difference was found between the solubility of the two forms. It was proved that the crystalline structure of the two polymorphs does not change during the measurement, and salt formation could be observed in the acidic pH range (pH ≤ 6.5). The counterion and solubility of the salt were found different in various buffer solutions.

 

Biography:

Erzsébet Csányi (csanyi@pharm.u-szeged.hu) is the Associate Professor of Institute of Pharmaceutical Technology and Regulatory Affairs. She is the head of Topically used liquids and semisolids R&D group. Her publication list is available:

 

Abstract:

Effective topical local anesthesia is a challenge, because most of the marketed formulations have moderate skin penetration properties, rapid but short effect. Innovative dermal formulations are needed to overcome the barrier function of the skin and provide sufficient and prolonged local anesthesia. We developed and investigated a lidocaine-containing nanostructured lipid carrier (NLC) system. NLCs as drug carrier systems offering many benefits: good physical stability, possibility of scale-up and controlled drug delivery, and low cost. Topically applied lipid particles can reduce transepidermal water loss (TEWL) and increase skin hydration, thereby they facilitate the penetration of the incorporated drug and support the physiological conditions of the skin.

NLC was prepared by ultrasonication method. To characterize the carrier system different in vitro investigations were performed: particle size and zeta potential measurements, Fourier- transform infrared and Raman spectroscopy, Differential Scanning Calorimetry and X-ray diffraction measurements. Release and skin penetration of lidocaine-NLC was examined by Franz diffusion cell and Raman spectroscopic mapping. The in vivo effect of the formulation was followed by measurement of skin hydration and TEWL.

Our results confirmed the developed lidocaine-NLC is a promising vehicle for topical local anesthesia. The considerable penetration properties of this NLC formulation was proved by Franz diffusion cell and Raman spectroscopic mapping experiments. Furthermore, skin hydrating and occlusive effect makes this NLC a favorable dermal carrier system.

 

Biography:

Yang Yuan has completed his master at the age of 27 years from Kunming Medical University. He is currently engaged in basic and clinical research of lung cancer.He has published more than 10 papers in journals around the world and has been serving as an oncology member of CSCO.

 

Abstract:

Lung cancer is a malignant respiratory tumor with rapid development and poor prognosis. VATS(video-assisted thoracic surgery) is the main treatment for early lung cancer, but the majority of patients are diagnosed at stage IIIB or IV. Platinum-based chemotherapy regimen is currently considered key components of first-line chemotherapy for advanced lung cancer; however, there are no standard treatment plans for lung cancer with KRAS mutation. Apatinib has been successfully applied as third-line treatment for advanced gastric cancer and has shown high efficacy in the treatment of various cancer. Herein we report a case of advanced lung cancer harboring KRAS mutation in which apatinib was administered and a partial response was achieved after four months of treatment. To date, a 10 months of progression-free survival have been achieved. Adverse reactions can be controlled and the patient's quality of life has improved. Apatinib provides a new option for clinicians to treat patients with advanced KRAS-mutation lung cancer.

 

Biography:

Khaled Greish is Associate Professor of Molecular Medicine, and head of the Nano-research unit, at Princes Al-Jawhara Centre, Arabian Gulf University, Kingdom of Bahrain, and Adjunct Associate Professor of Pharmaceutical Chemistry at University of Utah, USA. He Published > 80 peer reviewed papers, and 10 book chapters in the field of targeted anticancer drug delivery. Controlled Release Society (CRS) awarded him the CRS Postdoctoral Achievement award in 2008 and in 2010; he was elected as member of the CRC College of Fellows.

 

Abstract:

Breast cancers are the most common cancers diagnosed in women. The therapeutic decision relies primarily on the level of expression of three protein biomarkers namely: estrogen receptor-α (ER-α), progesterone receptor (PR), and HER2. These biomarkers are essential determinants of breast cancer biology, have guided the therapeutic strategies, and predicted the response to systemic therapies.

Triple-negative breast cancers (TNBC), lacking the expression of these three biomarkers, continue to experience the highest mortality rate.

Synthetic cannabinoid WIN55,212-2 (WIN) has shown promise as an anticancer agent but causes psychoactive side-effects.

In the present study, nano-micelles of styrene maleic acid (SMA)-conjugated WIN were synthesized to reduce side-effects and increase drug efficacy against triple negative breast cancer. Pharmacokinetics studies revealed the lower brain concentrations levels of WIN formulated Nano micelles, accompanied by almost 3 folds increase in its concentration levels in cancer tissues compared to free WIN. SMA-WIN formulation reduced tumor growth with milder psychoactive side effects when compared to the free drug. Moreover, low dosage of SMA-WIN, almost devoid of psychoactive side effects, in combination with an established chemotherapeutic agent achieved therapeutic efficacy and was sufficient to reduce the tumor volume of TNBC murine cancer model drastically

 

Biography:

Hiba Zallouma, Hamdi Mango Research Center for Scientific Research, The University of Jordan, Amman 11942, Jordan  

Abstract:

Targeting cancer through epigenetics is a recent era, where a specific gene is manipulated without destroying it. Lysine-specific demethylase 1 (LSD1) is one of the enzymes that are associated with chromatin for post-translational modifications, where it demethylates lysine amino acid in the chromatin H3 tail. LSD1 is associated with its corepressor protein CoREST, and utilises tetrahydrofolate as a cofactor to accept CH2 from the demethylation process. Many studies showed that inhibiting LSD1 could potentially be used to treat cancer epigenetically. The fact that the cofactor is best bound to the active site inspired us to explore its interactions to LSD1/CoREST enzyme complex utilizing molecular dynamics simulation, which aids designing novel and potent inhibitors. Also, the conformational existence of the enzyme complex bound to the cofactor has been investigated. According to the molecular dynamics simulation study, LSD1/CoREST complex is present in open and closed conformations. Furthermore, tetrahydrofolate was found to bind to two binding sub-sites with different binding modes. The model derived from the molecular dynamics simulation study and the key contacts to the active site were used in the subsequent structure based drug design and in-silico screening, which revealed a number of new chemical entities with a potential inhibitory effect of LSD1/CoREST complex. In silico mining on National Cancer Institute (NCI) database identified 60 promising and structurally diverse inhibitors.The cytotoxic activities of these compounds were tested against different cancer cell lines with different expression modes of LSD1/CoREST complex such as leukaemia K562, prostate cancer PC3 and neuroblastoma SH-SY5Y. All compounds were also tested against normal fibroblast cells to study their selectivity against cancer cells. Applying the abovementioned molecular modeling procedure yielded array of LSD1/CoREST inhibiters with IC50 < 5µM, when tested against different cancer cell lines. Three compounds inhibited the growth of PC3 prostate cells with IC50 = (2.68, 2.08 and 2.95µM), Four of them inhibited the growth of K562 leukaemia cells with IC50 = (1.20, 1.92, 2.70, and 1.20µM) and three of them inhibited the growth of SH-SY5Y neuroblastoma cells with IC50 = (0.27, 0.83 and 4.28µM). These compounds are excellent candidates for further optimization.

 

Biography:

Bijay Kumar Padhi has completed his PhD from The M.S.University of Baroda, INDIA on Pharmaceutics and Drug Delivery. He is the Associate Vice President and Head Formulation R&D at Unichem Laboratories Limited, INDIA. He has more than 18 years of industrial and research experience in formulation and drug delivery. He is the inventor for 5 USA granted patents, 1 Australian patent and more than 20 patent pending applications. He has authored more than 11 research publications in reputed journals

 

Abstract:

Increasing demand in new and complex delivery technologies for differentiated formulations urges to identify early indicative or predictive non clinical methods. Predicting in-vivo performance of dosage forms is critical to development of new drug delivery approaches. Physiological factors that influence in vivo performance of formulations include gastrointestinal condition, mechanical stress, effects of food, enzymatic or pH related degradation of drug and its excipients, in vivo drug release profile and the direct influence of some excipients on drug metabolism and transport etc.

 

Practicality of non-clinical studies during product development are discussed with case studies on novel oral lipid based formulations, nasal sprays and long acting depot formulations. Absorption studies in animal models are discussed on early stage formulations. Primary pharmacokinetic parameters of interests;  partial AUCs [e.g (AUC0-15min), (AUC0-30min), (AUC0-60min) etc] , AUC from baseline through Tmax of reference products (AUC0-RefTmax ), relative percentage of AUC0-T  with respect to reference exposure values and Cmax were evaluated to rank order various formulation approaches. Translation of preclinical pharmacokinetic parameters and dosage form performance in humans also discussed. Pharmacokinetics studies in appropriate animal models provides useful insights for further formulation development and help in minimizing both development time and risks.