Day 1 :
Keynote Forum
Vladimir P Torchilin
Keynote: Next generation of smart stimuli-sensitive siRNA/drug nanopreparations for cancer
Biography:
Vladimir P Torchilin, PhD, DSc is a University Distinguished Professor of Pharmaceutical Sciences and Director, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston. His interests include drug delivery and targeting, nanomedicine, multifunctional and stimuli-sensitive pharmaceutical nanocarriers, biomedical polymers, experimental cancer therapy. He has published more than 400 original papers, more than 150 reviews and book chapters, wrote and edited 12books, and holds more than 40 patents. Google Scholar shows more than 44,000 citations of his papers with H-index of 96. He is Editor-in-Chief of Current Drug Discovery Technologies, Drug Delivery, and OpenNano, Co-Editor of Current Pharmaceutical Biotechnology and on the Editorial Boards of many other journals. He received more than $30 M from the governmental and industrial sources in research funding. He has multiple honors and awards and in 2011, Times Higher Education ranked him number 2 among top world scientists in Pharmacology for the period of 2000-2010.
Abstract:
Tumor therapy, especially in the case of multidrug resistant cancers, could be significantly enhanced by using siRNA downregulating
the production of proteins, which are involved in cancer cell resistance, such as Pgp or survivin. Even better
response could be achieved is such siRNA could be delivered to tumors together with chemotherapeutic agent. This task is
complicated by low stability of siRNA in biological surrounding. Thus, the delivery system should simultaneously protect
siRNA from degradation. We have developed several types of lipid-core polymeric micelles based on PEG-phospholipid or
PEI-phospholipid conjugates, which are biologically inert, demonstrate prolonged circulation in the blood and can firmly
bind non-modified or reversibly-modified siRNA. Additionally, these nanopreparations can be loaded into their lipidic core
with poorly water soluble chemotherapeutic agents, such as paclitaxel or camptothecin. In experiments with cancer cell
monolayers, cancer cell 3D spheroids, and in animals with implanted tumors, it was shown that such co-loaded preparations
can significantly down-regulate target proteins in cancer cells, enhance drug activity, and reverse multidrug resistance. In order
to specifically unload such nanopreparations inside tumors, we made them sensitive to local tumor-specific stimuli, such as
lowered pH, hypoxia, or overexpressed certain enzymes, such as matrix metalloproteases. Using pH-, hypoxia-, or MMP2-
sensitive bonds between different components of nanopreparations co-loaded with siRNA and drugs, we were able to make
the systems specifically delivering biologically active agents in tumors, which resulted in significantly improved therapeutic
response.
Keynote Forum
Hiroshi Ohrui
Keynote: Development of extremely excellent anti-HIV active EFdA, focused on the design
Biography:
Hiroshi Ohrui received his PhD degree (1971) from The University of Tokyo. He joined RIKEN during 1966 and moved to Tokyo University in 1981 and moved to Yokohama University of Pharmacy in 2006. He worked for Dr. J J Fox at Sloan- Kettering Institute for Cancer Research during 1972-1973 and Dr. J G Moffatt at Syntex Research during 1973-1974. He received several awards including Inoue Prize for Science (2001), Japan Prize for Agricultural Sciences (2004), The Japan Society for Analytical Chemistry Award (2004), and Japan Academy Prize (2010). His research interests cover organic synthesis, chemical biology and chiral discrimination.
Abstract:
4’-C-Ethynl-2’-fluoro-2-deoxyadenosine (EFdA) has attracted much attention due to its extremely excellent anti-HIV
properties (1. prevent the emergence of resistant HIV mutants 2. over 400 times more active than AZT and several orders
of magnitude more active than the other clinical reverse-transcriptase inhibitor 2’, 3’-dideoxynucleoside drugs 3. very low toxic
4. long acting 5. could be used for prophylaxis, and so on). EFdA is now under clinical investigation as MK-8591 by Merck
& Co. In my talk, the development of EFdA, especially the design of it will　be presented and discussed. For the design of the
modified nucleoside which could solve the problems (1. emergence of drug-resistant HIV-mutants. 2. adverse effects by drugs.
3. necessary to take plenty number of drugs) that the clinical drugs have, I have proposed the following working hypotheses to
solve the problems. They are: (1) the way to prevent the emergence of resistant HIV mutants, (2) the way to decrease the toxicity
of modified nucleosides, (3) the way to provide the nucleoside with the stability to both enzymatic and acidic hydrolysis of
nucleobase. 4’-C-substituted-2’-deoxynucleoside was designed to meet the hypotheses (1), (3) and the 2-site-modification was
conducted to meet the hypothesis (2). The details of the hypotheses and the reason of the 4’-C-substitution will be discussed.
To prevent the deamination of adenine base, fluorine atom was introduced at the 2-position of adenine base. Finally, EFdA
which is modified at the two positions of the physiologic 2’-deoxyadenosine and has extremely excellent anti-HIV properties
been successfully developed.
Keynote Forum
Wilfried Dimpfel
University of Giessen, Germany
Keynote: Reverse pharmacology of sceletium tortuosum
Biography:
Wilfried Dimpfel is Honorary Professor at Justus-Liebig-University Giessen, Germany, since 1983. He is Pharmacologist and got his Neurophysiological Education during 1973-1974 as Max Kade stipend (New York) at the NIH Bethesda from Phil Nelson. Together with Hans-Carlos Hofmann, a Physicist and Mathematician, he developed quantitative EEG software for research and practice. He is Consultant and CSO at NeuroCode AG, Wetzlar, Germany. He published more than 150 papers in peer-reviewed
journals.
Abstract:
A “reverse pharmacology” approach was started with an extract of Sceletium tortuosum, currently sold as Zembrin® in
the USA, Canada, Brazil, Malaysia, and South Africa. It is a proprietary extract of a low-alkaloid cultivated selection of
Sceletium tortuosum, and is used by healthy people for enhancing mood, decreasing anxiety and stress and improving cognitive
function under stressful situations. As test model the hippocampus slice in vitro was chosen to compare its effects with four of its
alkaloid constituents, namely Mesembrine, Mesembrenone, Mesembrenol and Mesembranol. Measurement of the amplitude
of population spikes was performed in the presence of single shock stimulation and theta burst stimulation resulting in long
term potentiation (LTP). Rats were treated daily for one week with 5 or 10 mg/kg of Zembrin® before the hippocampus was
taken out for in vitro analysis. Amplitudes of the population spikes were dose dependently attenuated. Out of four glutamate
receptor agonists only Fluorowillardine was completely unable to induce its agonistic action. This points to an AMPA receptor
mediated attenuation of hippocampal excitability produced by repetitive dosing of Zembrin®. Superfusing the slices directly
with the alkaloids at nanomolar concentrations (3.5 – 35 nM) resulted in a concentration dependent attenuation of population
spike amplitudes. However, only Mesembrenol and Mesembranol were able to prevent the action of Fluorowillardine, thus
resembling the effect of the whole extract. Comparing now the chemical formula of the alkaloids in terms of a structure activity
relationship, the hydroxy group at C6 instead of a carbonyl group in mesembranol seems to be essential for interaction with
AMPA dependent transmission. Since attenuation of AMPA mediated transmission has been related to successful adjunctive
treatment of epileptic patients, Mesembranol - following the principle and methodology of “reverse pharmacology” - might
serve as chemical lead for the development of new drugs for the treatment of epilepsy.
Keynote Forum
Jamal Ouazzani
National Center for Scientific Research CNRS, Institute for Chemistry of Natural Products ICSN, France
Keynote: Ethnopharmacology and neurodegenerative diseases: Past achievements and future expectations
Biography:
Abstract:
Neurodegenerative diseases (NDs) cover various pathologies and associated disorders. The most known and disabling are
Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, causing motor disorders and dementia. NDs affect the
ageing population and represent one of the most challenging public health issues worldwide. The situation is particularly critical
due to the increasing number of patients, the cost of treatment, and the societal impact of day-to-day care and dependence. As
an example, around 7 million European citizens suffer from Alzheimer's disease with a total care cost reaching 155 billion euros
each year. Besides existing drugs addressing the symptoms rather than the cause, alternative natural solutions based on natural
extracts or pure compounds are driving growing interest. This presentation begins with an overview of the current state of the
art in the use of natural resources and the products they contain, to combat the potential causes and consequences of NDs.
We will then move on to the results we have obtained in the field, by using innovative extraction technologies and controlled
biotransformation processes to enhance the effectiveness and the safety of the end products.
Keynote Forum
Amots Dafni
Haifa University, Israel
Keynote: Rise and fall of mandragora autumnalis as a medicinal plant
Biography:
Abstract:
The earlier evidences for the medicinal uses of Mandragora autumnalis are from Sumer and the Bible. The main uses of the
mandrake (sometimes with a combination of other narcotic plants), along the generations, are: aphrodisiac, antispasmodic,
sedative, anesthetic, analgesic, emetic and antidote for snakebites. For each use I'll survey: the history and the intensity
throughout the history till the present day, the pharmacological background in relation to modern chemical analyses and pros
and cons. It is concluded that most of the uses of M. autumnalis, as a medicinal plant, were almost completely abandoned.
The reasons for this tendency are: 1. The poisonous and narcotic properties, as well as other uncontrolled side effects of the
mandrake. 2. The development of the modern safe and efficient drugs which successfully replaced the traditional uses of the
plant. The use of the mandrake as aphrodisiac still exists, maybe due to the deep belief rooted in mythology, religion and
history which are hard to be eradicated.
- Drug Delivery System of Biopharmaceutical Products | Clinical Trials on Biopharmaceutical Products | Drug Therapy | Biologics and Biosimilars | Biopharmaceutics: Drug Discovery and Development | Cellular and Gene Therapy | Biopharmaceutical Companies & Market Analysis
Chair
Vladimir P. Torchilin
Northeastern University, USA
Session Introduction
K Kvell
University of Pécs, Hungary
Title: Steroid-harboring nanoparticles provide anti-inflammatory response with less adverse effects
Biography:
K Kvell, MD PhD has primary expertise in Immunology and Biotechnology. He works in the field of Immune Senescence and its relation to steroid compounds.
Currently he is working at the Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, at the University of Pecs, Hungary. He is currently involved in
interdisciplinary research utilizing steroid compounds and nanoparticles. This field encouraged the collaborative research team to develop novel drug delivery
strategies of steroid treatment, to allow for targeted steroid treatment with potent anti-inflammatory effect, yet with reduced level side effects. kvell.krisztian@pte.hu
Abstract:
Statement of the Problem: Steroids are acknowledged anti-inflammatory drugs used in multiple conditions, including autoimmune
disease. Steroids provide strong suppression of inflammation however, their long-term utilization triggers numerous adverse
effects including obesity, diabetes, osteoporosis, edema retention etc. As a result, only inflammatory flares are treated with steroid
compounds, for short term.
Methodology & Theoretical Orientation: Our collaborative research team has produced nanoparticles of specific size harboring
steroid compounds. In theory, due to their specific size, steroid-harboring nanoparticles trigger phagocytosis in monocytes and
macrophages, but leave other (non-phagocytic) cells unaltered.
Findings: Our human in vitro data indicate that steroid particles show potent anti-inflammatory effect on monocytes / macrophages,
equivalent to that of steroid solution. However, their adverse effects are reduced using non-phagocytic cells. Liver cells, for example,
show increased viability with steroid particles as opposed to steroid solution.
Conclusion & Significance: Our working hypothesis was that steroid-particles of a specific size range can preferentially target
monocytes/macrophages, the major mediators of inflammation. Other (non-phagocytic) cell types shall largely be unaltered by
steroid particles, as opposed to steroid solution. This is confirmed by our data. Our technology allows for the production of regular
steroid compounds with significantly reduced side effects, with the promise of long-term use in human.
Theo Christie
NIHR Clinical Research Network, UK
Title: Biosimilars in the UK’s NHS: Attitudes, appetites and acceptance
Biography:
Divya Chadha Manek is the Head of Business Development (Commercial) for the NIHR Clinical Research Network (CRN). Her role is to maintain strategic
relationships with global and UK life sciences companies and the Clinical Research Network. She also leads on ensuring that the Clinical Research Network
is abreast of new study delivery innovations to ensure that the organization is evolving to service life sciences industry requirements. With a degree in Clinical
Psychology and a Master’s in Clinical Research, she has worked with the Clinical Research Network for the past nine years. Her first role with the CRN was
delivering commercial contract clinical research within a National Health Service (NHS) hospital. Prior to her current role, she worked as the Industry Manager
within the Mental Health team, performance managing and maintaining oversight of the national mental health portfolio of studies. She has experience of clinical
research from a site level and from a national perspective in the UK. She is currently studying PhD in Dementia Care.
Theo Christie is a Business Development Manager (Commercial) for the NIHR Clinical Research Network (CRN). Theo facilitates key discussions between industry
and the Clinical Research Network and is a point of contact for the life sciences companies engaging with the Clinical Research Network. Theo is able to provide
advice to companies on how they are able to tap into the Clinical Research Network study support services to ensure clinical studies are set up efficiently and
recruit to time and target. With a degree in Clinical Sciences, Theo has been with the Clinical Research Network for over four years. He previously worked within
the Research Delivery Directorate of the CRN, collaborating with the life sciences industry and national specialty groups across 10 therapeutic areas, providing
operational support through feasibility, set up and patient recruitment.
divya.chadhamanek@nihr.ac.uk
theo.christie@nihr.ac.uk
Abstract:
Is the NHS ready for the biosimilars boom? to most, biosimilars are a no-brainer. But as with anything new, there are early adopters
and sceptics. The NIHR CRN is an independent, government-funded organization which supports delivery of the majority of
clinical research in England - and with that comes unique insight. The NIHR CRN can report that attitudes, appetites and acceptance
in relation to biosimilars in the UK are changing. Despite being approximately ten years ahead of the US our approach and acceptance
of biosimilar drugs, in 2015 it came to light, some commercial trial sponsors were overlooking the UK as a destination for biosimilar
trials - claiming that the appetite for delivering these types of trials was low. The NIHR Clinical Research Network was drafted to
sharpen the UK’s competitive edge. In this presentation we will reveal why life science companies were overlooking the UK to deliver
their trials, and how these challenges are being overcome using the Clinical Research Network structure which is unique to the NHS
in England. Companies can now continue to place their biosimilar trial in UK with confidence and get ahead of the game when it
comes to study set-up, feasibility, and patient recruitment. This presentation will present a range of perspectives (via video clips)
which illustrate how the UK’s appetite, capacity and capabilities to deliver biosimilar clinical trials have developed in parallel with the
expansion of the biosimilars market. You will hear from those involved in conducting biosimilar trials - the clinicians, investigators
and nurses at the coal face of research delivery in the NHS. We’ve also captured the NHS Trust R&D viewpoint, along with some
thoughts from the NHS pharmacy team. The British Biosimilar Association offers up some interesting ideas, but probably the most
memorable perspective is that of the patient.
Claudia Menzel
University of Innsbruck, Austria
Title: 2,2’Dithiodinicotinyl ligands: Key to more reactive thiomers
Biography:
Claudia Menzel is a PhD student from the Institute of Pharmacy at University of Innsbruck. Her work focuses on the improvement of drug bioavailability and the
development of drug delivery systems for the non-invasive administration of poorly absorbed drugs. She has published three papers and one review article in
reputed journals.
claudia.menzel@uibk.ac.at
Abstract:
The goal of this study was to establish a new type of preactivated thiomers showing comparatively higher reactivity with mucus
and improved mucoadhesive properties. The dimeric form of 2-mercaptonicotinic acid (MNA-MNA) was directly attached
to the polymeric backbone of chitosan (CHI) to achieve a higher reactivity. Amide bond formation mediated by 1-ethyl-3-(3-
dimethylaminopropyl) carbodiimide (EDAC) was used as a coupling reagent. The remaining free amino groups were reacted with
succinic anhydride (Succ) to gain a homogeneously anionically charged polymer (CHI-Succ-MNA-MNA). Within our study, various
coupling rates of up to 170 μmol MNA-MNA per gram polymer were obtained. The coupling of the dimeric ligand resulted in
a preactivated thiomer with a more reactive disulfide substructure due to the additional nitrogen atom in conjugation over the
aromatic moieties. Furthermore, the obtained polymer is completely preactivated and therefore protected against unwanted oxidation
reactions. Our kinetic studies of disulfide exchange reactions showed a 3.8-fold higher reactivity of CHI-Succ-MNA-MNA compared
to a state-of-the-art preactivated thiomer. Rheological measurements showed that CHI-Succ-MNA-MNA with a coupling rate of 170
μmol (CHI-Succ-MNA-MNA 170) lead to a 5.7-fold higher mucus viscosity than the non-thiolated control polymer (CHI-Succ).
This indicates a rheological synergism due to mucoadhesive properties. These results were confirmed by an additional mucoadhesion
experiment, which showed a significantly prolonged retention time of CHI-Succ-MNA-MNA on the small intestinal mucosa
compared to CHI-Succ (P<0.02). According to the presented results, the double preactivation seems to be a promising strategy to
obtain entirely preactivated polymers with improved mucoadhesive properties.
Humaira shaheen
Agriculture University Rawalpindi, Pakistan
Title: An ethnopharmacological evaluation of indigenous plants used by the communities of district kotli, azad jammu kashmir
Biography:
Abstract:
Aim of the Study and Ethnopharmacological Relevance: District Kotli is a mountainous area ranging from scrub to alpine forests
which is sporadically known with reference to ethnopharmacological research. Such studies are mandatory for discovering new crud
drugs based on the folk knowledge. This study was aimed to collect knowledge of medicinal plants and folk herbal remedies from the
local inhabitants.
Materials and Methods: In all, 100 local informants including 55 were males and 45 were interviewed using semi-structured
questionnaire in addition to group discussions and field observations. Different ethnobotanical indices such as Spearmann test,
relative frequency of citation (RFC), Relative Importance (RI), Informants Consensus Factor (FIC) and Medicinal Importance (MI)
were calculated from the recorded data. Besides, to check the novelty of information, the recorded data was compared with the
literature from the recent past.
Results: In all, 80 medicinal plants were used in treating 58 diseases/ailments by the indigenous communities. Comparing the
knowledge held by men and women, men had much higher knowledge on medicinal plants (Z = -2.8; p < 0.05) and their uses (Z
= -0.252; p< 0.005): they reported 14.05 (±10.18) species and 6.12 (±4.13) uses, while women 8.55 (±6.06) species and 5.83 (±3.65)
uses. Abdominal pain was the most prevalent problem treated with nine species (7.38%), followed by acute injuries & pain (7 spp.,
5.74%) and diabetes (5 spp., 4.10%). The Informants' Consensus Factor (FIC) analysis indicated that among the 19 disease categories
used, mouth, ear and eye problems (0.91), skin and related symptoms (0.91), circulatory problems (0.90), allergies (0.90), hair related
problems (0.90) and diabetes (0.90) had the highest FIC values. Aerial parts (21spp.) and leaves (20 spp.) were highly utilized for
making recipes. The oral application of powder was the leading mode of application (21 spp., 26.25%). Zanthoxylum alatum possessed
the highest relative importance (93.75), followed by Adhatoda zeylanica (91.67).
Conclusions: The high informant consensus suggests that current use and knowledge of medicinal plants are still strong and local
inhabitants have a high dependency on medicinal plants in meeting their primary health care. This knowledge can be exploited in
validation of this knowledge for the drug development and pharmacological activities in addition to the conservation and management
of these valuable plant resources of this territory.
Keywords: Ethnopharmacological research, Local inhabitants, Frequency of Citation, Relative Importance, Informants Consensus
Factor, Medicinal Importance.
humaira.shaheen@comsats.edu.pk
Humaira shaheen
Agriculture University Rawalpindi, Pakistan
Title: An ethnopharmacological evaluation of indigenous plants used by the communities of district kotli, azad jammu kashmir
Biography:
Abstract:
Aim of the Study and Ethnopharmacological Relevance: District Kotli is a mountainous area ranging from scrub to alpine forests
which is sporadically known with reference to ethnopharmacological research. Such studies are mandatory for discovering new crud
drugs based on the folk knowledge. This study was aimed to collect knowledge of medicinal plants and folk herbal remedies from the
local inhabitants.
Materials and Methods: In all, 100 local informants including 55 were males and 45 were interviewed using semi-structured
questionnaire in addition to group discussions and field observations. Different ethnobotanical indices such as Spearmann test,
relative frequency of citation (RFC), Relative Importance (RI), Informants Consensus Factor (FIC) and Medicinal Importance (MI)
were calculated from the recorded data. Besides, to check the novelty of information, the recorded data was compared with the
literature from the recent past.
Results: In all, 80 medicinal plants were used in treating 58 diseases/ailments by the indigenous communities. Comparing the
knowledge held by men and women, men had much higher knowledge on medicinal plants (Z = -2.8; p < 0.05) and their uses (Z
= -0.252; p< 0.005): they reported 14.05 (±10.18) species and 6.12 (±4.13) uses, while women 8.55 (±6.06) species and 5.83 (±3.65)
uses. Abdominal pain was the most prevalent problem treated with nine species (7.38%), followed by acute injuries & pain (7 spp.,
5.74%) and diabetes (5 spp., 4.10%). The Informants' Consensus Factor (FIC) analysis indicated that among the 19 disease categories
used, mouth, ear and eye problems (0.91), skin and related symptoms (0.91), circulatory problems (0.90), allergies (0.90), hair related
problems (0.90) and diabetes (0.90) had the highest FIC values. Aerial parts (21spp.) and leaves (20 spp.) were highly utilized for
making recipes. The oral application of powder was the leading mode of application (21 spp., 26.25%). Zanthoxylum alatum possessed
the highest relative importance (93.75), followed by Adhatoda zeylanica (91.67).
Conclusions: The high informant consensus suggests that current use and knowledge of medicinal plants are still strong and local
inhabitants have a high dependency on medicinal plants in meeting their primary health care. This knowledge can be exploited in
validation of this knowledge for the drug development and pharmacological activities in addition to the conservation and management
of these valuable plant resources of this territory.
Keywords: Ethnopharmacological research, Local inhabitants, Frequency of Citation, Relative Importance, Informants Consensus
Factor, Medicinal Importance.
humaira.shaheen@comsats.edu.pk
- Ethnopharmacology of Medicinal Plants | Ethnoveterinary Medicines |Phytochemical Studies of Plants and Plant Extracts | Pharmacology and Toxicology | Clinical pharmacology | Natural Products Chemistry and Pharmacology | Immunopharmacology | Pharmacogenetics and Pharmacogenomics
Chair
Ning-Sun Yang
Session Introduction
Gabriela Hrckova
Institute of Parasitology, Slovak Academy of Sciences, Slovakia
Title: Hypoxic and aerobic culture systems influence activity of selected flavonoids in eukaryotic parasitic organism in vitro: An interesting model for pharmacological research
Biography:
Abstract:
Larval stage of flatworm, tetrathyridium, has ability of survival and asexual multiplication in a wide range of vertebrate hosts what
indicates a high biochemical and physiological potential for adaptation. We recently developed axenic long-term in vitro cultivation
systems of larvae under both hypoxic and aerobic conditions, representing the unique eukaryotic model for pharmacological and
molecular studies. This in vitro system allowed us to study the dose- and time-dependent effects of various natural compounds on
multiple biochemical and molecular pathways in larvae. We have focussed on flavonolignans (silybin, dehydrosilybin and silychristin)
prepared from silymarin, the main component of herb Silybum marrianum and two other flavonoids: bergenin and arbutin. Activity
of individual compounds on metabolic activity of larvae, which reflects activity of enzymes of complex I and II in mitochondria, was
dependent on oxygen tension in culture. Flavonolignans also modulated activity of other enzymes like GST, SOD, enzymes involved
in glucose transport, in lipogenesis, cell death and motility, indicating their complex activity on multiple targets in larvae.
Hrcka@saske.sk
Guillaume Arcile1
1Institut de Chimie des Substances Naturelles ICSN-CNRS, France
Title: Neuroprotective effect of SNC-1, a biocatalysis processed ayurvedic plant extract as a promising ethnopharmaceutic treatment for Alzheimer’s and Parkinson’s disease
Biography:
Abstract:
The three ayurvedic medicinal plants Withania somnifera, Emblica officinalis, and Bacopa monnieri, were extracted by high-pressure
static extraction using the Zippertex technology. The extracts were mixed to reach quantifiable amounts of active compounds
identified by HPLC-MS analysis. The mixture of extracts was incubated with resting cells of the fungus Beauveria bassiana ATCC
7159. The fermentation promoted the fluidization of the starting dense mixture, while HPLC monitoring evidenced the disappearance
of glucogallin from E. officinalis extract and the concomitant increase in Gallic acid content. While topical exposure of the chick
embryo chorioallantoic membrane (CAM) to the non-fermented extract led to an extensive necrosis, the fermented extract was
not toxic and reduced the CAM vascularization, supporting its antiangiogenic potency. The innocuity of the fermented extract was
demonstrated using the in vivo LD50 test, the morphological examination of internal organs of treated rats, as well as the evaluation
of blood biomarkers of liver damage (aspartate aminotransferase and alanine aminotransferase). The fermented extract SNC-1 was
developed as a nutraceutical antiangiogenic treatment of age-related macular degeneration and commercialized in an oral form
named Ethnodyne-Visio. Furthermore, study showed that SNC-1 (dried from of Ethnodyne-Visio) was able to significantly protect
neurons (cortical as well as dopaminergic neurons – in vitro models of Alzheimer’s and Parkinson’s diseases) from different injuries
(β amyloid, mitochondrial toxins, glutamate). Additionally, SNC-1 stimulated neurite outgrowth). Interestingly these effects were still
observed at low doses and were still efficient when the extract was applied up to 4h after the toxins application. Extensive efforts are
dedicated to the identification of the active compound responsible of these effects. Clinical trials are underway to confirm the benefit
of SNC-1 for Alzheimer and Parkinson patients.
Guillaume.ARCILE@cnrs.fr
Ngono Ngane R A
University of Douala, Cameroon
Title: A Review of ethnopharmacological research of some cameroonian medicinal plants
Biography:
Abstract:
The use of herbal medicines as complements or alternatives to modern medicines has been on the increase. This review summarizes
research carried out on some Cameroonian medicinal plants between 2007 and 2017 by our research team at the Faculty of
Science of the University of Douala in collaboration with some national and international scientists. Medicinal plants are resources of
traditional medicines and modern medicine derived from plants. This study was designed to outline some biologic activities of various
medicinal plants extracts used by the Cameroonians’ and central African people. Several medicinal plants growing in Cameroon were
identified as having pharmacological properties. These plants species which include Crassocephalum bauchiense, Dichaentanthera
africana, Harungana madagascariensis, Milletia conraui, Nauclea latifolia, Pecedanum zenkeri, Ptelopsis hylodendron, Schefflera
barteri, Strychnos icaja, Strychnos malacoclados with healing properties are listed alongside their traditional use and a summary of
the scientific research achieved are given. They were tested for their in vitro or in vivo biological activity by standard protocols. These
ten plants have shown antimicrobial, antioxidant, antiplasmodial, immunomodulatory, analgesic, antipyretic, anti-Herpes simplex
virus and α-glucosidase inhibitory activities. Natural products (diterpenoids, alkaloids and flavone) have been identified from five of
them. The results suggest that the plants extracts could be a promising rough material for the development of new and more effective
modern drugs. Based on these results, drugs from Crassocephalum were developed but no patent is obtained till today.
angono@yahoo.com
Hoang Le Tuan Anh
Mientrung Institute for Scientific Research, Vietnam
Title: Searching for drugs from Vietnamese ethno-medicine plants
Biography:
Abstract:
Vietnam is easternmost country in Southeast Asia where the climate changes considerably from place to place due to differences
in latitude. There are two World Natural Heritage Sites (Halong Bay and Phong Nha - Ke Bang National Park), and six biosphere
reverses (Can Gio Mangrove Forest, Cat Tien, Cat Ba, Kien Giang, the Red River Delta and Western Nghe An) in Vietnam. We
are one of 25 countries which possess a uniquely high level of Biodiversity. Vietnam is hometown to an estimated 12,000 species
of high-value plants; approximately 3,780 (~ 36%) medicinal plants; and account for approximately 11% of the 35,000 species of
medicinal plants known worldwide. There are 54 ethnic groups in Vietnam with their own characters (language, lifestyle and cultural
heritage). That’s why many ethno-medicine plants are not yet known and are used only by ethnic groups. Until now, hundreds of
Vietnamese medicinal plants were studied such as Physalis angulata, Cleistanthus indochinensis, Ophiopogon japonicus, Garnoderma
lucidum, Camellia bugiamapensis, Momordica charantia, Hedychium coronarium, Annona glabra, Callisia fragrans, Eurycoma
longifolia, Cudrania tricuspidata, Tacca species, Mallotus species, Glochidion species, Solanum species, Trichosanthes species, etc. A
lot of potential compounds were discovered from Vietnamese medicinal plants such as physalin B, D, F, G; malloapelta B, peaonol,
cleistantoxin, desgalactotigonin, berberin, rotundin, rutin, artemisinin, artesunat, etc. The opportunities to discover new drugs from
Vietnamese ethno-medicine plants with the collaborators worldwide are so big.
hoangletuananh@hotmail.com
Anat Elmann
Agricultural Research Organization, Austria
Title: Harnessing phytochemicals to protect neuronal and glial cells from oxidative stress
Biography:
Abstract:
Oxidative stress and amyloid beta toxicity are involved in the pathogenesis of Alzheimer's diseases. We have previously demonstrated
that an extract prepared of the plant Achillea fragrantissima (Af) protected cultured brain astrocytes from oxidative stressinduced
cell death and down regulated microglial activation. Using activity guided fractionation, we have purified from Af an active
flavonoid named 3,5,4-trihydroxy-6,7,3-trimethoxyflavone (TTF). TTF protected cultured astrocytes from H2O2–induced cell death
via interference with cell signaling (inhibition of SAPK/JNK, ERK 1/2, and MEK1 phosphorylation) and by reducing the levels of
oxidative stress-induced intracellular reactive oxygen species (ROS). The mechanism of the protective effect of TTF against H2O2-
cytotoxicity could not be attributed to a direct H2O2 scavenging but rather to the scavenging of free radicals as was shown in cell free
systems. In addition, TTF protected cultured neuronal cells from amyloid beta cytotoxicity via interference with cell signaling events
and by reducing the amyloid beta - induced levels of intracellular ROS. Moreover, TTF exhibited anti-inflammatory activities and
inhibited the LPS-elicited secretion of the proinflammatory cytokines Interleukin 6 (IL-6) and IL-1beta from microglial cells. Our
results suggest that TTF might be a therapeutic candidate for the treatment of Alzheimer’s disease as well as other neurodegenerative
diseases where oxidative stress, neuroinflammation and amyloid beta toxicity are part of the pathophysiology.
aelmann@volcani.agri.gov.il
Vincenzo Rispoli
University of Magna Graecia, Italy
Title: From popular medicine knowledge to evidence ethnopharmacolgy efficacy can nature give us the tools to fight human neurodegenerative diseases?
Biography:
Abstract:
From the night of time, Man has always tried to relieve his suffering by turning his attention to Nature and seeking remedies
to cure the ills of his body. In recent decades, phytotherapy has been re-evaluated, not only because of the growing number of
patients who use it, but, above, all, since numerous preclinical and clinical researches have been able to demonstrate and confirm
the pharmacological bases of plant-based treatment, since acquired in the past from traditional medicine in empirical way. Today
phytotherapy has become a medical discipline in all aspects, because it applies the method and the rigor of scientific evidence. Here
it is addressed the history, current as well as the future perspective of AD treatment by Ethnomedicine, taking into consideration
the probable causes and preventive mechanisms together with the treatment methods. Alzheimer's disease (AD) is an irreversible,
slowly progressive neuodegenerative disease of the brain, and it is characterized by memory deficits and progressive cognitive
impairment, accompanied by neuropsychiatric changes. It has become the fourth leading cause of death in developed countries.
The main symptoms of AD are primarily caused by a cholinergic dysfunction due to degeneration of basal cholinergic forebrain
(BCF). in particular, consistent neuronal loss into the nucleus basalis of Meynert (NBM), which produces a reduced cholinergic input
to target areas such as cerebral cortex and hippocampus. Pathogenic cause of AD remains incompletely understood. So, currently
acetylcholinesterase inhibitors (AChEIs), which decrease the breakdown of the neurotransmitter, has been the main symptomatic
therapy for mild to moderate Alzheimer’s patients, approved by FDA. To date, AChEIs are considered the main pharmacological
strategy in the palliative approach in the therapy of AD; they undoubtedly, temporarily restore the disrupted cholinergic transmission
in brain. Consequently, the search for novel compounds is necessary. In recent times, several chemical and pharmacological studies
have searched for new drugs, in an attempt to extract and isolate from plants novel compound or better understand the effects of those
already known, in an effort to fight this terrible disease.
Conclusions: AD is a multi-causal and multi-factorial progressive neurodegenerative disease with complicated pathogenesis. Thus it
is likely that multiple drugs or drugs with poly-pharmacological activities will be the best therapeutic approaches to address the diverse
pathological aspects of the disease.Anti-cholinesterasic activities, anti-Aβ aggregation and anti-Aβ-induced oxidative injury such as
anti-NMDA-induced toxicity and anti-inflammatory activity showed by many herbal compounds, encourage their use as potential
disease-modifying drugs for neurodegenerative disorders, opening to new insight and future perspectives for a multi-functional
phytomedicine. From this point of view, we have to overcome our way to think Ethnomedicine and official medicine opposed each
other, or that orthodox medicine is better than traditional medicine, as well as phytotherapeutic remedies as an alternative to synthetic
drugs. The two pharmacological approaches are often, and it should always be, complementary; that is, to be able to complement each
other. Science and consciousness of physician will depend on the correct integration of. In conclusion, Evidence based pharmacology
(EBP) is the conscientious, explicit, judicious and reasonable use of modern, best pharmacotherapeutic evidence in making decisions
about the care of individual patients. EBP must integrate clinical experience and patient values with the best available research
information.
Keywords: Alzheimer's disease, Neurodegeneration, Multi-target drus, Disease-modifying therapy, Phytotherapy, Preventive
Mechanism, Treatment Methods.
rispoli@unicz.it
Antonella Smeriglio
University of Messina, Italy
Title: Essential oil of Citrus lumia risso: Phytochemical profile, antioxidant properties and activity on the central nervous system
Biography:
Abstract:
Background: The use of essential oils (EOs) is known since long time in traditional medicine and aromatherapy for the management
of various oxidative stress-related disorders and is further increased recently for their neuroprotective and anti-aging potential as well
as for reducing anxiety and stress.
Purpose: To evaluate, for the first time, the chemical composition of Citrus lumia Risso EO and its antioxidant, anti-cholinesterase
as well as neuroactive properties by cell-free and cell-based assays. Citrus lumia Risso is one of the oldest cultivated limettes in Sicily,
Mediterranean Europe and North Africa by which distinguished for the fruit shape and mainly for the sweet, no-acidic juice.
Methods: The distribution and morphology of oil glands in the fruit peel were analysed microscopically, by SEM. A phytochemical
profile elucidation, by GC-FID and GC-MS analysis, an in vitro evaluation of antioxidant and free-radical scavenging properties
of the EO, using different in vitro methods (Folin-ciocalteu, DPPH, TEAC, FRAP, Fe2+-chelating capacity, ORAC and β-carotene
bleaching assays) as well as anti-cholinesterase activity were carried out. The impact on the spontaneous electrical activity of rat
neuronal networks by means of microelectrode array (MEA)-based system, was evaluated.
Results: The EO has shown strong antioxidant and free radical scavenging properties, particularly in hydrogen atom transfer based
assays (β-carotene bleaching and ORAC assay, IC50 22 μg/mL and 46 μg/mL, respectively), that can be attributed to the high content
of monoterpene and monoterpene derivatives, especially d-limonene (48.905%), and linalool (18.245%). Furthermore, has shown
an interesting anti-acetylcholinesterase activity (IC50 258.25 μg/mL). Data from MTT analysis indicate that the cytotoxicity of OE,
evaluated on L929 mouse fibroblasts, is very low, with an IC50 higher than 500 ug/mL at 48 h. Rat neuronal networks subjected to EO
showed a concentration-dependent inhibition of spontaneous electrical activity.
Conclusions: Results indicate that this EO could be an important source of natural antioxidants potentially useful in the detoxification
mechanisms of the organism, suggesting an important preventive role in the onset of oxidative stress-related pathologies.
asmeriglio@unime.it
Ning Sun Yang
Agricultural Biotechnology Research Centre, Taiwan
Title: Immune cell type or signaling-specific effects of four candidate phytomedicines for cancerous and inflammatory diseases
Biography:
Ning-Sung Yang is a Distinguished Professor and Distinguished Research Fellow of Academia Sinica and the associated universities in Taipei, Taiwan. He has
helped the development of gene gun technology and pioneered its application to mammalian transgene experimental systems and gene therapy approaches. After
thirty years of a research career in USA, Dr. Yang established the Agricultural Biotechnology Research Center in Academia Sinica, Taipei. He was elected in 2006
as a member of the American Association for the Advancement of Science (AAAS, USA). He has published more than 160 research papers, and obtained 14 USA
patents.
nsyang@gate.sinica.edu.tw
Abstract:
In our recent studies, we showed that many phytochemicals or their derivatives can confer diverse pharmacological activities in
preventing tumor metastasis (See References). These phytochemical activities regulate the immune system or non-malignant
cells in a tissue microenvironment under various in vivo conditions. And these activities cannot be effectively addressed by the
conventionally used cell culture systems in vitro. Our current strategy is to initiate our study through a combination of omics
approaches and specified in vivo tumor model systems. Specifically, we first make predictions for candidate specific pharmacological
activities according to the “omics screening” profile of differential responsive genes, proteins or involved metabolites. Then we make a
list of hypothesis in priority sequence. Finally, we detect/evaluate the candidate mechanistic signaling cells/molecules for suppression
of well-defined tumor metastasis activity. With this strategy, we have been successful in evaluating several pharmacological effects
of nature plant phytochemicals or their derivatives on immune cell systems or the surrounding nonmalignant cells in defined tumor
microenvironment. The omics approaches we used to predict and reveal the specific pharmacological activity of phytochemicals
or medicinal herbal extracts/fractions, including genomics, transcriptomics, proteomics, metabolomics and the next generation
sequencing (NGS) systems. The systematic analysis of the observed data is to “contemplate” the cellular or physiological responses,
according to the various pattern changes detected in different response elements. Technically, in our task on pathway and net-working
analyses, the overall or big trend/pattern of the different responsive elements or/and their signaling systems is the key for predicting
specific pharmacological mechanisms, instead of the “super” inducer or suppressor single gene activities. For instance, the “expression
pattern or trend”, rather than the “fold change”, of specific microRNA species is a much more important factor for predicting their
suppressive effect on target genes. As a result, the understanding and background knowledge of specific targets or signaling networking
pathways of specific disease targets are quite important and need to be carefully reviewed “first” before “searching the omics data” in a
totally randomized way. With this approach, whether the expression trend of their downstream genes can fit the proposed hypothesis
is also considered as a key factor.
Hesham R El-Seedi
University of Malaya, Malaysia
Title: Isolation and structure elucidation of new cytotoxic polypeptide from bee venom
Biography:
Abstract:
Honeybee is an important economic insect, which have vital role in the pollination for crops and wild flowers. In addition to
ecological importance, honeybee supplies with various products, including bee venom (BV). This venom has been used in
traditional medicine for thousands of years and there is an increasing interest in their applications in modern medicine. BV has
diverse biological activities as anticancer, antimicrobial, anti-inflammatory, antiviral and hepatoprotective. Today there is an urgent
call to find anticancer agents from the natural products with less ecological damage and minimum health and environmental hazards.
Our main aim is to identify and characterize the bioactive peptides from bee venom. These peptides have been poorly characterized,
partly because they are generally present in trace quantities. Isolated active peptides from the bee venom have been identified using
techniques including High Performance Liquid Chromatography (HPLC), Mass Spectrometry (MS, LC/MS, MS /MS), Amino Acid
Analysis (AAA) and 2D-Nuclear Magnetic Resonance Spectroscopy (2D-NMR). Polar fractionation prior to screening of anticancer
has been done. The bioassay-guided isolation for bee venom leads to isolation of four peptides melittin, apamin, MCD and secapin.
Melittin showed cytotoxic activity on three cancer cell lines: lymphoma cells U-937GTB, myeloma cells RPMI 8226/s, leukaemia
cells CCRF-CEM and two drug-resistant sub-lines (PRMI 8226/Dox40 and CEM/VM-1), with IC50 values of 1.3, 1.1, 1.4, 1.7, 2 μM,
respectively.
hesham.el-seedi@fkog.uu.se
- Latest Trends in Ethnopharmacology | Ethnopharmacology of Alkaloids | Ethnoveterinary Medicines | Pharmacognosy and Phytochemistry | Applied pharmacology | Cardiovascular Pharmacology | Ethnobotany | Ethnopharmacy | Biologics and Biosimilars
Chair
Anupam Bishayee
Larkin University, USA
Session Introduction
Spiro M Konstantinov
Medical University of Sofia, Bulgaria
Title: Antineoplastic activity of cannabidiol containing products
Biography:
Abstract:
Malignancies are the second cause of death in humans worldwide. Despite many newly introduced and approved targeted drugs,
the problem of multidrug resistance and serious side effects remain unsolved and open the search for effective natural products
with fewer side effects. Curcumin is a practically non-toxic compound of plant origin with own antineoplastic and NF-kB inhibitory
activities. Curcumin is one of the most popular drugs derived from Ayurveda traditions. We investigated the cytotoxic activity of
curcumin loaded electrospun mats in human hepatic and colon carcinoma cell lines (HEP-G2 and HT-29). Disks with 5 mm diameter
of the electrospun mats caused nearly 80% inhibition in HT-29 colorectal cells. The efficacy against the HEP-G2 hepatocellular
carcinoma cells was weaker. The mats showed antibacterial features and were found to be biocompatible with human tissues of different
origin. The tested polymeric mats increased the accumulation of curcumin inside of the malignant cells as estimated by fluorescent
microscopy. One of the polymeric mats represents fully water soluble form of curcumin that may have distinct pharmacokinetic
advantages. Taken together our experimental findings indicate that the non-toxic yellow pigment curcumin after inclusion into
electrospun polymeric mats can be used for topical treatment of liver lesions (e.g. colorectal cancer metastases) and these results are
promising in terms of further clinical application.
Maya M Zaharieva
Bulgarian Academy of Sciences, Bulgaria
Title: Curcumin based possibilities for targeting protein kinase B and nuclear factor kapa B In cutaneous T-cell lymphoma
Biography:
Abstract:
Cutaneous T-cell lymphoma (CTCL) is an orphan disease which primarily affects the skin by clonal accumulation of neoplastic
T-lymphocytes and is characterized by a 5-year overall survival of 32% of the patients, if the skin is involved and only 7%
for extracutaneous involvement. CTCL therapy is challenging, often empiric because of the limited insight into the genetic basis
and single drug therapy is usually not applicable. Curcumin is one well-known ethnopharmacological non-toxic drug with
limited bioavailability. The objective of our study was to investigate new treatment modalities for targeting CTCL by combining
nanoencapsulated curcumin with alkylphosphocholines thus affecting malignant cell proliferation, skin inflammation and related
infections. The nanoparticle size and zeta-potential of Nano-systems containing curcumin were determined by photon correlation
spectroscopy and electrophoretic laser Doppler velocimetry. Curcumin concentration was measured by HPLC. MTT- (ISO 10993-5)
and CFU-assays were performed on CTCL cell lines for evaluation of cell viability and clonogenicity. Cell death ELISA, microscopy,
Hoechst staining and Western blotting were used to monitor hallmarks of apoptosis. Antimicrobial activity was evaluated by ISO
20776-1:2006 (E). Chou & Thalalai software and response surface analysis of combination effects were used to design the experiments
and to estimate drug-drug interactions. The nano-sized curcumin delivery systems were prepared using two copolymeric carriers
with diameter less than 200 nm and negative surface charge. Encapsulated curcumin penetrated through the cell membranes of
CTCL cells faster than curcumin solubilized in ethanol. Combination effects were evaluated as additive to slight synergistic. We have
observed in treated samples induction of apoptosis and modulation of PKB/Akt and related signal proteins. Erufosine has exhibited
bacteriostatic activity against Gram-positive bacteria in concentrations ranging from 32 up to 100 μM. Combination of erufosine
with nano-sized curcumin has led to bactericidal effect. Taken together, our experimental findings clearly indicated that properly
designed combinations of curcumin with alkylphosphocholines may show higher antineoplastic potential than single compounds
and could be beneficial for the treatment of CTCL as orphan disease.
Wei-Hong Cong
Beijing University of Chinese Medicine, China
Title: Synergistic effects of chuanxiong-chishao herb-pair on promoting angiogenesis at network pharmacological and pharmacodynamic levels
Biography:
Abstract:
Objective: The objective of the study is to investigate the synergistic effects of Chuanxiong-Chishao herb-pair (CCHP) on promoting
angiogenesis in silico and in vivo.
Methods: The mechanisms of action of a herb-pair, Chuanxiong-Chishao, were investigated using the network pharmacological and
pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation.
A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including
prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao. Furthermore, the
therapeutic effects and putative molecular mechanisms of Chuanxiong-Chishao actions were experimentally validated in a chemicalinduced
vascular insufficiency model of transgenic zebrafish in vivo. The mRNA expression of the predicted targets was further
analyzed by real-time polymerase chain reaction (RT-PCR).
Results: The computational prediction results found that the compounds in Chuanxiong have antithrombotic, antihypertensive,
antiarrhythmic, and antiatherosclerotic activities, for hypoxic-ischemic encephalopathy, ischemic stroke, myocardial infarction and
heart failure.In addition, compounds in Chishao were found to participate in anti-inflammatory effect and analgesics. Particularly,
estrogen receptor α (ESRα) and hypoxia-inducible factor 1-α (HIF-1α) were the most important potential protein targets in the
predicted results. In vivo experimental validation showed that post-treatment of tetramethylpyrazine hydrochloride (TMP•HCl) and
paeoniflorin (PF) promoted the regeneration of new blood vessels in zebrafish involving up-regulating ESRα mRNA expression. Cotreatment
of TMP•HCl and PF could enhance the vessel sprouting in chemical-induced vascular insufficiency zebrafish at the optimal
compatibility proportion of PF 10 μmol/L with TMP•HCl 1 μmol/L.
Conclusions: The network pharmacological strategies combining drug target prediction and network analysis identified some
putative targets of CCHP. Moreover, the transgenic zebrafish experiments demonstrated that the Chuanxiong-Chishao combination
synergistically promoted angiogenic activity, probably involving ESRα signaling pathway.
- Clinical Trials on Biopharmaceutical Products | Drug Delivery Systems | Therapeutic Biological Products | Drug Delivery System of Biopharmaceutical Products |Drug Delivery System | Biotechnological Products | Drug Disposition & Pharmacokinetics | Pharmacodynamics
Chair
Hiroshi Ohrui
Yokohama University of Pharmacy, Japan
Session Introduction
Géraldine Le Goff
National Center for Scientific Research CNRS, Institute for Chemistry of Natural Products ICSN, France
Title: New compounds from Withania Somnifera with neuroprotective activities. Isolation, structure elucidation bioassays and scale-up production
Biography:
Abstract:
The prevalence of neurodegenerative diseases are increasing worldwide due to extensions in lifespan with more than 2.1 billion
people aged 60 and more in 2030. The most representative diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD),
Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Available treatments are limited in number and efficacy and
extensive efforts are dedicated to alternative herbal therapy. Among various promising plants, Withania somnifera roots and leaves
extracts demonstrated large spectrum activities on neural dysfunction (common name Ashwagandha). Based on our previous
encouraging results, our ongoing efforts are dedicated to identify new compounds from Ashwagandha and demonstrate their
mechanism of action and their relevance in neuroprotection. Besides the known major constituents, withanolides, withanone and
withaferin, now steroidal components were identified and their biological activity investigated.
Biography:
Chawita Netirojjanakul received her BSc in chemistry from MIT, conducting research in the laboratory of Prof. John Essigmann (MIT) and Prof. Steve Ley
(Cambridge). After graduation, she pursued her interest in science policy and commercialization studying MPhil in Technology Policy at University of Cambridge,
UK, as a Gates Scholar. She received HHMI International Student Research Fellowship to conduct PhD research under the supervision of Prof. Matthew Francis
in the Chemistry Department at UC Berkeley with a focus on "development and applications of well-defined antibody and antibody fragment bioconjugates." She
is a Scientist in Therapeutic Discovery Department at Amgen.
Abstract:
The use of automated high throughput screening in large molecule discovery research still lags behind that of small molecule
discovery. Recently we developed a high-throughput large molecule discovery platform to automate hundreds of bioconjugation
reaction setup in one setting. In addition, given LC-MS is a widespread analytical bottleneck, we also established a high-throughput
mass spectrometry (HT-MS) platform to accurately detect and rapidly quantitate protein conjugates. We showed that our HT-MS
platform can be used to quantitate the extent of covalent inhibitor adducts to a cysteine-containing protein construct (~19 kDa)
and of biotinylated adducts to mAbs and Fc domains (~150 and ~50 kDa, respectively). Sample acquisition time was ~20 seconds
per sample, 10-50x shorter time than traditional LC-MS methods. Site-specific bioconjugation of human Fc domains with cysteine
engineered at different positions were conducted under a matrix of reaction conditions varying equivalents of reductants, oxidants,
and alkylating agents using the high-throughput large molecule discovery platform. Using HT-MS, 4 x 384 well plates were analyzed
in ~8 hours, as opposed to ~11 days using traditional LC-MS. This approach facilitated rapid determination of DAR values for the
reduced and intact huFc domains and selection of optimized conditions for different cysteine-engineered Fc constructs which will be
used in preparation of Fc-peptide conjugates as therapeutic leads.
Marcin Pyrski
Institute of Plant Genetics - Polish Academy of Sciences, Poland
Title: Oral booster vaccine against hepatitis B in the form of low-dosed lyophilised plant tissue bearing S-HBsAg VLPs
Biography:
Marcin Pyrski is a PhD student in Bioengineering Team led by Dr. Tomasz Pniewski in the Institute of Plant Genetics, PAS. He completed Engineering and Master’s
degrees in Biotechnology at the University of Life Sciences in Poznań. He had attended one year training in plant micropropagation in Floralab Company. Actually
he is working with plant-based HBV antigens on their expression, functionality and immunogenicity.
Abstract:
The continued HBV high prevalence coupled with deficiencies in vaccination programmes stimulate research on a new type
of vaccines. Potential orally administered plant-based vaccine is highly attractive regarding efficacy, cost-effectiveness and
availability of mass hepatitis B prevention. Freeze-dried oral formulations facilitate elimination of complex purification steps, size
reduction and better stability during storage, as well as ensure controlled administration regime in minimised medical facilities.
Micropropagation of lettuce expressing S-HBsAg was optimised to provide repeatable uniform feedstock for plant-derived oral
vaccine manufacturing. Lyophilisation protocol facilitating successful processing of lettuce leaf tissue containing S-HBsAg assembled
into VLPs (Virus-Like Particles) was developed. Several drying profiles and excipients as well as effects of freezing rate and postprocess
residual moisture were analysed. The profile of 20ºC for 20 h for primary and 22ºC for 2 h for secondary drying as well as
sucrose proved the most efficient stabilisation of S-HBsAg during freeze-drying. The process was highly reproducible (86-97%), and
provided a product with VLP content up to 200 μg/g DW. Atmosphere of nitrogen proved to preserve S-HBsAg VLPs for minimum
one year at temperatures up to 37°C. Low-dosed (5-200 ng) preparation used as oral booster vaccine elicited anti-HBs response in
animals at level of commercial injection vaccine (around 1000 mIU/ml). As a result, a plant-derived semi-product with good longterm
stability and immunogenicity of S-HBsAg was obtained for the definite formulation of oral booster vaccine against HBV.
Hesham R El-Seedi
Uppsala University, Sweden
Title: Identification of bioactive peptides from enzymatic hydrolysis of royal jelly
Biography:
Abstract:
Royal jelly (RJ) has been widely used in traditional consumables and in skin creams and ointments for health promotion. RJ is rich
in bioactive constituents such as jelleines, 10-hydroxy-2-decenoic acid, royalisin as well as the major royal jelly proteins (MRJPs),
all of which have shown antimicrobial effect in vitro. However, the characterization of RJ is far from complete, and the development
of new characterization techniques is allowing the discovery of new compounds. Many new bioactive peptides have been identified
using enzymatic hydrolysis as a tool. Enzymatic hydrolysis of RJ has verified the presence of peptides with anti-oxidant and antihypertensive
activity. In the current work, using bioassay guided fractionation of RJ enzymatic digests; a total of 42 peptides were
identified. The peptides, all belonging to the Apis mellifera genome, were identified using a combination of mass spectrometry
and bioinformatics tools. Bioassay guided isolation led to the isolation and structure elucidation of three peptides with promising
antimicrobial activity. These finding support the use of RJ as food preservative and its potential application as antibiotic.
Yannick Elias
Janssen (Cilag AG), Switzerland
Title: Achieving Quality by Design for parenterals filling with a time-pressure setup
Biography:
Yannick Elias completed his PhD from Swiss Federal Institute of Technology Zurich (ETH Zürich) in Process Engineering, focusing on continuous heterogonous
reactions and has published several papers in reputed journals. Currently, he works for Janssen Pharmaceutical Development and Manufacturing Sciences
(PDMS) as a Process Engineer, focusing on development for parenterals fill and finish operations. He worked with Janssen for more than one and a half years and
is currently leading the strategic expansion of a large molecule drug product development laboratory.
Abstract:
Particulate matter in parenteral drug products is recognized by Health Authorities as a critical quality attribute. A strong focus of fill
and finish process development is put on the appropriate selection and operation of the filling system to reduce intrinsic particle
formation, often related to shear induced drug product degradation. Rotary Piston Pumps (RPP) have been a standard selection in
Janssen for many years, as they offer a simple, compact and robust design and show a very high dosing accuracy. However, as the
drug product acts as a pump lubricant, the product is exposed to very high shear rates, which in turn can cause enhanced intrinsic
particle formation. Thus, alternative filling technologies, such as peristaltic pumps (PP) or a time-pressure (TP) system, are required
for shear-sensitive products. A TP system consists essentially of a pressurized tank and a pinch valve. Dosing accuracy is achieved by
harmonizing the vessel over pressure and the valve opening duration. To improve the overall product quality during filling of shearsensitive
products, a Quality by Design and Right the First Time approach is chosen to ensure proper equipment operation. For this,
understanding the critical process parameters, risks associated with those parameters and their impact on critical product quality
attributed is crucial. Thus, a Design of Experiment study was performed to identify and characterize the impact of six distinct process
and equipment parameters on different solutions to obtain a Design Space for optimal TP filling operation.
Yannick Elias
Janssen (Cilag AG), Switzerland
Title: Achieving Quality by Design for parenterals filling with a time-pressure setup
Biography:
Yannick Elias completed his PhD from Swiss Federal Institute of Technology Zurich (ETH Zürich) in Process Engineering, focusing on continuous heterogonous
reactions and has published several papers in reputed journals. Currently, he works for Janssen Pharmaceutical Development and Manufacturing Sciences
(PDMS) as a Process Engineer, focusing on development for parenterals fill and finish operations. He worked with Janssen for more than one and a half years and
is currently leading the strategic expansion of a large molecule drug product development laboratory.
Abstract:
Particulate matter in parenteral drug products is recognized by Health Authorities as a critical quality attribute. A strong focus of fill
and finish process development is put on the appropriate selection and operation of the filling system to reduce intrinsic particle
formation, often related to shear induced drug product degradation. Rotary Piston Pumps (RPP) have been a standard selection in
Janssen for many years, as they offer a simple, compact and robust design and show a very high dosing accuracy. However, as the
drug product acts as a pump lubricant, the product is exposed to very high shear rates, which in turn can cause enhanced intrinsic
particle formation. Thus, alternative filling technologies, such as peristaltic pumps (PP) or a time-pressure (TP) system, are required
for shear-sensitive products. A TP system consists essentially of a pressurized tank and a pinch valve. Dosing accuracy is achieved by
harmonizing the vessel over pressure and the valve opening duration. To improve the overall product quality during filling of shearsensitive
products, a Quality by Design and Right the First Time approach is chosen to ensure proper equipment operation. For this,
understanding the critical process parameters, risks associated with those parameters and their impact on critical product quality
attributed is crucial. Thus, a Design of Experiment study was performed to identify and characterize the impact of six distinct process
and equipment parameters on different solutions to obtain a Design Space for optimal TP filling operation.
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