Day 2 :
- Drug Delivery Devices Approaches and Manufacturing | Transdermal & Intradermal Drug Delivery System | Pharmaceutical Formulations Academic and Industry Perspective | Pharmaceutical Research and Development | Drug Designing and Development | Pharmaceutical Excipients Development
Chair
Yavuz Selim Silay,
Istanbul ConsulÆŸ ng Group, Turkey
Session Introduction
Pooyan Makvandi
Damghan University, Italy
Title: Injectable anÆŸ bacterial hydrogels for potenÆŸ al applicaÆŸ ons in drug delivery
Time : 11:40-12:10
Biography:
Pooyan Makvandi received his PhD in polymer chemistry from University of Mazandaran, Iran, in 2017. Prior to compleÆŸ ng PhD, he was a visiÆŸ ng scholar at University of Salento, Italy, for 6 months. Currently, he is working atInsÆŸ tute for Polymers, Composites, and Biomaterials (IPCB), NaÆŸ onal Research Council (CNR) of Italy. His works focus on biomaterials for ÆŸ ssue regeneraÆŸ on, anÆŸ microbial compounds, dental materials, nanostructures and nanocomposites.
Abstract:
Hydrogels have aƩ racted research aƩ enƟ on for Ɵ ssue engineering. ThermosensiƟ ve amphiphilic block copolymers, polyethylene oxide-polypropylene oxide copolymers (Poloxamers or Pluronics, PPO-PEO-PPO), thanks to their ability to undergo thermal gelaƟ on, to their good tolerability, and low irritancy/ toxicity, have been used in the biomedical fi eld. These materials could be applied as drug/biomolecule carrier to protect them from a hosƟ le environment and modulaƟ ng delivery in response to temperaturechange. Hyaluronic acid (HA) is naturally occurring glycosaminoglycan, presents in mammalian connecƟ ve Ɵ ssues. It has been demonstrated that HA promotes dermal regeneraƟ on and for this, it is widely used as dermal fi llers, as wound dressings and substrates for dermal engineering applicaƟ ons. It has to be highlighted that infecƟ on is a crucial and generally unsolved issue in Ɵ ssue regeneraƟ on. Therefore,materials containing anƟ microbial compounds, such as quaternary ammonium salts, TiO2, and, Ag nanoparƟ cles have been uƟ lized. Among these compounds, Ag NPs have shown the capability to inhibit or decline infecƟ ons. Various techniques, including chemical and physical approaches, have been developed to synthesis Ag NPs. Unfortunately, in the aforemenƟ oned approaches, organic passivators, toxic both for the environment and the human body, are used. Biosynthesis of NPs, by using microorganisms and plants, has received considerable aƩ enƟ on due to the growing need to develop environmentally and non-toxic technologies. In this context, we propose novel and green nanocomposites injectable hydrogels based on HA, Pluronics, and AgNPs for Ɵ ssue regeneraƟ on and drug delivery applicaƟ ons.
Rezvan Jamaledin
Federico Secondo University, Italy
Title: Polymer microneedle patches for delivery of fi lamentous bacteriophage displaying the pepÆŸ de OVA257-264 for sÆŸ mulaÆŸ on of innate and adapÆŸ ve immunity
Time : 12:10-12:40
Biography:
Rezvan Jamaledin is a Ph.D. student in Industrial Product and Process Engineering at Federico Secondo University. She has received her Master degree from Shahid Chamran University, Ahvaz, Iran. Her fi eld is a vaccine, drug delivery by the microneedles.
Abstract:
Biodegradable polymer microneedles are recognized as a valuable route for transdermal drug andvaccine delivery. Biodegradable microneedle technologies have been used for transdermal sustained deliveries of diff erent drugs and vaccines. Bacteriophages enÆŸÆŸ es have aÆ© racted growing interest as opÆŸ mal vaccine delivery vehicles. The use of bacteriophage as an anÆŸ gen delivery system is based on a modifi caÆŸ on of the phage display technology. In parÆŸcular, it is designed to express the fi lamentousbacteriophage anÆŸ gen display mulÆŸ ple copies of exogenous pepÆŸ des (or polypepÆŸ des) as fusions to viral capsid proteins. Since dermis is highly populated by dendriÆŸ c cells, the system as a candidate vaccine delivery is able to induce both the innate and the adapÆŸ ve response. This work explores the development of controlled release microparÆŸ cles made of poly lacÆŸ c-co-glycolic acid (PLGA) that stably encapsulate phage. The microparÆŸ cles were prepared by double emulsion method. The size of the micro parÆŸ cles is around 15μm. Overall, Phage-encapsulated PLGA promises an outstanding future for the development ofdiff erent phage-based vaccine plaÆž orms.
Simona Gallorini
GSK Vaccines, Italy
Title: Improved skin delivery of vaccines by targeting antigens to C-lectin receptors on skin dendritic cells
Time : 12:40-13:10
Biography:
Simona Gallorini has completed his PhD in the immunology fi eld at the Bologna University and postdoctoral studies from FormulaÆŸ on and Deliverydepartment at NovarÆŸ s company. She is a scienÆŸ st in the Drug Product department of Technical Research and Development at GSK Vaccines organizaÆŸ on. She has a sound scienÆŸfi c experÆŸ se in technological plaÆž orms both for injectable formulaÆŸ ons and alternaÆŸ ve delivery which led to thepublicaÆŸ on of several patents and papers in reputed journals.
Abstract:
The potenÆŸ al benefi ts of skin delivery of vaccines derive from the presence of a network of anÆŸ gen presenÆŸ ng cells (APCs) in the skin layer. TargeÆŸ ng receptors, including the DecÆŸ n-1 receptor, present on skin dendriÆŸ c cells (SDCs) should result in enhanced immunogenicity of a vaccine. We focused our aÆ© enÆŸ on on the two major agonists of the DecÆŸ n-1 receptor, β-(1-3)-glucans and mannans, and we put in place two diff erent strategies to target the SDSs. In the fi rst one a syntheÆŸ c β-(1-3)-glucan hexasaccharide, that acÆŸ vates the innate immune response by interacÆŸ on with the C-type lecÆŸ n-like DecÆŸ n-1 receptor,was chemically conjugated to the geneÆŸ cally detoxifi ed diphtheria toxin anÆŸ gen. We demonstrated that the in vitro acÆŸ vaÆŸ on of the receptor was impacted by the presentaÆŸ on ofthe glucan on the protein carrier. In vivo results in mice showed that the conjugaÆŸ on of the syntheÆŸ c β-(1-3)-glucan when delivered intradermally resulted in higher anÆŸ body ÆŸ ters in comparison to intramuscular immunizaÆŸ on. In the second strategy a Mannose-cholesterol amine conjugate was incorporated to a Lipid NanoparÆŸ cles (LNP) to increase the uptake by APCs rich in C-type lecÆŸ ns and improve the potency of Self Amplifying mRNA (SAM) encoding Infl uenza hemaggluÆŸ nin. The mannosylated LNP (MLNP) was evaluated in mice, by both intramuscular and intradermal administraÆŸ ons. SAM MLNP exhibited in vitro enhanced uptake in comparison to unglycosylated LNP from dendriÆŸ c cells, and in vivo more rapid onset of the anÆŸ body response. The increased binding anÆŸ body levels also translated into higher funcÆŸ onal hemaggluÆŸ nin inhibiÆŸ on ÆŸ ters, parÆŸ cularly following intradermal administraÆŸ on. Hence, the present work illustrates the benefi t of targeÆŸ ng vaccines to the ÆŸ ssue resident APCs and respecÆŸ ve approaches could be parÆŸ cularlyvaluable for the development of novel skin delivery systems.
Luis CasÆŸ llo HenrÃquez
University of Costa Rica, Costa Rica
Title: Drug development through quality by design (QbD): PreformulaÆŸ on and formulaÆŸ on studies of Rupatadine Fumarate tablets
Biography:
Luis CasÆŸ llo has completed his bachelor’s studies at the age of 23 years from University of Costa Rica and is looking for the beginning of master studies on 2020. He has worked since 2017 in the Faculty of Pharmacy, University of Costa Rica as a physical chemistry and industrial pharmaceuÆŸ cal technology professor. Also, he is part of the InsÆŸ tute of PharmaceuÆŸ cal Research (INIFAR), where he does research about solid state, thermal analysis and development of drug formulaÆŸ ons. He has published 4 papers in reputed journals.
Abstract:
Given the need to produce medicines of the highest quality and improve compeÆŸÆŸ veness in the pharmaceuÆŸ cal, industrial and healthcare fi elds, many companies have adopted Quality by Design (QbD) to guarantee the quality of their products. The main objecÆŸ ve of this research is to develop an immediate release Rupatadine fumarate 10 mg tablets formulaÆŸ on by direct compression, through a Quality by Design approach in Costa Rica. Quality by Design elements such as Target Product Profi le, Quality Target Product Profi le and the CriÆŸ cal Quality AÆ© ributes were defi ned. In the preformulaÆŸ on study, compaÆŸ bility tests were carried out between the raw materials by Diff erenÆŸ al Scanning Calorimetry, Thermogravimetric analysis and Near Infrarred Spectroscopy. A Quality Risk Management done through Ishikawa’s diagram, allowed the defi niÆŸ on of the CriÆŸ cal Material AÆ© ributes. Three formulaÆŸ on prototypes were prepared by direct compression and the CriÆŸ cal Process Parameters were defi ned. In addiÆŸ on, the impact of compression on the crystalline state of the formulas was studied through Diff erenÆŸ al Scanning Calorimetry, Thermogravimetric analysis and X-Ray Diff racÆŸ on. The prototypes were analyzed in terms of organolepÆŸ c properÆŸ es, idenÆŸfi caÆŸ on, potency, content uniformity, dissoluÆŸ on, disintegraÆŸ on, friability and loss by drying. Therefore, the approaching of a Quality by Design model to the current development allowed to obtain saÆŸ sfactory results in all prototypes. The excipients to be used can be lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, pregelaÆŸnized starch, magnesium stearate, stearic acid and PVP K-30.
Pooyan Makvandi
Damghan University, Damghan, Italy
Title: Silver nanoparticles/polysaccharides-based injectable hydrogels: green synthesis, antibacterial activity, and their applications in tissue regeneration
Time : 14:40-15:10
Biography:
Pooyan Makvandi received his PhD in polymer chemistry from University of Mazandaran, Iran, in 2017. Prior to compleÆŸ ng PhD, he was a visiÆŸ ng scholar at University of Salento, Italy, for 6 months. Currently, he is working at InsÆŸ tute for Polymers, Composites, and Biomaterials (IPCB), NaÆŸ onal Research Council (CNR) of Italy. His works focus on biomaterials for ÆŸ ssue regeneraÆŸ on, anÆŸ microbial compounds, dental materials, nanostructures and nanocomposites.
Abstract:
Hydrogels have aƩ racted research aƩ enƟ on for Ɵ ssue engineering, e.g. wound healing and bone regeneraƟ on. ThermosensiƟ ve amphiphilic block copolymers, polyethylene oxide-polypropylene oxide copolymers (Poloxamers or Pluronics, PPO-PEO-PPO), thanks to their ability to undergo thermal gelaƟ on, to their good tolerability, and low irritancy/toxicity, have been used in the biomedical fi eld for instance for Ɵ ssue engineering and drug delivery applicaƟ ons [Hyaluronic acid (HA) is naturally occurring glycosaminoglycan, presents in mammalian connecƟ ve Ɵ ssues. It has been demonstrated that
HA promotes dermal regeneraƟ on and for this, it is widely used as dermal fi llers, as wound dressings and substrates for dermal engineering applicaƟ ons It has to be highlighted that infecƟ on is a crucial and generally unsolved issue in wound healing and bone regeneraƟ on. Therefore, materials containing anƟ microbial compounds, such as quaternary ammonium salts, TiO2, and, Ag nanoparƟ cles (Ag NPs) have been uƟ lized. Among these compounds, Ag NPs have shown the capability to inhibit or decline infecƟ ons. Various techniques, including chemical and physical approaches, have been developed to synthesise Ag NPs. Unfortunately, in the aforemenƟ oned approaches, organic passivators, toxic both for the environment and human body, are used. Biosynthesis of NPs, by using microorganisms and plants, has received considerable aƩ enƟ on due to the growing need to develop environmentally and non-toxic technologies. In this context, we propose novel and green nanocomposites injectable hydrogels based on HA, Pluronics and AgNPs for wound healing and bone regeneraƟ on applicaƟ ons.
Rezvan Jamaledin
Federico Secondo University, Italy
Title: MulÆŸ compartmental biodegradable polymer microneedles for controlled enzyme release
Time : 15:10-15:40
Biography:
Rezvan Jamaledin is a Ph.D. student in Industrial Product and Process Engineering at Federico Secondo University. She has received her Master degree
from Shahid Chamran University, Ahvaz, Iran. Her fi eld is a vaccine, drug delivery by the microneedles.
Abstract:
Transdermal drug delivery represents an appealing alternaÆŸ ve to convenÆŸ onal drug administraÆŸ on systems. The development of dissolvable and biodegradable polymer microneedles has recently aÆ© racted huge aÆ© enÆŸ on, due to their high paÆŸ ent compliance. Stamp based procedures guaranty high ÆŸ p resoluÆŸ on and reproducibility, but they generally present some constrains in terms of process ÆŸ me, low system engineering degree, possible contaminaÆŸ ons, and inability in using thermo-sensiÆŸ ve drugs. In this work, a novel stamp-based microneedle fabricaÆŸ on method is proposed, allowing a fast room temperature producÆŸ on of mulÆŸ -compartmental biodegradable polymeric microneedles for controlled intradermal drug release. In detail, microneedles are composed by a polyvinylpyrrolidone (PVP) fast dissolvable ÆŸ p and a slow dissolving body, made of assembled porous poly(lacÆŸ de-co-glycolide) (PLGA) micro parÆŸ cles (μPs). Microneedles ability to indent was assessed in a skin model. Controlled intradermal delivery was demonstrated loading both the ÆŸ p and the body of the microneedles with a model therapeuÆŸ cs, POXA1b laccase from Pleurotus ostreatus, a commercial enzyme used for the whitening of skin spots. Enzyme- loaded microneedles acÆŸ on and their indentaÆŸ on ability was assessed in an advanced in vitro skin model showing their ability to control the kineÆŸ c release of the encapsulated compound.
Yavuz Selim SILAY
Istanbul ConsulÆŸ ng Group, Turkey
Title: How to innovate in medicine in a university seƫ ng? The crucial role of venture capital funds & ethical angel investors networks: BioCube İstanbul bioentrepreneurship and innovaƟ on center as a global case example
Time : 15:55-17:00
Biography:
Yavuz is the Co-Founder & CEO of MAIN ( MaQasid Angel Investors Network) & chairman of Istanbul ConsulƟ ng Group. Yavuz is currently the Co-Founder of BioCube İstanbul Bioentrepreneurship & InnovaƟ on Center and Corporate CommunicaƟ on Director of Archem DiagnosƟ cs. He previously managed the largest distributor of Siemens Healthcare in Turkey managing 250 employees and director of Avcılar Hospital R&D Center. Previously he worked as the Market Access & Health Policy Director for AIFD in Turkey. Yavuz previously worked as the Vice President of Ipsen pharmaceuƟ cal and Director of Teva pharmaceuƟ cal in USA managing large clinical trials as well as InvesƟ gator IniƟ ated Trials and developing relaƟ onships with Key Opinion Leaders. Previously, Yavuz was the Associate Director at KV PharmaceuƟ cals and Director in Clinical Development department at Forest Laboratories.
Abstract:
Large PharmaceuÆŸ cal, Biotech and Medical Device companies are constantly evaluaÆŸ ng how to work with universiÆŸ es and startup companies and uÆŸ lize their know how. Istanbul ConsulÆŸ ng Group recently worked with Istanbul Aydın University to establish a themaÆŸ c program in Healthcare Bioentrepreneurship which has taken the road with the slogan of “Towards a Bright Future”, at the brightest spots of business life. Istanbul Aydın University is a city and campus university located in the center of Istanbul with its experienced academic staff who have gained a reputaÆŸ on for their scienÆŸfi c studies globally. At BioCube Ä°stanbul several healthcare startup companies are fl ourishing thanks to the coordinaÆŸ on of Technology Transfer and Project Managament offi ces succesful coordinaÆŸ on on innovaÆŸ on management with all key stakeholders To gain these criÆŸ cal insights for ThemaÆŸ c Management of Healthcare Bioentrepreneurship and InnovaÆŸ on Track in UniversiÆŸ es and how to accelerate innovaÆŸ ons in order to improve healthcare.We seek to empower entrepreneur academicians, doctors, other healthcare providers and with the informaÆŸ on, resources, connecÆŸ ons, and experience they need to commercialize their ideas, invenÆŸ ons and discoveries. Currrent Trends in InnovaÆŸ on Management in Medicine in a University SeÆ« ng and the BioCube Ä°stanbul Bioentrepreneurship and InnovaÆŸ on Center as a global case for USA Europe Turkey and Emerging Markets will be provided with unique cases.
Dr. Yavuz Selim SILAY a global physician leader and seasoned expert in Healthcare InnovaƟ on, Physician Entrepreneurship, Government engagement, Commercial Diplomacy, Corporate CommunicaƟ ons, Government aff airs & Medical Aff airs will discuss how BioCube İstanbul has been established and current engagements with academicians Venture Capital and angel InvesƩ ment networks for commercializing healthcare technologies will be discussed.
Josef Masek
Masaryk University, Czech Republic
Title: Protein binder-decorated liposomes targeted to fi brin for direct thrombus imaging
Time : 17:00-17:20
Biography:
Josef Mašek, Ph.D. is a researcher at the Veterinary Research Institute, Department of Pharmacology and Immunotherapy, Czech Republic. He completed his Ph.D. at the Masaryk University, Brno, Czech Republic. His research interests include development, characterisation and testing of targeted nanoparticle-based drug delivery systems, thrombus imaging, development of novel mucoadhesive drug delivery systems, nanofibre-based delivery systems and nanoparticle based vaccine formulations. He is the author or co-author of 30 scientific publications in the fields of pharmacy, pharmaceutical technology and vaccines.
Abstract:
Direct thrombus imaging represents an advanced approach for stroke diagnosis. Liposomes are an almost ideal and clinically proven platform for the construction of both, diagnostic contrast agents and nanotherapeutics. We constructed thrombus-targeted liposomal systems using protein binders with selectivity for fibrin domains uniquely formed on insoluble fibrin. Protein binders were selected using a highly complex combinatorial library derived from the scaffold of 46 amino acid albumin-binding domain of protein G, and ribosome display. D7 variant of protein binder was modified by His-Tag or double His-Tag enabling surface decoration of liposomes via metallochelating bond. The surface modification of liposomes was confirmed using different techniques including transmission electron microscopy, immunogold staining, dynamic light scattering, and isothermal titration. D7-modified liposomes were shown to bind to fibrin fibrils of the thrombus using laser scanning confocal microscopy and electron microscopy. Static conditions, as well as in-vitro flow model of middle cerebral artery, were tested. In conclusion, we present here the concept of liposomes functionalized with fibrin-targeted binders for direct thrombus imaging.
Eliška Mašková
Veterinary Research InsÆŸ tute, Czech Republic
Title: Transmucosal delivery of nanoparÆŸ cles and recombinant anÆŸ gens intended for mucosal vaccinaÆŸ on and therapeuÆŸ c applicaÆŸ ons
Time : 17:20-17:40
Biography:
Dr. Eliška Mašková is a researcher at the Veterinary Research InsÆŸ tute. She completed her Ph.D. at the Department of PharmaceuÆŸ cs, Faculty of Pharmacy. Her doctoral research invesÆŸ gates the use of the important pharmaceuÆŸ cal excipient, hypromellose in controlled release dosage forms, parÆŸ cularly in oral matrix tablets and in innovaÆŸ ve oromucosal mucoadhesive dosage forms. She currently works to develop a novel mucoadhesive fi lm formulaÆŸ ons intended for non-invasive oromucosal delivery of diff erent physiologically acÆŸ ve ingredients, mainly mucosal vaccines and therapeuÆŸ c nanoparÆŸ cles. She received the award for an innovaÆŸ ve step in the fi eld of medicine and pharmacy Discovery Award 2017.
Abstract:
Transmucosal drug delivery brings many advantages including delivery of macromolecules, recombinant anƟ gens, allergens and nanoparƟ cle-based therapeuƟ cs. The oral mucosa, especially its sublingual region, is densely populated with specialized dendriƟ c cells, and therefore has been recognized as a suitable immunoinducƟ ve area giving the opportunity for safe and effi cient mucosal vaccinaƟ on and immunomodulaƟ on. Easy access for self-administraƟ on, high permeability, a lack of enzymaƟ c barriers, mild pH values, avoiding fi rst-pass metabolism, all make the non-keraƟ nized oral regions aƩ racƟ ve sites for the applicaƟ on of drugs and vaccines. The innovaƟ ve dosage form for delivery of recombinant anƟ gens and therapeuƟ c nanoparƟ cles through mucosal Ɵ ssues consists of a protecƟ ve backing layer, a mucoadhesive layer, and an electrospun nanofi brous layer. The mucoadhesive fi lm layer was prepared by solvent-casƟ ng method, and it is responsible for Ɵ ght adhesion of the whole system to the oral mucosa.nThe electrospun nanofi brous reservoir layer prepared using the electrospinning process is intended to act as a reservoir for recombinant anƟ gen, allergens and nanoparƟ cles. As an example, the effi ciency of transmucosal delivery of model polymeric PLGA-PEG nanoparƟ cles was tested using home-made Franz diff usion cells on freshly excised porcine sublingual mucosa. Intramucosal delivery was observed on cross-secƟ oned porcine sublingual mucosa using confocal microscopy. Overcoming the mucosal barriers is the main prerequisite for successful delivery of nanoparƟ cle-based drugs and immunotherapeuƟ cs into submucosal Ɵ ssues. In this work, we demonstrated the capability of nanofi bre-based mucoadhesive films to eff ecƟ vely deliver nanoparƟ cles into the submucosal Ɵ ssue. It provides a novel approach in the development of non-invasive sublingual vaccines and immunotherapeuƟ cs.