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Session Three: Nanoencapsulation

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Table - Session 3 (Part II).png

Praveen Thoniyot

Institute of Chemical and Engineering Sciences, A*STAR, Singapore

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Praveen Thoniyot is a Senior Scientist and Team Leader at A*STAR’s Institute of Chemical and Engineering Sciences (ICES). In 2000, he obtained his PhD degree in organic chemistry at the National Chemical Laboratory, India, on a national fellowship from India’s Council of Scientific and Industrial Research. Thoniyot conducted post-doctoral research on a CNRS fellowship at the University of Nantes in France, where he worked on organic-inorganic hybrid materials. In 2002, he joined the Department of Chemistry and Biochemistry at the University of California, Santa Cruz, and worked on boron chemistry, polymerization chemistry and saccharide-sensing technologies. In 2005, he joined A*STAR and held various research positions before joining ICES in 2015. Thoniyot is passionate about incorporating sustainability and a systems-thinking approach into all his research projects.  His current focus is on encapsulation technology for various applications.

Title of Research Sharing: Biocompatible Nanospheres for Skin Care

Abstract of Research Sharing:  Polymer nanoparticles are thought to be excellent in stabilizing enhancing benefits for sensitive skin care actives and improve the efficacy.  However, for nanotechnology solutions to commercially succeed, there are several performance, manufacturing, and regulatory challenges to be overcome.  This talk will present an example of scalable production and compelling benefits of a polymer nanotechnology system developed in my lab in skin care products area.  The talk will also high light the importance of adhering to sustainable practices of polymer production and nanoencapsulation in pursuing polymer nanotechnology for various applications.

Praveen Thoniyot

Mary Chan

School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore


Mary Chan is presently a professor at the School of Chemical and Biomedical Engineering at the Nanyang Technological University Singapore (NTU Singapore). She is presently the Director of the Centre for Antimicrobial Bioengineering. Her expertise is in polymers for biotechnology and nanotechnology.  She has developed a class of cationic antimicrobial polymers and coatings that are selectively toxic to bacteria and have good biocompatibility. Her hydrogel materials for various biomedical applications (contact lens and wound dressing) have been licensed to companies.

She has been elected as a Fellow of the America Institute of Medical and Biological Engineering.  She is also an associate editor of ACS Applied Materials & Interfaces. She was the Acting Chair (2011-2013) and also a co-founder of the School of Chemical and Biomedical Engineering at NTU. She obtained her BEng (Chem) and PhD (polymers) from the National University of Singapore and MIT respectively.

Title of Research Sharing: Antibacterial and Antibiofilm Polymeric Materials

Abstract of Research Sharing:  Antimicrobial resistance has become a global healthcare crisis. Multi-drug resistant bacteria are a common and serious problem in clinical settings but can also be found increasingly commonly in the community. As an alternative to antibiotics and antimicrobial peptides, we exploit cationic antibacterial polymers that depend on hydrogen bonding to achieve good antibacterial efficacy. Our approach has been to make new cationic agents that rely less, or not at all, on hydrophobicity. To compensate for individual chain low molecular weight, we designed chitosan-derived peptidopolysaccharide molecules with strong hydrogen bonding (but low hydrophobic interactions) that spontaneously self-assemble into nanoparticles to aggregate charges and demonstrated good antibacterial effect without toxicity. We also designed glycosylated block co-beta-peptides to achieve good antibacterial potency with low toxicity. Importantly, these cationic polymers have low propensity to cause resistance in bacteria. The problem of drug resistance is compounded by bacteria in biofilm and non-replicative states which are not easily treatable by antibiotics. We showed that hydrophilic cationic block copolymers act effectively to penetrate biofilms and then attach to bacteria surfaces to remove them from the extracellular polymeric substances (EPSs). We also showed that glycosylated block co-beta-peptides can kill various sub-populations of MRSA, including the metabolically inactive persisters and biofilm-associated bacteria.

Mary Chan

Maria N. Antipina

Singapore Institute of Food and Biotechnology Innovation, A*STAR, Singapore

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Maria N. Antipina obtained her Ph.D. degree in biophysics from the Lomonosov Moscow State University (Russia) in 2004. She moved to the Max Planck Institute of Colloids and Interfaces (Potsdam, Germany) in 2005. In October 2005, she was awarded the Incoming International Fellowship of the Alexander von Humboldt Foundation to carry out a research project on artificial viruses for gene delivery. In 2007, she joined A*STAR (Singapore). She worked as a Research Scientist in the Institute of Materials Research and Engineering till June 2020 before moving to the Singapore Institute of Food and Biotechnology Innovation, where she is currently leading projects on microencapsulation and delivery of micronutrients.

Title of Research Sharing: Layer-by-Layer Capsules for Drug Delivery via Intravenous Injections

Abstract of Research Sharing:  Despite being a powerful tool for targeted drug delivery,1 polymeric multilayer capsules assembled via alternative binding of complementary molecules or nanoparticles often lack one or several essential features hampering their translation and implementation for the disease treatment. Among those features are biodegradability, size, harmless loading procedure, and good retentiveness for the encapsulated drug. This chapter discusses a novel fabrication strategy for encapsulation of anticancer drugs in a biodegradable polymeric layered assembly that includes the template design,2 adjustments of the loading method, and further compaction of the obtained capsules down to the nanoscale.3 The effectiveness of the developed drug delivery systems to penetrate cancer tissue after intravenous injection was confirmed on the mice model of lung cancer. It was also shown that the capsules could be used in combinatory cancer therapy by targeting both the fast-growing cancer cells and the cancer-promoting microenvironment.

Maria N. Antipina
Rinti Banerjee

Rinti Banerjee

Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, India

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Rinti Banerjee is the Madhuri Sinha Chair Professor and ex-Head at the Department of Biosciences & Bioengineering, IIT Bombay. She is an Associate Editor of ACS Biomaterials Science and Engineering & is on the editorial board of Scientific Reports and many other international journals. She is a Fellow of the Indian Academy of Sciences, Bangalore, Fellow of the National Academy of Sciences India and Fellow of the Society of Biomaterials and Artificial Organs India. She works in the areas of trigger responsive biomaterials, nanomedicine, drug delivery, and point of care diagnostics. Dr Banerjee has an MBBS from BJ Medical College Pune, a PhD in Biomedical Engineering from IIT Bombay in collaboration with Royal Hospital for Sick Children Glasgow, and a postdoctoral from University of California, San Francisco. She is also certified in areas of global health, social entrepreneurship, intellectual property law and business strategies for social impact. She has published over 200 papers including invited editorials and has more than 5000 citations. She has more than 40 patents to her credit and 26 technologies licensed or commercialised. She has received several awards including NASI-Reliance Industries Platinum Jubilee Award for Biological Sciences, CDRI Award for Excellence in Drug Research, HH Mathur Award for Excellence in Research in Applied Sciences, Lockheed Martin India Innovation Award, National Award for Women Bioscientists, BSBE IITB Excellence in Teaching Award and Indo-US Frontiers of Engineering Award. She is an awardee of the Grand Challenges program from the Bill and Melinda Gates Foundation for microneedle platforms for contraceptive delivery and twice awardee of the Gates Foundation’s Grand Challenges Explorations program for micronutrient loaded cosmetics for adolescent girls and women of child bearing age, colour changing transdermal amoxycillin delivery platforms for childhood pneumonia and twice recipient of the Samsung Global Research Outreach program for ultrasound responsive theranostic agents in cancers. She serves on many international expert panels including CEFIPRA, Cancer Research UK, New Zealand Health Research Agency, EU group on medical devices, Slovak National Research Agency and several national agencies and research advisory board of several institutions. The research of her group has led to licensing, commercialization and widespread impact due to many technologies including Duraprot wash resistant antiviral coated masks against SARS-nCOV2, reusable Duraprot plus coated N95 masks free of plastics, alcohol free disinfectant sprays, transdermal nanoparticles, fortified infant oils, intravesical in situ gels, nutraceuticals, and many others are being translated.

Title of Research Sharing: Nanoparticle and in situ Gel Strategies to Overcome Barriers for Drug Delivery

Abstract of Research Sharing:  Drug delivery strategies have the potential to increase the bioavailability of drugs and penetrate across anatomical barriers to reach deeper target tissues. Biodegradable and trigger responsive nanoparticles and in situ gels act as platforms for the design of efficient drug delivery carriers. Biomimetic, trigger responsiveness, nanosize based penetration, site specific self assembly and sol gel transitions act as platform strategies to design smart biomaterials specifically suited for drug delivery in various systems. Several examples of these strategies and their translation will be covered in the talk. Amphiphilic phospholipid nanovesicles mimic the pulmonary surfactant and can be optimised to form respirable aerosols with deep penetration into the alveoli with non-invasive nebulisation techniques. These act as platforms for anti-oxidant, anti-inflammatory and anticancer drugs with synergistic pulmonary surfactant actions for therapy in acute respiratory distress syndrome and pulmonary metastasis respectively. Transdermal delivery requires strategies to pass through the ceramide rich stratum corneum barrier. Nanoparticles of fluidising phospholipids and fatty acids can be modulated to alter bilayer packing and act as platforms to pass through the stratum corneum, or pass along the follicular route for dermal and systemic effects. Stabilisation of the platform in oils have led to micronutrient loaded infant massage oils containing multivitamins and iron for neonatal development, leveraging traditional practices of infant massage with nanotechnology. Nanoparticle in biopolymeric microneedle platforms having conical morphology pass through the stratum corneum to form dermal depots for sustained release of drugs. Ultrasound responsive biomaterials consisting of sulphur hexafluoride loaded microbubbles linked to drug loaded lipopolymeric nanoparticles undergo cavitation in the presence of an ultrasound trigger. This phenomenon can be utilised for triggered drug release while the contrast enhancing property produces theranostic advantages for site specific therapy in cancers. Another barrier for drug delivery to the central nervous system is the blood brain barrier. Nanoparticle in slow degrading amphiphilic in situ gels act as depot formulations for post surgical delivery of chemotherapeutics in glioblastoma with minimal systemic accumulation. Miltefosine based lipid nanoparticles that are mucoadhesive and stable nasal fluid, can exploit the intranasal route along the olfactory nerves for direct nose to brain delivery. The urothelium of the urinary bladder poses another challenge to delivery of drugs to the urinary bladder. Intravesical delivery is limited by decreased retention and urinary excretion and poor penetration through the urothelium. Nanoparticle in in situ gels which are stable in variable pH and in the presence of urine are optimised for enhanced penetration through the urothelium. The platforms have potential in superficial bladder carcinoma, deep muscle penetrating stages and interstitial cystitis for enhanced effectiveness over several weeks. Core shell trigger responsive nanoparticles for posterior segment ocular drug delivery and for sequential delivery of multiple drugs are also explored. Nanocomposite gels have been developed that act as quick hemostatic, multifunctional agents for trauma care with hemostatic, antibacterial and wound healing properties. The talk will highlight some of these technologies, the strategies underlying the innovations and their translation.  

Svetlana Gelperina and Julia Malinovskaya

D. Mendeleev University of Chemical Technology of Russia, Russia

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Svetlana Gelperina and Julia Malinovskaya, scientists at the D. Mendeleev University of Chemical Technology of Russia, together explore the delivery of drugs into the brain and peripheral tumors. Svetlana has more than 25-years of experience in pharmaceutical nanotechnology. Julia has recently completed her PhD project focused on the development and evaluation of the PLGA-based nanoformulation of doxorubicin for the chemotherapy of brain tumors.

Dr Gelperina and Dr Malinovskaya's presentation is kindly sponsored by Corbion.

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Title of Research Sharing: Investigation of Doxorubicin-Loaded PLGA Nanoparticles

Abstract of Research Sharing:  The PLGA-based nanoformulation of doxorubicin (Dox-PLGA) is a drug candidate for systemic chemotherapy of glioblastoma. The technology is based on brain delivery by PLGA NP overcoated with Poloxamer 188. The surface-modified PLGA NP represent a self-assembling delivery system acquiring biological vectors – apolipoproteins ‑ from the blood, which enables doxorubicin delivery to the intracranial tumour. Dox-PLGA produced a considerable antitumor effect against the intracranial 101.8 glioblastoma in rats. Safety and good tolerability of Dox-PLGA was confirmed in the phase I clinical trial. The targeting parameters of Dox-PLGA NP depend on the drug release rate. This influence was predicted by a physiologically based biopharmaceutical model and further confirmed by the IVM image analysis of the drug accumulation in the preitumoral area of a sc 4T1 murine tumour. In the case of the fast-releasing Dox-PLGA NP, Dox penetration into the peritumoral area through the macro- and microleakages was observed immediately after IV injection, yielding a maximal fluorescence peak within 15 min, whereas the slow releasing Dox-PLGA NP produced a linear accumulation profile.

Svetlana & Julia

Shakti Nagpal

Department of Pharmacy, National University of Singapore, Singapore

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Shakti Nagpal is a graduate student at Department of Pharmacy, NUS pursuing a Ph.D in Pharmaceutical Sciences under the supervision of A/Prof. Matthias G. Wacker. He completed his Bachelors in Pharmacy from University of Health Sciences Rohtak (UHSR), Haryana, India. He holds a Masters in Pharmacy specialized in Pharmaceutics from Birla Institute of Technology and Science (BITS), Pilani, Rajasthan, India. He joined as a technical trainee (Junior Scientist) in Formulation R&D Oral Solids division at Dr Reddys Laboratories, IPDO-Hyderabad, India. Later he worked at Institute of Nanoscience and Technology, Mohali, Punjab, India as a Junior research fellow. Currently he is working on Quality by design (QbD) driven formulation development, Physiologically-based Nanocarrier Biopharmaceutics (PBNB) Modelling of Nanomedicine.

Title of Research Sharing: High-Throughput Nanoformulation Development, A QbD-based Approach

Abstract of Research Sharing:  For high-throughput development of nanopharmaceuticals, an improved understanding of plasma pharmacokinetics is required. The development of a suitable in vitro assay to predict this biopharmaceutical behavior is one cornerstone of Quality by Design (QbD). The physiologically-based nano-carrier biopharmaceutics model describes the system dynamics for nano-carrier based delivery by integrating the physiological and pharmacokinetic parameters. A high-throughput formulation development is a need of hour. Herein, a liposomal delivery system is being developed using microfluidic flow-focusing (MFF). A particle size of approximately 120nm±10nm is achieved by optimizing process parameters. The release kinetics of the developed formulation will be measured using the dispersion releaser to predict the in-vivo performance using the validated model.

Shakti Nagpal
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