Today’s Research, Tomorrow’s Cures

PHARMACYRESEARCH DAY

2018

12 June 20189 AM - 5 PM

NUS University HallAuditorium, Level 2Lee Kong Chian Wing

Programme

1

Time Event09.00 – 09.10 Opening Address

Prof. Christina Chai, Head of Department, NUS Pharmacy

09.10 – 09.35 Genome mining for posttranslational modifications

Asst Prof Brandon Morinaka

09.40 – 09.55 Genome Mining of Bacterial rSAM Enzymes for Natural Product Discovery

Mr. Tooh Yi Wei, FYP Winner (PC category)

10.00 – 10.20 Indolyl Azaspiroketal Mannich Bases Are Potent Anti-my-cobacterial Agents with Selective Membrane Permeabiliz-ing Effects and In Vivo Activity

Samuel Agyei Nyantakyi (PC category)

10.20 – 10.45 AM tea break and poster viewing

10.45 – 11.10 Synthetic Peptide-Based Antimicrobials & Their Delivery: Prospects & Challenges

A/P Rachel Ee

11.15 – 11.30 Understanding the Release Performance of Pellets with Hydrophobic Inclusions in Sustained-Release Coatings

Mr. Tiang Yi Long, FYP winner (PT category)

11.35 – 11.55 The Development of A Novel Hybrid Delivery System For Transfection of Hard-To-Transfect Cells

Zou Shui (PT category)

12.00 – 13.30 Group photo, lunch and poster selection

13.30 – 13.55 Isorhapontigenin: a promising candidate for nutraceutical

Asst Prof Lin Haishu

Time Event14.00 – 14.15 Pharmacokinetic and Pharmaacodynamic Characterisation

of Abiraterone in Metastatic Castration-Resistant Prostate Cancer

Ms. Rebecca Neo Wan Yi, FYP winner (PK category)

14.20 – 14.40 Titanium dioxide nanoparticles induces endothelial leaki-ness and promotes cancer metastasis in vitro and in vivo

Tee Jie Kai (PK category)

14.45 – 15.10 Evaluation of the Impact of Pharmacist-Led Pharmacoki-netic Services and Protocols in Optimizing Vancomycin Dosing and Monitoring

Dr. Han Zhe

15.15 – 15.30 Evaluating the Safety Profile of Sodium-Glucose Cotrans-porter-2 Inhibitors

Ms. Bernice Leow Li Hsia, FYP winner (PP category)

15.35 – 15.55 Evaluating the Impact of Self-monitoring of Blood Glucose Frequencies on Glucose Control in Patients with Type 2 Diabetes who do not use Insulin: A systematic Review and Meta-analysis

Xu Yingqi (PP category)

16.00 – 16.20 PM tea break16.20 – 16.40 Pharmacokinetics of Levetiracetam in Neurosurgical ICU

Patients

Ong Chiat Ling, Jasmine (Pharm.D. programme)

16.45 – 17.00 Best Poster Awards

17.00 – 17.10 Concluding remarks

Programme

2

Brandon I Morinaka, Ph.D.

Assistant Professor, Department of PharmacyNational University of Singapore

Email: phambi@nus.edu.sg

Genome mining for posttranslational modifications

In fundamental biochemistry, ribosomal biosynthesis is based exclusively on α-amino acids of the L-configuration. Here I will discuss the genome-guided discovery of bacterial pathways that post-translationally create either D-configured or β-amino acid-containing products. These transformations are widespread in bacteria and are catalyzed by two different subfamilies of en-

zymes belonging to previously uncharacterized members of the radical S-adenosylmethionine (rSAM) superfamily. The D-configured amino acids are introduced by an rSAM epimerase while the β-amino acids are introduced by a radical mediated protein splicing process. These reactions can be used to incorporate diverse and multiple D- or β-amino acids into genetically encoded precursors in E. coli. I will show some initial insights into these reactions and demonstrate potential use in biotechnological applications. Finally, I will show how the rSAM superfamily is a potential source of additional post-translational modifying enzymes which leads into my work here at NUS.

Biography

Brandon earned his B.S. in Chemistry from the University of California, Santa Cruz. He obtained his Ph.D. in Chemistry from the University of California, San Diego under the guidance of Prof Tadeusz F. Molinski. He then moved overseas to the University of Bonn and the ETH Zurich for postdoctoral re-search with Professor Joern Piel. He is currently Assistant Professor in the Department of Pharmacy at NUS with research interests in the genome mining approaches to natural products discovery.

Keynote Speakers

3

EE Pui Lai, Rachel, Ph.D.

Associate Professor, Department of PharmacyNational University of Singapore

Email: phaeplr@nus.edu.sg

Synthetic Peptide-Based Antimicrobials & Their Delivery: Prospects & Challenges

The dramatic increase in antibiotic-resistant infections has created a pressing need for new and more efficacious antibi-otics. An area that has garnered renewed interest is the devel-opment of antimicrobial peptides (AMPs) and proteins. AMPs are a distinctive class of potent, broad-spectrum antibiotics

produced by the body’s innate immune system and act as the first line of defense against disease-causing microbes. By using natural AMPs as templates, our team has developed synthetic AMPs effective against a variety of microorganisms, including drug-resistant clinical isolates of Mycobacterium tuberculosis and Pseudomonas bacteria. Because AMPs are small, expensive to produce and labile in biological systems, our team also systematically evaluated various physically crosslinked hydrogel systems with strong electrostatic interactions with cationic peptides for effective loading and controlled drug release. Several developmental prospects and challenges will be highlighted in order for this unique class of therapeutics to emerge as integral tools for combating drug resistant infections.

Biography

Dr Rachel P. L. Ee completed a PhD in Pharmaceutics at the College of Pharmacy, University of Illinois at Chicago. She is currently an Associate Professor and Domain Leader in the Department of Phar-macy, National University of Singapore (NUS), as well as a member of the NUS Graduate School for Integrative Sciences and Engineering. Her research is focused on the design and development of novel biotherapeutics and hydrogel formulations for the delivery of drugs, genes and cells. Dr Ee is active in administration as the Director of the new Pharmaceutical Science Programme, coordinator of industry internships and alumni affairs in NUS Pharmacy. She recently received the Deutscher Akademischer Austausch Dienst (DAAD) Research Exchange Fellowship and UCLA-Banco Santander W30: Women Leaders in University Administration Program Award as recognition of her research and administrativeexcellence.

Keynote Speakers

4

Lin Haishu, Ph.D.

Assistant Professor, Department of PharmacyNational University of Singapore

Email: phalh@nus.edu.sg

Isorhapontigenin: a promising candidate for nutraceutical

Isorhapontigenin (trans-3,5,4′-trihydroxy-3′-methoxystilbene, ISO) is a methoxylated resveratrol (trans-3,5,4′-trihydroxystilbe-ne, RES) derivative present in grapes and some Chinese herbs. This study aimed to assess its health-promoting effects in com-parison to RES. The anti-inflammatory activities were examined in primary human airway epithelial cells derived from healthy

and chronic obstructive pulmonary disease (COPD) subjects, and A549 epithelial cells. The pharmacokinetic profiles were assessed in Sprague-Dawley rats and measured by liquid chromatography tandem mass spectrometer (LC-MS/MS). The plasma samples collected from rats received one-week daily oral administration of ISO were subjected to metabolomic profiling using gas chromatography tandem mass spectrometer (GC-MS/MS). ISO concentration-de-pendently inhibited IL-6 and CXCL8 release, with IC50 values at least twofold lower than those of RES. The molecular mechanisms of ISO were found to be different from corticosteroids. Upon intravenous administration (90 µmol/kg), ISO exhibited a fairly rapid clearance (Cl) and short mean residence time (MRT). After a single oral administration (100 µmol/kg), ISO was rapidly absorbed and showed a long residence in the systemic circulation. Dose-escalation to 200 µmol/kg led to higher dose-normalized maximal plasma concentrations (Cmax/Dose), dose-normalized plasma exposures (AUC/Dose) and oral bioavailability (F). One-week repeated daily dosing of ISO did not change its major oral pharma-cokinetic parameters. Pharmacokinetic comparisons clearly indicated that ISO possessed pharmaco-kinetic profiles superior to resveratrol as its Cmax/Dose, AUC/Dose and F were ~ 2 to 3 folds greater than resveratrol. Metabolomic investigation further showed its impact on metabolic pathways related to health-promoting effects. Since ISO displayed favorable anti-inflammatory activities and superior pharmacokinetic profiles, it has emerged as a promising nutraceutical for further development.

Biography

Dr. Lin Haishu received his first degree in biochemistry from the Sun Yat-Sen University. He complet-ed his graduate study in the Department of Pharmacy, National University of Singapore. After he got his Ph.D. in 2002, he furthered his post-doctoral training in NUS, Monash University (Melbourne) and ProSkelia (Paris). His current researches are focused on the anti-inflammatory pharmacology, pharma-cokinetics, metabolomics and drug delivery system of dietary / herbal natural products. Dr. Lin has ~ 50 publications on peer-reviewed journals and serves as an ad hoc reviewer for ~ 50 journals.

Keynote Speakers

5

Han Zhe, Pharm.D., BCPS (AQ-ID)

Lecturer, Department of PharmacyNational University of Singapore

Email: phahz@nus.edu.sg

Vancomycin Dosing and Therapeutic Drug Monitoring: Defining Current Practices and Identifying Areas of Improvement

Vancomycin is widely used for the treatment of gram-positive in-fections, including those caused by methicillin-resistant Staphy-lococcus aureus. Vancomycin therapeutic drug monitoring (TDM) is recommended to optimize efficacy and minimize toxicities and is a common area in which pharmacists’ expertise is sought

in clinical practice. While international guidelines offer general principles on vancomycin dosing and TDM, institutions frequently develop their own protocols to guide practice in specific areas unad-dressed by the guidelines and to tailor to their own practice needs.

The impact of pharmacists’ interventions on optimizing vancomycin therapy had been described by various groups around the world. However, differences in pharmacy practice models and poorly de-scribed pharmacists’ interventions and dosing protocols limit applicability in other contexts. In this session, we will review an evaluation of a local vancomycin dosing and TDM protocol and its impact on therapeutic target attainment. We will also review the dosing and TDM challenges in the elderly patient population.

Biography

Dr. Han Zhe is a lecturer with the department of Pharmacy at the National University of Singapore (NUS). She also maintains an active clinical practice with the infectious disease service at the Ng Teng Fong General Hospital. Dr. Han completed her Doctor of Pharmacy (Pharm.D.) degree from the Uni-versity of Michigan, Ann Arbor, USA and went on to complete her post-graduate year 1 (PGY1) phar-macy practice residency and PGY2 infectious disease pharmacy residency at the University of Chicago, Illinois, USA. She then practiced as an infectious disease pharmacist specialist at the University of Chicago Medicine for 4 years prior to joining NUS. During which, she obtained her board certification as a pharmacotherapy specialist. Dr. Han’s main research interests are in evaluating the impact and demonstrating the value of pharmacist-led services and antimicrobial stewardship initiatives. She has published peer-reviewed manuscripts demonstrating the impact of pharmacy services and pharma-cists’ interventions on improving clinical guideline compliance, optimizing antimicrobial selection, dos-ing, monitoring and enhancing patient safety. Dr. Han is also interested in pharmacy education, clinical training and professional development of pharmacists.

Keynote Speakers

6

FYP Oral PresentationPharmaceutical Chemistry (PC)Tooh Yi Wei

GENOME MINING OF BACTERIAL RSAM ENZYMES FOR NATURAL PRODUCT DISCOVERY (PC-1) (The Enzyme Ml5B from Micromonospora sp. Catalyzes a Novel Post-Translational Modification)

Peptides offer advantages over conventional small molecule drugs in terms of safety and efficacy and are also able to modulate previously undruggable targets. However, their use as therapeutics is impeded by their susceptibility to proteolysis and poor pharmacokinetic profile. Modification of peptides through the use of enzymes can potentially increase their stability, and also improve efficacy and selectivity. Radical S-Adenosylmethionine (rSAM) enzymes are of particular interest as they are able to catalyse otherwise chemically difficult reactions, and the number of characterised rSAM enzymes is but a miniscule fraction of that predicted to exist in nature. Using genome mining approaches, we examined rSAM enzymes predicted to be involved in the post-translational modification of precursor peptides en route to natural products. Plasmids containing gene sequences for precursor peptides were transformed with and without the genes for their modifying rSAM enzymes into Escherichia coli for heterologous expression. Purified peptide sam-ples were then subject to SDS-PAGE and LC-MS to screen for rSAM enzyme activity. Activity was detected for rSAM enzymes encoded by genes chlB and ml5B from Chlorogloeopsis sp. PCC 7702 and Micromono-spora sp. L5 respectively. Further investigation into a Ml5 peptide product using LC-MS/MS revealed a pre-viously unreported post-translational modification that resulted in the addition of a degree of unsaturation to the C-terminus of the precursor peptide. This study paves the way for the introduction of new rSAM enzymes for the engineering of peptide therapeutics.

Pharmaceutical Biology & Pharmacokinetics (PK)Rebecca Neo Wan Yi

PK-04: PHARMACOKINETIC AND PHARMACODYNAMIC CHARACTERISATION OF ABIRATERONE IN META-STATIC CASTRATION-RESISTANT PROSTATE CANCER (Pharmacodynamic characterisation of the CYP17A1 inhibition kinetics of abiraterone and its active me-tabolite D4A)

Indicated for metastatic castration-resistant prostate cancer (mCRPC), abiraterone is a CYP17A1 inhibitor that has achieved significant clinical efficacy including improved progression-free survival. However, the complex inhibition kinetics of CYP17A1 by abiraterone and its pharmacologically active metabolite, Δ4-abi-raterone (D4A) remain unexplored.

This study aimed to characterise the inhibition kinetics of abiraterone and D4A against CYP17A1. We hy-pothesized that abiraterone and D4A are slow, tight-binding inhibitors of CYP17A1. Pre-incubation time-de-pendent inhibition assays were conducted to determine the observed first-order rate constants for enzyme inhibition (kobs) and the microscopic dissociation constants using progesterone and 17α-hydroxypregnen-olone as probe substrates for the 17α-hydroxylation and C17,20-lyase reactions respectively. Next, inhi-bition constants were obtained via analyses of concentration-response plots of fractional velocity against inhibitor concentration (Ki,app) and reversible inhibition assays (corrected Ki). Lastly, established equations were applied to elucidate the true inhibitory potential (Ki*) and dissociation half-life of enzyme-inhibitor complexes.

7

FYP Oral Presentation

8

Here, abiraterone and D4A are shown to exhibit slow, tight-binding inhibition of CYP17A1 via a two-step binding mechanism. Long dissociation half-life (>40 h) for the CYP17A1-inhibitor complex was observed for both abiraterone and D4A. Relative to the turnover rate of CYP17A1, abiraterone and D4A may potentially yield pseudo-irreversible inhibition of CYP17A1 in vivo. Examination of Ki* revealed D4A as the more po-tent CYP17A1 inhibitor as compared to abiraterone. However, abiraterone displayed greater selectivity for the desired C17,20-lyase activity over the off-target 17α-hydroxylation. In all, abiraterone and D4A are like-ly to be comparable in their clinical benefits with the sole evaluation criterion being CYP17A1 inhibition.

Clinical Pharmacy Services & Pharmacy Practice (PP)Bernice Leow Li Hsia

PP-09: EVALUATING THE SAFETY PROFILE OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS(Risk of Diabetic Ketoacidosis among Type 2 Diabetes Patients Treated with Sodium-Glucose Cotrans-porter-2 Inhibitors in Singapore: A Retrospective Cohort Study)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a novel class of anti-hyperglycemic agents (AHAs) with the added benefits of weight loss, blood pressure reduction, and possible cardiopro-tection and renoprotection. However, warnings regarding increased diabetic ketoacidosis (DKA) risk with SGLT2i have emerged.

Objectives: To determine the incidence of DKA associated with SGLT2i in Singaporean type 2 diabetes (T2D) patients and to describe the clinical characteristics of SGLT2i-associated DKA.

Methods: This was a single-centre, retrospective cohort study conducted in Khoo Teck Puat Hospital. Elec-tronic medical records between April 1, 2014 and November 30, 2017 were used. SGLT2i-users and non-SGLT2i AHAs users were matched 1:1 using optimal propensity-score matching. Comparative analysis was evaluated using Cox proportional hazards model which gave adjusted hazard ratios for DKA. Clinical charac-teristics of SGLT2i-associated DKA were obtained by manually reviewing the patients’ case notes.

Results: 680 SGLT2i-users and 680 non-users were identified after matching. Overall incidence rates per 1000 patient-years were 9.07 [95%CI:3.61-18.38] in SGLT2i-users and 6.80 [95%CI:3.74-11.19] in non-us-ers. The hazard ratio for DKA comparing SGLT2i-users with non-users was 2.02 [p=0.20, 95%CI:0.69-5.91]. Of the six SGLT2i-associated DKA identified, all had DKA-precipitating factors and three had low blood glucose levels (≤13.9mmol/L).

Conclusion: Our findings indicated no statistically significant difference in DKA risk between SGLT2i-users and non-users. However, the possibility of increased DKA risk with SGLT2i cannot be excluded, especially when DKA-precipitating factors are present. Some SGLT2i-associated DKA were also ‘euglycemic’ which is usually rare in T2D. Further studies with larger sample population are warranted to validate our findings.

FYP Oral Presentation

9

Drug Delivery & Pharmaceutical Technology (PT)Tiang Yi Long

PT-6: UNDERSTANDING THE RELEASE PERFORMANCE OF PELLETS WITH HYDROPHOBIC INCLUSIONS IN SUSTAINED-RELEASE COATINGS (UV imaging of drug dissolution profile from sustained-release pellets with hydrophobic inclusions in pellet coat)

Background: Ultraviolet (UV) array imaging provides a real time visualisation of the dissolution process, giving spectrally, temporally and spatially resolved information. This may reveal insights on dissolution profiles of the dosage forms evaluated. To date, UV imaging has not been used to study pellet dissolution behaviour. Sustained-release pellets can reduce dosing frequency of medications, hence improving patient compli-ance. Adding hydrophobic agents in the pellet coat has the potential to further sustain drug release at the same coat thickness. However, its effects in pellets has not been extensively studied. This study aimed to provide insights on the drug release characteristics from sustained-release pellets by UV imaging and to examine the impact of adding hydrophobic inclusions in sustained-release pellet coating on drug release.

Methods: Pellets containing metformin hydrochloride and microcrystalline cellulose were prepared using extrusion-spheronisation. They were then coated with different sustained-release polymers (polymethac-rylate copolymer and ethylcellulose) with and without hydrophobic inclusions (stearic acid 50 and hydro-genated castor oil). Different coating levels were applied. Drug release studies were then conducted using UV imaging.

Results: Ethylcellulose pellets with hydrophobic inclusions displayed a slower release profile than pellets without hydrophobic inclusions. Sigmoidal-like increase in intrinsic dissolution rate was observed for poly-methacrylate copolymer pellets. For all pellets, increasing coating thickness enhanced sustained-release profile of pellets.

Conclusion: This study highlighted the potential of using hydrophobic inclusions to further sustain drug release. In addition, SDI was successfully used for visualization of the drug release from coated pellets, revealing insights of its initial dissolution characteristics.

PG Oral Presentation

10

Pharmaceutical Chemistry (PC)Samuel Agyei Nyantakyi

INDOLYL AZASPIROKETAL MANNICH BASES ARE POTENT ANTI-MYCOBACTERIAL AGENTS WITH SELECTIVE MEMBRANE PERMEABILIZING EFFECTS AND IN VIVO ACTIVITY

Cationic amphiphilic 1-octylindolyl Mannich bases have been reported to be membrane active mycobac-tericidal agents. Their membrane disruptive properties were inferred from perturbation of phospholipid vesicles, permeabilization of mycobacterial cultures and induction of cell envelope stress. Noting that one of the more potent members possessed a unique azaspiroketal side chain, we focused on structur-ally modifying this feature as a means of optimizing potency. A series of indolyl azaspirocyclic Mannich bases were synthesized and evaluated for antimycobacterial activity. SAR revealed that it was not the azaspiroketal per se but its presence in a Mannich base that was pivotal for potent activity. We identified NTB8 as a promising advanced hit candidate with submicromolar bactericidal activity. When administered to mice, it was well tolerated with a PK profile that revealed preferential partitioning in lung tissue. NTB8 displayed in vivo activity in an acute mouse model of TB. On mycobacteria, NTB8 increased cell envelope stress, induced permeabilization but not membrane depolarization. Whereas resistant mycobacteria could not be isolated for a less potent indolyl Mannich base, NTB8 had a low spontaneous resistance mutation frequency. This was unusual for membrane targeting agents and suggest the involvement of an additional envelope-related target in its mechanism of action.

Clinical Pharmacy Services & Pharmacy Practice (PP)Xu Yingqi

EVALUATING THE IMPACT OF SELF-MONITORING OF BLOOD GLUCOSE FREQUENCIES ON GLUCOSE CONTROL IN PATIENTS WITH TYPE 2 DIABETES WHO DO NOT USE INSULIN: A SYSTEMATIC REVIEW AND META-ANALYSIS

“Objective: The present study aimed to assess the impact of SMBG frequencies on the glucose control and other clinical outcomes of non-insulin-treated patients with T2D.

Methods: A literature search was performed in PubMed, Web of science and Cochrane library from Janu-ary 2007 to March 2018. Randomised controlled trials with ≥ 6-month follow up duration that compared the impact of different frequencies of SMBG on glycated haemoglobin (HbA1c) were included. The impact of SMBG frequencies on other clinical outcomes such as body mass index (BMI) and total cholesterol (TC) were also evaluated.

Results: 12 RCTs with a total of 3,094 patients met the inclusion criteria. More frequent SMBG (≥ 4 time/week) was correlated with better HbA1c control (Mean Difference -0.13%, 95% CI -0.14 to -0.12). Specif-ically, performing SMBG for 7-10 times/week and 10-14 times/week reduced HbA1c by 0.30% and 0.12% over at least 6-month follow up, respectively. In addition, performing SMBG frequently was also associated with improved BMI and TC. Frequent SMBG did not significantly increase the probability of detecting a hypoglycaemia (Risk Ratio 0.69, 95% CI 0.57 to 0.84).

Conclusions: Frequent SMBG (≥ 4 times/week) is associated with an improved glycaemic control and re-duced BMI and TC in T2D patients with non-insulin-treatment.”

PG Oral Presentation

11

Pharmaceutical Biology & Pharmacokinetics (PK)Tee Jie Kai

TITANIUM DIOXIDE NANOPARTICLES INDUCES ENDOTHELIAL LEAKINESS AND PROMOTES CANCER METASTASIS IN VITRO AND IN VIVO

The use of inorganic nanoparticles in biomedicine have raised concerns on their potential toxicity in hu-man organs and tissues. Although blood vessels are seldom the target organ of many drugs, most nano-medicine will interact with the endothelium during its circulation in the blood. Previous studies have shown that titanium dioxide nanoparticles (TiO2 NPs) could induce endothelial leakiness by disrupting the homophilic interaction of vascular endothelial cadherin (VE-Cad), thereby separating the endothelial cells. In this study, we showed that TiO2 NPs induced endothelial leakiness in human microvascular endothelial cells (HMVECs) through the phosphorylation of VE-Cad at Y658 and Y731. While an uncontrolled and per-sistent leakiness could lead to promiscuous transport of molecules and cells across the barrier, we further observed an increase in the migration of human skin cancer cell A431 across the leaky endothelial barrier using an in vitro metastasis model. Interestingly, tail vein injection of TiO2 NPs in NSG mice facilitated the intravasation and extravasation of MDA-MB-231 breast cancer cells across the blood vessels, which could further exacerbate cancer metastasis. Overall, our results provided insights into a novel interaction of nanoparticles in biological systems and highlighted the possible inadvertent metastasis triggered by inor-ganic nanoparticles.

Drug Delivery & Pharmaceutical Technology (PT)Zou Shui

THE DEVELOPMENT OF NOVEL DELIVERY SYSTEMS FOR ANTI-OBESITY TREATMENT

Obesity is a worldwide pandemic, with nearly one-third of the global population now considered overweight or obese. Despite the gravity of the problem, there is currently a lack of safe yet effective treatment modal-ities for obesity. A novel approach to tackle the issue of obesity is to promote the transformation of White Adipose Tissue (WAT) to Beige Adipose Tissue, thereby increasing energy expenditure and fat oxidation. A search of the literature revealed that several miRNAs are able to induce the browning process. However, this approach suffers from a lack of suitable delivery systems that facilitate the specific transportation of miRNAs to adipocytes. Although exosomes (endogenous nanovesicles) are able to transfer miRNA, mRNA, DNA and other biomolecules between cells, the isolation yield of exosomes from cells is low, procedurally complex and present with issues regarding efficient loading of miRNAs into exosomes or its mimetics, Cell-Derived Nanovesicles (CDNs). Therefore, we aim to develop an effective system for delivery of miRNAs to adipocytes. In this project, we developed a novel fused delivery platform termed micro Cell Vesicle Technology (mCVT). mCVTs produced from different CGs have a similar size and zeta potential profile (<500 nm and around 40 mV, respectively). Compared to the industry transfection standard lipofectamine 3000 (LF3000), mCVTs have demonstrated greater transfection efficiency and moderate cytotoxicity. The transfection studies were con-ducted on preadipocytes 3T3-L1, a cell line known to be Hard-To-Transfect (HTT). 3T3-L1 were successfully transfected with mCVTs derived from 3T3-L1 itself, and also from the monocytic U937, with greater transfec-tion efficiency, pointing towards cell specificity of the delivery platform. The successful development of such a delivery system will not only facilitate the study of the browning process in adipocytes and the associated metabolic dynamics, it would also pave the way for novel anti-obesity treatments.

Poster Session

Auditorium

PC-1A

PC-2APC-2B

PC-4APC-1G

PC-2GPC-3G

PC-4G

PC-5G

PP-4APP-1G

PT-7APT-6A

PT-4BPT-4A

PT-3G

PT-2G

PT-1G

PP-30BPP-25B

PP-14BPP-22A

PP-18APP-17A

PP-13A

PP-9A

PP-8A

-

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PK-14BPK-9B

PK-9APK-3A

PK-2A

PK-1G

PHARMACY RESEARCH DAY 2018

12 June 20189 AM – 5 PM

NUS University Hall

Poster Presentation Map

Link Bridge (Level 2)

From innovative science to optimal health outcomesResearch domains in Department of Pharmacy:PC: Pharmaceutical ChemistryPK: Pharmaceutical Biology & PharmacokineticsPT: Drug Delivery & Pharmaceutical TechnologyPP: Clinical Pharmacy & Pharmacy Practice

12

Poster SessionPharmaceutical Chemistry (PC)

PC-1AGENOME MINING OF BACTERIAL RSAM EN-ZYMES FOR NATURAL PRODUCT DISCOVERYYong How Sheng Rubin & Tooh Yi Wei

PC-2ASYNTHESIS OF C-14 AND C-12 ANDROGRA-PHOLIDEDERIVATIVES AND THEIR ANTI-INFLAMMA-TORY ACTIVITIESNur Fatima Bte Baginda Ali & Wong Kit Yarn

PC-4ADEVELOPMENT OF 2,4-DIHYDROXYL-N-PHEN-YLBENZAMIDE ANALOGUES TARGETING THE NUCLEOTIDE BINDING SITE OF FTO Imran Shah & Austin Tan

PC-2BSYNTHESIS OF INDOLE DERIVATIVES FOR THE POTENTIAL TREATMENT OF CHIKUNGUNYA FEVERLai Xingchen & Lee Boon Chin Adrian

PC-1GINDOLYL AZASPIROKETAL MANNICH BASES ARE POTENT ANTI-MYCOBACTERIAL AGENTS WITH SELECTIVE MEMBRANE PERMEABILIZ-ING EFFECTS AND IN VIVO ACTIVITYSamuel Agyei Nyantakyi

PC-2GCALCARATARIN D ATTENUATES INFLAMMA-TORY RESPONSES THROUGH THE INHIBITION OF NF-KB ACTIVATIONTran Thi Ngoc Quy

PC-3GNOVEL WATER-SOLUBLE COPPER(II) COM-PLEXES WITH MORPHOLINE-THIOSEMICAR-BAZONE HYBRIDS AS TARGET-SPECIFIC ANTI-CANCER DRUGSMaria Babak

PC-4GTHE STRUCTURE-STABILITY-TOXICITY RELA-TIONSHIPS OF L-DOPA AND DOPAMINE THIO-ETHERS IN NEURONAL CULTURESSanzhar Karatayev

PC-5G FROM ADENOSINE A2A BINDER TO ADENOS-INE A3 AGONIST: COMPUTER GUIDED DRUG MODIFICATION FOR COLORECTAL CANCER THERAPYTan Boon Wu Aaron

13

Pharmaceutical Biology &

Pharmacokinetics (PK)

PK-2AUNTARGETED METABOLOMICS OF SERUM SAMPLES FROM PATIENTS WITH NON-PRO-LIFERATIVE DIABETIC RETINOPATHY USING UPLC-MSJoel Quek Xu Ming & Soo Yi Hao

PK-3AGENE EXPRESSION PROFILING AND POTEN-TIAL APPLICATIONS TO DRUG DEVELOPMENT AND THERAPIES IN CNS DISEASESNguyen Thi Phuong Diep & Nicholas Chiam

PK-9ACHARACTERISATION OF TIO2-NP5 INDUCED LEAKINESS ON LSECS AND ITS IMPLICATION ON DRUG DELIVERYNg Li Yang & Hannah Koh Yih Yun

PK-9BTHE ROLE OF MICRORNA EXPRESSION PRO-FILING AS NOVEL BIOMARKERS FOR LYMPHO-MA & SARCOMA CLASSIFICATIONTang Wei Tat Lloyd & Teo Poh Yin

PK-14BNIMBOLIDE INDUCES APOPTOSIS AND INHIB-ITS INVASION AND MIGRATION IN NASOPHA-RYNGEAL CARCINOMA CELLSGoh Wei Zong & Ryan Goh Wen Xuan

PK-1GTITANIUM DIOXIDE NANOPARTICLES INDUC-ES ENDOTHELIAL LEAKINESS AND PROMOTES CANCER METASTASIS IN VITRO AND IN VIVOTee Jie Kai

14

Drug Delivery & Pharmaceutical Technology (PT)

PT-4ATHE DEVELOPMENT OF NOVEL TARGET-SPE-CIFIC ANTICANCER DRUGS AND DRUG DE-LIVERY SYSTEMSRachel Lim Xue Ting & Tay Hui Hsien

PT-6AUNDERSTANDING THE RELEASE PERFOR-MANCE OF PELLETS WITH HYDROPHOBIC INCLUSIONS IN SUSTAINED-RELEASE COAT-INGSTiang Yi Long & Tan Li Hui Desiree

PT-7AEFFECTS OF PARTICLE SURFACE ROUGHNESS ON TABLETING AND DRY POWDER INHALER EFFICIENCYLim Chiu Yue Doreen & Kok Wen Ting, Berlinda

PT-4B INVESTIGATION OF THE EFFECTS OF SUR-FACTANTS, DRUG PARTICLE SIZE AND LIPID MODIFIERS ON PARAFFIN WAX IN THE DE-VELOPMENT OF DRUG DELIVERY SYSTEMS BY SPRAY CONGEALINGAng Chen Yee & Poh Shi Yin Annabel

PT-1G DEVELOPMENT OF DRUG DELIVERY SYS-TEMS TARGETING INFLAMMATIONLee Choon Keong

PT-2G DESIGN AND EVALUATION OF NOVEL BE-TA-HAIRPIN PEPTIDES AS ANTI-INFECTIVESTram Dai Thien Nhan

PT-3G EVALUATING BACTERIAL GHOSTS FOR THE TREATMENT OF TUBERCULOSIS Lim Jieling

Clinical Pharmacy Services &

Pharmacy Practice (PP)

PP-4APREVALENCE, MANAGEMENT, RISK FACTORS AND OUTCOMES OF MULTIDRUG-RESIS-TANT ORGANISMS INFECTIONS AMONG SINGAPORE’S NURSING HOME RESIDENTS ADMITTED TO HOSPITALSChua Jia Hui & Christopher Cheah Guo Shin

PP-8AVANCOMYCIN DOSING AND THERAPEUTIC DRUG MONITORING: DEFINING CURRENT PRACTICES AND IDENTIFYING AREAS FOR PRACTICE IMPROVEMENTWong Wan Qing Elizabeth & Khoo Jingyi, Maple

Poster Session

Poster Session

15

PP-9AEVALUATING THE SAFETY PROFILE OF SO-DIUM-GLUCOSE COTRANSPORTER-2 INHIBI-TORSBernice Leow Li Hsia & Tong Yu Min Queeny

PP-13AMEDICATION USE OF CANCER AND NON-CANCER PATIENTS IN HOME HOSPICE CARE: A RETROSPECTIVE REVIEWSamuel Lau Keng Siang & Lim Yong Quan

PP-17ASAFETY AND EFFECTIVENESS OF AZATHIO-PRINE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN SINGAPORE Foo Sheng Kai Elston & Gan Jia Min

PP-18ADEVELOPMENT OF AN ALGORITHM TO DE-TECT DRUG-INDUCED ACUTE KIDNEY INJU-RY USING ELECTRONIC MEDICAL RECORDSAzrina Imran Tan & Celestine Tan Si Yan PP-22ACONSUMERS’ KNOWLEDGE, ATTITUDES AND PRACTICES OF PAIN MANAGEMENT AND THE USE OF PAIN MEDICATIONSNg Geok Teng & Lim Zhi Wei

PP-14BANTIMICROBIAL PRESCRIBING IN NURSING HOMES: A POINT PREVALENCE SURVEYYang Jing Xi & Wong Chee Liang

PP-25BA RETROSPECTIVE STUDY TO QUANTIFY COST AND IDENTIFY FACTORS ASSOCIATED WITH MEDICATION WASTAGE WITH TRANS-FER OF CARE Verena Ng Zi Yun & Ang Jian Wei

PP-30BCOMPARISON OF TOPICAL CORTICOSTE-ROID PHOBIA INTENSITIES BETWEEN HEALTHCARE AND NON-HEALTHCARE PRO-FESSION STUDENTS IN NATIONAL UNIVERSI-TY OF SINGAPORE (NUS): A CROSS-SECTION-AL STUDY Chan See Kei & Law Xue En Rachel

PP-1GEVALUATING THE IMPACT OF SELF-MON-ITORING OF BLOOD GLUCOSE FREQUEN-CIES ON GLUCOSE CONTROL IN PATIENTS WITH TYPE 2 DIABETES WHO DO NOT USE INSULIN: A SYSTEMATIC REVIEW AND ME-TA-ANALYSISXu Yingqi

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