Faculty of Science

Department of Pharmacy

Our research focuses on medicinal chemistry involving adenosine receptor antagonist molecules and potential biomedical applications of various nanomaterials.

Research Focus:

Synthesis, characterization, Molecular Modelling and quantitative structure-activity relationship (QSAR) studies of potent antagonists towards different adenosine receptors' subtypes.

Adenosine Receptor Antagonists

As the world population is getting older, neurodegenerative diseases outface modern society and become a serious social problem affecting also, due to their specificity, quality of life of people other than direct victims. Recently, adenosine receptors have been shown to be an attractive target for modulating dopaminergic neuronal death in Parkinson’s disease and other neurodegenerative disorders, including ischemic and hemorrhagic brain injury, Huntington's disease, multiple sclerosis and Alzheimer’s disease. Currently, there is no specific adenosine receptor antagonist approved for using in neurological practice. Extensive studies in this area conducted by academia and pharmaceutical companies resulted in several agents, which are at the different stages of development.

In the search for adenosine receptor antagonists, several heterocyclic systems were investigated. Based on our previous computer modelling results, we are designing new fused heterocyclic compounds. We hypothesize that research in this direction may result in the invention of principally new type of adenosine receptor modulators, particularly antagonists of adenosine receptors.
Therefore we believe that the results of these exploratory projects may be effectively translated to the improvement of therapy of neurodegenerative disorders (1) directly by development of new potential therapeutic agents or (2) indirectly e.g. by (a) creation of new knowledge in form of structure-activity relationship, (b) identification of new heterocyclic cores, effective as lead compounds for the construction of potent and selective adenosine receptor antagonists and (c) improvement of ligand-receptor interaction models. The results will show the direction for further investigations and stimulate development of new approaches for the therapy of neurodegenerative diseases.

 

Nano-bottles for Incorporation, Storage and Drug Release from CNTs.

Nano Bottles

Once functionalized, carbon nanotubes can trigger interesting properties that allow the incorporation of several bioactive molecules that suffers from limited applications due to their low solubility, their intrinsic toxicity or their tendency to degrade easily. Therefore, we have developed a nano-extraction methodology in order to obtain intriguing “carbon nano-bottles”encapsulating a drug and sealed with suitable caps. In particular we conducted a double loading experiment in which we showed that it is possible to close the opened ends of the CNTs, loaded with a lipophilic anticancer drug (Hexamethylmelamine), by simply using fullerenes (C60) as “caps”.

 

Thin films of Graphene and CNTs as Scaffold for Bone Tisssue Engineering involving Human Mesenchymal Stem Cells.

Human Mesenchymal Stem Cells on Thin Film of CNTs

We have investigated the effects of a thin film of pegylated multiwalled carbon nanotubes spray dried onto preheated coverslips in terms of their ability to influence human mesenchymal stem cells' proliferation, morphology, and final differentiation into osteoblasts. Results clearly indicated that the homogeneous layer of functionalized nanotubes did not show any cytotoxicity and accelerated cell differentiation to a higher extent than carboxylated nanotubes or uncoated coverslips, by creating a more viable microenvironment for stem cells. Currently we are trying to replicate the above result in case of Graphene also.

 

Functionalized nanotubes as a multimodal drug carrier against breast cancer.

Targeted Drug Delivery

Cancer is the leading global health crisis and breast cancer poses a significant threat to woman. WHO estimated that 519 000 deaths annually in the world are caused by breast cancer. In Singapore, breast cancer is the most common cancer among women in which about 1,100 women are diagnosed with breast cancer each year. Depends on disease condition and status, chemotherapy is administered by physicians to the patients. However, most common chemotherapeutic drugs suffer from problems such as solubility, bioavailability, adverse reactions, inability to penetrate solid tumour. Thus, a “carrier” is thought to be needed to improve the above-mentioned limitations. Nano-carriers are increasingly attracting the interest as drug-vehicles due to their favourable size (which renders them able to escape from the normal phagocytic defences in the body) and intrinsic characteristics such as mechanical strength, thermal conductivity, as well as interesting magnetic and optical properties. Therefore our objective is to encapsulate bioactive compounds inside functionalized carbon nanotubes to selectively target tumour cells mitochondria while preserving the drugs from inactivation due to interaction with the environment. This ambitious goal has not been achieved and it represents a valuable challenge for researchers.

 

Nanophotonic mechanism, Lab-on-chip (LOC), Nanomedicine, Drug delivery, cancer cells.

Lab On a Chip

Single-cell detection is a crucial aspect in several branches of medicine and biology, allowing the study of immune system function, disease diagnosis and natural cell death. With regards to biology, an in-depth evaluation of the activities associated with a particular cell, in terms of its molecular uptake or production of unique features at its surface. Similarly, in the case of medicine, the clear understanding of cells’ behaviour, on the basis of their exposure to particular stimuli and conditions, represents a fundamental requirement in the development of bioactive agents aimed to target a specific cell subtype without unwanted side effects.
Therefore, in this project we present a novel cytometric system consisting of an advanced device that is able to isolate a few cells among a heterogeneous mixture, and to enhance the entrapment yields, which still represent the limiting aspect of this methodology. To that purpose, we will combine a micromechanical fluidic approach with a nanophotonic mechanism within a unique cell-based lab-on-chip (LOC) device, in order to provide a fast and effective tool able to entrap cells mainly on the basis of their dimensions. The realization of the LOC device required an initial phase of platform design, in which we chose samples of blood as it is made up of heterogeneous cells and platelets, with dimensions ranging from a few micrometers (e.g. erythrocytes, of 6-8 mm) to huge macrophages (of about 21 mm). The basic separation principle, analyzed with 3 main simulation designs, makes use of the inherent characteristic size differences between the different cell populations, to provide a quick and simple separation method. Coupled with micromechanical filters and microfluidics designs, some cell prototypes (e.g. cancer cells) have demonstrated to be effectively segregated from the majority of other cells without the need for additional active control or external forces.

 

Collaborators:

Local Collaborators

Place & Country

Start

Outcomes

Prof Paola Castagnoli
SIgN (Singapore)
2009
Grant of > 1,000,000 SGD
Prof Birgit Lane
IMB (Singapore)
2009
Grant of > 1,000,000 SGD
Prof Chorng Haur Sow
Dept of Physiscs (NUS)
2007
Grant of > 1,000,000 SGD
Prof Victor Yu
Dept of Pharmacy (NUS)
2010
Co-Supervision of PhD students
Dr Han Kiat Ho
Dept of Pharmacy (NUS)
2009
Publication in ACS Nano (2010) and Grant of > 1,000,000 SGD
Dr Barbaros OZYILMAZ
Dept of Physics (NUS)
2010
Invention Disclosure
Dr Vincent Lee
Dept of Electrical & Computer Engineering (NUS)
2008
Grant of > 1,000,000 SGD, Lab on Chip and Transdermal delivery
Dr Sylvie Alonso
Dept of Microbiology (NUS)
2010
Project on Transdermal Delivery of Vaccine

 

International Collaborators

Place & Country

Start

Outcomes

Prof Giampiero Spalluto
University of Trieste (Italy)
2000
Several publications in top journals in the field of Medicinal Chemistry
Prof Stefano Moro
University of Padua (Italy)
2000
Several publications in top journals in the field of Medicinal Chemistry
Prof Yupeng Ren
Shanghai Institute of Materia Medica (China)
2008
One artcile in Advanved Materials (2008) and one in ACS Nano (2010)
Prof Sundara Ramaprabhu
Indian Institute of Technology, Madras (India)
2008
One article in Current Nanoscience (2010)
Dr Harendra Paira
University of Queensland (Australia)
2010
Joint PhD scholarship

Dr Peter Griffiths

University of Cardiff (Wales)
2009
Overseas Attachment programme
Dr Khalid Al-Rubeaan

King Saud University (Saudi Arabia)

2009
NanoCore scholaship and project on Diabetes

Funding :

Grant/s Awarded (current)

Project Title

Funding Agency/ies

Amount Requested (S$)

Duration of Award

1
Nanoneedle devices for transdermal vaccine delivery
MOE-Tier 2
1,017,020 (Non-AcRF)
June 2010-May 2010
2
Quantum Dots-based Nanofluidic Device for determining the ethiology of Rhinitis
SERC-TSRP (A-STAR)
1,194,040 (Non-AcRF)
May 2010-April 2013
3
Strategic functionalizations of Carbon Nanotubes for transport, protection and delivery of Drugs
FRC
165,054 (AcRF)
April 2010-March 2010
4
NanoTechnology for Transdermal Delivery
King Saud University
5 Millions (Non-AcRF)
2009-2013
 
 

Total

2,376,114

 

 

Grant/s Awarded (Completed)

Project Title

Funding Agency/ies

Amount Awarded (S$)

Duration of Award

1
Design, synthesis and evaluation of Heterocyclic molecules as potent and selective antagonists towards adenosine receptor subtypes
FRC
180,000 (AcRF)
Dec 2006-June 2009
2
Investigations of new lead compounds as Adenosine receptors antagonists and their potential application in the treatment of neurodegenerative Diseases
NMRC/NIG
200,000 (Non-AcRF)
June 2008-May-2010
 
 

Total

380,000

 

 

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