https://hdl.handle.net/1721.1/35731 2026-04-06T10:13:31Z https://hdl.handle.net/1721.1/35874 Micro-porous Paclitaxel-Loaded PLGA Foams -- a New Implant Material for Controlled Release of Chemotherapeutic Agents Lee, Lai Yeng; Wang, Chi Hwa; Smith, Kenneth A. Supercritical gas foaming using CO₂ was used to fabricate blank poly DL lactide-co-glycolide (PLGA) micro-porous foams. Paclitaxel-loaded PLGA foams were also produced for the first time using a modification of the supercritical gas foaming technique whereby pacltitaxel-loaded PLGA microparticle powders obtained from spray drying was foamed. In this study, it was found that using polymer powders, more compact foams and smaller pores foams may be achieved with lower saturation pressures and time which is due to the much higher surface area to volume ratio of the microparticle powders. Experiments were carried out with varying lactide to glycolide ratio of the copolymer PLGA and it was shown that the pore size, in vitro swelling behavior and drug release profiles may be altered by changing the copolymer composition used. The foams fabricated also have good mechanical strength which makes it suitable to be applied as an implantation material for the post-surgical controlled delivery of chemotherapeutic drugs. The residual organic solvent content of the paclitaxel-foams were well below the allowable limit set by the US Pharmacopeia as shown in the present study. The in vitro release profiles over a period of 5 weeks showed close to linear release. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35876 Secondary Flow and Upstream Dynamics in Double Bifurcation Model Leong, Fong Yew; Smith, Kenneth A.; Wang, Chi-Hwa Flow behavior in bifurcation models is of great importance to health risk assessments and pulmonary drug delivery. This is particularly true of secondary flow behavior in multi-bifurcation models. Previously, both numerical and experimental methods have shown that four-vortex secondary flow structures can develop in the cross-sections of grand-daughter branches. This work shows that the development of secondary flow in the grand-daughter tubes is due to local stretching of vortex lines in the upstream DT. Scaling arguments have been used to derive two critical parameters governing this particular vorticity transport problem. A simple model for vorticity generation and transport is proposed, taking into account the geometric limitations imposed by the rigid walls of the tubes. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35875 On the Droplet Formation Process in Electrohydrodynamic Atomization Lim, Liang Kuang; Xie, Jingwei; Hua, Jinsong; Wang, Chi-Hwa; Smith, Kenneth A. A novel method of using a secondary electrical field source to control both the spray mode and the droplet size in the electrohydrodynamic atomization process is presented. Size of particles fabricated using the electrohydrodynamic atomization process can also be controlled using the same method. To further understand the electrohydrodynamic atomization process and the effect of a secondary electrical field source, a Front Tracking/Finite Difference method was employed for the Computational Fluid Dynamic Simulation of the Electrohydrodynamic Atomization process. To take into account of the electrical stresses, the Maxwell Stress tensor was included in the Navier-Stokes equation. Special care was taken to accurately include a secondary electrical field source. The formation of the Taylor Cone, jet and liquid droplets was successfully simulated. The simulated results were compared to the experimental results and the comparison was found to be reasonable when empirically determined charge density on the surface of the liquid was used as a simulation input. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35873 Synthesis and Complexation Behavior of Pluronic-b-Poly(acrylic Acid) Copolymer with Doxorubicin Tian, Y.; Tam, Michael K. C.; Hatton, T. Alan; Bromberg, Lev Poly(acrylic acid) (PAA) was attached on both termini of Pluronic P85 copolymer (EO27PO39EO27)) via atom transfer radical polymerization (ATRP) to produce a novel block copolymer, PAA-b-P85-b-PAA (P85PAA). The P85PAA-DOX complex formation and drug loading were strongly dependent on the PAA segment and pH, where the protonation of the carboxyl groups in the PAA segment at pH<7.2 reduced the binding sites of DOX onto P85PAA chains, resulting less DOX uptake at low pH. The composition of the copolymer-DOX complexes that at pH 7.2 was close to the stoichiometric (1:1 mol Dox:carboxyl ratio), indicating the dominance of the electrostatic interactions between cationic DOX molecules and carboxyl groups. DOX loading at pH 5.0 reduced to 0.6:1 molar ratio of DOX:carboxyl indicated that protonation of the carboxyl reduced the DOX binding to the P85PAA block copolymer. DOX release from the complex is highly pH-responsive process, where 57% of encapsulated DOX was released in 30h at pH7.2, and the cumulative release fraction was accelerated to 95% by decreasing the pH to 5.0. Thus, complexation of DOX with P85PAA yielded a drug delivery system affording a pH-triggered release of DOX in acidic environment pH5.0. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35879 Understanding the Induced Self-Assembly System Between PEO-b-PAA and Iron Sondjaja, H. Ronny; Tam, Michael K.C.; Yap, Miranda G.S.; Hatton, T. Alan The induced self-assembly phenomenon between PEO-b-PAA and Fe(II) was investigated. It was revealed that the electrostatic interaction between Fe(II) in the form of green rust (GR²⁺) particles and the COO- groups from the PAA backbone at pH 7 causes the formation of stable aggregates with Dh~156 nm. While it is stable at pH 7, the induced self-assembly structure, however, is disordered during the transformation of GR²⁺ into Fe₃O₄. The pH increment and the oxidation process itself were found to affect the stability. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35878 Three-Dimensional Simulation of Carmustine Delivery to a Patient-Specific Brain Tumor Arifin, Davis Yohanes; Wang, Chi-Hwa; Smith, Kenneth A. This study presents the recent development of three-dimensional patient-specific simulation of carmustine delivery to brain tumor that highlights several crucial factors affecting the delivery. The simulation utilizes the full-brain three-dimensional geometry constructed from magnetic resonance images (MRI) of a brain tumor patient. Prior to the simulation with tumor, the baseline simulation is initially done to obtain the interstitial fluid homeostasis in the normal brain so that the real picture of brain fluid dynamics in human brain is obtained. The simulation is conducted by coupling equations of continuity, motion, and carmustine species conservation, which, in turn, are solved simultaneously to calculate pressure, flow, and drug concentration fields, respectively. Carmustine is delivered by using the commercially available Gliadel wafers following the surgical removal of the tumor. The possible effects of vasogenic edema (due to surgery trauma) to brain fluid dynamics is also included. Here, the compiled results highlight that the drug release profile is, if not more than, as important as the dosage and the possible increase of convection due to edema. This study also reveals that a new strategy, namely convection enhanced delivery (CED) is able to increase drug penetration by enhancing interstitial fluid convection; but, over-enhanced convection may cause toxicity complications to surrounding healthy tissue during later stages of treatment. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35877 Synthesis and Self-Assembly Behavior of Poly(acrylic Acid)-b-Poly(l-Amino Acid) System Sinaga, Akasta; Ravi, P.; Hatton, T. Alan; Tam, Michael K. C. The talk will present the synthesis and characterization of a new class of hybrid amphiphilic system between an electrolyte polyacrylic acid (PAA) synthetic segment, and a hydrophobic beta-sheet forming peptide segment, poly(L-valine) (PLVAL). The synthesis of monodispersed copolymers (Mw/Mn < 1.3) was achieved through a combination of atom transfer radical polymerization, click chemistry, and nickel-catalyzed ring opening of N-carboxy anhydrides. The click chemistry is demonstrated to be an excellent method for the intermediate -amino functionalization step to afford macroinitiators that are free from deactivating or interfering molecules with degree of functionality about 90%. Light scattering and circular dichroism characterization of PAAx-block-PLVALy (x-y of 80-100, 80-80, 80-60, and 40-100) show a correlation of the formation of spherical core-shell micelles to the ability of the peptide segment to form ordered beta-sheet structures. Generally, the beta sheet formation is stabilized by a low pH condition (low charge on PAA), higher Val/PAA ratio (less interference from PAA-Val hydrogen bondings), and degree of core shielding by PAA in the presence of disrupting agents, e.g. urea. At higher pH, the beta-sheet structure was also found to counteract the charge repulsions of PAA units, which allows the micelles to retain their overall size and shape. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35872 Multivariate Perturbation of a Growth Factor-Cytokine Signalling Network Reveals Complex Systemic Responses in Glioblastoma Cells Tang, Yew Chung; Wan, Guoqiang; Stephanopoulos, Gregory; Too, Heng-Phon Glioblastoma cells can evade TRAIL-induced apoptosis through various strategies involving the growth factor-activated MEK–MAPK/ERK and PI3K–Akt/PKB pro-survival signalling cascades. Although these signalling cascades have been studied extensively, our understanding of how they interact and participate in modulating apoptosis as part of a dynamic cell-wide network of signalling proteins is limited by traditional univariate experimental paradigms. Here, we study three human glioblastoma cell lines with differential response to TRAIL-induced apoptosis: LN229 (resistant), T98G, and A172 (both susceptible). We show that differential TRAIL susceptibility in these cell lines is unrelated to expression levels of agonist (DR4 and DR5) or antagonist (DcR1, DcR2, and OPG) receptors for TRAIL and thus TRAIL-induced apoptosis in these cell lines is modulated at the intracellular signalling level. Serum, comprising multiple factors that regulate cellular activity, enhances TRAIL resistance in T98G but not LN229 and A172 cell lines. This protective effect against TRAIL-induced apoptosis is recapitulated by the prototypical survival factor PDGF in T98G cells. Univariate inhibition of cell survival signalling cascades with MEK inhibitor U0126 and PI3K inhibitor LY294002 sensitized T98G cells to TRAIL but did not abrogate PDGF-mediated protection. However, further perturbation with inhibitors in a combinatorial and multivariate manner reveal synergistic effects and complex systemic responses which may be a basis for uncovering novel insights into the regulation of TRAIL-induced apoptosis. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35871 Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection Simeon, Fritz; Tam, Michael K.C.; Hatton, T. Alan; Too, Heng-Phon Development of safe and efficient synthetic gene delivery vectors is hampered with limited understanding the fundamental correlation of physicochemical properties of the vectors with their biological activities. Five major barriers contributing to poor transfection efficiency of synthetic vectors include cellular association, endosomal escape, intracellular trafficking, nuclear translocation and transcription of exogenous genes. In this study, the correlation of physicochemical properties of polymer-based synthetic gene delivery vectors (polyplexes) with cellular association as the first barrier for in vitro transfection was investigated. Polyethylene oxide block copolymer with poly(2-(dimethylamino)ethyl methacryate) (PEO-b-pDMAEMA) was chosen as the model in this study. Cellular association and transfection efficiency of block copolymer complexes were studied in Neuro2A cells. Quantitative real time polymerase chain reaction (PCR) was applied to elucidate the cellular association of polyplexes. Physicochemical properties of the vectors including size and surface charge were characterized using light scattering measurements. Formation of aggregate was found as the major indication for high cellular association and uptake for in vitro transfection. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35870 Preparation of DNA-Functionalised CdSe/ZnS Quantum Dots Pong, Boon Kin; Trout, Bernhardt L.; Lee, Jim Yang We functionalised core-shell CdSe/ZnS quantum dots (QDots) with short-chain 3-mercaptopropionic acid (3MPA) to render these nanocrystalline semiconductor water-soluble. The ligand-exchange reaction was significantly improved with the use of an organic base to first remove the thiolic hydrogen. Non-bound 3MPA could be removed from the colloid by dialysis, but it was found that the choice of membrane is important. Cellulose membrane obliterated the photoluminescence of the QDots, while cellulose-acetate membrane worked well. Amine-modified DNA was then attached to the QDots through amide bond linkage, using EDC and NHS as reaction promoters. The pH of the reaction medium has an important impact on the successful attachment of functional DNA on the QDots. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35869 DNA Directed Assembly Probe for Detecting DNA-Protein Interaction in Microarray Format Ng, Jin Kiat; Ajikumar, Parayil Kumaran; Tang, Yew Chung; Stephanopoulos, Gregory; Too, Heng-Phon Quantifying DNA-protein interaction using DNA microarrays are gaining increasing attention due to their ability to profile specificity of interactions in a high-throughput manner. This paper describes a new approach that used the ability of ssDNA-dsDNA probe to complex with DNA binding proteins in the solution phase and then spatially immobilized onto microarray through specific DNA hybridization. In one case, the Spatially Addressable DNA Array (SADA) approach demonstrated that enzymatic cleavage in solution is more efficient than if conducted heterogeneously. In addition, binding of RNA polymerase with promoter DNA could be detected with this strategy. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35868 Biological Routes to Gold Nanoplates Xie, Jianping; Lee, Jim Yang; Wang, Daniel I.C.; Ting, Yen Peng Gold nanoplates are promising for optical and electronic applications; but their synthesis is complex, often requiring a seeded growth process or spherical to triangle morphology transformation. We have discovered a biological protocol to promote the anisotropic growth of different crystal planes under ambient conditions. Thin, flat, single-crystalline gold nanoplates were produced when aqueous chloroaurate ions reacted with the mycelia-free spent medium. While the exact mechanism for this shape-controlled synthesis is not clear at this time, the possibility of achieving nanoparticle shape control in a fungal based system is exciting. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35867 Prediction of Glycerol-Effect on Antigen-Antibody Binding Affinity from Molecular Dynamics Simulations Vagenende, Vincent; Yap, Miranda G.S.; Trout, Bernhardt L. Many biological and biotechnological processes are controlled by protein-protein interactions in solution. In order to understand, predict and optimize such processes, it is valuable to understand how additives such as salts, sugars, polyols and denaturants affect protein-protein interactions. Currently, no methodology to foretell the effect of additives on protein-protein interactions has been established and frequently and extensive empirical screening to identify additives beneficial to the protein process is resorted to. In this work, we developed a methodology enabling the prediction of the additive-effect on the protein reaction equilibrium. The only prerequisite is that the atomic structure of the protein reactants and products are known. The methodology is based on the thermodynamic model for preferential interactions and makes use of molecular dynamics simulations to gauge additive-protein interactions. In order to validate our methodology, the change in binding affinity of the antibody fragment Y32S Fv D1.3 for lysozyme in the presence of varying glycerol concentrations is being calculated and the results will be compared with experimental data from literature. Finally, our methodology will be used to predict the glycerol effect on the binding affinity of wild type Fv D1.3 and various mutants. 2007-01-01T00:00:00Z https://hdl.handle.net/1721.1/35866 Simple and Versatile Route to the Synthesis of Anisotropic Bimetallic Core-Shell and Monometallic Hollow Nanostructures: Ag (AgCl)-Pt Core-Shell Nanocubes and Pt Nanoboxes Tan, Yen Nee; Wang, Daniel I.C.; Lee, Jim Yang We report herewith a simple and versatile route for the preparation of anisotropic Ag(AgCl)-Pt core-shell nanocubes and Pt nanoboxes. The core-shell nanocubes were first synthesized through the simultaneous reduction method and then treated with bis-(p-sulfonatophenyl)-phenylphosphine (BSPP) to remove the core materials. The changes in morphology, structure and composition during these syntheses were carefully followed. We found that, BSPP, in addition to being an effective silver oxidant, is also a good solubilizer for AgCl nanoparticles at room temperature. This allowed us to prepare pure Pt nanoboxes easily from the as-synthesized Ag (AgCl)-Pt nanocubes using a greatly simplified post-treatment for AgCl, which is the perennial impurity byproduct in the preparation of hollow nanostructures by the replacement reactions. 2007-01-01T00:00:00Z