http://hdl.handle.net/1721.1/35731 http://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. http://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. http://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. http://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.