Singapore-MIT Alliance (SMA)

Micro-porous Paclitaxel-Loaded PLGA Foams -- a New Implant Material for Controlled Release of Chemotherapeutic Agents

Mon, 01 Jan 2007 00:00:00 GMT

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.

Secondary Flow and Upstream Dynamics in Double Bifurcation Model

Mon, 01 Jan 2007 00:00:00 GMT

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.

Synthesis and Complexation Behavior of Pluronic-b-Poly(acrylic Acid) Copolymer with Doxorubicin

Mon, 01 Jan 2007 00:00:00 GMT

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.

On the Droplet Formation Process in Electrohydrodynamic Atomization

Mon, 01 Jan 2007 00:00:00 GMT

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.