Author: Fen Ye

Publisher:

Published: 2007

Total Pages: 111

ISBN-13:

"During last decades, significant progress has been made in the field of drug delivery with the development in materials synthesis. Polymer drug delivery systems can realize the prolonged release of drugs, enhance effective drug solubility, protect drug from degradation by enzymes, and reduce drug toxicity. Recently porous materials have been developed as the controlled release host of bioactive reagents, and have shown better controlled release of reagents. Microemulsions are thermodynamically stable, isotropic and transparent dispersions of two normally immiscible fluids stabilized by surfactants and often cosurfactants. Microemulsions have been investigated in a wide range of application including enhanced oil recovery, detergents, bioreactors, drug delivery and to template polymerization. Polymerization of bicontinuous microemulsions can produce materials with defined porous structures. Various surfactants have been reports to form bicontinuous microemulsion for the polymerization of porous materials. Application of biocompaticle surfactants eliminate the need for residual surfactant removal after microemulsion polymerization, and the porous polymeric materials obtained can be used in drug delivery to improve the drug diffusion and enhance the deposition of drug within body. The objective of this study is to develop the biocompatible porous polymeric materials suitable for protein and lipids delivery using methyl methacrylate (MMA) as monomer and 2-hydroxyethyl methacrylate (HEMA) or acrylic acid (AA) as comonomer. Four biocompatible surfactants were tested for the capacity of forming single phase microemulsion at high aqueous content. The Winsor-IV microemulsions formulated with 3:1 HEMA to MMA and surfactant of L1695, T1307 or F127 were studied for the microstructure by viscosity and conductivity measurements. Conductivity and vicsocity measurements confirmed that microstructure of microemulsion was dependent on the aqueous content. With the increase of aqueous content, the structure progressed from W/O droplets, to bicontinuous networks, and finally to O/W droplets. The structure of polymerized microemulsions formulated with various surfactants was studied by scanning electron microscopy (SEM) and the non-invasive freezing point depression (FPD) method. Under SEM, nanopores were observed from the system formulated with 3:1 HEMA to MMA and surfactant of L1695, T1307 or F127. The FPD results were consistent with SEM morphology examination, and demonstrated that the radiuses of nanopores presented in these three systems were mostly in the range of 10-50 nm. Moreover, the nanopores had a distribution dependent on aqueous content. Micropores were observed in the SEM image of the stimuli-responsive partially neutralized 3:2 AA/MMA/10 % F77 system. The incorporation of drugs didn't change the microstructure of polymers. Polymers derived from microemulsions stabilized by four surfactants were applied to encapsulate drugs, and the drug release profiles were investigated. The nanoporous polymer particle suspension exhibited controlled release of Rhodamine B. The release rate was four times lower than the drug loaded to 10% F127 solution. Nanoporous monoliths derived from L1695 or T1307 stabilize microemulsions could realize the gradual release of B-galactosidase within 6 hours. The pH of precursor microemulsion stablized by T1307 was 8, and higher than that of the L1695 stabilized microemulsion. Enzymes released from L1695 system displayed higher apparent activity since lower pH favors enzyme catalysis when pH is larger than 5. The partially neutralized system demonstrated swelling behavior dependent on the pH of aqueous medium. Lipase lost activity in pH=1.2 medium, while lipase released from pH-sensitive system in pH=6.8 buffer showed increased activity over time. The release of lipase because stable after 6 hours. These release profiles suggested that the porous systems could achieve prolonged release of drugs, and all the systems are promising for the application in drug deliver."--Abstract.