Highlights

Morphology of Functionalized and Drug-loaded, Biodegradable Microspheres

Scientific Achievement

We have been investigating the potential for encapsulating DNA and enzymes within biodegradable nanospheres and microspheres as a vehicle for drug transport and delivery.  This study involves synthesis of drug-loaded nanospheres and then characterization.  The characterization routinely involves physical evaluation of the morphology of the nanospheres, which is done by electron microscopy.  The electron microscopy provides information on the size distribution of nanosphere populations and visual evidence of the shape and any surface defects that can be resolved. 

We have been working with the Microscopy Center to improve the resolution of our soft materials.  This is significant because many of the materials commonly interrogated at the Facility are hard metal or ceramic samples.  We, thus, used the environmental SEM (FEI Quanta-400 FEG ESEM) and with the help of R. Cook, began varying the microscope parameters to determine the parameters for best resolution.  These were compared to the S-4700 SEM in ultra-high resolution mode.  We found that the images obtained with the GSED detector were superior to those obtained with the low kV PLA large field detector but that the image resolution was poorer than those obtained by the S-4700 SEM in high-resolution mode.  However, even though the images obtained by the ESEM were poorer resolution, the samples did not require pre-coating of conductive material, which can create surface artifacts in the sample.

Significance

The work to develop suitable nanospheres to act as drug vehicles continues.  Significant challenges must be overcome.  These include correlating drug loading within the nanospheres to successful transfection in the cell (DNA release from nanospheres and subsequent action by the DNA on cell function) or action on the organ (such as dissolution of blood clots).  Some of the procedures that have been developed for drug encapsulation and characterized at the Microscopy Center have moved on to in vitro and in vivo testing to determine the efficacy of the drug delivery vehicle as published in Thrombosis Res. 121 (6), 799-811 (2008), J. Magn. Magn. Mater. 311, 376-378 (2007), and J. Control. Rel. 119, 52-58 (2007).

The research will continue.  The focus for 2008 is to develop magnetic micropsheres that can spontaneously release drug after exposure to a variable magnetic field and to encapsulate small molecule drugs such as DNA fragments and small molecule inhibitors.

Performers

M. D. Kaminski, C. J. Mertz (Argonne-CSE); R. Kraig, A. J. Rosengart (U. Chicago)